.ipynb

{
 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Corona paper analysis\n",
    "\n",
    "## \"ab.csv\" abstract part of include corona related papers. Each line is taken from different paper."
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# İLAYDA BÜYÜKAKOVA\n",
    "# B1405.090024\n",
    "# SEN430 DATA ANALYSIS"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.\n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    These first authors contributed equally to this article BACKGROUND As of February 29, 2020, nearly 80 thousand confirmed novel coronavirus (SARS-CoV-2) infection cases had been reported in China. Risk factors for transmission remain largely uncharacteri\n",
       "2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We've also identified four historical mutations that are able to produce a \"GST-like\" S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.\n",
       "3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. OPEN ACCESS Citation: Brinkmann C, Hoffmann M, Lübke A, Nehlmeier I, Krämer-Kühl A, Winkler M, et al. (2017) The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells. PLoS ONE 12(12): e0189073. https://doi.org/10.\n",
       "4    (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. This study was performed to investigate the effects of stress caused by dialysis treatment under isolation. Plasma samples from the HD patients and medical staff were collected at the time of isolation(M0), the following month(M1), and three months after isolation(M3). Parameters for stress included circulating cell-free genomic DNA(ccf-gDNA), circulating cell-free mitochondria DNA(ccf-mtDNA), and pentraxin-3(PTX-3). Decreased values of Hct, kt/v and ca x p were recovered after the end of two weeks of isolation. The levels of ccf-gDNA and ccf-mtDNA were the highest at M0 and decreased gradually in both HD patients and the medical staff. The normalization of ccf-gDNA and ccf-mtDNA was significantly delayed in HD patients compared with the response in the medical staff. PTX-3 increased only in HD patients and was highest at M0, and it then gradually decreased. Medical isolation and subnormal quality of care during the MERS outbreak caused extreme stress in HD patients. Plasma cell-free DNA and PTX-3 seems to be good indicators of stress and quality of care in HD patients. Measurement of plasma cell-free genomic DNA and cell-free mitochondria DNA. Circulating cf-DNA was extracted from 200 μL of plasma using a QIAamp DNeasy Blood and Tissue kit (Qiagen, Valencia, Calif). The ccf-gDNA and ccf-mtDNA were amplified using a StepOnePlus real-time PCR system (Applied Biosystems, Massachusetts). Primers for the human NADH1 dehydrogenase 1 gene (ND1) were used for mtDNA, and primers for the human lipoprotein lipase gene (LPL) were used for gDNA. Standard DNA fragments of ND1 and LPL were synthesized using an Integrated DNA Technologies kit (IDT, Coralville, IA) for absolute quantification. The fragment solutions were 10-fold serially diluted. The concentrations of DNA were converted to copy number using the Andrew Staroscik Calculator for the absolute copy number from a template 33 . All samples were analyzed in duplicate, and a no-template negative control was included in every analysis.\n",
       "Name: Content, dtype: object"
      ]
     },
     "execution_count": 1,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#Download data\n",
    "\n",
    "# scraping\n",
    "import pandas as pd\n",
    "import numpy as np\n",
    "\n",
    "import seaborn as sns\n",
    "from scipy import stats\n",
    "import warnings\n",
    "warnings.filterwarnings(\"ignore\")\n",
    "\n",
    "# text preprocessing\n",
    "import re\n",
    "import nltk\n",
    "\n",
    "from collections import Counter\n",
    "from nltk.corpus import stopwords \n",
    "from nltk.tokenize import word_tokenize\n",
    "from nltk.tokenize import RegexpTokenizer\n",
    "from nltk.probability import FreqDist\n",
    "from nltk.corpus import stopwords\n",
    "\n",
    "from nltk.stem import WordNetLemmatizer\n",
    "\n",
    "# visualization\n",
    "import matplotlib.pyplot as plt\n",
    "pd.options.display.max_colwidth = 8000\n",
    "\n",
    "# other\n",
    "import os\n",
    "import sys\n",
    "\n",
    "# Set pandas view options\n",
    "pd.set_option('max_rows',50)\n",
    "pd.set_option('max_columns',50)\n",
    "\n",
    "\n",
    "\n",
    "x = pd.read_csv('ab.csv', delimiter ='##', encoding='utf-8', engine='python')  \n",
    "#x.head()\n",
    "y= x['Content']\n",
    "\n",
    "y.head()\n"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# What is the most frequent words?"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "count          10581\n",
       "unique          9691\n",
       "top       Background\n",
       "freq               5\n",
       "Name: Content, dtype: object"
      ]
     },
     "execution_count": 2,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "y.describe()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "['Unnamed: 0' 'Content' 'Unnamed: 2']\n"
     ]
    }
   ],
   "source": [
    "print(x.columns.values)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Content</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>These first authors contributed equally to this article BACKGROUND As of February 29, 2020, nearly 80 thousand confirmed novel coronavirus (SARS-CoV-2) infection cases had been reported in China. Risk factors for transmission remain largely uncharacteri</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>(GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We've also identified four historical mutations that are able to produce a \"GST-like\" S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>(IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. OPEN ACCESS Citation: Brinkmann C, Hoffmann M, Lübke A, Nehlmeier I, Krämer-Kühl A, Winkler M, et al. (2017) The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells. PLoS ONE 12(12): e0189073. https://doi.org/10.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>(n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. This study was performed to investigate the effects of stress caused by dialysis treatment under isolation. Plasma samples from the HD patients and medical staff were collected at the time of isolation(M0), the following month(M1), and three months after isolation(M3). Parameters for stress included circulating cell-free genomic DNA(ccf-gDNA), circulating cell-free mitochondria DNA(ccf-mtDNA), and pentraxin-3(PTX-3). Decreased values of Hct, kt/v and ca x p were recovered after the end of two weeks of isolation. The levels of ccf-gDNA and ccf-mtDNA were the highest at M0 and decreased gradually in both HD patients and the medical staff. The normalization of ccf-gDNA and ccf-mtDNA was significantly delayed in HD patients compared with the response in the medical staff. PTX-3 increased only in HD patients and was highest at M0, and it then gradually decreased. Medical isolation and subnormal quality of care during the MERS outbreak caused extreme stress in HD patients. Plasma cell-free DNA and PTX-3 seems to be good indicators of stress and quality of care in HD patients. Measurement of plasma cell-free genomic DNA and cell-free mitochondria DNA. Circulating cf-DNA was extracted from 200 μL of plasma using a QIAamp DNeasy Blood and Tissue kit (Qiagen, Valencia, Calif). The ccf-gDNA and ccf-mtDNA were amplified using a StepOnePlus real-time PCR system (Applied Biosystems, Massachusetts). Primers for the human NADH1 dehydrogenase 1 gene (ND1) were used for mtDNA, and primers for the human lipoprotein lipase gene (LPL) were used for gDNA. Standard DNA fragments of ND1 and LPL were synthesized using an Integrated DNA Technologies kit (IDT, Coralville, IA) for absolute quantification. The fragment solutions were 10-fold serially diluted. The concentrations of DNA were converted to copy number using the Andrew Staroscik Calculator for the absolute copy number from a template 33 . All samples were analyzed in duplicate, and a no-template negative control was included in every analysis.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10576</th>\n",
       "      <td>Zoonosis is the leading cause of emerging infectious diseases. In a recent article, R. S. Shabman et al. (mSphere 1[1]:e00070-15, 2016, 10.1128 report the identification of a novel gammaherpesvirus in a cell line derived from the microbat Myotis velifer incautus. This is the first report on a replicating, infectious gammaherpesvirus from bats. The new virus is named bat gammaherpesvirus 8 (BGHV8), also known as Myotis gammaherpesvirus 8, and is able to infect multiple cell lines, including those of human origin. Using nextgeneration sequencing technology, the authors constructed a full-length annotated genomic map of BGHV8. Phylogenetic analysis of several genes from BGHV8 revealed similarity to several mammalian gammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV). Citation Host KM, Damania B. 2016. Discovery of a novel bat gammaherpesvirus. mSphere 1(1):e00016-16.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10577</th>\n",
       "      <td>Zoonotic avian influenza poses a major risk to China, and other parts of the world. H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China. This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10578</th>\n",
       "      <td>Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 . Host immune responses to CoV are complex and regulated in part through antiviral interferons.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10579</th>\n",
       "      <td>Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in lowresource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10580</th>\n",
       "      <td>Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens. IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>10581 rows × 1 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Content\n",
       "0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.\n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      These first authors contributed equally to this article BACKGROUND As of February 29, 2020, nearly 80 thousand confirmed novel coronavirus (SARS-CoV-2) infection cases had been reported in China. Risk factors for transmission remain largely uncharacteri\n",
       "2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We've also identified four historical mutations that are able to produce a \"GST-like\" S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.\n",
       "3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. OPEN ACCESS Citation: Brinkmann C, Hoffmann M, Lübke A, Nehlmeier I, Krämer-Kühl A, Winkler M, et al. (2017) The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells. PLoS ONE 12(12): e0189073. https://doi.org/10.\n",
       "4      (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. This study was performed to investigate the effects of stress caused by dialysis treatment under isolation. Plasma samples from the HD patients and medical staff were collected at the time of isolation(M0), the following month(M1), and three months after isolation(M3). Parameters for stress included circulating cell-free genomic DNA(ccf-gDNA), circulating cell-free mitochondria DNA(ccf-mtDNA), and pentraxin-3(PTX-3). Decreased values of Hct, kt/v and ca x p were recovered after the end of two weeks of isolation. The levels of ccf-gDNA and ccf-mtDNA were the highest at M0 and decreased gradually in both HD patients and the medical staff. The normalization of ccf-gDNA and ccf-mtDNA was significantly delayed in HD patients compared with the response in the medical staff. PTX-3 increased only in HD patients and was highest at M0, and it then gradually decreased. Medical isolation and subnormal quality of care during the MERS outbreak caused extreme stress in HD patients. Plasma cell-free DNA and PTX-3 seems to be good indicators of stress and quality of care in HD patients. Measurement of plasma cell-free genomic DNA and cell-free mitochondria DNA. Circulating cf-DNA was extracted from 200 μL of plasma using a QIAamp DNeasy Blood and Tissue kit (Qiagen, Valencia, Calif). The ccf-gDNA and ccf-mtDNA were amplified using a StepOnePlus real-time PCR system (Applied Biosystems, Massachusetts). Primers for the human NADH1 dehydrogenase 1 gene (ND1) were used for mtDNA, and primers for the human lipoprotein lipase gene (LPL) were used for gDNA. Standard DNA fragments of ND1 and LPL were synthesized using an Integrated DNA Technologies kit (IDT, Coralville, IA) for absolute quantification. The fragment solutions were 10-fold serially diluted. The concentrations of DNA were converted to copy number using the Andrew Staroscik Calculator for the absolute copy number from a template 33 . All samples were analyzed in duplicate, and a no-template negative control was included in every analysis.\n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              ...\n",
       "10576                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Zoonosis is the leading cause of emerging infectious diseases. In a recent article, R. S. Shabman et al. (mSphere 1[1]:e00070-15, 2016, 10.1128 report the identification of a novel gammaherpesvirus in a cell line derived from the microbat Myotis velifer incautus. This is the first report on a replicating, infectious gammaherpesvirus from bats. The new virus is named bat gammaherpesvirus 8 (BGHV8), also known as Myotis gammaherpesvirus 8, and is able to infect multiple cell lines, including those of human origin. Using nextgeneration sequencing technology, the authors constructed a full-length annotated genomic map of BGHV8. Phylogenetic analysis of several genes from BGHV8 revealed similarity to several mammalian gammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV). Citation Host KM, Damania B. 2016. Discovery of a novel bat gammaherpesvirus. mSphere 1(1):e00016-16.\n",
       "10577                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     Zoonotic avian influenza poses a major risk to China, and other parts of the world. H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China. This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China.\n",
       "10578                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 . Host immune responses to CoV are complex and regulated in part through antiviral interferons.\n",
       "10579                                              Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in lowresource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.\n",
       "10580                                              Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens. IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.\n",
       "\n",
       "[10581 rows x 1 columns]"
      ]
     },
     "execution_count": 4,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "y = np.array(y)\n",
    "df_y = pd.DataFrame({'Content': y })\n",
    "df_y = df_y[[ 'Content']]\n",
    "df_y"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "['Content']\n"
     ]
    }
   ],
   "source": [
    "print(df_y.columns.values)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               the interaction of dc-sign with pathogens triggers specific signaling events that modulate dc-maturation and activity and regulate t-cell activation by dcs. in this work we evaluate whether f. hepatica glycans can immune modulate dcs via dc-sign. we demonstrate that dc-sign interacts with f. hepatica glycoconjugates through mannose and fucose residues. we also show that mannose is present in high-mannose structures, hybrid and trimannosyl n-glycans with terminal glcnac. furthermore, we demonstrate that f. hepatica glycans induce dc-sign triggering leading to a strong production of tlr-induced il-10 and il-27p28. in addition, parasite glycans induced regulatory dcs via dc-sign that decrease allogeneic t cell proliferation, via the induction of anergic/regulatory t cells, highlighting the role of dc-sign in the regulation of innate and adaptive immune responses by f. hepatica. our data confirm the immunomodulatory properties of dc-sign triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.\n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        these first authors contributed equally to this article background as of february 29, 2020, nearly 80 thousand confirmed novel coronavirus (sars-cov-2) infection cases had been reported in china. risk factors for transmission remain largely uncharacteri\n",
       "2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   (gst) with various homologs differentially expressed in the lens. however, there is no direct structural information that helps to delineate the mechanisms by which s-crystallin could have evolved. here we report the structural and biochemical characterization of novel s-crystallin-glutathione complex. the 2.35-å crystal structure of a s-crystallin mutant from octopus vulgaris reveals an active-site architecture that is different from that of gst. s-crystallin has a preference for glutathione binding, although almost lost its gst enzymatic activity. we've also identified four historical mutations that are able to produce a \"gst-like\" s-crystallin that has regained activity. this protein recapitulates the evolution of s-crystallin from gst. protein stability studies suggest that s-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with gst-σ, which do not possess this protection. we suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.\n",
       "3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                (ifn)-inducible antiviral host cell factor tetherin (bst-2, cd317). however, several viruses encode tetherin antagonists and it is at present unknown whether residual vsv spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. here, we show that the viral glycoprotein (vsv-g) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the hiv-1 vpu protein. tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a gxxxg motif in the transmembrane domain of vsv-g. however, mutation of the gxxxg motif did not modulate tetherin sensitivity of infectious vsv. these results identify vsv-g as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. open access citation: brinkmann c, hoffmann m, lübke a, nehlmeier i, krämer-kühl a, winkler m, et al. (2017) the glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells. plos one 12(12): e0189073. https://doi.org/10.\n",
       "4        (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. this study was performed to investigate the effects of stress caused by dialysis treatment under isolation. plasma samples from the hd patients and medical staff were collected at the time of isolation(m0), the following month(m1), and three months after isolation(m3). parameters for stress included circulating cell-free genomic dna(ccf-gdna), circulating cell-free mitochondria dna(ccf-mtdna), and pentraxin-3(ptx-3). decreased values of hct, kt/v and ca x p were recovered after the end of two weeks of isolation. the levels of ccf-gdna and ccf-mtdna were the highest at m0 and decreased gradually in both hd patients and the medical staff. the normalization of ccf-gdna and ccf-mtdna was significantly delayed in hd patients compared with the response in the medical staff. ptx-3 increased only in hd patients and was highest at m0, and it then gradually decreased. medical isolation and subnormal quality of care during the mers outbreak caused extreme stress in hd patients. plasma cell-free dna and ptx-3 seems to be good indicators of stress and quality of care in hd patients. measurement of plasma cell-free genomic dna and cell-free mitochondria dna. circulating cf-dna was extracted from 200 μl of plasma using a qiaamp dneasy blood and tissue kit (qiagen, valencia, calif). the ccf-gdna and ccf-mtdna were amplified using a steponeplus real-time pcr system (applied biosystems, massachusetts). primers for the human nadh1 dehydrogenase 1 gene (nd1) were used for mtdna, and primers for the human lipoprotein lipase gene (lpl) were used for gdna. standard dna fragments of nd1 and lpl were synthesized using an integrated dna technologies kit (idt, coralville, ia) for absolute quantification. the fragment solutions were 10-fold serially diluted. the concentrations of dna were converted to copy number using the andrew staroscik calculator for the absolute copy number from a template 33 . all samples were analyzed in duplicate, and a no-template negative control was included in every analysis.\n",
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     ...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              \n",
       "10576                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           zoonosis is the leading cause of emerging infectious diseases. in a recent article, r. s. shabman et al. (msphere 1[1]:e00070-15, 2016, 10.1128 report the identification of a novel gammaherpesvirus in a cell line derived from the microbat myotis velifer incautus. this is the first report on a replicating, infectious gammaherpesvirus from bats. the new virus is named bat gammaherpesvirus 8 (bghv8), also known as myotis gammaherpesvirus 8, and is able to infect multiple cell lines, including those of human origin. using nextgeneration sequencing technology, the authors constructed a full-length annotated genomic map of bghv8. phylogenetic analysis of several genes from bghv8 revealed similarity to several mammalian gammaherpesviruses, including kaposi's sarcoma-associated herpesvirus (kshv). citation host km, damania b. 2016. discovery of a novel bat gammaherpesvirus. msphere 1(1):e00016-16.\n",
       "10577                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       zoonotic avian influenza poses a major risk to china, and other parts of the world. h5n1 has remained endemic in china and globally for nearly two decades, and in 2013, a novel zoonotic influenza a subtype h7n9 emerged in china. this study aimed to improve upon our current understanding of the spreading mechanisms of h7n9 and h5n1 by generating spatial risk profiles for each of the two virus subtypes across mainland china.\n",
       "10578                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 zoonotic coronaviruses (covs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) 1 . host immune responses to cov are complex and regulated in part through antiviral interferons.\n",
       "10579                                                zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. today, approximately 75% of newly emerging infectious diseases (eids) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. these interrelated driving forces make it difficult to predict and to prevent zoonotic eids. although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic eids remain a major global concern, and such threats are expanding, especially in less developed regions. the current ebola epidemic in west africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a one health approach. the complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of global one health in lowresource settings is crucial. the veterinary public health and biotechnology (vph-biotec) global consortium launched the international congress on pathogens at the human-animal interface (icophai) in order to address important challenges and needs for capacity building. the inaugural icophai (addis ababa, ethiopia, 2011) and the second congress (porto de galinhas, brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. in addition to strong scientific reports in eight thematic areas that necessitate one health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. the aim of this review is to highlight advances in key zoonotic disease areas and the one health capacity needs.\n",
       "10580                                                zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. in this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated venezuelan equine encephalitis (vee) virus vaccine, strain 3526 (vrp 3526). using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the vrp 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. importantly, packaging under biosafety level 2 (bsl2) conditions distinguishes vrp 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. in addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated vrp approaches. taking these results together, the vrp 3526 platform represents a safe and highly portable system that can be rapidly deployed under bsl2 conditions for generation of candidate vaccines against emerging microbial pathogens. importance while vee virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. in this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. together, the new system represents a highly portable, safe system for use in the context of disease emergence.\n",
       "Name: Content, Length: 10581, dtype: object"
      ]
     },
     "execution_count": 6,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#change text to lowercase\n",
    "df_y[\"Content\"] = df_y[\"Content\"].str.lower()\n",
    "df_y[\"Content\"]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [],
   "source": [
    "stop_words_list = stopwords.words(\"english\")\n",
    "def text_cleanning(text):\n",
    "    \n",
    "    # All characters in the text are in lowercase.\n",
    "    text = str(text)\n",
    "    text = text.lower()\n",
    "    \n",
    "    #All html tags and attributes (i.e., /<[^>]+>/) are removed\n",
    "    regex_pattern = re.compile('[^A-Za-z0-9\\s-]')\n",
    "    text = re.sub(regex_pattern, ' ', text)\n",
    "    \n",
    "    #Remove duplicate spaces and strp front and end spaces\n",
    "    text = re.sub(' +',' ',text)\n",
    "    text = text.strip()\n",
    "    \n",
    "    #make text to a list of words\n",
    "    text_list = text.split(' ')\n",
    "    \n",
    "    # All stop words are removed. \n",
    "    text_drop_stop_words_list = [x for x in text_list if x not in stop_words_list]\n",
    "    \n",
    "    text = \" \".join(text_drop_stop_words_list)\n",
    "    return text"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Content</th>\n",
       "      <th>Cleaned_Content</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>the interaction of dc-sign with pathogens triggers specific signaling events that modulate dc-maturation and activity and regulate t-cell activation by dcs. in this work we evaluate whether f. hepatica glycans can immune modulate dcs via dc-sign. we demonstrate that dc-sign interacts with f. hepatica glycoconjugates through mannose and fucose residues. we also show that mannose is present in high-mannose structures, hybrid and trimannosyl n-glycans with terminal glcnac. furthermore, we demonstrate that f. hepatica glycans induce dc-sign triggering leading to a strong production of tlr-induced il-10 and il-27p28. in addition, parasite glycans induced regulatory dcs via dc-sign that decrease allogeneic t cell proliferation, via the induction of anergic/regulatory t cells, highlighting the role of dc-sign in the regulation of innate and adaptive immune responses by f. hepatica. our data confirm the immunomodulatory properties of dc-sign triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.</td>\n",
       "      <td>interaction dc-sign pathogens triggers specific signaling events modulate dc-maturation activity regulate t-cell activation dcs work evaluate whether f hepatica glycans immune modulate dcs via dc-sign demonstrate dc-sign interacts f hepatica glycoconjugates mannose fucose residues also show mannose present high-mannose structures hybrid trimannosyl n-glycans terminal glcnac furthermore demonstrate f hepatica glycans induce dc-sign triggering leading strong production tlr-induced il-10 il-27p28 addition parasite glycans induced regulatory dcs via dc-sign decrease allogeneic cell proliferation via induction anergic regulatory cells highlighting role dc-sign regulation innate adaptive immune responses f hepatica data confirm immunomodulatory properties dc-sign triggered pathogen-derived glycans contribute identification immunomodulatory glyans helminths might eventually useful design vaccines fasciolosis</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>these first authors contributed equally to this article background as of february 29, 2020, nearly 80 thousand confirmed novel coronavirus (sars-cov-2) infection cases had been reported in china. risk factors for transmission remain largely uncharacteri</td>\n",
       "      <td>first authors contributed equally article background february 29 2020 nearly 80 thousand confirmed novel coronavirus sars-cov-2 infection cases reported china risk factors transmission remain largely uncharacteri</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>(gst) with various homologs differentially expressed in the lens. however, there is no direct structural information that helps to delineate the mechanisms by which s-crystallin could have evolved. here we report the structural and biochemical characterization of novel s-crystallin-glutathione complex. the 2.35-å crystal structure of a s-crystallin mutant from octopus vulgaris reveals an active-site architecture that is different from that of gst. s-crystallin has a preference for glutathione binding, although almost lost its gst enzymatic activity. we've also identified four historical mutations that are able to produce a \"gst-like\" s-crystallin that has regained activity. this protein recapitulates the evolution of s-crystallin from gst. protein stability studies suggest that s-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with gst-σ, which do not possess this protection. we suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.</td>\n",
       "      <td>gst various homologs differentially expressed lens however direct structural information helps delineate mechanisms s-crystallin could evolved report structural biochemical characterization novel s-crystallin-glutathione complex 2 35- crystal structure s-crystallin mutant octopus vulgaris reveals active-site architecture different gst s-crystallin preference glutathione binding although almost lost gst enzymatic activity also identified four historical mutations able produce gst-like s-crystallin regained activity protein recapitulates evolution s-crystallin gst protein stability studies suggest s-crystallin stabilized glutathione binding prevent aggregation contrasts gst- possess protection suggest tradeoff enzyme activity stability lens protein might one major driving force behind lens evolution</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>(ifn)-inducible antiviral host cell factor tetherin (bst-2, cd317). however, several viruses encode tetherin antagonists and it is at present unknown whether residual vsv spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. here, we show that the viral glycoprotein (vsv-g) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the hiv-1 vpu protein. tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a gxxxg motif in the transmembrane domain of vsv-g. however, mutation of the gxxxg motif did not modulate tetherin sensitivity of infectious vsv. these results identify vsv-g as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. open access citation: brinkmann c, hoffmann m, lübke a, nehlmeier i, krämer-kühl a, winkler m, et al. (2017) the glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells. plos one 12(12): e0189073. https://doi.org/10.</td>\n",
       "      <td>ifn -inducible antiviral host cell factor tetherin bst-2 cd317 however several viruses encode tetherin antagonists present unknown whether residual vsv spread tetherin-positive cells also promoted virus-encoded tetherin antagonist show viral glycoprotein vsv-g antagonizes tetherin transfected cells although reduced efficiency compared hiv-1 vpu protein tetherin antagonism involve alteration tetherin expression partially dependent gxxxg motif transmembrane domain vsv-g however mutation gxxxg motif modulate tetherin sensitivity infectious vsv results identify vsv-g tetherin antagonist transfected cells fail provide evidence contribution tetherin antagonism viral spread open access citation brinkmann c hoffmann l bke nehlmeier kr mer-k hl winkler et al 2017 glycoprotein vesicular stomatitis virus promotes release virus-like particles tetherin-positive cells plos one 12 12 e0189073 https doi org 10</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>(n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. this study was performed to investigate the effects of stress caused by dialysis treatment under isolation. plasma samples from the hd patients and medical staff were collected at the time of isolation(m0), the following month(m1), and three months after isolation(m3). parameters for stress included circulating cell-free genomic dna(ccf-gdna), circulating cell-free mitochondria dna(ccf-mtdna), and pentraxin-3(ptx-3). decreased values of hct, kt/v and ca x p were recovered after the end of two weeks of isolation. the levels of ccf-gdna and ccf-mtdna were the highest at m0 and decreased gradually in both hd patients and the medical staff. the normalization of ccf-gdna and ccf-mtdna was significantly delayed in hd patients compared with the response in the medical staff. ptx-3 increased only in hd patients and was highest at m0, and it then gradually decreased. medical isolation and subnormal quality of care during the mers outbreak caused extreme stress in hd patients. plasma cell-free dna and ptx-3 seems to be good indicators of stress and quality of care in hd patients. measurement of plasma cell-free genomic dna and cell-free mitochondria dna. circulating cf-dna was extracted from 200 μl of plasma using a qiaamp dneasy blood and tissue kit (qiagen, valencia, calif). the ccf-gdna and ccf-mtdna were amplified using a steponeplus real-time pcr system (applied biosystems, massachusetts). primers for the human nadh1 dehydrogenase 1 gene (nd1) were used for mtdna, and primers for the human lipoprotein lipase gene (lpl) were used for gdna. standard dna fragments of nd1 and lpl were synthesized using an integrated dna technologies kit (idt, coralville, ia) for absolute quantification. the fragment solutions were 10-fold serially diluted. the concentrations of dna were converted to copy number using the andrew staroscik calculator for the absolute copy number from a template 33 . all samples were analyzed in duplicate, and a no-template negative control was included in every analysis.</td>\n",
       "      <td>n 83 medical staff n 12 undergo dialysis treatment isolated environment study performed investigate effects stress caused dialysis treatment isolation plasma samples hd patients medical staff collected time isolation m0 following month m1 three months isolation m3 parameters stress included circulating cell-free genomic dna ccf-gdna circulating cell-free mitochondria dna ccf-mtdna pentraxin-3 ptx-3 decreased values hct kt v ca x p recovered end two weeks isolation levels ccf-gdna ccf-mtdna highest m0 decreased gradually hd patients medical staff normalization ccf-gdna ccf-mtdna significantly delayed hd patients compared response medical staff ptx-3 increased hd patients highest m0 gradually decreased medical isolation subnormal quality care mers outbreak caused extreme stress hd patients plasma cell-free dna ptx-3 seems good indicators stress quality care hd patients measurement plasma cell-free genomic dna cell-free mitochondria dna circulating cf-dna extracted 200 l plasma using qiaamp dneasy blood tissue kit qiagen valencia calif ccf-gdna ccf-mtdna amplified using steponeplus real-time pcr system applied biosystems massachusetts primers human nadh1 dehydrogenase 1 gene nd1 used mtdna primers human lipoprotein lipase gene lpl used gdna standard dna fragments nd1 lpl synthesized using integrated dna technologies kit idt coralville ia absolute quantification fragment solutions 10-fold serially diluted concentrations dna converted copy number using andrew staroscik calculator absolute copy number template 33 samples analyzed duplicate no-template negative control included every analysis</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Content  \\\n",
       "0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         the interaction of dc-sign with pathogens triggers specific signaling events that modulate dc-maturation and activity and regulate t-cell activation by dcs. in this work we evaluate whether f. hepatica glycans can immune modulate dcs via dc-sign. we demonstrate that dc-sign interacts with f. hepatica glycoconjugates through mannose and fucose residues. we also show that mannose is present in high-mannose structures, hybrid and trimannosyl n-glycans with terminal glcnac. furthermore, we demonstrate that f. hepatica glycans induce dc-sign triggering leading to a strong production of tlr-induced il-10 and il-27p28. in addition, parasite glycans induced regulatory dcs via dc-sign that decrease allogeneic t cell proliferation, via the induction of anergic/regulatory t cells, highlighting the role of dc-sign in the regulation of innate and adaptive immune responses by f. hepatica. our data confirm the immunomodulatory properties of dc-sign triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.   \n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  these first authors contributed equally to this article background as of february 29, 2020, nearly 80 thousand confirmed novel coronavirus (sars-cov-2) infection cases had been reported in china. risk factors for transmission remain largely uncharacteri   \n",
       "2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             (gst) with various homologs differentially expressed in the lens. however, there is no direct structural information that helps to delineate the mechanisms by which s-crystallin could have evolved. here we report the structural and biochemical characterization of novel s-crystallin-glutathione complex. the 2.35-å crystal structure of a s-crystallin mutant from octopus vulgaris reveals an active-site architecture that is different from that of gst. s-crystallin has a preference for glutathione binding, although almost lost its gst enzymatic activity. we've also identified four historical mutations that are able to produce a \"gst-like\" s-crystallin that has regained activity. this protein recapitulates the evolution of s-crystallin from gst. protein stability studies suggest that s-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with gst-σ, which do not possess this protection. we suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.   \n",
       "3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          (ifn)-inducible antiviral host cell factor tetherin (bst-2, cd317). however, several viruses encode tetherin antagonists and it is at present unknown whether residual vsv spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. here, we show that the viral glycoprotein (vsv-g) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the hiv-1 vpu protein. tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a gxxxg motif in the transmembrane domain of vsv-g. however, mutation of the gxxxg motif did not modulate tetherin sensitivity of infectious vsv. these results identify vsv-g as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. open access citation: brinkmann c, hoffmann m, lübke a, nehlmeier i, krämer-kühl a, winkler m, et al. (2017) the glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells. plos one 12(12): e0189073. https://doi.org/10.   \n",
       "4  (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. this study was performed to investigate the effects of stress caused by dialysis treatment under isolation. plasma samples from the hd patients and medical staff were collected at the time of isolation(m0), the following month(m1), and three months after isolation(m3). parameters for stress included circulating cell-free genomic dna(ccf-gdna), circulating cell-free mitochondria dna(ccf-mtdna), and pentraxin-3(ptx-3). decreased values of hct, kt/v and ca x p were recovered after the end of two weeks of isolation. the levels of ccf-gdna and ccf-mtdna were the highest at m0 and decreased gradually in both hd patients and the medical staff. the normalization of ccf-gdna and ccf-mtdna was significantly delayed in hd patients compared with the response in the medical staff. ptx-3 increased only in hd patients and was highest at m0, and it then gradually decreased. medical isolation and subnormal quality of care during the mers outbreak caused extreme stress in hd patients. plasma cell-free dna and ptx-3 seems to be good indicators of stress and quality of care in hd patients. measurement of plasma cell-free genomic dna and cell-free mitochondria dna. circulating cf-dna was extracted from 200 μl of plasma using a qiaamp dneasy blood and tissue kit (qiagen, valencia, calif). the ccf-gdna and ccf-mtdna were amplified using a steponeplus real-time pcr system (applied biosystems, massachusetts). primers for the human nadh1 dehydrogenase 1 gene (nd1) were used for mtdna, and primers for the human lipoprotein lipase gene (lpl) were used for gdna. standard dna fragments of nd1 and lpl were synthesized using an integrated dna technologies kit (idt, coralville, ia) for absolute quantification. the fragment solutions were 10-fold serially diluted. the concentrations of dna were converted to copy number using the andrew staroscik calculator for the absolute copy number from a template 33 . all samples were analyzed in duplicate, and a no-template negative control was included in every analysis.   \n",
       "\n",
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                Cleaned_Content  \n",
       "0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            interaction dc-sign pathogens triggers specific signaling events modulate dc-maturation activity regulate t-cell activation dcs work evaluate whether f hepatica glycans immune modulate dcs via dc-sign demonstrate dc-sign interacts f hepatica glycoconjugates mannose fucose residues also show mannose present high-mannose structures hybrid trimannosyl n-glycans terminal glcnac furthermore demonstrate f hepatica glycans induce dc-sign triggering leading strong production tlr-induced il-10 il-27p28 addition parasite glycans induced regulatory dcs via dc-sign decrease allogeneic cell proliferation via induction anergic regulatory cells highlighting role dc-sign regulation innate adaptive immune responses f hepatica data confirm immunomodulatory properties dc-sign triggered pathogen-derived glycans contribute identification immunomodulatory glyans helminths might eventually useful design vaccines fasciolosis  \n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          first authors contributed equally article background february 29 2020 nearly 80 thousand confirmed novel coronavirus sars-cov-2 infection cases reported china risk factors transmission remain largely uncharacteri  \n",
       "2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      gst various homologs differentially expressed lens however direct structural information helps delineate mechanisms s-crystallin could evolved report structural biochemical characterization novel s-crystallin-glutathione complex 2 35- crystal structure s-crystallin mutant octopus vulgaris reveals active-site architecture different gst s-crystallin preference glutathione binding although almost lost gst enzymatic activity also identified four historical mutations able produce gst-like s-crystallin regained activity protein recapitulates evolution s-crystallin gst protein stability studies suggest s-crystallin stabilized glutathione binding prevent aggregation contrasts gst- possess protection suggest tradeoff enzyme activity stability lens protein might one major driving force behind lens evolution  \n",
       "3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   ifn -inducible antiviral host cell factor tetherin bst-2 cd317 however several viruses encode tetherin antagonists present unknown whether residual vsv spread tetherin-positive cells also promoted virus-encoded tetherin antagonist show viral glycoprotein vsv-g antagonizes tetherin transfected cells although reduced efficiency compared hiv-1 vpu protein tetherin antagonism involve alteration tetherin expression partially dependent gxxxg motif transmembrane domain vsv-g however mutation gxxxg motif modulate tetherin sensitivity infectious vsv results identify vsv-g tetherin antagonist transfected cells fail provide evidence contribution tetherin antagonism viral spread open access citation brinkmann c hoffmann l bke nehlmeier kr mer-k hl winkler et al 2017 glycoprotein vesicular stomatitis virus promotes release virus-like particles tetherin-positive cells plos one 12 12 e0189073 https doi org 10  \n",
       "4  n 83 medical staff n 12 undergo dialysis treatment isolated environment study performed investigate effects stress caused dialysis treatment isolation plasma samples hd patients medical staff collected time isolation m0 following month m1 three months isolation m3 parameters stress included circulating cell-free genomic dna ccf-gdna circulating cell-free mitochondria dna ccf-mtdna pentraxin-3 ptx-3 decreased values hct kt v ca x p recovered end two weeks isolation levels ccf-gdna ccf-mtdna highest m0 decreased gradually hd patients medical staff normalization ccf-gdna ccf-mtdna significantly delayed hd patients compared response medical staff ptx-3 increased hd patients highest m0 gradually decreased medical isolation subnormal quality care mers outbreak caused extreme stress hd patients plasma cell-free dna ptx-3 seems good indicators stress quality care hd patients measurement plasma cell-free genomic dna cell-free mitochondria dna circulating cf-dna extracted 200 l plasma using qiaamp dneasy blood tissue kit qiagen valencia calif ccf-gdna ccf-mtdna amplified using steponeplus real-time pcr system applied biosystems massachusetts primers human nadh1 dehydrogenase 1 gene nd1 used mtdna primers human lipoprotein lipase gene lpl used gdna standard dna fragments nd1 lpl synthesized using integrated dna technologies kit idt coralville ia absolute quantification fragment solutions 10-fold serially diluted concentrations dna converted copy number using andrew staroscik calculator absolute copy number template 33 samples analyzed duplicate no-template negative control included every analysis  "
      ]
     },
     "execution_count": 8,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "df_y['Cleaned_Content'] = df_y['Content'].apply(text_cleanning)\n",
    "\n",
    "#Apply Lemmatization\n",
    "df_y['Cleaned_Content'] = df_y['Cleaned_Content'].apply(lambda x: WordNetLemmatizer().lemmatize(x,'v'))\n",
    "\n",
    "df_y= df_y.dropna()\n",
    "df_y.head()\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "metadata": {
    "scrolled": true
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "The size of dataset after cleaning is:\n",
      " (10581, 2)\n"
     ]
    }
   ],
   "source": [
    "print(\"The size of dataset after cleaning is:\\n\",df_y.shape)\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 10,
   "metadata": {},
   "outputs": [],
   "source": [
    "top_n_words = 50"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 11,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
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       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Word</th>\n",
       "      <th>Frequency</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>240</th>\n",
       "      <td>virus</td>\n",
       "      <td>8553</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>96</th>\n",
       "      <td>infection</td>\n",
       "      <td>6584</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>193</th>\n",
       "      <td>viral</td>\n",
       "      <td>6074</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>57</th>\n",
       "      <td>cells</td>\n",
       "      <td>5112</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>261</th>\n",
       "      <td>study</td>\n",
       "      <td>4383</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "          Word  Frequency\n",
       "240      virus       8553\n",
       "96   infection       6584\n",
       "193      viral       6074\n",
       "57       cells       5112\n",
       "261      study       4383"
      ]
     },
     "execution_count": 11,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "tokens = ' '.join(df_y['Cleaned_Content']).split(' ')\n",
    "fd = FreqDist(tokens)\n",
    "word_freq = pd.DataFrame(list(fd.items()), columns = [\"Word\", \"Frequency\"])\\\n",
    ".sort_values(by = 'Frequency', ascending = False)\n",
    "top_50_words = word_freq[:top_n_words]\n",
    "top_50_words.head()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Find lines that include treatment... What is the most frequent words in these specific group."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Content</th>\n",
       "      <th>Cleaned_Content</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>(n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. this study was performed to investigate the effects of stress caused by dialysis treatment under isolation. plasma samples from the hd patients and medical staff were collected at the time of isolation(m0), the following month(m1), and three months after isolation(m3). parameters for stress included circulating cell-free genomic dna(ccf-gdna), circulating cell-free mitochondria dna(ccf-mtdna), and pentraxin-3(ptx-3). decreased values of hct, kt/v and ca x p were recovered after the end of two weeks of isolation. the levels of ccf-gdna and ccf-mtdna were the highest at m0 and decreased gradually in both hd patients and the medical staff. the normalization of ccf-gdna and ccf-mtdna was significantly delayed in hd patients compared with the response in the medical staff. ptx-3 increased only in hd patients and was highest at m0, and it then gradually decreased. medical isolation and subnormal quality of care during the mers outbreak caused extreme stress in hd patients. plasma cell-free dna and ptx-3 seems to be good indicators of stress and quality of care in hd patients. measurement of plasma cell-free genomic dna and cell-free mitochondria dna. circulating cf-dna was extracted from 200 μl of plasma using a qiaamp dneasy blood and tissue kit (qiagen, valencia, calif). the ccf-gdna and ccf-mtdna were amplified using a steponeplus real-time pcr system (applied biosystems, massachusetts). primers for the human nadh1 dehydrogenase 1 gene (nd1) were used for mtdna, and primers for the human lipoprotein lipase gene (lpl) were used for gdna. standard dna fragments of nd1 and lpl were synthesized using an integrated dna technologies kit (idt, coralville, ia) for absolute quantification. the fragment solutions were 10-fold serially diluted. the concentrations of dna were converted to copy number using the andrew staroscik calculator for the absolute copy number from a template 33 . all samples were analyzed in duplicate, and a no-template negative control was included in every analysis.</td>\n",
       "      <td>n 83 medical staff n 12 undergo dialysis treatment isolated environment study performed investigate effects stress caused dialysis treatment isolation plasma samples hd patients medical staff collected time isolation m0 following month m1 three months isolation m3 parameters stress included circulating cell-free genomic dna ccf-gdna circulating cell-free mitochondria dna ccf-mtdna pentraxin-3 ptx-3 decreased values hct kt v ca x p recovered end two weeks isolation levels ccf-gdna ccf-mtdna highest m0 decreased gradually hd patients medical staff normalization ccf-gdna ccf-mtdna significantly delayed hd patients compared response medical staff ptx-3 increased hd patients highest m0 gradually decreased medical isolation subnormal quality care mers outbreak caused extreme stress hd patients plasma cell-free dna ptx-3 seems good indicators stress quality care hd patients measurement plasma cell-free genomic dna cell-free mitochondria dna circulating cf-dna extracted 200 l plasma using qiaamp dneasy blood tissue kit qiagen valencia calif ccf-gdna ccf-mtdna amplified using steponeplus real-time pcr system applied biosystems massachusetts primers human nadh1 dehydrogenase 1 gene nd1 used mtdna primers human lipoprotein lipase gene lpl used gdna standard dna fragments nd1 lpl synthesized using integrated dna technologies kit idt coralville ia absolute quantification fragment solutions 10-fold serially diluted concentrations dna converted copy number using andrew staroscik calculator absolute copy number template 33 samples analyzed duplicate no-template negative control included every analysis</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>43</th>\n",
       "      <td>a 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified plasmodium falciparum sporozoites to induce protective immunity against malaria. fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (chmi) by the bites of five p. falciparum-infected mosquitoes. eleven days post-chmi a thick blood smear was positive (6 p. falciparum/μl blood) and treatment was initiated with atovaquone/proguanil (malarone®). on the second day of treatment, day 12 post-chmi, troponin t, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/l (upper range of normal = 14 ng/l) on day 16 post-chmi. the volunteer had one~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-chmi. ecg at the time revealed minor repolarization disturbances, and cardiac mri demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. a diagnosis of myocarditis was made. troponin t levels were normal within 16 days and the volunteer recovered without clinical sequelae. follow-up cardiac mri at almost five months showed normal function of both ventricles and disappearance of oedema. delayed enhancement of subepicardial and midwall regions decreased, but was still present. with the exception of a throat swab that was positive for rhinovirus on day 14 post-chmi, no other tests for potential aetiologies of the myocarditis were positive. a number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) p. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the chmi), v) atovaquone/proguanil treatment, or vi) a combination of these factors. definitive aetiology and pathophysiological mechanism for the myocarditis have not been established.</td>\n",
       "      <td>23-year-old healthy male volunteer took part clinical trial volunteer took chloroquine chemoprophylaxis received three intradermal doses four-week intervals aseptic purified plasmodium falciparum sporozoites induce protective immunity malaria fifty-nine days last administration sporozoites 32 days last dose chloroquine volunteer underwent controlled human malaria infection chmi bites five p falciparum-infected mosquitoes eleven days post-chmi thick blood smear positive 6 p falciparum l blood treatment initiated atovaquone proguanil malarone second day treatment day 12 post-chmi troponin marker cardiac tissue damage began rise normal reached maximum 1 115 ng l upper range normal 14 ng l day 16 post-chmi volunteer one 20 minute episode retrosternal chest pain heavy feeling left arm day 14 post-chmi ecg time revealed minor repolarization disturbances cardiac mri demonstrated focal areas subepicardial midwall delayed enhancement left ventricle oedema hypokinesia diagnosis myocarditis made troponin levels normal within 16 days volunteer recovered without clinical sequelae follow-up cardiac mri almost five months showed normal function ventricles disappearance oedema delayed enhancement subepicardial midwall regions decreased still present exception throat swab positive rhinovirus day 14 post-chmi tests potential aetiologies myocarditis positive number possible aetiological factors may explain contributed case myocarditis including p falciparum infection ii rhinovirus infection iii unidentified pathogens iv hyper-immunization volunteer received six travel vaccines last immunization chmi v atovaquone proguanil treatment vi combination factors definitive aetiology pathophysiological mechanism myocarditis established</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>46</th>\n",
       "      <td>a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.</td>\n",
       "      <td>71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>47</th>\n",
       "      <td>a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.</td>\n",
       "      <td>71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>48</th>\n",
       "      <td>a 7-month-old female intact domestic shorthair/ british blue crossbreed cat was referred to the queen mother hospital for animals (qmha) of the royal veterinary college for further investigation of progressive lethargy preceded by 48 hours of mixed bowel diarrhea, moderate pyrexia (39.9°c; 103.8°f), and unproductive retching. laboratory tests performed at the primary practice identified marked hypercalcemia (serum total calcium concentration). despite treatment with iv fluids and potentiated amoxicillin, the cat deteriorated clinically, prompting referral. on presentation to the qmha, the cat was dull but responsive with poor body condition (3.5/9) and pyrexia (39.2°c; 102.6°f). firm white lingual plaques were observed (fig 1) . both kidneys were subjectively mildly enlarged. the remainder of the physical examination was unremarkable. with the exception of the cat's decreased mentation, neurologic examination was considered normal. no neurologic deficits suggesting a structural intracranial lesion were found at any point throughout the time the cat was hospitalized, but the level of obtundation would wax and wane. no association between the cat's mentation and the treatments administered was apparent.</td>\n",
       "      <td>7-month-old female intact domestic shorthair british blue crossbreed cat referred queen mother hospital animals qmha royal veterinary college investigation progressive lethargy preceded 48 hours mixed bowel diarrhea moderate pyrexia 39 9 c 103 8 f unproductive retching laboratory tests performed primary practice identified marked hypercalcemia serum total calcium concentration despite treatment iv fluids potentiated amoxicillin cat deteriorated clinically prompting referral presentation qmha cat dull responsive poor body condition 3 5 9 pyrexia 39 2 c 102 6 f firm white lingual plaques observed fig 1 kidneys subjectively mildly enlarged remainder physical examination unremarkable exception cat decreased mentation neurologic examination considered normal neurologic deficits suggesting structural intracranial lesion found point throughout time cat hospitalized level obtundation would wax wane association cat mentation treatments administered apparent</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10560</th>\n",
       "      <td>zika virus (zikv) was a re-emerging arbovirus associated with guillain-barré syndrome in adult and congenital zika syndrome in fetus and infant. although zikv was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. zikv can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. however, no drug has been approved for prevention or treatment of zikv infection, especially infection in male testicular tissue. previously reported peptide z2 could inactivate zikv, inhibiting zikv infection in vitro and in vivo. importantly, z2 could inhibit vertical transmission of zikv in pregnant mice, reducing zikv infection in fetus. here we showed that intraperitoneally administered z2 could also be distributed to testis and epididymis, resulting in the reduction of zikv rna copies in testicular tissue and protection of testis and epididymis against zikv-induced pathological damage and poor sperm quality in type i interferon receptor-deficient a129 mice. thus, z2, a zikv inactivator, could serve as an antiviral agent for treatment of zikv infection and attenuation of zikv-induced testicular tissue damage.</td>\n",
       "      <td>zika virus zikv re-emerging arbovirus associated guillain-barr syndrome adult congenital zika syndrome fetus infant although zikv mainly transmitted mosquito bites many sexual transmission cases reported since outbreak 2015 zikv persist testis semen long time causing testicular tissue damage reducing sperm quality however drug approved prevention treatment zikv infection especially infection male testicular tissue previously reported peptide z2 could inactivate zikv inhibiting zikv infection vitro vivo importantly z2 could inhibit vertical transmission zikv pregnant mice reducing zikv infection fetus showed intraperitoneally administered z2 could also distributed testis epididymis resulting reduction zikv rna copies testicular tissue protection testis epididymis zikv-induced pathological damage poor sperm quality type interferon receptor-deficient a129 mice thus z2 zikv inactivator could serve antiviral agent treatment zikv infection attenuation zikv-induced testicular tissue damage</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10562</th>\n",
       "      <td>zika virus (zikv), a member of the flaviviridae family, is the most recent emerging arbovirus with pandemic potential. during infection, viruses trigger the host cell stress response, leading to changes in rna translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (sgs). several reports demonstrate that flaviviruses modulate the assembly of stress granules (sg). as an emerging pathogen, little is known however about how zikv modulates the host cell stress response. in this work, we investigate how zikv modulates sg assembly. we demonstrate that zikv negatively impacts sg assembly under oxidative stress conditions induced by sodium arsenite (ars), a treatment that leads to the phosphorylation of eif2α. by contrast, no measurable difference in sg assembly was observed between mock and zikv-infected cells treated with sodium selenite (se) or pateamine a (pata), compounds that trigger eif2α-independent sg assembly. interestingly, zikv infection markedly impaired the phosphorylation of eif2α triggered in ars-treated infected cells, and the abrogation of sg assembly in zikv-infected cells is, at least in part, dependent on eif2α dephosphorylation. these data demonstrate that zikv elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication.</td>\n",
       "      <td>zika virus zikv member flaviviridae family recent emerging arbovirus pandemic potential infection viruses trigger host cell stress response leading changes rna translation assembly large aggregates stalled translation preinitiation complexes termed stress granules sgs several reports demonstrate flaviviruses modulate assembly stress granules sg emerging pathogen little known however zikv modulates host cell stress response work investigate zikv modulates sg assembly demonstrate zikv negatively impacts sg assembly oxidative stress conditions induced sodium arsenite ars treatment leads phosphorylation eif2 contrast measurable difference sg assembly observed mock zikv-infected cells treated sodium selenite se pateamine pata compounds trigger eif2 -independent sg assembly interestingly zikv infection markedly impaired phosphorylation eif2 triggered ars-treated infected cells abrogation sg assembly zikv-infected cells least part dependent eif2 dephosphorylation data demonstrate zikv elicits mechanisms counteract host anti-viral stress responses promote cellular environment propitious viral replication</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10565</th>\n",
       "      <td>zika virus (zikv), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. currently, no specific antiviral therapy against zikv is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. nevertheless, lately, search for antivirals has been a major aim in zikv investigations. to do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. here, we present an updated review of current knowledge about anti-zikv strategies, focusing on host-directed antivirals as a realistic alternative to combat zikv infection.</td>\n",
       "      <td>zika virus zikv mosquito-borne flavivirus almost neglected pathogen introduction americas 2015 responsible threat global health causing great social sanitary alarm due increased virulence rapid spread association severe neurological ophthalmological complications currently specific antiviral therapy zikv available treatments palliative mainly directed toward relief symptoms fever rash administering antipyretics anti-histamines fluids dehydration nevertheless lately search antivirals major aim zikv investigations screening libraries different sources testing natural compounds repurposing drugs known antiviral activity allowed identification several antiviral candidates directed viral structural proteins enzymes cellular elements present updated review current knowledge anti-zikv strategies focusing host-directed antivirals realistic alternative combat zikv infection</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10566</th>\n",
       "      <td>zika virus (zikv), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. however, no specific vaccines or antiviral drugs are currently available to prevent or treat zikv infection. here we report that a synthetic peptide derived from the stem region of zikv envelope protein, designated z2, potently inhibits infection of zikv and other flaviviruses in vitro. we show that z2 interacts with zikv surface protein and disrupts the integrity of the viral membrane. z2 can penetrate the placental barrier to enter fetal tissues and is safe for use in pregnant mice. intraperitoneal administration of z2 inhibits vertical transmission of zikv in pregnant c57bl/6 mice and protects type i or type i/ii interferon receptor-deficient mice against lethal zikv challenge. thus, z2 has potential to be further developed as an antiviral treatment against zikv infection in high-risk populations, particularly pregnant women.</td>\n",
       "      <td>zika virus zikv re-emerging flavivirus associated neurological disorders spread rapidly 70 countries territories however specific vaccines antiviral drugs currently available prevent treat zikv infection report synthetic peptide derived stem region zikv envelope protein designated z2 potently inhibits infection zikv flaviviruses vitro show z2 interacts zikv surface protein disrupts integrity viral membrane z2 penetrate placental barrier enter fetal tissues safe use pregnant mice intraperitoneal administration z2 inhibits vertical transmission zikv pregnant c57bl 6 mice protects type type ii interferon receptor-deficient mice lethal zikv challenge thus z2 potential developed antiviral treatment zikv infection high-risk populations particularly pregnant women</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10570</th>\n",
       "      <td>zika virus is spread mainly by the bite of an infected mosquito, which can be passed from a pregnant woman to her fetus, thus leading to birth defects including more than microcephaly. it has been recently estimated that one-third of the world population will be infected by zika in the near future, but unfortunately so far there is no vaccine or medicine for zika. in particular, the special concern on the vaccine treatment to zika and dengue arising from antibody-dependent enhancement strongly emphasizes the key role of its ns2b-ns3 protease (ns2b-ns3pro) as a target for anti-zika drug discovery/design due to its absolutely-essential role in viral replication.</td>\n",
       "      <td>zika virus spread mainly bite infected mosquito passed pregnant woman fetus thus leading birth defects including microcephaly recently estimated one-third world population infected zika near future unfortunately far vaccine medicine zika particular special concern vaccine treatment zika dengue arising antibody-dependent enhancement strongly emphasizes key role ns2b-ns3 protease ns2b-ns3pro target anti-zika drug discovery design due absolutely-essential role viral replication</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>1147 rows × 2 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Content  \\\n",
       "4                                                                                                 (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. this study was performed to investigate the effects of stress caused by dialysis treatment under isolation. plasma samples from the hd patients and medical staff were collected at the time of isolation(m0), the following month(m1), and three months after isolation(m3). parameters for stress included circulating cell-free genomic dna(ccf-gdna), circulating cell-free mitochondria dna(ccf-mtdna), and pentraxin-3(ptx-3). decreased values of hct, kt/v and ca x p were recovered after the end of two weeks of isolation. the levels of ccf-gdna and ccf-mtdna were the highest at m0 and decreased gradually in both hd patients and the medical staff. the normalization of ccf-gdna and ccf-mtdna was significantly delayed in hd patients compared with the response in the medical staff. ptx-3 increased only in hd patients and was highest at m0, and it then gradually decreased. medical isolation and subnormal quality of care during the mers outbreak caused extreme stress in hd patients. plasma cell-free dna and ptx-3 seems to be good indicators of stress and quality of care in hd patients. measurement of plasma cell-free genomic dna and cell-free mitochondria dna. circulating cf-dna was extracted from 200 μl of plasma using a qiaamp dneasy blood and tissue kit (qiagen, valencia, calif). the ccf-gdna and ccf-mtdna were amplified using a steponeplus real-time pcr system (applied biosystems, massachusetts). primers for the human nadh1 dehydrogenase 1 gene (nd1) were used for mtdna, and primers for the human lipoprotein lipase gene (lpl) were used for gdna. standard dna fragments of nd1 and lpl were synthesized using an integrated dna technologies kit (idt, coralville, ia) for absolute quantification. the fragment solutions were 10-fold serially diluted. the concentrations of dna were converted to copy number using the andrew staroscik calculator for the absolute copy number from a template 33 . all samples were analyzed in duplicate, and a no-template negative control was included in every analysis.   \n",
       "43     a 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified plasmodium falciparum sporozoites to induce protective immunity against malaria. fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (chmi) by the bites of five p. falciparum-infected mosquitoes. eleven days post-chmi a thick blood smear was positive (6 p. falciparum/μl blood) and treatment was initiated with atovaquone/proguanil (malarone®). on the second day of treatment, day 12 post-chmi, troponin t, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/l (upper range of normal = 14 ng/l) on day 16 post-chmi. the volunteer had one~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-chmi. ecg at the time revealed minor repolarization disturbances, and cardiac mri demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. a diagnosis of myocarditis was made. troponin t levels were normal within 16 days and the volunteer recovered without clinical sequelae. follow-up cardiac mri at almost five months showed normal function of both ventricles and disappearance of oedema. delayed enhancement of subepicardial and midwall regions decreased, but was still present. with the exception of a throat swab that was positive for rhinovirus on day 14 post-chmi, no other tests for potential aetiologies of the myocarditis were positive. a number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) p. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the chmi), v) atovaquone/proguanil treatment, or vi) a combination of these factors. definitive aetiology and pathophysiological mechanism for the myocarditis have not been established.   \n",
       "46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.   \n",
       "47                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.   \n",
       "48                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         a 7-month-old female intact domestic shorthair/ british blue crossbreed cat was referred to the queen mother hospital for animals (qmha) of the royal veterinary college for further investigation of progressive lethargy preceded by 48 hours of mixed bowel diarrhea, moderate pyrexia (39.9°c; 103.8°f), and unproductive retching. laboratory tests performed at the primary practice identified marked hypercalcemia (serum total calcium concentration). despite treatment with iv fluids and potentiated amoxicillin, the cat deteriorated clinically, prompting referral. on presentation to the qmha, the cat was dull but responsive with poor body condition (3.5/9) and pyrexia (39.2°c; 102.6°f). firm white lingual plaques were observed (fig 1) . both kidneys were subjectively mildly enlarged. the remainder of the physical examination was unremarkable. with the exception of the cat's decreased mentation, neurologic examination was considered normal. no neurologic deficits suggesting a structural intracranial lesion were found at any point throughout the time the cat was hospitalized, but the level of obtundation would wax and wane. no association between the cat's mentation and the treatments administered was apparent.   \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         ...   \n",
       "10560                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       zika virus (zikv) was a re-emerging arbovirus associated with guillain-barré syndrome in adult and congenital zika syndrome in fetus and infant. although zikv was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. zikv can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. however, no drug has been approved for prevention or treatment of zikv infection, especially infection in male testicular tissue. previously reported peptide z2 could inactivate zikv, inhibiting zikv infection in vitro and in vivo. importantly, z2 could inhibit vertical transmission of zikv in pregnant mice, reducing zikv infection in fetus. here we showed that intraperitoneally administered z2 could also be distributed to testis and epididymis, resulting in the reduction of zikv rna copies in testicular tissue and protection of testis and epididymis against zikv-induced pathological damage and poor sperm quality in type i interferon receptor-deficient a129 mice. thus, z2, a zikv inactivator, could serve as an antiviral agent for treatment of zikv infection and attenuation of zikv-induced testicular tissue damage.   \n",
       "10562                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           zika virus (zikv), a member of the flaviviridae family, is the most recent emerging arbovirus with pandemic potential. during infection, viruses trigger the host cell stress response, leading to changes in rna translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (sgs). several reports demonstrate that flaviviruses modulate the assembly of stress granules (sg). as an emerging pathogen, little is known however about how zikv modulates the host cell stress response. in this work, we investigate how zikv modulates sg assembly. we demonstrate that zikv negatively impacts sg assembly under oxidative stress conditions induced by sodium arsenite (ars), a treatment that leads to the phosphorylation of eif2α. by contrast, no measurable difference in sg assembly was observed between mock and zikv-infected cells treated with sodium selenite (se) or pateamine a (pata), compounds that trigger eif2α-independent sg assembly. interestingly, zikv infection markedly impaired the phosphorylation of eif2α triggered in ars-treated infected cells, and the abrogation of sg assembly in zikv-infected cells is, at least in part, dependent on eif2α dephosphorylation. these data demonstrate that zikv elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication.   \n",
       "10565                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       zika virus (zikv), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. currently, no specific antiviral therapy against zikv is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. nevertheless, lately, search for antivirals has been a major aim in zikv investigations. to do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. here, we present an updated review of current knowledge about anti-zikv strategies, focusing on host-directed antivirals as a realistic alternative to combat zikv infection.   \n",
       "10566                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                zika virus (zikv), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. however, no specific vaccines or antiviral drugs are currently available to prevent or treat zikv infection. here we report that a synthetic peptide derived from the stem region of zikv envelope protein, designated z2, potently inhibits infection of zikv and other flaviviruses in vitro. we show that z2 interacts with zikv surface protein and disrupts the integrity of the viral membrane. z2 can penetrate the placental barrier to enter fetal tissues and is safe for use in pregnant mice. intraperitoneal administration of z2 inhibits vertical transmission of zikv in pregnant c57bl/6 mice and protects type i or type i/ii interferon receptor-deficient mice against lethal zikv challenge. thus, z2 has potential to be further developed as an antiviral treatment against zikv infection in high-risk populations, particularly pregnant women.   \n",
       "10570                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              zika virus is spread mainly by the bite of an infected mosquito, which can be passed from a pregnant woman to her fetus, thus leading to birth defects including more than microcephaly. it has been recently estimated that one-third of the world population will be infected by zika in the near future, but unfortunately so far there is no vaccine or medicine for zika. in particular, the special concern on the vaccine treatment to zika and dengue arising from antibody-dependent enhancement strongly emphasizes the key role of its ns2b-ns3 protease (ns2b-ns3pro) as a target for anti-zika drug discovery/design due to its absolutely-essential role in viral replication.   \n",
       "\n",
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 Cleaned_Content  \n",
       "4                                                                                                                                   n 83 medical staff n 12 undergo dialysis treatment isolated environment study performed investigate effects stress caused dialysis treatment isolation plasma samples hd patients medical staff collected time isolation m0 following month m1 three months isolation m3 parameters stress included circulating cell-free genomic dna ccf-gdna circulating cell-free mitochondria dna ccf-mtdna pentraxin-3 ptx-3 decreased values hct kt v ca x p recovered end two weeks isolation levels ccf-gdna ccf-mtdna highest m0 decreased gradually hd patients medical staff normalization ccf-gdna ccf-mtdna significantly delayed hd patients compared response medical staff ptx-3 increased hd patients highest m0 gradually decreased medical isolation subnormal quality care mers outbreak caused extreme stress hd patients plasma cell-free dna ptx-3 seems good indicators stress quality care hd patients measurement plasma cell-free genomic dna cell-free mitochondria dna circulating cf-dna extracted 200 l plasma using qiaamp dneasy blood tissue kit qiagen valencia calif ccf-gdna ccf-mtdna amplified using steponeplus real-time pcr system applied biosystems massachusetts primers human nadh1 dehydrogenase 1 gene nd1 used mtdna primers human lipoprotein lipase gene lpl used gdna standard dna fragments nd1 lpl synthesized using integrated dna technologies kit idt coralville ia absolute quantification fragment solutions 10-fold serially diluted concentrations dna converted copy number using andrew staroscik calculator absolute copy number template 33 samples analyzed duplicate no-template negative control included every analysis  \n",
       "43     23-year-old healthy male volunteer took part clinical trial volunteer took chloroquine chemoprophylaxis received three intradermal doses four-week intervals aseptic purified plasmodium falciparum sporozoites induce protective immunity malaria fifty-nine days last administration sporozoites 32 days last dose chloroquine volunteer underwent controlled human malaria infection chmi bites five p falciparum-infected mosquitoes eleven days post-chmi thick blood smear positive 6 p falciparum l blood treatment initiated atovaquone proguanil malarone second day treatment day 12 post-chmi troponin marker cardiac tissue damage began rise normal reached maximum 1 115 ng l upper range normal 14 ng l day 16 post-chmi volunteer one 20 minute episode retrosternal chest pain heavy feeling left arm day 14 post-chmi ecg time revealed minor repolarization disturbances cardiac mri demonstrated focal areas subepicardial midwall delayed enhancement left ventricle oedema hypokinesia diagnosis myocarditis made troponin levels normal within 16 days volunteer recovered without clinical sequelae follow-up cardiac mri almost five months showed normal function ventricles disappearance oedema delayed enhancement subepicardial midwall regions decreased still present exception throat swab positive rhinovirus day 14 post-chmi tests potential aetiologies myocarditis positive number possible aetiological factors may explain contributed case myocarditis including p falciparum infection ii rhinovirus infection iii unidentified pathogens iv hyper-immunization volunteer received six travel vaccines last immunization chmi v atovaquone proguanil treatment vi combination factors definitive aetiology pathophysiological mechanism myocarditis established  \n",
       "46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments  \n",
       "47                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments  \n",
       "48                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            7-month-old female intact domestic shorthair british blue crossbreed cat referred queen mother hospital animals qmha royal veterinary college investigation progressive lethargy preceded 48 hours mixed bowel diarrhea moderate pyrexia 39 9 c 103 8 f unproductive retching laboratory tests performed primary practice identified marked hypercalcemia serum total calcium concentration despite treatment iv fluids potentiated amoxicillin cat deteriorated clinically prompting referral presentation qmha cat dull responsive poor body condition 3 5 9 pyrexia 39 2 c 102 6 f firm white lingual plaques observed fig 1 kidneys subjectively mildly enlarged remainder physical examination unremarkable exception cat decreased mentation neurologic examination considered normal neurologic deficits suggesting structural intracranial lesion found point throughout time cat hospitalized level obtundation would wax wane association cat mentation treatments administered apparent  \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          ...  \n",
       "10560                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      zika virus zikv re-emerging arbovirus associated guillain-barr syndrome adult congenital zika syndrome fetus infant although zikv mainly transmitted mosquito bites many sexual transmission cases reported since outbreak 2015 zikv persist testis semen long time causing testicular tissue damage reducing sperm quality however drug approved prevention treatment zikv infection especially infection male testicular tissue previously reported peptide z2 could inactivate zikv inhibiting zikv infection vitro vivo importantly z2 could inhibit vertical transmission zikv pregnant mice reducing zikv infection fetus showed intraperitoneally administered z2 could also distributed testis epididymis resulting reduction zikv rna copies testicular tissue protection testis epididymis zikv-induced pathological damage poor sperm quality type interferon receptor-deficient a129 mice thus z2 zikv inactivator could serve antiviral agent treatment zikv infection attenuation zikv-induced testicular tissue damage  \n",
       "10562                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  zika virus zikv member flaviviridae family recent emerging arbovirus pandemic potential infection viruses trigger host cell stress response leading changes rna translation assembly large aggregates stalled translation preinitiation complexes termed stress granules sgs several reports demonstrate flaviviruses modulate assembly stress granules sg emerging pathogen little known however zikv modulates host cell stress response work investigate zikv modulates sg assembly demonstrate zikv negatively impacts sg assembly oxidative stress conditions induced sodium arsenite ars treatment leads phosphorylation eif2 contrast measurable difference sg assembly observed mock zikv-infected cells treated sodium selenite se pateamine pata compounds trigger eif2 -independent sg assembly interestingly zikv infection markedly impaired phosphorylation eif2 triggered ars-treated infected cells abrogation sg assembly zikv-infected cells least part dependent eif2 dephosphorylation data demonstrate zikv elicits mechanisms counteract host anti-viral stress responses promote cellular environment propitious viral replication  \n",
       "10565                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              zika virus zikv mosquito-borne flavivirus almost neglected pathogen introduction americas 2015 responsible threat global health causing great social sanitary alarm due increased virulence rapid spread association severe neurological ophthalmological complications currently specific antiviral therapy zikv available treatments palliative mainly directed toward relief symptoms fever rash administering antipyretics anti-histamines fluids dehydration nevertheless lately search antivirals major aim zikv investigations screening libraries different sources testing natural compounds repurposing drugs known antiviral activity allowed identification several antiviral candidates directed viral structural proteins enzymes cellular elements present updated review current knowledge anti-zikv strategies focusing host-directed antivirals realistic alternative combat zikv infection  \n",
       "10566                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            zika virus zikv re-emerging flavivirus associated neurological disorders spread rapidly 70 countries territories however specific vaccines antiviral drugs currently available prevent treat zikv infection report synthetic peptide derived stem region zikv envelope protein designated z2 potently inhibits infection zikv flaviviruses vitro show z2 interacts zikv surface protein disrupts integrity viral membrane z2 penetrate placental barrier enter fetal tissues safe use pregnant mice intraperitoneal administration z2 inhibits vertical transmission zikv pregnant c57bl 6 mice protects type type ii interferon receptor-deficient mice lethal zikv challenge thus z2 potential developed antiviral treatment zikv infection high-risk populations particularly pregnant women  \n",
       "10570                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            zika virus spread mainly bite infected mosquito passed pregnant woman fetus thus leading birth defects including microcephaly recently estimated one-third world population infected zika near future unfortunately far vaccine medicine zika particular special concern vaccine treatment zika dengue arising antibody-dependent enhancement strongly emphasizes key role ns2b-ns3 protease ns2b-ns3pro target anti-zika drug discovery design due absolutely-essential role viral replication  \n",
       "\n",
       "[1147 rows x 2 columns]"
      ]
     },
     "execution_count": 12,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "treatment = df_y[df_y['Cleaned_Content'].str.contains('treatment')]\n",
    "\n",
    "treatment"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Number of  treatment keywords were found :  1147\n"
     ]
    }
   ],
   "source": [
    "\n",
    "treatment_texts = treatment['Cleaned_Content'].values\n",
    "print(\"Number of  treatment keywords were found : \",len(treatment_texts))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 14,
   "metadata": {},
   "outputs": [],
   "source": [
    "top_n_words = 50"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 15,
   "metadata": {},
   "outputs": [
    {
     "data": {
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       "      <th>7</th>\n",
       "      <td>treatment</td>\n",
       "      <td>1485</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>280</th>\n",
       "      <td>virus</td>\n",
       "      <td>1116</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>169</th>\n",
       "      <td>infection</td>\n",
       "      <td>1071</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>546</th>\n",
       "      <td>cells</td>\n",
       "      <td>918</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>309</th>\n",
       "      <td>viral</td>\n",
       "      <td>908</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "          Word  Frequency\n",
       "7    treatment       1485\n",
       "280      virus       1116\n",
       "169  infection       1071\n",
       "546      cells        918\n",
       "309      viral        908"
      ]
     },
     "execution_count": 15,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "tokens = ' '.join(treatment['Cleaned_Content']).split(' ')\n",
    "fd = FreqDist(tokens)\n",
    "word_freq = pd.DataFrame(list(fd.items()), columns = [\"Word\", \"Frequency\"])\\\n",
    ".sort_values(by = 'Frequency', ascending = False)\n",
    "top_50_words = word_freq[:top_n_words]\n",
    "top_50_words.head()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Find the corona and \"stress\", \"alchol\" and \"sugar\" relation if exists in papers"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 16,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "    .dataframe tbody tr th {\n",
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       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
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       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Content</th>\n",
       "      <th>Cleaned_Content</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>these first authors contributed equally to this article background as of february 29, 2020, nearly 80 thousand confirmed novel coronavirus (sars-cov-2) infection cases had been reported in china. risk factors for transmission remain largely uncharacteri</td>\n",
       "      <td>first authors contributed equally article background february 29 2020 nearly 80 thousand confirmed novel coronavirus sars-cov-2 infection cases reported china risk factors transmission remain largely uncharacteri</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>21</th>\n",
       "      <td>2019 novel coronavirus (2019-ncov) had typical clinical manifestations (fever and cough) ,and presented with characteristic chest ct imaging features (multiple lesions in both lungs, often accompanied by ggo, vascular enlargement and cobblestone/reticular pattern), which are helpful to the radiologist in the early detection and diagnosis of this emerging global health emergency. in addition, changes in these main ct features can indicate development of the disease.</td>\n",
       "      <td>2019 novel coronavirus 2019-ncov typical clinical manifestations fever cough presented characteristic chest ct imaging features multiple lesions lungs often accompanied ggo vascular enlargement cobblestone reticular pattern helpful radiologist early detection diagnosis emerging global health emergency addition changes main ct features indicate development disease</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>22</th>\n",
       "      <td>2019 novel coronavirus (2019-ncov) is a virus identified as the cause of the outbreak of pneumonia first detected in wuhan, china. investigations on the transmissibility, severity, and other features associated with this virus are ongoing. currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. in contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. the main protease of sars-cov is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-ncov, is considered to be an attractive target for drug development. in this study, we have identified 4 small molecular drugs with high binding capacity with sars-cov main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-ncov.</td>\n",
       "      <td>2019 novel coronavirus 2019-ncov virus identified cause outbreak pneumonia first detected wuhan china investigations transmissibility severity features associated virus ongoing currently vaccine therapeutic antibody prevent infection time required develop effective immune strategy pathogen contrast specific inhibitors targeting key protease involved replication proliferation virus effective means alleviate epidemic main protease sars-cov essential life cycle virus showed 96 1 similarity main proteaseof 2019-ncov considered attractive target drug development study identified 4 small molecular drugs high binding capacity sars-cov main protease high-throughput screening based 8 000 clinical drug libraries drugs widely used clinical applications guaranteed safety may serve promising candidates treat infection 2019-ncov</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>25</th>\n",
       "      <td>2019-ncov is a newly identified coronavirus with high similarity to sars-cov. we performed a structural analysis of the receptor binding domain (rbd) of spike glycoprotein responsible for entry of coronaviruses into host cells. the rbds from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. however, 2019-ncov has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in sars-cov. molecular modeling revealed that 2019-ncov rbd has a stronger interaction with angiotensin converting enzyme 2 (ace2). a unique phenylalanine f486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ace2. ace2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. structural analysis suggests that ace2 from these animals can potentially bind rbd of 2019-ncov, making them all possible natural hosts for the virus. 2019-ncov is thought to be transmitted through respiratory droplets. however, since ace2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. finally, antibodies and small molecular inhibitors that can block the interaction of ace2 with rbd should be developed to combat the virus.</td>\n",
       "      <td>2019-ncov newly identified coronavirus high similarity sars-cov performed structural analysis receptor binding domain rbd spike glycoprotein responsible entry coronaviruses host cells rbds two viruses share 72 identity amino acid sequences molecular simulation reveals highly similar ternary structures however 2019-ncov distinct loop flexible glycyl residues replacing rigid prolyl residues sars-cov molecular modeling revealed 2019-ncov rbd stronger interaction angiotensin converting enzyme 2 ace2 unique phenylalanine f486 flexible loop likely plays major role penetration deep hydrophobic pocket ace2 ace2 widely expressed conserved primary structures throughout animal kingdom fish amphibians reptiles birds mammals structural analysis suggests ace2 animals potentially bind rbd 2019-ncov making possible natural hosts virus 2019-ncov thought transmitted respiratory droplets however since ace2 predominantly expressed intestines testis kidney fecal-oral routes transmission also possible finally antibodies small molecular inhibitors block interaction ace2 rbd developed combat virus</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>27</th>\n",
       "      <td>26 previous findings of middle east respiratory syndrome coronavirus (mers-cov)-27 related viruses in bats, and the ability of tylonycteris-batcov hku4 spike protein to utilize 28 mers-cov receptor, human dipeptidyl peptidase 4 hdpp4, suggest a bat ancestral origin of 29 mers-cov. we developed 12 primary bat cell lines from seven bat species, including 30 tylonycteris pachypus, pipistrellus abramus and rhinolophus sinicus (hosts of tylonycteris-31 batcov hku4, pipistrellus-batcov hku5 and sars-related-cov respectively), and tested 32 their susceptibilities to mers-covs, sars-cov and human coronavirus 229e (hcov-229e). 33 five cell lines, including p. abramus and r. sinicus but not t. pachypus cells, were susceptible 34 to human mers-cov emc/2012. however, three tested camel mers-cov strains showed 35 different infectivities, with only two strains capable of infecting three and one cell lines 36 respectively. sars-cov can only replicate in r. sinicus cells, while hcov-229e cannot 37 replicate in any bat cells. bat dipeptidyl peptidase 4 (dpp4) sequences were closely related to 38 those of human and non-human primates but distinct from dromedary dpp4 sequence. critical 39 residues for binding to mers-cov spike protein were mostly conserved in bat dpp4. dpp4 40 was expressed in the five bat cells susceptible to mers-cov, with significantly higher mrna 41 expression levels than those in non-susceptible cells (p=0.0174), supporting that dpp4 42 expression is critical for mers-cov infection in bats. however, overexpression of t. pachypus 43 dpp4 failed to confer mers-cov susceptibility in t. pachypus cells, suggesting other cellular 44 factors in determining viral replication. the broad cellular tropism of mers-cov should 45 prompt further exploration of host diversity of related viruses to identify its ancestral origin. 46 47 all rights reserved. no reuse allowed without permission.</td>\n",
       "      <td>26 previous findings middle east respiratory syndrome coronavirus mers-cov -27 related viruses bats ability tylonycteris-batcov hku4 spike protein utilize 28 mers-cov receptor human dipeptidyl peptidase 4 hdpp4 suggest bat ancestral origin 29 mers-cov developed 12 primary bat cell lines seven bat species including 30 tylonycteris pachypus pipistrellus abramus rhinolophus sinicus hosts tylonycteris-31 batcov hku4 pipistrellus-batcov hku5 sars-related-cov respectively tested 32 susceptibilities mers-covs sars-cov human coronavirus 229e hcov-229e 33 five cell lines including p abramus r sinicus pachypus cells susceptible 34 human mers-cov emc 2012 however three tested camel mers-cov strains showed 35 different infectivities two strains capable infecting three one cell lines 36 respectively sars-cov replicate r sinicus cells hcov-229e cannot 37 replicate bat cells bat dipeptidyl peptidase 4 dpp4 sequences closely related 38 human non-human primates distinct dromedary dpp4 sequence critical 39 residues binding mers-cov spike protein mostly conserved bat dpp4 dpp4 40 expressed five bat cells susceptible mers-cov significantly higher mrna 41 expression levels non-susceptible cells p 0 0174 supporting dpp4 42 expression critical mers-cov infection bats however overexpression pachypus 43 dpp4 failed confer mers-cov susceptibility pachypus cells suggesting cellular 44 factors determining viral replication broad cellular tropism mers-cov 45 prompt exploration host diversity related viruses identify ancestral origin 46 47 rights reserved reuse allowed without permission</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10512</th>\n",
       "      <td>wuhan coronavirus, called 2019-ncov, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by january 30, 2020. currently, there is no effective treatment for this epidemic. however, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. fortunately, the sequence identity of the 2019-ncov protease and that of severe-acute respiratory syndrome virus (sars-cov) is as high as 96.1%. we show that the protease inhibitor binding sites of 2019-ncov and sars-cov are almost identical, which means all potential anti-sars-cov chemotherapies are also potential 2019-ncov drugs. here, we report a family of potential 2019-ncov drugs generated by a machine intelligence-based generative network complex (gnc). the potential effectiveness of treating 2019-ncov by using some existing hiv drugs is also analyzed.</td>\n",
       "      <td>wuhan coronavirus called 2019-ncov newly emerged virus infected 9692 people leads 213 fatalities january 30 2020 currently effective treatment epidemic however viral protease coronavirus well-known essential replication thus effective drug target fortunately sequence identity 2019-ncov protease severe-acute respiratory syndrome virus sars-cov high 96 1 show protease inhibitor binding sites 2019-ncov sars-cov almost identical means potential anti-sars-cov chemotherapies also potential 2019-ncov drugs report family potential 2019-ncov drugs generated machine intelligence-based generative network complex gnc potential effectiveness treating 2019-ncov using existing hiv drugs also analyzed</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10513</th>\n",
       "      <td>wuhan novel coronavirus disease outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading.</td>\n",
       "      <td>wuhan novel coronavirus disease outbreak become global outbreak raised concern scientific community design discover definitive cure deadly virus caused deaths numerous infected people upon infection spreading</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10514</th>\n",
       "      <td>wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus for hubei province. to achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. we excluded those without relevant epidemiological descriptions, working or living in wuhan for a long time, or hard to determine the possible exposure time. we proposed a monte caro simulation approach to estimate the incubation of covid-19 as well as employed nonparametric ways. we also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. all rights reserved. no reuse allowed without permission.</td>\n",
       "      <td>wuhan pneumonia acute infectious disease caused 2019 novel coronavirus hubei province achieve accurate calculation incubation period involved officially confirmed cases clear history exposure time onset excluded without relevant epidemiological descriptions working living wuhan long time hard determine possible exposure time proposed monte caro simulation approach estimate incubation covid-19 well employed nonparametric ways also employed manifold learning related statistical analysis decipher incubation relationships different age gender groups rights reserved reuse allowed without permission</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10578</th>\n",
       "      <td>zoonotic coronaviruses (covs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) 1 . host immune responses to cov are complex and regulated in part through antiviral interferons.</td>\n",
       "      <td>zoonotic coronaviruses covs significant threats global health exemplified recent emergence severe acute respiratory syndrome coronavirus 2 sars-cov-2 1 host immune responses cov complex regulated part antiviral interferons</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10580</th>\n",
       "      <td>zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. in this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated venezuelan equine encephalitis (vee) virus vaccine, strain 3526 (vrp 3526). using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the vrp 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. importantly, packaging under biosafety level 2 (bsl2) conditions distinguishes vrp 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. in addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated vrp approaches. taking these results together, the vrp 3526 platform represents a safe and highly portable system that can be rapidly deployed under bsl2 conditions for generation of candidate vaccines against emerging microbial pathogens. importance while vee virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. in this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. together, the new system represents a highly portable, safe system for use in the context of disease emergence.</td>\n",
       "      <td>zoonotic viruses circulate swarms animal reservoirs emerge human populations causing epidemics adversely affect public health portable safe effective vaccine platforms needed context outbreak emergence situations work report generation characterization alphavirus replicon vaccine platform based non-select agent attenuated venezuelan equine encephalitis vee virus vaccine strain 3526 vrp 3526 using noroviruses coronaviruses model systems demonstrate utility vrp 3526 platform generation recombinant proteins production virus-like particles vivo efficacy vaccine emergent viruses importantly packaging biosafety level 2 bsl2 conditions distinguishes vrp 3526 previously reported alphavirus platforms makes approach accessible majority laboratories around world addition improved outcomes vulnerable aged models well heterologous challenge suggest improved efficacy compared previously attenuated vrp approaches taking results together vrp 3526 platform represents safe highly portable system rapidly deployed bsl2 conditions generation candidate vaccines emerging microbial pathogens importance vee virus replicon particles provide robust established platform antigen expression vaccination utility limited requirement high-containment-level facilities production packaging work utilize attenuated vaccine strain capable use lower biocontainment level retaining capacity wild-type replicon particle importantly new replicon platform provides equal protection aged mice following heterologous challenge distinguishes attenuated replicon platforms together new system represents highly portable safe system use context disease emergence</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>1521 rows × 2 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 Content  \\\n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          these first authors contributed equally to this article background as of february 29, 2020, nearly 80 thousand confirmed novel coronavirus (sars-cov-2) infection cases had been reported in china. risk factors for transmission remain largely uncharacteri   \n",
       "21                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 2019 novel coronavirus (2019-ncov) had typical clinical manifestations (fever and cough) ,and presented with characteristic chest ct imaging features (multiple lesions in both lungs, often accompanied by ggo, vascular enlargement and cobblestone/reticular pattern), which are helpful to the radiologist in the early detection and diagnosis of this emerging global health emergency. in addition, changes in these main ct features can indicate development of the disease.   \n",
       "22                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     2019 novel coronavirus (2019-ncov) is a virus identified as the cause of the outbreak of pneumonia first detected in wuhan, china. investigations on the transmissibility, severity, and other features associated with this virus are ongoing. currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. in contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. the main protease of sars-cov is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-ncov, is considered to be an attractive target for drug development. in this study, we have identified 4 small molecular drugs with high binding capacity with sars-cov main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-ncov.   \n",
       "25                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           2019-ncov is a newly identified coronavirus with high similarity to sars-cov. we performed a structural analysis of the receptor binding domain (rbd) of spike glycoprotein responsible for entry of coronaviruses into host cells. the rbds from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. however, 2019-ncov has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in sars-cov. molecular modeling revealed that 2019-ncov rbd has a stronger interaction with angiotensin converting enzyme 2 (ace2). a unique phenylalanine f486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ace2. ace2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. structural analysis suggests that ace2 from these animals can potentially bind rbd of 2019-ncov, making them all possible natural hosts for the virus. 2019-ncov is thought to be transmitted through respiratory droplets. however, since ace2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. finally, antibodies and small molecular inhibitors that can block the interaction of ace2 with rbd should be developed to combat the virus.   \n",
       "27                                                                                                                                                                26 previous findings of middle east respiratory syndrome coronavirus (mers-cov)-27 related viruses in bats, and the ability of tylonycteris-batcov hku4 spike protein to utilize 28 mers-cov receptor, human dipeptidyl peptidase 4 hdpp4, suggest a bat ancestral origin of 29 mers-cov. we developed 12 primary bat cell lines from seven bat species, including 30 tylonycteris pachypus, pipistrellus abramus and rhinolophus sinicus (hosts of tylonycteris-31 batcov hku4, pipistrellus-batcov hku5 and sars-related-cov respectively), and tested 32 their susceptibilities to mers-covs, sars-cov and human coronavirus 229e (hcov-229e). 33 five cell lines, including p. abramus and r. sinicus but not t. pachypus cells, were susceptible 34 to human mers-cov emc/2012. however, three tested camel mers-cov strains showed 35 different infectivities, with only two strains capable of infecting three and one cell lines 36 respectively. sars-cov can only replicate in r. sinicus cells, while hcov-229e cannot 37 replicate in any bat cells. bat dipeptidyl peptidase 4 (dpp4) sequences were closely related to 38 those of human and non-human primates but distinct from dromedary dpp4 sequence. critical 39 residues for binding to mers-cov spike protein were mostly conserved in bat dpp4. dpp4 40 was expressed in the five bat cells susceptible to mers-cov, with significantly higher mrna 41 expression levels than those in non-susceptible cells (p=0.0174), supporting that dpp4 42 expression is critical for mers-cov infection in bats. however, overexpression of t. pachypus 43 dpp4 failed to confer mers-cov susceptibility in t. pachypus cells, suggesting other cellular 44 factors in determining viral replication. the broad cellular tropism of mers-cov should 45 prompt further exploration of host diversity of related viruses to identify its ancestral origin. 46 47 all rights reserved. no reuse allowed without permission.   \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  ...   \n",
       "10512                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               wuhan coronavirus, called 2019-ncov, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by january 30, 2020. currently, there is no effective treatment for this epidemic. however, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. fortunately, the sequence identity of the 2019-ncov protease and that of severe-acute respiratory syndrome virus (sars-cov) is as high as 96.1%. we show that the protease inhibitor binding sites of 2019-ncov and sars-cov are almost identical, which means all potential anti-sars-cov chemotherapies are also potential 2019-ncov drugs. here, we report a family of potential 2019-ncov drugs generated by a machine intelligence-based generative network complex (gnc). the potential effectiveness of treating 2019-ncov by using some existing hiv drugs is also analyzed.   \n",
       "10513                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    wuhan novel coronavirus disease outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading.   \n",
       "10514                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus for hubei province. to achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. we excluded those without relevant epidemiological descriptions, working or living in wuhan for a long time, or hard to determine the possible exposure time. we proposed a monte caro simulation approach to estimate the incubation of covid-19 as well as employed nonparametric ways. we also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. all rights reserved. no reuse allowed without permission.   \n",
       "10578                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   zoonotic coronaviruses (covs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) 1 . host immune responses to cov are complex and regulated in part through antiviral interferons.   \n",
       "10580  zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. in this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated venezuelan equine encephalitis (vee) virus vaccine, strain 3526 (vrp 3526). using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the vrp 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. importantly, packaging under biosafety level 2 (bsl2) conditions distinguishes vrp 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. in addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated vrp approaches. taking these results together, the vrp 3526 platform represents a safe and highly portable system that can be rapidly deployed under bsl2 conditions for generation of candidate vaccines against emerging microbial pathogens. importance while vee virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. in this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. together, the new system represents a highly portable, safe system for use in the context of disease emergence.   \n",
       "\n",
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Cleaned_Content  \n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     first authors contributed equally article background february 29 2020 nearly 80 thousand confirmed novel coronavirus sars-cov-2 infection cases reported china risk factors transmission remain largely uncharacteri  \n",
       "21                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           2019 novel coronavirus 2019-ncov typical clinical manifestations fever cough presented characteristic chest ct imaging features multiple lesions lungs often accompanied ggo vascular enlargement cobblestone reticular pattern helpful radiologist early detection diagnosis emerging global health emergency addition changes main ct features indicate development disease  \n",
       "22                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2019 novel coronavirus 2019-ncov virus identified cause outbreak pneumonia first detected wuhan china investigations transmissibility severity features associated virus ongoing currently vaccine therapeutic antibody prevent infection time required develop effective immune strategy pathogen contrast specific inhibitors targeting key protease involved replication proliferation virus effective means alleviate epidemic main protease sars-cov essential life cycle virus showed 96 1 similarity main proteaseof 2019-ncov considered attractive target drug development study identified 4 small molecular drugs high binding capacity sars-cov main protease high-throughput screening based 8 000 clinical drug libraries drugs widely used clinical applications guaranteed safety may serve promising candidates treat infection 2019-ncov  \n",
       "25                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2019-ncov newly identified coronavirus high similarity sars-cov performed structural analysis receptor binding domain rbd spike glycoprotein responsible entry coronaviruses host cells rbds two viruses share 72 identity amino acid sequences molecular simulation reveals highly similar ternary structures however 2019-ncov distinct loop flexible glycyl residues replacing rigid prolyl residues sars-cov molecular modeling revealed 2019-ncov rbd stronger interaction angiotensin converting enzyme 2 ace2 unique phenylalanine f486 flexible loop likely plays major role penetration deep hydrophobic pocket ace2 ace2 widely expressed conserved primary structures throughout animal kingdom fish amphibians reptiles birds mammals structural analysis suggests ace2 animals potentially bind rbd 2019-ncov making possible natural hosts virus 2019-ncov thought transmitted respiratory droplets however since ace2 predominantly expressed intestines testis kidney fecal-oral routes transmission also possible finally antibodies small molecular inhibitors block interaction ace2 rbd developed combat virus  \n",
       "27                                                        26 previous findings middle east respiratory syndrome coronavirus mers-cov -27 related viruses bats ability tylonycteris-batcov hku4 spike protein utilize 28 mers-cov receptor human dipeptidyl peptidase 4 hdpp4 suggest bat ancestral origin 29 mers-cov developed 12 primary bat cell lines seven bat species including 30 tylonycteris pachypus pipistrellus abramus rhinolophus sinicus hosts tylonycteris-31 batcov hku4 pipistrellus-batcov hku5 sars-related-cov respectively tested 32 susceptibilities mers-covs sars-cov human coronavirus 229e hcov-229e 33 five cell lines including p abramus r sinicus pachypus cells susceptible 34 human mers-cov emc 2012 however three tested camel mers-cov strains showed 35 different infectivities two strains capable infecting three one cell lines 36 respectively sars-cov replicate r sinicus cells hcov-229e cannot 37 replicate bat cells bat dipeptidyl peptidase 4 dpp4 sequences closely related 38 human non-human primates distinct dromedary dpp4 sequence critical 39 residues binding mers-cov spike protein mostly conserved bat dpp4 dpp4 40 expressed five bat cells susceptible mers-cov significantly higher mrna 41 expression levels non-susceptible cells p 0 0174 supporting dpp4 42 expression critical mers-cov infection bats however overexpression pachypus 43 dpp4 failed confer mers-cov susceptibility pachypus cells suggesting cellular 44 factors determining viral replication broad cellular tropism mers-cov 45 prompt exploration host diversity related viruses identify ancestral origin 46 47 rights reserved reuse allowed without permission  \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    ...  \n",
       "10512                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               wuhan coronavirus called 2019-ncov newly emerged virus infected 9692 people leads 213 fatalities january 30 2020 currently effective treatment epidemic however viral protease coronavirus well-known essential replication thus effective drug target fortunately sequence identity 2019-ncov protease severe-acute respiratory syndrome virus sars-cov high 96 1 show protease inhibitor binding sites 2019-ncov sars-cov almost identical means potential anti-sars-cov chemotherapies also potential 2019-ncov drugs report family potential 2019-ncov drugs generated machine intelligence-based generative network complex gnc potential effectiveness treating 2019-ncov using existing hiv drugs also analyzed  \n",
       "10513                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     wuhan novel coronavirus disease outbreak become global outbreak raised concern scientific community design discover definitive cure deadly virus caused deaths numerous infected people upon infection spreading  \n",
       "10514                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             wuhan pneumonia acute infectious disease caused 2019 novel coronavirus hubei province achieve accurate calculation incubation period involved officially confirmed cases clear history exposure time onset excluded without relevant epidemiological descriptions working living wuhan long time hard determine possible exposure time proposed monte caro simulation approach estimate incubation covid-19 well employed nonparametric ways also employed manifold learning related statistical analysis decipher incubation relationships different age gender groups rights reserved reuse allowed without permission  \n",
       "10578                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       zoonotic coronaviruses covs significant threats global health exemplified recent emergence severe acute respiratory syndrome coronavirus 2 sars-cov-2 1 host immune responses cov complex regulated part antiviral interferons  \n",
       "10580  zoonotic viruses circulate swarms animal reservoirs emerge human populations causing epidemics adversely affect public health portable safe effective vaccine platforms needed context outbreak emergence situations work report generation characterization alphavirus replicon vaccine platform based non-select agent attenuated venezuelan equine encephalitis vee virus vaccine strain 3526 vrp 3526 using noroviruses coronaviruses model systems demonstrate utility vrp 3526 platform generation recombinant proteins production virus-like particles vivo efficacy vaccine emergent viruses importantly packaging biosafety level 2 bsl2 conditions distinguishes vrp 3526 previously reported alphavirus platforms makes approach accessible majority laboratories around world addition improved outcomes vulnerable aged models well heterologous challenge suggest improved efficacy compared previously attenuated vrp approaches taking results together vrp 3526 platform represents safe highly portable system rapidly deployed bsl2 conditions generation candidate vaccines emerging microbial pathogens importance vee virus replicon particles provide robust established platform antigen expression vaccination utility limited requirement high-containment-level facilities production packaging work utilize attenuated vaccine strain capable use lower biocontainment level retaining capacity wild-type replicon particle importantly new replicon platform provides equal protection aged mice following heterologous challenge distinguishes attenuated replicon platforms together new system represents highly portable safe system use context disease emergence  \n",
       "\n",
       "[1521 rows x 2 columns]"
      ]
     },
     "execution_count": 16,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "corona = df_y[df_y['Cleaned_Content'].str.contains('corona')]\n",
    "\n",
    "corona"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 17,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Number of corona keywords were found :  1521\n"
     ]
    }
   ],
   "source": [
    "corona_texts = corona['Cleaned_Content'].values\n",
    "print(\"Number of corona keywords were found : \",len(corona_texts))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 19,
   "metadata": {},
   "outputs": [],
   "source": [
    "##There is a values of paragraph sugar,stress,alchol"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 20,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "('novel coronavirus 2019-ncov originating wuhan china presents potential respiratory viral pandemic world population current efforts focused containment quarantine infected individuals ultimately outbreak could controlled protective vaccine prevent 2019-ncov infection vaccine research pursued intensely exists today therapy treat 2019-ncov upon infection despite urgent need find options help patients preclude potential death herein review potential options treat 2019-ncov patients emphasis necessity speed timeliness developing new effective therapies outbreak consider options drug repurposing developing neutralizing monoclonal antibody therapy oligonucleotide strategy targeting viral rna genome emphasizing promise pitfalls approaches finally advocate fastest strategy develop treatment could resistant mutations virus may future proposal biologic blocks 2019-ncov entry using soluble version viral receptor angiotensin-converting enzyme 2 ace2 fused immunoglobulin fc domain ace2-fc providing neutralizing antibody maximal breath avoid viral escape also helping recruit immune system build lasting immunity ace2-fc therapy would also supplement decreased ace2 levels lungs infection thereby directly treating acute respiratory distress pathophysiology third mechanism action sequence ace2-fc protein provided investigators allowing possible use recombinant protein expression systems start producing drug today treat patients compassionate use formal clinical trials later undertaken treatment could help infected patients protective vaccine developed widely available coming months year', 'stress', ' pathophysiology third mechanism action sequence ace2-fc protein provided investigators allowing possible use recombinant protein expression systems start producing drug today treat patients compassionate use formal clinical trials later undertaken treatment could help infected patients protective vaccine developed widely available coming months year')\n",
      "('novel coronavirus 2019-ncov originating wuhan china presents potential respiratory viral pandemic world population current efforts focused containment quarantine infected individuals ultimately outbreak could controlled protective vaccine prevent 2019-ncov infection vaccine research pursued intensely exists today therapy treat 2019-ncov upon infection despite urgent need find options help patients preclude potential death herein review potential options treat 2019-ncov patients emphasis necessity speed timeliness developing new effective therapies outbreak consider options drug repurposing developing neutralizing monoclonal antibody therapy oligonucleotide strategy targeting viral rna genome emphasizing promise pitfalls approaches finally advocate fastest strategy develop treatment could resistant mutations virus may future proposal biologic blocks 2019-ncov entry using soluble version viral receptor angiotensin-converting enzyme 2 ace2 fused immunoglobulin fc domain ace2-fc providing neutralizing antibody maximal breath avoid viral escape also helping recruit immune system build lasting immunity ace2-fc therapy would also supplement decreased ace2 levels lungs infection thereby directly treating acute respiratory distress pathophysiology third mechanism action sequence ace2-fc protein provided investigators allowing possible use recombinant protein expression systems start producing drug today treat patients compassionate use formal clinical trials later undertaken treatment could help infected patients protective vaccine developed widely available coming months year', 'stress', ' pathophysiology third mechanism action sequence ace2-fc protein provided investigators allowing possible use recombinant protein expression systems start producing drug today treat patients compassionate use formal clinical trials later undertaken treatment could help infected patients protective vaccine developed widely available coming months year')\n",
      "('novel coronavirus 2019-ncov first identified wuhan hubei province spreads provinces china decides determine public health emergency international concern pheic 2019-ncov 2019-ncov reported share receptor angiotensin-converting enzyme 2 ace2 sars-cov based public single-cell rna-seq datasets analyzed ace2 rna expression profile tissues different locations respiratory tract result indicates ace2 expression appears nasal epithelial cells found size population ace2-expressing nasal epithelial cells comparable size population ace2-expression type ii alveolar cells at2 asian sample reported yu zhao et al detected 2019-ncov polymerase chain reaction pcr nasal-swab throat-swab seven suspected cases found 2019-ncov tends higher concentration nasal-swab comparing throat-swab could attribute ace2-expressing nasal epithelial cells hope study could informative virus-prevention strategy development especially treatment nasal mucus severe infection 2019-ncov could result acute respiratory distress syndrome ards sepsis causing death approximately 2 infected individuals 1 contacted human airway spike proteins 2019-ncov bind surface receptors sensitive cells mediate virus enter target cells recently xu et al modeled spike protein indicated angiotensin-converting enzyme 2 ace2 could receptor 2019-ncov 2 zhou et al showed ace2 essential 2019-ncov enter hela cells 3', 'stress', ' syndrome ards sepsis causing death approximately 2 infected individuals 1 contacted human airway spike proteins 2019-ncov bind surface receptors sensitive cells mediate virus enter target cells recently xu et al modeled spike protein indicated angiotensin-converting enzyme 2 ace2 could receptor 2019-ncov 2 zhou et al showed ace2 essential 2019-ncov enter hela cells 3')\n",
      "('acute respiratory distress syndrome ards immune-driven pathologies observed severe cases severe acute respiratory syndrome coronavirus sars-cov infection sars-cov emerged 2002 2003 led global outbreak sars outcome human infection intranasal infection c57bl 6j mice mouse-adapted sars-cov results high-titer virus replication within lung induction inflammatory cytokines chemokines immune cell infiltration within lung using model investigated role complement system sars-cov infection observed activation complement cascade lung early day 1 following sars-cov infection test whether activation contributed protective pathologic outcomes utilized mice deficient c3 c3 - - central component complement system relative c57bl 6j control mice sars-cov-infected c3 - mice exhibited significantly less weight loss less respiratory dysfunction despite equivalent viral loads lung significantly fewer neutrophils inflammatory monocytes present lungs c3 - mice c56bl 6j controls subsequent studies revealed reduced lung pathology lower cytokine chemokine levels lungs sera c3 - mice controls studies identify complement system important host mediator sars-cov-induced disease suggest complement activation regulates systemic proinflammatory response sars-cov infection furthermore data suggest sars-cov-mediated disease largely immune driven inhibiting complement signaling sars-cov infection might function effective immune therapeutic importance complement system critical part host defense many bacterial viral fungal infections works alongside pattern recognition receptors stimulate host defense systems advance activation adaptive immune response study directly test role complement sars-cov pathogenesis using mouse model show respiratory disease significantly reduced absence complement even though viral load unchanged complement-deficient mice reduced neutrophilia lungs reduced systemic inflammation consistent observation sars-cov pathogenesis immune-driven disease data suggest inhibition complement signaling might effective treatment option following coronavirus infection', 'stress', ' syndrome ards immune-driven pathologies observed severe cases severe acute respiratory syndrome coronavirus sars-cov infection sars-cov emerged 2002 2003 led global outbreak sars outcome human infection intranasal infection c57bl 6j mice mouse-adapted sars-cov results high-titer virus replication within lung induction inflammatory cytokines chemokines immune cell infiltration within lung using model investigated role complement system sars-cov infection observed activation complement cascade lung early day 1 following sars-cov infection test whether activation contributed protective pathologic outcomes utilized mice deficient c3 c3 - - central component complement system relative c57bl 6j control mice sars-cov-infected c3 - mice exhibited significantly less weight loss less respiratory dysfunction despite equivalent viral loads lung significantly fewer neutrophils inflammatory monocytes present lungs c3 - mice c56bl 6j controls subsequent studies revealed reduced lung pathology lower cytokine chemokine levels lungs sera c3 - mice controls studies identify complement system important host mediator sars-cov-induced disease suggest complement activation regulates systemic proinflammatory response sars-cov infection furthermore data suggest sars-cov-mediated disease largely immune driven inhibiting complement signaling sars-cov infection might function effective immune therapeutic importance complement system critical part host defense many bacterial viral fungal infections works alongside pattern recognition receptors stimulate host defense systems advance activation adaptive immune response study directly test role complement sars-cov pathogenesis using mouse model show respiratory disease significantly reduced absence complement even though viral load unchanged complement-deficient mice reduced neutrophilia lungs reduced systemic inflammation consistent observation sars-cov pathogenesis immune-driven disease data suggest inhibition complement signaling might effective treatment option following coronavirus infection')\n",
      "('positive strand rna viruses known replicate genomes close association intracellular membranes case hepatitis c virus hcv member family flaviviridae infected cells contain accumulations vesicles forming membranous web mw thought site viral rna replication however little known biogenesis three-dimensional structure mw study used combination immunofluorescence-and electron microscopy em -based methods analyze membranous structures induced hcv infected cells found mw derived primarily endoplasmic reticulum er contains markers rough er well markers early late endosomes cop vesicles mitochondria lipid droplets lds main constituents mw single double membrane vesicles dmvs latter predominate kinetic appearance correlates kinetics viral rna replication dmvs induced primarily ns5a whereas ns4b induces single membrane vesicles arguing mw formation requires concerted action several hcv replicase proteins three-dimensional reconstructions identify dmvs protrusions er membrane cytosol frequently connected er membrane via neck-like structure addition late infection multi-membrane vesicles become evident presumably result stress-induced reaction thus morphology membranous rearrangements induced hcv-infected cells resemble unrelated picorna- corona-and arteriviruses clearly distinct closely related flaviviruses results reveal unexpected similarities hcv distantly related positive-strand rna viruses presumably reflecting similarities cellular pathways exploited viruses establish membranous replication factories citation romero-brey merz chiramel lee j-y chlanda p et al 2012 three-dimensional architecture biogenesis membrane structures associated hepatitis c virus replication plos pathog 8 12 e1003056', 'stress', '-induced reaction thus morphology membranous rearrangements induced hcv-infected cells resemble unrelated picorna- corona-and arteriviruses clearly distinct closely related flaviviruses results reveal unexpected similarities hcv distantly related positive-strand rna viruses presumably reflecting similarities cellular pathways exploited viruses establish membranous replication factories citation romero-brey merz chiramel lee j-y chlanda p et al 2012 three-dimensional architecture biogenesis membrane structures associated hepatitis c virus replication plos pathog 8 12 e1003056')\n",
      "('although different groups coronaviruses severe acute respiratory syndrome-coronavirus sars-cov nl63 use receptor angiotensin converting enzyme ace -2 entry host cell despite common receptor consequence entry different severe respiratory distress case sars-cov frequently mild respiratory infection nl63 using wholly recombinant system investigated ability virus receptor-binding protein spike protein bind ace-2 solution cell surface assays find nl63 protein weaker interaction ace-2 sars-cov protein particularly solution binding residues required contact similar also confirm ace-2-binding site nl63 lies residues 190 739 lower-affinity interaction ace-2 might partly explain different pathological consequences infection sars-cov nl63', 'stress', ' case sars-cov frequently mild respiratory infection nl63 using wholly recombinant system investigated ability virus receptor-binding protein spike protein bind ace-2 solution cell surface assays find nl63 protein weaker interaction ace-2 sars-cov protein particularly solution binding residues required contact similar also confirm ace-2-binding site nl63 lies residues 190 739 lower-affinity interaction ace-2 might partly explain different pathological consequences infection sars-cov nl63')\n",
      "('animal coronaviruses infectious bronchitis virus ibv arteriviruses porcine reproductive respiratory syndrome virus prrsv able manifest highly contagious infections specific native hosts thereby arising critical economic damage animal industries review discusses recent progress studies virus-host interactions animal human coronavirus arterivirus infections emphasis ibv-host cell interactions interactions may directly involved viral replication lead alteration certain signaling pathways cell stress response innate immunity facilitate viral replication pathogenesis', 'stress', ' response innate immunity facilitate viral replication pathogenesis')\n",
      "('autophagy conserved eukaryotic process mediates lysosomal degradation cytoplasmic macromolecules damaged organelles also exerting important role elimination intracellular pathogens despite antiviral role autophagy many studies suggest positive-stranded rna viruses exploit pathway facilitate replication study demonstrate equine torovirus berne virus bev prototype member torovirus genus coronaviridae family nidovirales order induces autophagy late times post-infection conversion microtubule associated protein 1b light chain 3 lc3 cytosolic lc3 membrane associated form lc3 ii canonical marker autophagosome formation enhanced bev infected cells however neither autophagy induction via starvation pharmacological blockade significantly affect bev replication similarly bev infection altered autophagy deficient cells lacking either beclin 1 lc3b protein expression unexpectedly cargo receptor p62 selective autophagy receptor aggregates within region bev main protease pro localizes finding coupled observation bev replication also induces er stress time selective autophagy taking place suggests autophagy pathway activated response hefty accumulation virus-encoded polypeptides late phase bev infection', 'stress', ' time selective autophagy taking place suggests autophagy pathway activated response hefty accumulation virus-encoded polypeptides late phase bev infection')\n",
      "('background morocco pediatric pneumonia remains serious public health problem constitutes first cause mortality due infectious diseases e etiological diagnosis acute respiratory tract infections difficult erefore necessary use multiplex real-time polymerase chain reaction assay tests routine setting exact fast identification objectives paper present clinical results pediatric pneumonia describe etiology using molecular diagnosis study design tracheal secretion collected infants presenting respiratory distress isolated associated systemic signs attending unit neonatology december 1 2016 mai 31 2018 samples tested multiplex respifinder smart 22 fast potentially detects 18 viruses 4 bacteria results 86 infants considered study mean age 31 19 days suspected acute respiratory tract infections 71 83 positive one multiple viruses bacteria e majority acute respiratory tract infections viral origin 95 respiratory syncytial viruses b 49 rhinovirus 21 coronaviruses 229e 11 humain metapneumovirus 5 influenza 3 influenza h1n1 1 adenovirus 2 parainfluenza virus type 4 2 among patients 6 mycoplasma pneumoniae coinfections associated severe respiratory symptoms conclusion e clinical spectrum respiratory infections complex often nonspecific us early fast detection related causative agents crucial e use multiplex real time polymerase chain reaction may help choose accurate treatment reduce overall use unnecessary antibiotics preserve intestinal flora decrease nosocomial infection reducing length hospitalization', 'stress', ' isolated associated systemic signs attending unit neonatology december 1 2016 mai 31 2018 samples tested multiplex respifinder smart 22 fast potentially detects 18 viruses 4 bacteria results 86 infants considered study mean age 31 19 days suspected acute respiratory tract infections 71 83 positive one multiple viruses bacteria e majority acute respiratory tract infections viral origin 95 respiratory syncytial viruses b 49 rhinovirus 21 coronaviruses 229e 11 humain metapneumovirus 5 influenza 3 influenza h1n1 1 adenovirus 2 parainfluenza virus type 4 2 among patients 6 mycoplasma pneumoniae coinfections associated severe respiratory symptoms conclusion e clinical spectrum respiratory infections complex often nonspecific us early fast detection related causative agents crucial e use multiplex real time polymerase chain reaction may help choose accurate treatment reduce overall use unnecessary antibiotics preserve intestinal flora decrease nosocomial infection reducing length hospitalization')\n",
      "('background avian infectious bronchitis ib one serious diseases economic importance chickens caused avian infectious coronavirus ibv information remains limited comparative protein expression profiles chicken embryonic tissues response ibv infection ovo study analyzed changes protein expression trachea kidney tissues chicken embryos following ibv infection ovo using two-dimensional gel electrophoresis 2-de coupled matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry maldi-tof-tof ms results 17 differentially expressed proteins tracheal tissues 19 differentially expressed proteins kidney tissues identified proteins mostly related cytoskeleton binding calcium ions stress response anti-oxidative macromolecular metabolism altered proteins confirmed mrna level using real-time rt-pcr moreover western blotting analysis confirmed changes annexin a5 hspb1 ibv infection conclusions best knowledge performed first analysis proteomic changes chicken embryonic trachea kidney tissues ibv infection ovo data obtained facilitate better understanding pathogenesis ibv infection', 'stress', ' response anti-oxidative macromolecular metabolism altered proteins confirmed mrna level using real-time rt-pcr moreover western blotting analysis confirmed changes annexin a5 hspb1 ibv infection conclusions best knowledge performed first analysis proteomic changes chicken embryonic trachea kidney tissues ibv infection ovo data obtained facilitate better understanding pathogenesis ibv infection')\n",
      "('background feed contaminated feces infected pigs believed potential route transmission porcine delta coronavirus pdcov objective study determine addition commercial feed additives e acids salt sugar swine feed effective strategy inactive pdcov results six commercial feed acids ultraacid p activate da kemgest acid booster luprosil amasil salt sugar evaluated acids added recommended concentrations 5 g aliquots complete feed also inoculated 1 ml pdcov incubated 0 7 14 21 28 35 days another experiment double recommended concentrations additives also added feed samples incubated 0 1 3 7 10 days samples stored room temperature 25 c followed removal aliquots 0 7 14 21 28 35 days surviving virus eluted buffer solution titrated swine testicular cells feed samples without additive used controls weibull log-linear kinetic models used analyze virus survival curves presence tail virus inactivation curves indicated deviations linear behavior hence weibull model chosen characterizing inactivation responses due better fit recommended concentrations delta values days decrease virus concentration 1 log ranged 0 62-1 72 days differences virus survival among feed samples without additives manufacturers recommended concentrations doubling concentration additives reduced delta value 0 28 days p 0 05 additives except amasil delta values 0 86 vs 4 95 days feed additives contained phosphoric acid citric acid fumaric acid effective reducing virus survival although none additives completely inactivated virus 10-days post-inoculation conclusions commercial feed additives acidifiers salt may utilized strategy decrease risk pdcov feed specially commercial feed acidifiers double recommended concentrations reduced pdcov survival complete feed storage room temperature however none additives completely inactivated virus', 'sugar', ' evaluated acids added recommended concentrations 5 g aliquots complete feed also inoculated 1 ml pdcov incubated 0 7 14 21 28 35 days another experiment double recommended concentrations additives also added feed samples incubated 0 1 3 7 10 days samples stored room temperature 25 c followed removal aliquots 0 7 14 21 28 35 days surviving virus eluted buffer solution titrated swine testicular cells feed samples without additive used controls weibull log-linear kinetic models used analyze virus survival curves presence tail virus inactivation curves indicated deviations linear behavior hence weibull model chosen characterizing inactivation responses due better fit recommended concentrations delta values days decrease virus concentration 1 log ranged 0 62-1 72 days differences virus survival among feed samples without additives manufacturers recommended concentrations doubling concentration additives reduced delta value 0 28 days p 0 05 additives except amasil delta values 0 86 vs 4 95 days feed additives contained phosphoric acid citric acid fumaric acid effective reducing virus survival although none additives completely inactivated virus 10-days post-inoculation conclusions commercial feed additives acidifiers salt may utilized strategy decrease risk pdcov feed specially commercial feed acidifiers double recommended concentrations reduced pdcov survival complete feed storage room temperature however none additives completely inactivated virus')\n",
      "('background postulated genetic predisposition may influence susceptibility sarscoronavirus infection disease outcomes recent study suggested deletion allele allele angiotensin converting enzyme ace gene associated hypoxemia sars patients moreover ace allele shown prevalent patients suffering adult respiratory distress syndrome ards previous study thus investigated association ace insertion deletion polymorphism progression ards requirement intensive care sars patients', 'stress', ' syndrome ards previous study thus investigated association ace insertion deletion polymorphism progression ards requirement intensive care sars patients')\n",
      "('background mortality high among patients middle east respiratory syndrome coronavirus mers-cov infection aimed determine hospital mortality factors associated cohort mers-cov patients methods reviewed hospital records confirmed cases detection virus polymerase chain reaction respiratory tract samples mers-cov patients n 63 admitted buraidah central hospital al-qassim saudi arabia 2014 2017 abstracted data demography vital signs associated conditions presented admission pre-existing chronic diseases treatment vital status bi-variate comparisons multiple logistic regressions choice data analyses results mean age 60 years sd 18 2 patients male 74 6 saudi citizens 81 two patients treated ribavirin plus interferon hospital mortality 25 4 patients admitted septic shock organ failure significantly likely die patients admitted pneumonia acute respiratory distress syndrome 47 9 95 ci 3 9 585 5 p-value 0 002 age sex presence chronic conditions significantly associated mortality conclusion hospital mortality 25 septic shock organ failure admittance significant predictor mortality', 'stress', ' syndrome 47 9 95 ci 3 9 585 5 p-value 0 002 age sex presence chronic conditions significantly associated mortality conclusion hospital mortality 25 septic shock organ failure admittance significant predictor mortality')\n",
      "('background severe acute respiratory syndrome sars recent epidemic human disease caused novel coronavirus sars-cov first reported asia sars quickly spread worldwide international travelling july 2003 world health organization reported total 8 437 people afflicted sars 9 6 mortality rate although immunopathological damages may account severity respiratory distress little known genome-wide gene expression host changes attack sars-cov', 'stress', ' little known genome-wide gene expression host changes attack sars-cov')\n",
      "('bats known reservoirs wide variety viruses rarely result overt clinical disease bat host however anthropogenic influences landscape climate change species assemblages interactions well undermine host-resilience cumulative result disturbance bat-pathogen dynamics facilitate spillover events sympatric species may threaten bat communities already facing synergistic stressors ecological change therefore characterisation viral pathogens bat communities provides important basal information monitor predict emergence diseases relevant conservation public health study used targeted molecular techniques serological assays next generation sequencing characterise adenoviruses coronaviruses paramyxoviruses 11 species insectivorous bats within south west botanical province western australia phylogenetic analysis indicated complex ecological interactions including virus-host associations cross-species infections multiple viral strains circulating concurrently within selected bat populations additionally describe entire coding sequences five alphacoronaviruses representing four putative new species one novel adenovirus results indicate viral burden prevalence richness homogeneous among species chalinolobus gouldii identified key epidemiological element within studied communities', 'stress', 'ors ecological change therefore characterisation viral pathogens bat communities provides important basal information monitor predict emergence diseases relevant conservation public health study used targeted molecular techniques serological assays next generation sequencing characterise adenoviruses coronaviruses paramyxoviruses 11 species insectivorous bats within south west botanical province western australia phylogenetic analysis indicated complex ecological interactions including virus-host associations cross-species infections multiple viral strains circulating concurrently within selected bat populations additionally describe entire coding sequences five alphacoronaviruses representing four putative new species one novel adenovirus results indicate viral burden prevalence richness homogeneous among species chalinolobus gouldii identified key epidemiological element within studied communities')\n",
      "('coronavirus cov envelope e protein small structural protein critical virion morphogenesis release recently characterized e protein ion channel activity eic also implicated modulating viral pathogenesis study used infectious bronchitis coronavirus ibv model study eic two recombinant ibvs ribvs harboring eic-inactivating mutations -rt16a ra26f -were serially passaged several compensatory mutations identified transmembrane domain tmd two ribvs harboring putative eicreverting mutations -rt16a a26v ra26f f14n -were recovered compared parental ribv-p65 control four eic mutants exhibited comparable levels intracellular rna synthesis structural protein production virion assembly results showed ibv eic contributed induction er stress response up-regulation er stress-related genes markedly reduced cells infected eic-defective mutants eic-defective mutants also formed smaller plaques released significantly less infectious virions culture supernatant lower levels viral fitness cell culture significantly defective phenotypes restored cells infected putative eic revertants eic mutations also implicated regulating ibv-induced apoptosis induction pro-inflammatory cytokines viral pathogenicity vivo taken together study highlights importance cov eic modulating virion release various aspects cov -host interaction', 'stress', '-related genes markedly reduced cells infected eic-defective mutants eic-defective mutants also formed smaller plaques released significantly less infectious virions culture supernatant lower levels viral fitness cell culture significantly defective phenotypes restored cells infected putative eic revertants eic mutations also implicated regulating ibv-induced apoptosis induction pro-inflammatory cytokines viral pathogenicity vivo taken together study highlights importance cov eic modulating virion release various aspects cov -host interaction')\n",
      "('coronaviruses covs continuously threaten human health however date evolutionary mechanisms govern cov strain persistence human populations fully understood study characterized evolution major antigen-spike gene prevalent human coronavirus hcov oc43 using phylogenetic phylodynamic analysis among five known hcov-oc43 genotypes e higher substitution rates dn ds values well positive selection sites detected gene genotype corresponding dominant hcov epidemic recent years analysis showed majority substitutions located s1 subunit among seven positive selection sites chronologically traced temporal evolution routes genotype six located around critical sugar binding region n-terminal domain ntd protein important sugar binding domain cov findings suggest genetic drift gene may play important role genotype persistence human populations providing insights mechanisms hcov-oc43 adaptive evolution', 'sugar', ' binding domain cov findings suggest genetic drift gene may play important role genotype persistence human populations providing insights mechanisms hcov-oc43 adaptive evolution')\n",
      "('coronaviruses positive-stranded rna viruses infect variety hosts resulting range symptoms gastrointestinal illness respiratory distress bats reservoirs high diversity coronaviruses focused surveillance detected several strains genetically similar mers-coronavirus sars-coronavirus human coronaviruses 229e nl63 bat fauna central asia link china eastern europe relatively less studied regions world kazakhstan world ninth largest country however little understood prevalence diversity bat-borne viruses study bat guano collected bat caves three different sites southern kazakhstan tested positive coronaviruses phylogenetic reconstruction indicates novel bat coronaviruses belong genus alphacoronavirus addition two distinct lineages kazakhstan bat coronaviruses detected lineages closely related bat coronaviruses china france spain south africa suggesting co-circulation coronaviruses common multiple bat species overlapping geographical distributions study highlights need collaborative efforts understudied countries increase integrated surveillance capabilities toward better monitoring detection infectious diseases', 'stress', ' bats reservoirs high diversity coronaviruses focused surveillance detected several strains genetically similar mers-coronavirus sars-coronavirus human coronaviruses 229e nl63 bat fauna central asia link china eastern europe relatively less studied regions world kazakhstan world ninth largest country however little understood prevalence diversity bat-borne viruses study bat guano collected bat caves three different sites southern kazakhstan tested positive coronaviruses phylogenetic reconstruction indicates novel bat coronaviruses belong genus alphacoronavirus addition two distinct lineages kazakhstan bat coronaviruses detected lineages closely related bat coronaviruses china france spain south africa suggesting co-circulation coronaviruses common multiple bat species overlapping geographical distributions study highlights need collaborative efforts understudied countries increase integrated surveillance capabilities toward better monitoring detection infectious diseases')\n",
      "('coronaviruses demonstrated contribute substantially respiratory tract infections among child population though infected children commonly present mild upper airway symptoms high-risk patients underlying conditions particularly immunocompromised children pathogens may lead severe lung infection extrapulmonary disorders paper provide first report case 15-month-old child severe combined immunodeficiency coronavirus hku1-related pneumonia fatal respiratory distress syndrome', 'stress', ' syndrome')\n",
      "('coronaviruses demonstrated contribute substantially respiratory tract infections among child population though infected children commonly present mild upper airway symptoms high-risk patients underlying conditions particularly immunocompromised children pathogens may lead severe lung infection extrapulmonary disorders paper provide first report case 15-month-old child severe combined immunodeficiency coronavirus hku1-related pneumonia fatal respiratory distress syndrome', 'stress', ' syndrome')\n",
      "('deletion severe acute respiratory syndrome coronavirus sars-cov envelope e gene attenuates virus e gene encodes small multifunctional protein possesses ion channel ic activity important function virus-host interaction test contribution e protein ic activity virus pathogenesis two recombinant mouse-adapted sars-covs containing one single amino acid mutation suppressed ion conductivity engineered serial infections mutant viruses general incorporated compensatory mutations within e gene rendered active ion channels furthermore ic activity conferred better fitness competition assays suggesting ion conductivity represents advantage virus interestingly mice infected viruses displaying e protein ic activity either wild-type e protein sequence revertants restored ion transport rapidly lost weight died contrast mice infected mutants lacking ic activity incorporate mutations within e gene experiment recovered disease survived knocking e protein ic activity significantly affect virus growth infected mice decreased edema accumulation major determinant acute respiratory distress syndrome ards leading death reduced edema correlated lung epithelia integrity proper localization na k atpase participates edema resolution levels inflammasome-activated il-1b reduced lung airways animals infected viruses lacking e protein ic activity indicating e protein ic function required inflammasome activation reduction il-1b accompanied diminished amounts tnf il-6 absence e protein ion conductivity key cytokines promote progression lung damage ards pathology conclusion e protein ic activity represents new determinant sars-cov virulence', 'stress', ' syndrome ards leading death reduced edema correlated lung epithelia integrity proper localization na k atpase participates edema resolution levels inflammasome-activated il-1b reduced lung airways animals infected viruses lacking e protein ic activity indicating e protein ic function required inflammasome activation reduction il-1b accompanied diminished amounts tnf il-6 absence e protein ion conductivity key cytokines promote progression lung damage ards pathology conclusion e protein ic activity represents new determinant sars-cov virulence')\n",
      "('first year enhanced mers coronavirus surveillance england 77 persons traveling middle east acute respiratory illness tested virus infection confirmed 2 travelers acute respiratory distress syndrome 2 contacts patients less severe manifestations tested negative', 'stress', ' syndrome 2 contacts patients less severe manifestations tested negative')\n",
      "('first year enhanced mers coronavirus surveillance england 77 persons traveling middle east acute respiratory illness tested virus infection confirmed 2 travelers acute respiratory distress syndrome 2 contacts patients less severe manifestations tested negative', 'stress', ' syndrome 2 contacts patients less severe manifestations tested negative')\n",
      "('entry -coronavirus porcine epidemic diarrhea virus pedv requires specific proteases activate spike protein membrane fusion virion host cell following receptor binding herein pedv isolate 85-7 could proliferate induce cell-cell fusion trypsin independent manner vero cells eight homologous mutation strains screened continuous proliferation absence trypsin vero cells according whole genome sequence comparative analysis identified four major variations located nonstructural protein 2 open reading frame 3 envelope e genes respectively comparative analyses genomic variations proliferation characteristics identified single mutation within s2 cleavage site c30 c40 mutants substitution conserved arginine r glycine g r895g change resulted weaker cell-cell fusion smaller plaque morphology higher virus titer serious microfilament condensation analysis confirmed mutation responsible optimal cell-adaptation determinant trypsin-dependent entry pedv otherwise novel variation 16-20 aa deletion l25p mutation transmembrane domain e protein affected multiple infection processes including up-regulation production er stress indicator grp78 improving expression pro-inflammatory cytokines il-6 il-8 promoting apoptosis results study provide better understanding potential mechanisms viral functional proteins pedv replication infection fitness', 'stress', ' indicator grp78 improving expression pro-inflammatory cytokines il-6 il-8 promoting apoptosis results study provide better understanding potential mechanisms viral functional proteins pedv replication infection fitness')\n",
      "('glucose-6-phosphate dehydrogenase g6pd provides reducing agent nadph meet cellular needs reductive biosynthesis maintenance redox homeostasis g6pd-deficient cells experience high level oxidative stress increased susceptibility viral infections cyclooxygenase-2 cox-2 key mediator regulation viral replication inflammatory response current study role g6pd inflammatory response determined scramble control g6pd-knockdown g6pd-kd a549 cells upon tumor necrosis factor- tnf- stimulation decreased expression pattern induced cox-2 reduced production downstream pge 2 occurred upon tnf- stimulation g6pd-kd a549 cells compared scramble control a549 cells tnf- -induced antiviral activity revealed decreased cox-2 expression enhanced susceptibility coronavirus 229e infection g6pd-kd a549 cells result decreased phosphorylation levels mapk p38 erk1 2 nf- b impaired inflammatory response g6pd-kd a549 cells found mediated nadph oxidase nox signaling elucidated cell pretreatment nox2-sirna nox inhibitor diphenyleneiodonium chloride dpi addition nox activity tnf- treatment g6pd-kd a549 cells up-regulated coupled decrease nox subunit expression transcriptional level implying tnf- -mediated nox signaling requires participation g6pd together data suggest g6pd deficiency affects cellular inflammatory response decreased tnf- -mediated antiviral response g6pd-kd a549 cells result dysregulated nox mapk nf- b cox-2 signaling', 'stress', ' increased susceptibility viral infections cyclooxygenase-2 cox-2 key mediator regulation viral replication inflammatory response current study role g6pd inflammatory response determined scramble control g6pd-knockdown g6pd-kd a549 cells upon tumor necrosis factor- tnf- stimulation decreased expression pattern induced cox-2 reduced production downstream pge 2 occurred upon tnf- stimulation g6pd-kd a549 cells compared scramble control a549 cells tnf- -induced antiviral activity revealed decreased cox-2 expression enhanced susceptibility coronavirus 229e infection g6pd-kd a549 cells result decreased phosphorylation levels mapk p38 erk1 2 nf- b impaired inflammatory response g6pd-kd a549 cells found mediated nadph oxidase nox signaling elucidated cell pretreatment nox2-sirna nox inhibitor diphenyleneiodonium chloride dpi addition nox activity tnf- treatment g6pd-kd a549 cells up-regulated coupled decrease nox subunit expression transcriptional level implying tnf- -mediated nox signaling requires participation g6pd together data suggest g6pd deficiency affects cellular inflammatory response decreased tnf- -mediated antiviral response g6pd-kd a549 cells result dysregulated nox mapk nf- b cox-2 signaling')\n",
      "('glycoproteins s2 subunit spike glycoprotein severe acute respiratory syndrome sars coronavirus cov contains internal domains called fusion peptides fp play essential roles virus entry although membrane fusion broadly studied still major gaps molecular details lipid rearrangements bilayer fusion peptide-membrane interactions employed differential scanning calorimetry dsc electron spin resonance esr gather information membrane fusion mechanism promoted two putative sars fps dsc data showed peptides strongly perturb structural integrity anionic vesicles support hypothesis peptides generate opposing curvature stresses phosphatidylethanolamine membranes esr showed fps increase lipid packing head group ordering well reduce intramembrane water content anionic membranes therefore bending moment bilayer could generated promoting negative curvature significance ordering effect membrane dehydration changes curvature properties possible role negatively charged phospholipids helping overcome high kinetic barrier involved different stages sars-cov-mediated membrane fusion discussed', 'stress', 'es phosphatidylethanolamine membranes esr showed fps increase lipid packing head group ordering well reduce intramembrane water content anionic membranes therefore bending moment bilayer could generated promoting negative curvature significance ordering effect membrane dehydration changes curvature properties possible role negatively charged phospholipids helping overcome high kinetic barrier involved different stages sars-cov-mediated membrane fusion discussed')\n",
      "('human coronavirus 229e hcov-229e one first coronavirus strains described linked common cold symptoms healthy adults younger children elderly considered vulnerable developing lower respiratory tract infections lrtis particular immunocompromised patients reported severe life-threatening lrtis attributed hcov-229e report first time case lrti acute respiratory distress syndrome developed healthy adult comorbidities hcov-229e strain identified causative agent 45-year-old female clear medical history presented fever cough headache respiratory tract infection diagnosed empirical antibiotics started within two days developed bilateral pleural effusions diffuse consolidations ground glass opacities involving lung fields needed immediate oxygen supply abgs deteriorated chest imaging pao 2 fio 2 indicated ards early administration systemic corticosteroids led gradual clinical improvement multiplex pcr nasal secretions positive hcov-229e negative multiple pathogens remains elucidated immunocompetent adult developed life-threatening lrti caused benign considered coronavirus strain hcov-229e', 'stress', ' syndrome developed healthy adult comorbidities hcov-229e strain identified causative agent 45-year-old female clear medical history presented fever cough headache respiratory tract infection diagnosed empirical antibiotics started within two days developed bilateral pleural effusions diffuse consolidations ground glass opacities involving lung fields needed immediate oxygen supply abgs deteriorated chest imaging pao 2 fio 2 indicated ards early administration systemic corticosteroids led gradual clinical improvement multiplex pcr nasal secretions positive hcov-229e negative multiple pathogens remains elucidated immunocompetent adult developed life-threatening lrti caused benign considered coronavirus strain hcov-229e')\n",
      "('human coronaviruses hcovs known respiratory pathogens associated range respiratory outcomes past 14 years onset severe acute respiratory syndrome coronavirus sars-cov middle east respiratory syndrome coronavirus mers-cov thrust hcovs spotlight research community due high pathogenicity humans study hcov-host interactions contributed extensively understanding hcov pathogenesis review discuss recent findings host cell factors might exploited hcovs facilitate replication cycle also discuss various cellular processes apoptosis innate immunity er stress response mitogen-activated protein kinase mapk pathway nuclear factor kappa b nf- b pathway may modulated hcovs', 'stress', ' response mitogen-activated protein kinase mapk pathway nuclear factor kappa b nf- b pathway may modulated hcovs')\n",
      "('influenza infection pneumonia known cause much mortality inducing acute respiratory distress syndrome ards severe form acute lung injury ali angiotensin-converting enzyme 2 ace2 negative regulator angiotensin ii renin-angiotensin system reported crucial role ali downregulation ace2 always associated ali ards induced avian influenza virus severe acute respiratory syndrome-coronavirus respiratory syncytial virus sepsis however molecular mechanism decreased expression ace2 ali unclear show avian influenza virus h5n1 induced upregulation mir-200c-3p demonstrated target 3 -untranslated region ace2 found nonstructural protein 1 viral rna h5n1 contributed induction mir-200c-3p viral infection additionally synthetic analog viral double-stranded rna poly c bacterial lipopolysaccharide lipoteichoic acid markedly increase expression mir-200c-3p nuclear factor- b-dependent manner furthermore markedly elevated plasma levels mir-200c-3p observed severe pneumonia patients inhibition mir-200c-3p ameliorated ali induced h5n1 virus infection vivo indicating potential therapeutic target therefore identify shared mechanism viral bacterial lung infection-induced ali ards via nuclear factor- b-dependent upregulation mir-200c-3p reduce ace2 levels leads increased angiotensin ii levels subsequently causes lung injury', 'stress', ' syndrome ards severe form acute lung injury ali angiotensin-converting enzyme 2 ace2 negative regulator angiotensin ii renin-angiotensin system reported crucial role ali downregulation ace2 always associated ali ards induced avian influenza virus severe acute respiratory syndrome-coronavirus respiratory syncytial virus sepsis however molecular mechanism decreased expression ace2 ali unclear show avian influenza virus h5n1 induced upregulation mir-200c-3p demonstrated target 3 -untranslated region ace2 found nonstructural protein 1 viral rna h5n1 contributed induction mir-200c-3p viral infection additionally synthetic analog viral double-stranded rna poly c bacterial lipopolysaccharide lipoteichoic acid markedly increase expression mir-200c-3p nuclear factor- b-dependent manner furthermore markedly elevated plasma levels mir-200c-3p observed severe pneumonia patients inhibition mir-200c-3p ameliorated ali induced h5n1 virus infection vivo indicating potential therapeutic target therefore identify shared mechanism viral bacterial lung infection-induced ali ards via nuclear factor- b-dependent upregulation mir-200c-3p reduce ace2 levels leads increased angiotensin ii levels subsequently causes lung injury')\n",
      "('middle east respiratory syndrome coronavirus mers-cov causes severe respiratory infections life-threatening establish infection spread mers-cov like viruses must navigate intricate network antiviral host responses besides well-known type interferon ifn- response protein kinase r pkr -mediated stress response recognized important innate response pathway upon detecting viral dsrna pkr phosphorylates eif2 leading inhibition cellular viral translation formation stress granules sgs increasingly recognized platforms antiviral signaling pathways unknown whether cellular infection mers-cov activates stress response pathway whether virus evolved strategies suppress infection-limiting pathway show cellular infection mers-cov lead formation sgs transiently expressing mers-cov accessory proteins individually identified role protein 4a p4a preventing activation stress response pathway expression mers-cov p4a impeded dsrna-mediated pkr activation thereby rescuing translation inhibition preventing sg formation contrast p4a failed suppress stress response pathway activation independent pkr dsrna mers-cov p4a dsrna binding protein', 'stress', ' response pathway activation independent pkr dsrna mers-cov p4a dsrna binding protein')\n",
      "('middle east respiratory syndrome coronavirus mers-cov evolved navigate sophisticated network host immune system immune evasion mechanism including type 1 interferon protein kinase r-mediated antiviral stress responses recently attributed involvement mers-cov protein 4a p4a masks viral dsrna however structural mechanism p4a recognizes establishes contacts dsrna well explained study report dynamic mechanism deployed p4a engage viral dsrna make unavailable host immune system multiple variants p4a-dsrna created investigated extensive molecular dynamics procedures highlight crucial interfacial residues may used potential pharmacophores future drug development structural analysis revealed p4a exhibits typical fold structure found dsrna-binding proteins 1 helix 1- 2 loop play crucial role recognizing establishing contacts minor grooves dsrna mutational binding free energy analyses suggested addition k63 k67 two residues k27 w45 might also crucial p4a-dsrna stability', 'stress', ' responses recently attributed involvement mers-cov protein 4a p4a masks viral dsrna however structural mechanism p4a recognizes establishes contacts dsrna well explained study report dynamic mechanism deployed p4a engage viral dsrna make unavailable host immune system multiple variants p4a-dsrna created investigated extensive molecular dynamics procedures highlight crucial interfacial residues may used potential pharmacophores future drug development structural analysis revealed p4a exhibits typical fold structure found dsrna-binding proteins 1 helix 1- 2 loop play crucial role recognizing establishing contacts minor grooves dsrna mutational binding free energy analyses suggested addition k63 k67 two residues k27 w45 might also crucial p4a-dsrna stability')\n",
      "('middle east respiratory syndrome coronavirus mers-cov induces severe aggravating respiratory failure infected patients frequently resulting mechanical ventilation limited therapeutic antibody accumulated lung tissue following systemic administration inhalation newly recognized alternative possibly better route therapeutic antibody pulmonary diseases nebulization process however generates diverse physiological stresses thus therapeutic antibody must resistant stresses remain stable form minimal aggregates first isolated mers-cov neutralizing antibody reactive receptor-binding domain rbd spike glycoprotein increase stability introduced mutations complementarity-determining regions cdrs antibody hcdrs excluding hcdr3 clone two hydrophobic residues replaced glu two residues replaced asp four residues replaced positively charged amino acids lcdrs two leu residues replaced val modifications successfully generated clone significantly greater stability equivalent reactivity neutralizing activity following nebulization compared original clone summary generated mers-cov neutralizing human antibody reactive recombinant mers-cov rbd protein delivery via pulmonary route introducing stabilizing mutations five cdrs', 'stress', 'es remain stable form minimal aggregates first isolated mers-cov neutralizing antibody reactive receptor-binding domain rbd spike glycoprotein increase stability introduced mutations complementarity-determining regions cdrs antibody hcdrs excluding hcdr3 clone two hydrophobic residues replaced glu two residues replaced asp four residues replaced positively charged amino acids lcdrs two leu residues replaced val modifications successfully generated clone significantly greater stability equivalent reactivity neutralizing activity following nebulization compared original clone summary generated mers-cov neutralizing human antibody reactive recombinant mers-cov rbd protein delivery via pulmonary route introducing stabilizing mutations five cdrs')\n",
      "('middle east respiratory syndrome coronavirus mers-cov novel human coronavirus emerged 2012 causing severe pneumonia acute respiratory distress syndrome ards case fatality rate 36 expressed isolation cov accessory proteins shown interfere innate antiviral signaling pathways however limited information specific contribution mers-cov accessory protein 4b repression innate antiviral response context infection found mers-cov 4b required prevent robust nf- b dependent response infection wild-type virus infected cells 4b localized nucleus nf- b retained cytoplasm contrast absence 4b presence cytoplasmic 4b mutants lacking nuclear localization signal nls nf- b translocated nucleus leading expression pro-inflammatory cytokines indicates nf- b repression required nuclear import 4b mediated specific nls interestingly also found isolation infection 4b interacted -karyopherin proteins nls-dependent manner particular 4b strong preference binding karyopherin- 4 kpna4 known translocate nf- b protein complex nucleus binding 4b kpna4 infection inhibited interaction nf- b-p65 subunit thereby propose model 4b outcompetes nf- b kpna4 binding translocation nucleus mechanism interference nf- b-mediated innate immune response', 'stress', ' syndrome ards case fatality rate 36 expressed isolation cov accessory proteins shown interfere innate antiviral signaling pathways however limited information specific contribution mers-cov accessory protein 4b repression innate antiviral response context infection found mers-cov 4b required prevent robust nf- b dependent response infection wild-type virus infected cells 4b localized nucleus nf- b retained cytoplasm contrast absence 4b presence cytoplasmic 4b mutants lacking nuclear localization signal nls nf- b translocated nucleus leading expression pro-inflammatory cytokines indicates nf- b repression required nuclear import 4b mediated specific nls interestingly also found isolation infection 4b interacted -karyopherin proteins nls-dependent manner particular 4b strong preference binding karyopherin- 4 kpna4 known translocate nf- b protein complex nucleus binding 4b kpna4 infection inhibited interaction nf- b-p65 subunit thereby propose model 4b outcompetes nf- b kpna4 binding translocation nucleus mechanism interference nf- b-mediated innate immune response')\n",
      "('porcine epidemic diarrhea virus pedv member alphacoronavirus caused huge economic losses global pork industry recently spike protein mediates pedv entry host cells herein investigated interactions protein receptor porcine aminopeptidase n papn co-receptor sugars c-terminal domain ctd s1 domain bound papn prototype strain demonstrated similar receptor-binding activity compared variant field isolate three loops tips -barrel domains play crucial roles pedv s-papn association indicating pedv conforms different receptor recognition model compared transmissible gastroenteritis virus tgev porcine respiratory cov prcv human coronavirus nl63 hcov-nl63 n-terminal domain ntd pedv s1 domain could bind sugar possible co-receptor pedv prototype strain exhibited weaker sugar-binding activity compared variant field isolate strategies targeting receptor binding domain rbd may helpful developing vaccines antiviral drugs pedv understanding differences receptor binding prototype variant strains may provide insight pedv pathogenesis viruses 2016 8 55 2 15', 'sugar', '-binding activity compared variant field isolate strategies targeting receptor binding domain rbd may helpful developing vaccines antiviral drugs pedv understanding differences receptor binding prototype variant strains may provide insight pedv pathogenesis viruses 2016 8 55 2 15')\n",
      "('respiratory viruses infect human upper respiratory tract mostly causing mild diseases however vulnerable populations newborns infants elderly immune-compromised individuals opportunistic pathogens also affect lower respiratory tract causing severe disease e g pneumonia respiratory viruses also exacerbate asthma lead various types respiratory distress syndromes furthermore adapt fast cross species barrier pathogens like influenza sars-cov occasionally caused epidemics pandemics associated serious clinical diseases even mortality decades data reported scientific literature also demonstrated several respiratory viruses neuroinvasive capacities since spread respiratory tract central nervous system cns viruses infecting human cns cells could cause different types encephalopathy including encephalitis long-term neurological diseases like well-recognized neuroinvasive human viruses respiratory viruses may damage cns result misdirected host immune responses could associated autoimmunity susceptible individuals virus-induced neuro-immunopathology viral replication directly causes damage cns cells virus-induced neuropathology etiological agent several neurological disorders remains unidentified opportunistic human respiratory pathogens could associated triggering exacerbation disorders whose etiology remains poorly understood herein present global portrait prevalent emerging human respiratory viruses associated possible pathogenic processes cns infection special emphasis human coronaviruses', 'stress', ' syndromes furthermore adapt fast cross species barrier pathogens like influenza sars-cov occasionally caused epidemics pandemics associated serious clinical diseases even mortality decades data reported scientific literature also demonstrated several respiratory viruses neuroinvasive capacities since spread respiratory tract central nervous system cns viruses infecting human cns cells could cause different types encephalopathy including encephalitis long-term neurological diseases like well-recognized neuroinvasive human viruses respiratory viruses may damage cns result misdirected host immune responses could associated autoimmunity susceptible individuals virus-induced neuro-immunopathology viral replication directly causes damage cns cells virus-induced neuropathology etiological agent several neurological disorders remains unidentified opportunistic human respiratory pathogens could associated triggering exacerbation disorders whose etiology remains poorly understood herein present global portrait prevalent emerging human respiratory viruses associated possible pathogenic processes cns infection special emphasis human coronaviruses')\n",
      "('similar viruses coronavirus infection triggers cellular stress responses infected host cells close association coronavirus replication endoplasmic reticulum er results er stress responses impose challenge viruses viruses turn come various mechanisms block subvert responses one er stress responses inhibition global protein synthesis reduce amount unfolded proteins inside er lumen viruses evolved capacity overcome protein translation shutoff ensure viral protein production review strategies exploited coronavirus modulate cellular stress response pathways involvement coronavirus-induced stress responses translational control viral pathogenesis also briefly discussed', 'stress', ' responses translational control viral pathogenesis also briefly discussed')\n",
      "('since december 2019 79 000 people diagnosed infection corona virus disease 2019 large number medical staff dispersed wuhan city hubei province aid covid-19 control psychological stress especially vicarious traumatization vt caused covid-19 pandemic ignored address concern study employed total 214 general public gp 526 nurses evaluate vt scores via mobile app-based questionnaire results showed vt scores slightly increased across periods aiding covid-19 control although statistical difference noted p 0 083', 'stress', ' especially vicarious traumatization vt caused covid-19 pandemic ignored address concern study employed total 214 general public gp 526 nurses evaluate vt scores via mobile app-based questionnaire results showed vt scores slightly increased across periods aiding covid-19 control although statistical difference noted p 0 083')\n",
      "('since emergence 2012 2 260 cases 803 deaths due middle east respiratory syndrome coronavirus mers-cov reported world health organization cases due transmission healthcare settings sometimes causing large outbreaks analyzed epidemiologic clinical data laboratory-confirmed mers-cov cases eleven healthcare-associated outbreaks kingdom saudi arabia republic korea 2015-2017 quantified key epidemiological differences outbreaks twenty-five percent n 105 422 mers cases acquired infection hospital setting healthcare personnel multivariate analyses age 65 4 8 95 ci 2 6-8 7 presence underlying comorbidities 2 7 95 ci 1 3-5 7 associated increased mortality whereas working healthcare personnel protective 0 07 95 ci 0 01-0 34 start outbreaks reproduction number ranged 1 0 5 7 dropped 1 within 2 6 weeks study provides comprehensive characterization mers hca-outbreaks results highlight heterogeneities epidemiological profile healthcareassociated outbreaks limitations study stress urgent need standardized data collection high-threat respiratory pathogens mers-cov', 'stress', ' urgent need standardized data collection high-threat respiratory pathogens mers-cov')\n",
      "('avian coronavirus avcov infectious bronchitis virus ibv major poultry pathogen characteristic feature ibv occurrence many different strains belonging different serotypes makes complete control disease vaccinations challenging task reasons differences tissue tropism pathogenicity ibv strains e g predilection kidneys oviduct still open question strains qx genotype major pathogens poultry flocks asia europe parts world cause severe problems kidney disease reproductive tract disorders analysed infectivity binding properties qx strain compared nephropathogenic strain b1648 ibv strains infect permanent cell lines show infection primary chicken cells target organs developed culture system chicken oviduct explants epithelial cells oviduct showed high susceptibility infection qx strain almost resistant infection nephropathogenic b1648 strain binding tests isolated primary oviduct epithelial cells soluble s1 proteins revealed s1 proteins two ibv strains bound efficiency oviduct epithelial cells attachment sialic acid dependent indicating sugar binding property ibv spike proteins limiting factor differences infection efficiency oviduct corresponding viruses', 'sugar', ' binding property ibv spike proteins limiting factor differences infection efficiency oviduct corresponding viruses')\n",
      "('coronavirus e protein small membrane protein important role assembly virions recent studies indicated e protein functions infection beyond assembly including virus egress host stress response additionally e protein ion channel activity interacts host proteins may multiple membrane topologies goal review highlight properties functions e protein speculate may related', 'stress', ' response additionally e protein ion channel activity interacts host proteins may multiple membrane topologies goal review highlight properties functions e protein speculate may related')\n",
      "('emergence viral respiratory pathogens pandemic potential severe acute respiratory syndrome coronavirus sars-cov influenza h5n1 urges need deciphering pathogenesis develop new intervention strategies sars-cov infection causes acute lung injury ali may develop life-threatening acute respiratory distress syndrome ards advanced age correlating positively adverse disease outcome molecular pathways however cause virus-induced ali ards aged individuals ill-defined show sars-covinfected aged macaques develop severe pathology young adult animals even though viral replication levels similar comprehensive genomic analyses indicate aged macaques stronger host response virus infection young adult macaques increase differential expression genes associated inflammation nf-kb central player whereas expression type interferon ifn -b reduced therapeutic treatment sars-cov-infected aged macaques type ifn reduces pathology diminishes pro-inflammatory gene expression including interleukin-8 il-8 levels without affecting virus replication lungs thus ali sars-cov-infected aged macaques developed result exacerbated innate host response anti-inflammatory action type ifn reveals potential intervention strategy virus-induced ali', 'stress', ' syndrome ards advanced age correlating positively adverse disease outcome molecular pathways however cause virus-induced ali ards aged individuals ill-defined show sars-covinfected aged macaques develop severe pathology young adult animals even though viral replication levels similar comprehensive genomic analyses indicate aged macaques stronger host response virus infection young adult macaques increase differential expression genes associated inflammation nf-kb central player whereas expression type interferon ifn -b reduced therapeutic treatment sars-cov-infected aged macaques type ifn reduces pathology diminishes pro-inflammatory gene expression including interleukin-8 il-8 levels without affecting virus replication lungs thus ali sars-cov-infected aged macaques developed result exacerbated innate host response anti-inflammatory action type ifn reveals potential intervention strategy virus-induced ali')\n",
      "('first known cases middle east respiratory syndrome mers associated infection novel coronavirus cov occurred 2012 jordan reported retrospectively case first publicly reported jeddah kingdom saudi arabia ksa since mers-cov sequences found bat many dromedary camels dc mers-cov enzootic dc across arabian peninsula parts africa causing mild upper respiratory tract illness camel reservoir sporadic relatively rare human infections precisely virus transmits humans remains unknown close lengthy exposure appears requirement ksa focal point mers majority human cases humans mers mostly known lower respiratory tract lrt disease involving fever cough breathing difficulties pneumonia may progress acute respiratory distress syndrome multiorgan failure death 20 40 infected however mers-cov also detected mild influenza-like illnesses signs symptoms older males obviously suffer severe disease mers patients often comorbidities compared severe acute respiratory syndrome sars another sometimes-fatal zoonotic coronavirus disease since disappeared mers progresses rapidly respiratory failure acute kidney injury also affinity growth kidney cells laboratory conditions frequently reported patients underlying disease often fatal human cases mers linked lapses infection prevention control ipc healthcare settings approximately 20 virus detections reported among healthcare workers hcws higher exposures occupations bring close contact camels sero-surveys found widespread evidence past infection adult camels limited past exposure among humans sensitive validated reverse transcriptase real-time polymerase chain reaction rt-rtpcr -based diagnostics available almost start emergence mers basic virology mers-cov advanced past three years understanding interplay camel environment human remains limited', 'stress', ' syndrome multiorgan failure death 20 40 infected however mers-cov also detected mild influenza-like illnesses signs symptoms older males obviously suffer severe disease mers patients often comorbidities compared severe acute respiratory syndrome sars another sometimes-fatal zoonotic coronavirus disease since disappeared mers progresses rapidly respiratory failure acute kidney injury also affinity growth kidney cells laboratory conditions frequently reported patients underlying disease often fatal human cases mers linked lapses infection prevention control ipc healthcare settings approximately 20 virus detections reported among healthcare workers hcws higher exposures occupations bring close contact camels sero-surveys found widespread evidence past infection adult camels limited past exposure among humans sensitive validated reverse transcriptase real-time polymerase chain reaction rt-rtpcr -based diagnostics available almost start emergence mers basic virology mers-cov advanced past three years understanding interplay camel environment human remains limited')\n",
      "('human coronavirus hcov-19 infection cause acute respiratory distress syndrome 47 ards hypercoagulability hypertension extrapulmonary multiorgan dysfunction effective 48 antiviral anti-coagulation agents safe clinical profiles urgently needed improve 49 overall prognosis screened fda approved drug library found anticoagulant agent 50 dipyridamole dip suppressed hcov-19 replication ec50 100 nm vitro also elicited 51 potent type interferon responses ameliorated lung pathology viral pneumonia model 52 analysis twelve hcov-19 infected patients prophylactic anti-coagulation therapy found 53 dip supplementation associated significantly increased platelet lymphocyte counts 54 decreased d-dimer levels comparison control patients two weeks initiation dip 55 treatment 3 6 severe cases 60 4 mild cases 100 discharged 56 hospital one critically ill patient extremely high levels d-dimer lymphopenia time 57 receiving dip passed away patients clinical remission summary hcov-19 58 infected patients could potentially benefit dip adjunctive therapy reducing viral replication 59 suppressing hypercoagulability enhancing immune recovery larger scale clinical trials dip 60 needed validate therapeutic effects', 'stress', ' syndrome 47 ards hypercoagulability hypertension extrapulmonary multiorgan dysfunction effective 48 antiviral anti-coagulation agents safe clinical profiles urgently needed improve 49 overall prognosis screened fda approved drug library found anticoagulant agent 50 dipyridamole dip suppressed hcov-19 replication ec50 100 nm vitro also elicited 51 potent type interferon responses ameliorated lung pathology viral pneumonia model 52 analysis twelve hcov-19 infected patients prophylactic anti-coagulation therapy found 53 dip supplementation associated significantly increased platelet lymphocyte counts 54 decreased d-dimer levels comparison control patients two weeks initiation dip 55 treatment 3 6 severe cases 60 4 mild cases 100 discharged 56 hospital one critically ill patient extremely high levels d-dimer lymphopenia time 57 receiving dip passed away patients clinical remission summary hcov-19 58 infected patients could potentially benefit dip adjunctive therapy reducing viral replication 59 suppressing hypercoagulability enhancing immune recovery larger scale clinical trials dip 60 needed validate therapeutic effects')\n",
      "('interactions occurring virus host cell viral infection complex purpose paper analyze altered cellular protein levels porcine transmissible gastroenteritis coronavirus tgev -infected swine testicular st cells order determine potential virus-host interactions proteomic approach using isobaric tags relative absolute quantitation itraq -coupled two-dimensional liquid chromatography-tandem mass spectrometry identification conducted tgev-infected st cells results showed 4-plex itraq-based quantitative approach identified 4 112 proteins 146 showed significant changes expression 48 h infection 64 h post infection 219 proteins showed significant change indicating larger number proteomic changes appear occur later stages infection gene ontology analysis altered proteins showed enrichment multiple biological processes including cell adhesion response stress generation precursor metabolites energy cell motility protein complex assembly growth developmental maturation immune system process extracellular matrix organization locomotion cell-cell signaling neurological system process cell junction organization changes expression levels transforming growth factor beta 1 tgf-b1 caspase-8 heat shock protein 90 alpha hsp90a also verified western blot analysis knowledge study first time response profile st host cells following tgev infection analyzed using itraq technology description late proteomic changes occurring time vigorous viral production novel therefore study provides solid foundation investigation likely help us better understand mechanisms tgev infection pathogenesis', 'stress', ' generation precursor metabolites energy cell motility protein complex assembly growth developmental maturation immune system process extracellular matrix organization locomotion cell-cell signaling neurological system process cell junction organization changes expression levels transforming growth factor beta 1 tgf-b1 caspase-8 heat shock protein 90 alpha hsp90a also verified western blot analysis knowledge study first time response profile st host cells following tgev infection analyzed using itraq technology description late proteomic changes occurring time vigorous viral production novel therefore study provides solid foundation investigation likely help us better understand mechanisms tgev infection pathogenesis')\n",
      "('molecular basis severe acute respiratory syndrome sars coronavirus cov induced pathology still largely unclear many sars patients suffer respiratory distress brought interstitial infiltration frequently show peripheral blood lymphopenia occasional leucopenia one possible cause could interstitial inflammation following localized host response study therefore examine immune response sars-cov human peripheral blood mononuclear cells pbmcs first 24 hours', 'stress', ' brought interstitial infiltration frequently show peripheral blood lymphopenia occasional leucopenia one possible cause could interstitial inflammation following localized host response study therefore examine immune response sars-cov human peripheral blood mononuclear cells pbmcs first 24 hours')\n",
      "('pathogenesis severe acute respiratory syndrome coronavirus sars-cov likely mediated disproportional immune responses ability virus circumvent innate immunity using functional genomics analyzed early host responses sars-cov infection lungs adolescent cynomolgus macaques macaca fascicularis show lung pathology similar observed human adults sars analysis gene signatures revealed induction strong innate immune response characterized stimulation various cytokine chemokine genes including interleukin il -6 il-8 ip-10 corresponds host response seen acute respiratory distress syndrome opposed many vitro experiments sars-cov induced wide range type interferons ifns nuclear translocation phosphorylated signal transducer activator transcription 1 lungs macaques using immunohistochemistry revealed antiviral signaling pathways differentially regulated distinctive subsets cells studies emphasize induction early ifn signaling may critical confer protection sars-cov infection highlight strength combining functional genomics immunohistochemistry unravel pathogenesis sars citation de lang baas teal leijten lm rain b et al 2007 functional genomics highlights differential induction antiviral pathways lungs sars-covinfected macaques plos pathog 3 8 e112', 'stress', ' syndrome opposed many vitro experiments sars-cov induced wide range type interferons ifns nuclear translocation phosphorylated signal transducer activator transcription 1 lungs macaques using immunohistochemistry revealed antiviral signaling pathways differentially regulated distinctive subsets cells studies emphasize induction early ifn signaling may critical confer protection sars-cov infection highlight strength combining functional genomics immunohistochemistry unravel pathogenesis sars citation de lang baas teal leijten lm rain b et al 2007 functional genomics highlights differential induction antiviral pathways lungs sars-covinfected macaques plos pathog 3 8 e112')\n",
      "('present outbreak lower respiratory tract infections including respiratory distress syndrome third spillover two decades animal coronavirus humans resulting major epidemic coronavirus study group csg international committee taxonomy viruses responsible developing official classification viruses taxa naming taxonomy coronaviridae family assessed novelty human pathogen tentatively named 2019-ncov based phylogeny taxonomy established practice csg formally recognizes virus sister severe acute respiratory syndrome coronaviruses sars-covs species severe acute respiratory syndrome-related coronavirus designates severe acute respiratory syndrome coronavirus 2 sars-cov-2 facilitate communication csg proposes use following naming convention individual isolates sars-cov-2 isolate host date location spectrum clinical manifestations associated sars-cov-2 infections humans remains determined independent zoonotic transmission sars-cov sars-cov-2 highlights need studying entire virus species complement research focused individual pathogenic viruses immediate significance research improve understanding virus-host interactions ever-changing environment enhance preparedness future outbreaks biorxiv preprint defining novelty place sars-cov-2 within taxonomy coronaviridae family 21 st century researchers studying coronaviruses -a family enveloped positivestranded rna viruses vertebrates 8 -were confronted several times question coronavirus novelty including two times severe even life-threatening disease introduced humans zoonotic reservoir happened severe acute respiratory', 'stress', ' syndrome third spillover two decades animal coronavirus humans resulting major epidemic coronavirus study group csg international committee taxonomy viruses responsible developing official classification viruses taxa naming taxonomy coronaviridae family assessed novelty human pathogen tentatively named 2019-ncov based phylogeny taxonomy established practice csg formally recognizes virus sister severe acute respiratory syndrome coronaviruses sars-covs species severe acute respiratory syndrome-related coronavirus designates severe acute respiratory syndrome coronavirus 2 sars-cov-2 facilitate communication csg proposes use following naming convention individual isolates sars-cov-2 isolate host date location spectrum clinical manifestations associated sars-cov-2 infections humans remains determined independent zoonotic transmission sars-cov sars-cov-2 highlights need studying entire virus species complement research focused individual pathogenic viruses immediate significance research improve understanding virus-host interactions ever-changing environment enhance preparedness future outbreaks biorxiv preprint defining novelty place sars-cov-2 within taxonomy coronaviridae family 21 st century researchers studying coronaviruses -a family enveloped positivestranded rna viruses vertebrates 8 -were confronted several times question coronavirus novelty including two times severe even life-threatening disease introduced humans zoonotic reservoir happened severe acute respiratory')\n",
      "('replication coronavirus family important animal human pathogens closely associated cellular membrane compartments especially endoplasmic reticulum er coronavirus infection cultured cells previously shown cause er stress induce unfolded protein response upr process aims restore er homeostasis global translation shutdown increasing er folding capacity however prolonged er stress upr also induce apoptotic cell death accumulating evidence recent studies shown induction er stress upr may constitute major aspect coronavirus-host interaction activation three branches upr modulates wide variety signaling pathways mitogen-activated protein map kinase activation autophagy apoptosis innate immune response er stress upr activation may therefore contribute significantly viral replication pathogenesis coronavirus infection review summarize current knowledge coronavirus-induced er stress upr activation emphasis cross-talking apoptotic signaling', 'stress', ' upr activation emphasis cross-talking apoptotic signaling')\n",
      "('sars severe acute respiratory syndrome outbreak caused coronavirus cov named sars-cov sars pathology propagated direct cytotoxic effects virus aberrant activation innate immune response identify several mechanisms sars-cov open reading frame orf activates intracellular stress pathways targets innate immune response show orf8b forms insoluble intracellular aggregates dependent valine residue 77 aggregated orf8b induces endoplasmic reticulum er stress lysosomal damage subsequent activation master regulator autophagy lysosome machinery transcription factor eb tfeb orf8b causes cell death epithelial cells partially rescued reducing ability aggregate macrophages orf8b robustly activates nlrp3 inflammasome providing potent signal 2 required activation mechanistically orf8b interacts directly leucine rich repeat domain nlrp3 localizes nlrp3 asc cytosolic dot-like structures orf8b triggers cell death consistent pyroptotic cell death macrophages cells lacking nlrp3 accumulating orf8b cytosolic aggregates cause er stress mitochondrial dysfunction caspase-independent cell death', 'stress', ' mitochondrial dysfunction caspase-independent cell death')\n",
      "('severe acute respiratory syndrome coronavirus sars-cov reported cause apoptosis infected cells several proteins including 3a accessory protein pro-apoptotic since 3a protein localizes endoplasmic reticulum er -golgi compartment role causing er stress investigated transiently transfected cells cells expressing 3a proteins showed er stress based activation genes er chaperones grp78 grp94 since er stress cause differential modulation unfolded protein response upr includes inositol-requiring enzyme 1 ire-1 activating transcription factor 6 atf6 pkr-like er kinase perk pathways individually tested 3a-expressing cells perk pathway found activated 3a-expressing cells based 1 increased phosphorylation eukaryotic initiation factor 2 alpha eif2a inhibitory effects dominant-negative form eif2a grp78 promoter activity 2 increased translation activating transcription factor 4 atf4 mrna 3 atf4dependent activation c ebp homologous protein chop gene promoter activation perk affects innate immunity suppression type 1 interferon ifn signaling 3a protein found induce serine phosphorylation within ifn alpha-receptor subunit 1 ifnar1 degradation motif increase ifnar1 ubiquitination confocal microscopic analysis showed increased translocation ifnar1 lysosomal compartment flow cytometry showed reduced levels ifnar1 3a-expressing cells results provide mechanistic details pro-apoptotic effects sars-cov 3a protein suggest potential role attenuating interferon responses innate immunity', 'stress', ' cause differential modulation unfolded protein response upr includes inositol-requiring enzyme 1 ire-1 activating transcription factor 6 atf6 pkr-like er kinase perk pathways individually tested 3a-expressing cells perk pathway found activated 3a-expressing cells based 1 increased phosphorylation eukaryotic initiation factor 2 alpha eif2a inhibitory effects dominant-negative form eif2a grp78 promoter activity 2 increased translation activating transcription factor 4 atf4 mrna 3 atf4dependent activation c ebp homologous protein chop gene promoter activation perk affects innate immunity suppression type 1 interferon ifn signaling 3a protein found induce serine phosphorylation within ifn alpha-receptor subunit 1 ifnar1 degradation motif increase ifnar1 ubiquitination confocal microscopic analysis showed increased translocation ifnar1 lysosomal compartment flow cytometry showed reduced levels ifnar1 3a-expressing cells results provide mechanistic details pro-apoptotic effects sars-cov 3a protein suggest potential role attenuating interferon responses innate immunity')\n",
      "('spread novel coronavirus sars-cov-2 triggered global emergency demands urgent solutions detection therapy prevent escalating health social economic impacts spike protein virus enables binding human receptor ace2 hence presents prime target vaccines preventing viral entry host cells 1 proteins sars-cov-1 sars-cov-2 similar 2 structural differences receptor binding domain rbd preclude use sars-cov-1-specific neutralizing antibodies inhibit sars-cov-2 3 used comparative pangenomic analysis sequenced betacoronaviruses reveal among core gene clusters present viruses envelope protein e shows variant shared sars sars-cov2 two completely-conserved key functional features ion-channel pdz-binding motif pbm features trigger cytokine storm activates inflammasome leading increased edema lungs causing acute respiratory distress syndrome ards 4-6 leading cause death sars-cov-1 sars-cov-2 infection 7 8 however three drugs approved human use may inhibit sars-cov-1 sars-cov-2 protein e either acting upon ion channel amantadine hexamethylene amiloride 9 10 pbm sb203580 5 thereby potentially increasing survival host already demonstrated sars-cov-1in animal models hence blocking sars protein e inhibits development ards vivo given results demonstrate protein e subcluster sars clade quasi-identical key functional regions sars-cov-1 sars-cov-2 conclude use approved drugs shown act sars e protein inhibitors help prevent casualties covid-2019 vaccines preventive measures developed', 'stress', ' syndrome ards 4-6 leading cause death sars-cov-1 sars-cov-2 infection 7 8 however three drugs approved human use may inhibit sars-cov-1 sars-cov-2 protein e either acting upon ion channel amantadine hexamethylene amiloride 9 10 pbm sb203580 5 thereby potentially increasing survival host already demonstrated sars-cov-1in animal models hence blocking sars protein e inhibits development ards vivo given results demonstrate protein e subcluster sars clade quasi-identical key functional regions sars-cov-1 sars-cov-2 conclude use approved drugs shown act sars e protein inhibitors help prevent casualties covid-2019 vaccines preventive measures developed')\n",
      "('viroporins members rapidly growing family channel-forming small polypeptides found viruses present review focused recent structural protein-protein interaction information involving two viroporins found enveloped viruses target respiratory tract envelope protein coronaviruses ii small hydrophobic protein paramyxoviruses deletion two viroporins leads viral attenuation vivo whereas data cell culture shows involvement regulation stress inflammation channel activity structure representative members viroporins recently characterized detail addition searches protein-protein interactions using yeast-two hybrid techniques shed light possible functional roles exposed cytoplasmic domains deeper analysis interactions provide complete overview multiple functions viroporins also suggest novel strategies target protein-protein interactions much needed antivirals complement current efforts block viroporin channel activity', 'stress', ' inflammation channel activity structure representative members viroporins recently characterized detail addition searches protein-protein interactions using yeast-two hybrid techniques shed light possible functional roles exposed cytoplasmic domains deeper analysis interactions provide complete overview multiple functions viroporins also suggest novel strategies target protein-protein interactions much needed antivirals complement current efforts block viroporin channel activity')\n",
      "('virus-induced apoptosis viral mechanisms regulate cell death program key issues understanding virushost interactions viral pathogenesis like many human animal viruses coronavirus infection mammalian cells induces apoptosis study global gene expression profiles first determined ibv-infected vero cells 24 hours post-infection affymetrix array using avian coronavirus infectious bronchitis virus ibv model system reveals up-regulation transcriptional level pro-apoptotic bak pro-survival myeloid cell leukemia-1 mcl-1 results confirmed vivo vitro ibv-infected embryonated chicken eggs chicken fibroblast cells mammalian cells transcriptional translational levels respectively interestingly onset apoptosis occurred earlier ibv-infected mammalian cells silenced short interfering rna targeting mcl-1 simcl-1 delayed cells silenced sibak ibv progeny production release increased infected mcl-1 knockdown cells compared similarly infected control cells contrary observed infected bak knockdown cells furthermore ibv infection-induced up-regulation gadd153 regulated expression mcl-1 inhibition mitogenactivated protein extracellular signal-regulated kinase mek erk phosphoinositide 3-kinase pi3k akt signaling pathways chemical inhibitors knockdown gadd153 sirna demonstrated involvement er-stress response regulation ibv-induced mcl-1 expression results illustrate sophisticated regulatory strategies evolved coronavirus modulate virus-induced apoptosis viral replication replication cycle', 'stress', ' response regulation ibv-induced mcl-1 expression results illustrate sophisticated regulatory strategies evolved coronavirus modulate virus-induced apoptosis viral replication replication cycle')\n"
     ]
    }
   ],
   "source": [
    "search_words = ['stress', 'sugar', 'alchol']\n",
    "\n",
    "patten = re.compile(\"(.*(stress|sugar|alchol)(.*))\")\n",
    "\n",
    "for i in [re.search(patten,line).groups() for line in corona_texts if re.search(patten,line) != None]: print(i)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# diet.txt include the diet items that may be helpful for treatment. Is there any of these items in papers?"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 21,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "['oregano', 'sage', 'basil', 'fennel', 'garlic', 'lemon', 'balm', 'peppermint', 'rosemary', 'echinacea', 'sambucus', 'licorice', 'astragalus', 'ginger', 'ginseng', 'dandelion', 'colostrum', 'probiotics', 'vitamin', 'd', 'wellmune', 'sodium', 'bicarbonate', 'baking', 'soda', 'water', 'chicken', 'soup', 'broths', 'coconut', 'water', 'honey', 'bananas', 'oatmeal', 'yogurt', 'fruits', 'lemon', 'orange', 'c', 'vitamin', 'avocado', 'vegetable', 'salmon', 'broccoli', 'olive', 'oil', 'egg', 'apple', 'turmeric', 'chamomile', 'walnuts', 'pomegranate', 'kefir', 'pepper', 'strawberries', 'quercetin', 'echinacea', 'zinc', 'toddy', 'saline', 'irrigation', 'sleep', 'elderbery', 'sambucus', 'beta', 'glukan', 'flexseed', 'stress', 'alchol', 'sugar']\n"
     ]
    }
   ],
   "source": [
    "read_text=open('diet.txt','r')\n",
    "\n",
    "diet=read_text.read().lower()\n",
    "\n",
    "diet=diet.split()\n",
    "\n",
    "\n",
    "print (diet)\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 22,
   "metadata": {
    "scrolled": true
   },
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>word</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>oregano</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>sage</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>basil</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>fennel</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>garlic</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>65</th>\n",
       "      <td>glukan</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>66</th>\n",
       "      <td>flexseed</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>67</th>\n",
       "      <td>stress</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>68</th>\n",
       "      <td>alchol</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>69</th>\n",
       "      <td>sugar</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>70 rows × 1 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "        word\n",
       "0    oregano\n",
       "1       sage\n",
       "2      basil\n",
       "3     fennel\n",
       "4     garlic\n",
       "..       ...\n",
       "65    glukan\n",
       "66  flexseed\n",
       "67    stress\n",
       "68    alchol\n",
       "69     sugar\n",
       "\n",
       "[70 rows x 1 columns]"
      ]
     },
     "execution_count": 22,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "dietdf = pd.DataFrame(diet, columns = ['word'])\n",
    "\n",
    "dietdf"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Find lines that include symptom... What is the most frequent words in these specific group."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 23,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Content</th>\n",
       "      <th>Cleaned_Content</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>44</th>\n",
       "      <td>a 24-year-old african-american man presented with malaise and low back pain and was found to have acute severe rhabdomyolysis followed by acute hemolysis. glucose-6-phosphate dehydrogenase (g6pd) deficiency was suspected by the presence of blister cells on peripheral smear and was confirmed by a low enzyme activity assay. our patient reported playing football, along with upper respiratory infection symptoms, prior to presentation. extensive infectious and toxicology workup was negative; however, several inflammatory proteins were markedly elevated. we hypothesized the large inflammatory burden led to an increased reactive oxygen radical burden that overwhelmed muscle and erythrocyte reducing power. severe rhabdomyolysis in g6pd deficiency is not a common presentation because skeletal muscles are more resistant to oxidative damage compared to red blood cells. our case adds to the few existing reports of myolysis in the setting of g6pd deficiency.</td>\n",
       "      <td>24-year-old african-american man presented malaise low back pain found acute severe rhabdomyolysis followed acute hemolysis glucose-6-phosphate dehydrogenase g6pd deficiency suspected presence blister cells peripheral smear confirmed low enzyme activity assay patient reported playing football along upper respiratory infection symptoms prior presentation extensive infectious toxicology workup negative however several inflammatory proteins markedly elevated hypothesized large inflammatory burden led increased reactive oxygen radical burden overwhelmed muscle erythrocyte reducing power severe rhabdomyolysis g6pd deficiency common presentation skeletal muscles resistant oxidative damage compared red blood cells case adds existing reports myolysis setting g6pd deficiency</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>46</th>\n",
       "      <td>a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.</td>\n",
       "      <td>71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>47</th>\n",
       "      <td>a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.</td>\n",
       "      <td>71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>81</th>\n",
       "      <td>a divergent human gammapapillomavirus (␥-hpv) genome in a nasal swab from an elderly finnish patient with respiratory symptoms was genetically characterized. the l1 gene of hpv-fin864 shared &lt;70% nucleotide identity to other reported ␥-hpv genomes, provisionally qualifying it as a new species in the gammapapillomavirus genus.</td>\n",
       "      <td>divergent human gammapapillomavirus -hpv genome nasal swab elderly finnish patient respiratory symptoms genetically characterized l1 gene hpv-fin864 shared 70 nucleotide identity reported -hpv genomes provisionally qualifying new species gammapapillomavirus genus</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>106</th>\n",
       "      <td>a large number of human genes associated with viral infections contain single nucleotide polymorphisms (snps), which represent a genetic variation caused by the change of a single nucleotide in the dna sequence. snps are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. as a consequence of this exhaustive exploration, an association between the presence of some specific snps and the susceptibility or severity of many infectious diseases in some risk population groups has been found. in this review, we discuss the relevance of snps that are important to understand the pathology derived from influenza a virus (iav) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. we also discuss the importance of snps for iav vaccine effectiveness. multiple mechanisms, although there are some differences between strains. for that genome plasticity, iav take advantage of multiple strategies, such as alternative splicing, frameshift mechanisms, and overlapping open reading frames (orfs) [7] [8] [9] . in addition, the coding capability of the viral genome is extended by encoding multifunctional proteins that act at different steps during virus infection. of synthetized vrnp, ensuring that the vrnps are available for packaging [24] . moreover, nep has also other functions during iav infection, contributing to viral budding and to regulate viral rna synthesis. ns1 is a multifunctional protein and a key viral factor that counteracts the host antiviral responses. ns1 has been shown to inhibit the production of interferon (ifn), the activity and expression of multiple interferon-induced genes (isg) and the processing and nuclear transport of host mrnas causing cellular shut-off [25, 26] . segment 3 of iav also encodes two proteins, the polymerase component pa and pa-x. pa is translated directly from the pa mrna, whereas pa-x is translated using a +1 frameshift mechanism from the same open reading frame (orf) [9] . synergistically with ns1, pa-x is also able to block the cellular antiviral responses by inhibiting host protein expression. moreover, the pa-x protein has been shown to modulate host inflammation, immune responses, apoptosis, and virus pathogenesis [25] [26] [27] [28] [29] [30] .</td>\n",
       "      <td>large number human genes associated viral infections contain single nucleotide polymorphisms snps represent genetic variation caused change single nucleotide dna sequence snps located coding non-coding genomic regions affect gene expression protein function different mechanisms furthermore linked multiple human diseases highlighting medical relevance therefore identification analysis kind polymorphisms human genome gained high importance research community increasing number studies published last years consequence exhaustive exploration association presence specific snps susceptibility severity many infectious diseases risk population groups found review discuss relevance snps important understand pathology derived influenza virus iav infections humans susceptibility individuals suffer severe symptoms also discuss importance snps iav vaccine effectiveness multiple mechanisms although differences strains genome plasticity iav take advantage multiple strategies alternative splicing frameshift mechanisms overlapping open reading frames orfs 7 8 9 addition coding capability viral genome extended encoding multifunctional proteins act different steps virus infection synthetized vrnp ensuring vrnps available packaging 24 moreover nep also functions iav infection contributing viral budding regulate viral rna synthesis ns1 multifunctional protein key viral factor counteracts host antiviral responses ns1 shown inhibit production interferon ifn activity expression multiple interferon-induced genes isg processing nuclear transport host mrnas causing cellular shut-off 25 26 segment 3 iav also encodes two proteins polymerase component pa pa-x pa translated directly pa mrna whereas pa-x translated using 1 frameshift mechanism open reading frame orf 9 synergistically ns1 pa-x also able block cellular antiviral responses inhibiting host protein expression moreover pa-x protein shown modulate host inflammation immune responses apoptosis virus pathogenesis 25 26 27 28 29 30</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10553</th>\n",
       "      <td>zika virus (zikv) is an emerging mosquito-borne flavivirus that can potentially threaten south china. a chinese family of four returning from venezuela to china was found to be positive for zikv when the youngest son's fever was first detected at an airport immigration inspection. they were isolated temporarily in a local hospital in enping city, guangdong province, where their clinical data were recorded and urine and saliva were collected to isolate zikv and to obtain viral sequences. all of them except the mother presented mild symptoms of rash and fever. envelope gene sequences from the father, daughter and son were completely identical. phylogenetic analysis demonstrated that this strain is similar to several imported strains reported in recent months, which are all clustered into a group isolated from 2015 zika outbreaks in brazil. together with the climatic features in venezuela, new york and guangdong in february, it can be concluded that our subjects are imported cases from venezuela. with the same viral sequence being shared between family members, neither direct human-to-human nor vector transmission can be ruled out in this study, but the former seems more likely. although our subjects had mild illness, epidemiologists and public health officials should be aware of the risk of further expansion of zikv transmission by local competent vectors.</td>\n",
       "      <td>zika virus zikv emerging mosquito-borne flavivirus potentially threaten south china chinese family four returning venezuela china found positive zikv youngest son fever first detected airport immigration inspection isolated temporarily local hospital enping city guangdong province clinical data recorded urine saliva collected isolate zikv obtain viral sequences except mother presented mild symptoms rash fever envelope gene sequences father daughter son completely identical phylogenetic analysis demonstrated strain similar several imported strains reported recent months clustered group isolated 2015 zika outbreaks brazil together climatic features venezuela new york guangdong february concluded subjects imported cases venezuela viral sequence shared family members neither direct human-to-human vector transmission ruled study former seems likely although subjects mild illness epidemiologists public health officials aware risk expansion zikv transmission local competent vectors</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10559</th>\n",
       "      <td>zika virus (zikv) specific neutralizing antibodies hold great promise for antibody-based interventions and vaccine design against zikv infection. however, their development in infected patients remains unclear. here, we applied next-generation sequencing (ngs) to probe the dynamic development of a potent and protective zikv e diii-specific antibody zk2b10 isolated from a zikv convalescent individual. the unbiased repertoire analysis showed dramatic changes in the usage of antibody variable region germline genes. however, lineage tracing of zk2b10 revealed limited somatic hypermutation and transient expansion during the 12 months following the onset of symptoms. the ngs-derived, germline-like zk2b10 somatic variants neutralized zikv potently and protected mice from lethal challenge of zikv without detectable cross-reactivity with dengue virus (denv). site-directed mutagenesis identified two residues within the λ chain, n31 and s91, that are essential to the functional maturation of zk2b10. the repertoire and lineage features unveiled here will help elucidate the developmental process and protective potential of e diii-directed antibodies against zikv infection.</td>\n",
       "      <td>zika virus zikv specific neutralizing antibodies hold great promise antibody-based interventions vaccine design zikv infection however development infected patients remains unclear applied next-generation sequencing ngs probe dynamic development potent protective zikv e diii-specific antibody zk2b10 isolated zikv convalescent individual unbiased repertoire analysis showed dramatic changes usage antibody variable region germline genes however lineage tracing zk2b10 revealed limited somatic hypermutation transient expansion 12 months following onset symptoms ngs-derived germline-like zk2b10 somatic variants neutralized zikv potently protected mice lethal challenge zikv without detectable cross-reactivity dengue virus denv site-directed mutagenesis identified two residues within chain n31 s91 essential functional maturation zk2b10 repertoire lineage features unveiled help elucidate developmental process protective potential e diii-directed antibodies zikv infection</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10561</th>\n",
       "      <td>zika virus (zikv) was first discovered in 1947 in africa. since then, sporadic zikv infections of humans have been reported in africa and asia. for a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. however, during the 2015-2016 epidemic in central and south america, when millions of people were infected, it was discovered that zikv causes microcephaly in the babies of mothers infected during pregnancy. an examination of the m and c proteins of the zikv shell using the disorder predictor pondr vlxt revealed that the m protein contains relatively high disorder levels comparable only to those of the yellow fever virus (yfv). on the other hand, the disorder levels in the c protein are relatively low, which can account for the low case fatality rate (cfr) of this virus in contrast to the more virulent yfv, which is characterized by high disorder in its c protein. a larger variation was found in the percentage of intrinsic disorder (pid) in the c protein of various zikv strains. strains of african lineage are characterized by higher pids. using both in vivo and in vitro experiments, laboratories have also previously shown that strains of african origin have a greater potential to inflict higher fetal morbidity than do strains of asian lineage, with dengue-2 virus (denv-2) having the least potential. strong correlations were found between the potential to inflict fetal morbidity and shell disorder in zikv (r 2 = 0.9) and denv-2 (denv-2 + zikv, r 2 = 0.8). a strong correlation between cfr and pid was also observed when zikv was included in an analysis of sets of shell proteins from a variety of flaviviruses (r 2 = 0.8). these observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.</td>\n",
       "      <td>zika virus zikv first discovered 1947 africa since sporadic zikv infections humans reported africa asia long time virus mostly unnoticed due mild symptoms low fatality rates however 2015-2016 epidemic central south america millions people infected discovered zikv causes microcephaly babies mothers infected pregnancy examination c proteins zikv shell using disorder predictor pondr vlxt revealed protein contains relatively high disorder levels comparable yellow fever virus yfv hand disorder levels c protein relatively low account low case fatality rate cfr virus contrast virulent yfv characterized high disorder c protein larger variation found percentage intrinsic disorder pid c protein various zikv strains strains african lineage characterized higher pids using vivo vitro experiments laboratories also previously shown strains african origin greater potential inflict higher fetal morbidity strains asian lineage dengue-2 virus denv-2 least potential strong correlations found potential inflict fetal morbidity shell disorder zikv r 2 0 9 denv-2 denv-2 zikv r 2 0 8 strong correlation cfr pid also observed zikv included analysis sets shell proteins variety flaviviruses r 2 0 8 observations potential implications antiviral vaccine development design cancer therapeutics terms developing therapeutic viruses penetrate hard-to-reach organs</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10565</th>\n",
       "      <td>zika virus (zikv), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. currently, no specific antiviral therapy against zikv is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. nevertheless, lately, search for antivirals has been a major aim in zikv investigations. to do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. here, we present an updated review of current knowledge about anti-zikv strategies, focusing on host-directed antivirals as a realistic alternative to combat zikv infection.</td>\n",
       "      <td>zika virus zikv mosquito-borne flavivirus almost neglected pathogen introduction americas 2015 responsible threat global health causing great social sanitary alarm due increased virulence rapid spread association severe neurological ophthalmological complications currently specific antiviral therapy zikv available treatments palliative mainly directed toward relief symptoms fever rash administering antipyretics anti-histamines fluids dehydration nevertheless lately search antivirals major aim zikv investigations screening libraries different sources testing natural compounds repurposing drugs known antiviral activity allowed identification several antiviral candidates directed viral structural proteins enzymes cellular elements present updated review current knowledge anti-zikv strategies focusing host-directed antivirals realistic alternative combat zikv infection</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10572</th>\n",
       "      <td>zoonoses are diseases transmitted from animals to humans, posing a great threat to the health and life of people all over the world. according to who estimations, 600 million cases of diseases caused by contaminated food were noted in 2010, including almost 350 million caused by pathogenic bacteria. campylobacter, salmonella, as well as yersinia enterocolitica and listeria monocytogenes may dwell in livestock (poultry, cattle, and swine) but are also found in wild animals, pets, fish, and rodents. animals, often being asymptomatic carriers of pathogens, excrete them with faeces, thus delivering them to the environment. therefore, pathogens may invade new individuals, as well as reside on vegetables and fruits. pathogenic bacteria also penetrate food production areas and may remain there in the form of a biofilm covering the surfaces of machines and equipment. a common occurrence of microbes in food products, as well as their improper or careless processing, leads to common poisonings. symptoms of foodborne infections may be mild, sometimes flu-like, but they also may be accompanied by severe complications, some even fatal. the aim of the paper is to summarize and provide information on campylobacteriosis, salmonellosis, yersiniosis, and listeriosis and the aetiological factors of those diseases, along with the general characteristics of pathogens, virulence factors, and reservoirs.</td>\n",
       "      <td>zoonoses diseases transmitted animals humans posing great threat health life people world according estimations 600 million cases diseases caused contaminated food noted 2010 including almost 350 million caused pathogenic bacteria campylobacter salmonella well yersinia enterocolitica listeria monocytogenes may dwell livestock poultry cattle swine also found wild animals pets fish rodents animals often asymptomatic carriers pathogens excrete faeces thus delivering environment therefore pathogens may invade new individuals well reside vegetables fruits pathogenic bacteria also penetrate food production areas may remain form biofilm covering surfaces machines equipment common occurrence microbes food products well improper careless processing leads common poisonings symptoms foodborne infections may mild sometimes flu-like also may accompanied severe complications even fatal aim paper summarize provide information campylobacteriosis salmonellosis yersiniosis listeriosis aetiological factors diseases along general characteristics pathogens virulence factors reservoirs</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>665 rows × 2 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Content  \\\n",
       "44                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                a 24-year-old african-american man presented with malaise and low back pain and was found to have acute severe rhabdomyolysis followed by acute hemolysis. glucose-6-phosphate dehydrogenase (g6pd) deficiency was suspected by the presence of blister cells on peripheral smear and was confirmed by a low enzyme activity assay. our patient reported playing football, along with upper respiratory infection symptoms, prior to presentation. extensive infectious and toxicology workup was negative; however, several inflammatory proteins were markedly elevated. we hypothesized the large inflammatory burden led to an increased reactive oxygen radical burden that overwhelmed muscle and erythrocyte reducing power. severe rhabdomyolysis in g6pd deficiency is not a common presentation because skeletal muscles are more resistant to oxidative damage compared to red blood cells. our case adds to the few existing reports of myolysis in the setting of g6pd deficiency.   \n",
       "46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.   \n",
       "47                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               a 71-year-old female patient with hepatitis c virus genotype 1 had previously discontinued interferon (ifn)-a plus ribavirin therapy, pegylated ifn-a (pegifna) monotherapy, and natural ifn-a monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. she subsequently completed 72 weeks of natural ifn-b plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of ifn-a and ifn-b. thus, natural ifn-b plus ribavirin therapy may be a treatment option for patients with poor tolerance to ifn-a or pegifna treatments.   \n",
       "81                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        a divergent human gammapapillomavirus (␥-hpv) genome in a nasal swab from an elderly finnish patient with respiratory symptoms was genetically characterized. the l1 gene of hpv-fin864 shared <70% nucleotide identity to other reported ␥-hpv genomes, provisionally qualifying it as a new species in the gammapapillomavirus genus.   \n",
       "106    a large number of human genes associated with viral infections contain single nucleotide polymorphisms (snps), which represent a genetic variation caused by the change of a single nucleotide in the dna sequence. snps are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. as a consequence of this exhaustive exploration, an association between the presence of some specific snps and the susceptibility or severity of many infectious diseases in some risk population groups has been found. in this review, we discuss the relevance of snps that are important to understand the pathology derived from influenza a virus (iav) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. we also discuss the importance of snps for iav vaccine effectiveness. multiple mechanisms, although there are some differences between strains. for that genome plasticity, iav take advantage of multiple strategies, such as alternative splicing, frameshift mechanisms, and overlapping open reading frames (orfs) [7] [8] [9] . in addition, the coding capability of the viral genome is extended by encoding multifunctional proteins that act at different steps during virus infection. of synthetized vrnp, ensuring that the vrnps are available for packaging [24] . moreover, nep has also other functions during iav infection, contributing to viral budding and to regulate viral rna synthesis. ns1 is a multifunctional protein and a key viral factor that counteracts the host antiviral responses. ns1 has been shown to inhibit the production of interferon (ifn), the activity and expression of multiple interferon-induced genes (isg) and the processing and nuclear transport of host mrnas causing cellular shut-off [25, 26] . segment 3 of iav also encodes two proteins, the polymerase component pa and pa-x. pa is translated directly from the pa mrna, whereas pa-x is translated using a +1 frameshift mechanism from the same open reading frame (orf) [9] . synergistically with ns1, pa-x is also able to block the cellular antiviral responses by inhibiting host protein expression. moreover, the pa-x protein has been shown to modulate host inflammation, immune responses, apoptosis, and virus pathogenesis [25] [26] [27] [28] [29] [30] .   \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           ...   \n",
       "10553                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            zika virus (zikv) is an emerging mosquito-borne flavivirus that can potentially threaten south china. a chinese family of four returning from venezuela to china was found to be positive for zikv when the youngest son's fever was first detected at an airport immigration inspection. they were isolated temporarily in a local hospital in enping city, guangdong province, where their clinical data were recorded and urine and saliva were collected to isolate zikv and to obtain viral sequences. all of them except the mother presented mild symptoms of rash and fever. envelope gene sequences from the father, daughter and son were completely identical. phylogenetic analysis demonstrated that this strain is similar to several imported strains reported in recent months, which are all clustered into a group isolated from 2015 zika outbreaks in brazil. together with the climatic features in venezuela, new york and guangdong in february, it can be concluded that our subjects are imported cases from venezuela. with the same viral sequence being shared between family members, neither direct human-to-human nor vector transmission can be ruled out in this study, but the former seems more likely. although our subjects had mild illness, epidemiologists and public health officials should be aware of the risk of further expansion of zikv transmission by local competent vectors.   \n",
       "10559                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  zika virus (zikv) specific neutralizing antibodies hold great promise for antibody-based interventions and vaccine design against zikv infection. however, their development in infected patients remains unclear. here, we applied next-generation sequencing (ngs) to probe the dynamic development of a potent and protective zikv e diii-specific antibody zk2b10 isolated from a zikv convalescent individual. the unbiased repertoire analysis showed dramatic changes in the usage of antibody variable region germline genes. however, lineage tracing of zk2b10 revealed limited somatic hypermutation and transient expansion during the 12 months following the onset of symptoms. the ngs-derived, germline-like zk2b10 somatic variants neutralized zikv potently and protected mice from lethal challenge of zikv without detectable cross-reactivity with dengue virus (denv). site-directed mutagenesis identified two residues within the λ chain, n31 and s91, that are essential to the functional maturation of zk2b10. the repertoire and lineage features unveiled here will help elucidate the developmental process and protective potential of e diii-directed antibodies against zikv infection.   \n",
       "10561                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              zika virus (zikv) was first discovered in 1947 in africa. since then, sporadic zikv infections of humans have been reported in africa and asia. for a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. however, during the 2015-2016 epidemic in central and south america, when millions of people were infected, it was discovered that zikv causes microcephaly in the babies of mothers infected during pregnancy. an examination of the m and c proteins of the zikv shell using the disorder predictor pondr vlxt revealed that the m protein contains relatively high disorder levels comparable only to those of the yellow fever virus (yfv). on the other hand, the disorder levels in the c protein are relatively low, which can account for the low case fatality rate (cfr) of this virus in contrast to the more virulent yfv, which is characterized by high disorder in its c protein. a larger variation was found in the percentage of intrinsic disorder (pid) in the c protein of various zikv strains. strains of african lineage are characterized by higher pids. using both in vivo and in vitro experiments, laboratories have also previously shown that strains of african origin have a greater potential to inflict higher fetal morbidity than do strains of asian lineage, with dengue-2 virus (denv-2) having the least potential. strong correlations were found between the potential to inflict fetal morbidity and shell disorder in zikv (r 2 = 0.9) and denv-2 (denv-2 + zikv, r 2 = 0.8). a strong correlation between cfr and pid was also observed when zikv was included in an analysis of sets of shell proteins from a variety of flaviviruses (r 2 = 0.8). these observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.   \n",
       "10565                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         zika virus (zikv), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. currently, no specific antiviral therapy against zikv is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. nevertheless, lately, search for antivirals has been a major aim in zikv investigations. to do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. here, we present an updated review of current knowledge about anti-zikv strategies, focusing on host-directed antivirals as a realistic alternative to combat zikv infection.   \n",
       "10572                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                zoonoses are diseases transmitted from animals to humans, posing a great threat to the health and life of people all over the world. according to who estimations, 600 million cases of diseases caused by contaminated food were noted in 2010, including almost 350 million caused by pathogenic bacteria. campylobacter, salmonella, as well as yersinia enterocolitica and listeria monocytogenes may dwell in livestock (poultry, cattle, and swine) but are also found in wild animals, pets, fish, and rodents. animals, often being asymptomatic carriers of pathogens, excrete them with faeces, thus delivering them to the environment. therefore, pathogens may invade new individuals, as well as reside on vegetables and fruits. pathogenic bacteria also penetrate food production areas and may remain there in the form of a biofilm covering the surfaces of machines and equipment. a common occurrence of microbes in food products, as well as their improper or careless processing, leads to common poisonings. symptoms of foodborne infections may be mild, sometimes flu-like, but they also may be accompanied by severe complications, some even fatal. the aim of the paper is to summarize and provide information on campylobacteriosis, salmonellosis, yersiniosis, and listeriosis and the aetiological factors of those diseases, along with the general characteristics of pathogens, virulence factors, and reservoirs.   \n",
       "\n",
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Cleaned_Content  \n",
       "44                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  24-year-old african-american man presented malaise low back pain found acute severe rhabdomyolysis followed acute hemolysis glucose-6-phosphate dehydrogenase g6pd deficiency suspected presence blister cells peripheral smear confirmed low enzyme activity assay patient reported playing football along upper respiratory infection symptoms prior presentation extensive infectious toxicology workup negative however several inflammatory proteins markedly elevated hypothesized large inflammatory burden led increased reactive oxygen radical burden overwhelmed muscle erythrocyte reducing power severe rhabdomyolysis g6pd deficiency common presentation skeletal muscles resistant oxidative damage compared red blood cells case adds existing reports myolysis setting g6pd deficiency  \n",
       "46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments  \n",
       "47                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       71-year-old female patient hepatitis c virus genotype 1 previously discontinued interferon ifn -a plus ribavirin therapy pegylated ifn-a pegifna monotherapy natural ifn-a monotherapy arrhythmia interstitial pneumonia severe neurovegetative symptoms subsequently completed 72 weeks natural ifn-b plus ribavirin therapy without remarkable adverse effects achieved sustained viral response suggesting differences pharmacological properties biological effects ifn-a ifn-b thus natural ifn-b plus ribavirin therapy may treatment option patients poor tolerance ifn-a pegifna treatments  \n",
       "81                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   divergent human gammapapillomavirus -hpv genome nasal swab elderly finnish patient respiratory symptoms genetically characterized l1 gene hpv-fin864 shared 70 nucleotide identity reported -hpv genomes provisionally qualifying new species gammapapillomavirus genus  \n",
       "106    large number human genes associated viral infections contain single nucleotide polymorphisms snps represent genetic variation caused change single nucleotide dna sequence snps located coding non-coding genomic regions affect gene expression protein function different mechanisms furthermore linked multiple human diseases highlighting medical relevance therefore identification analysis kind polymorphisms human genome gained high importance research community increasing number studies published last years consequence exhaustive exploration association presence specific snps susceptibility severity many infectious diseases risk population groups found review discuss relevance snps important understand pathology derived influenza virus iav infections humans susceptibility individuals suffer severe symptoms also discuss importance snps iav vaccine effectiveness multiple mechanisms although differences strains genome plasticity iav take advantage multiple strategies alternative splicing frameshift mechanisms overlapping open reading frames orfs 7 8 9 addition coding capability viral genome extended encoding multifunctional proteins act different steps virus infection synthetized vrnp ensuring vrnps available packaging 24 moreover nep also functions iav infection contributing viral budding regulate viral rna synthesis ns1 multifunctional protein key viral factor counteracts host antiviral responses ns1 shown inhibit production interferon ifn activity expression multiple interferon-induced genes isg processing nuclear transport host mrnas causing cellular shut-off 25 26 segment 3 iav also encodes two proteins polymerase component pa pa-x pa translated directly pa mrna whereas pa-x translated using 1 frameshift mechanism open reading frame orf 9 synergistically ns1 pa-x also able block cellular antiviral responses inhibiting host protein expression moreover pa-x protein shown modulate host inflammation immune responses apoptosis virus pathogenesis 25 26 27 28 29 30  \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      ...  \n",
       "10553                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          zika virus zikv emerging mosquito-borne flavivirus potentially threaten south china chinese family four returning venezuela china found positive zikv youngest son fever first detected airport immigration inspection isolated temporarily local hospital enping city guangdong province clinical data recorded urine saliva collected isolate zikv obtain viral sequences except mother presented mild symptoms rash fever envelope gene sequences father daughter son completely identical phylogenetic analysis demonstrated strain similar several imported strains reported recent months clustered group isolated 2015 zika outbreaks brazil together climatic features venezuela new york guangdong february concluded subjects imported cases venezuela viral sequence shared family members neither direct human-to-human vector transmission ruled study former seems likely although subjects mild illness epidemiologists public health officials aware risk expansion zikv transmission local competent vectors  \n",
       "10559                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       zika virus zikv specific neutralizing antibodies hold great promise antibody-based interventions vaccine design zikv infection however development infected patients remains unclear applied next-generation sequencing ngs probe dynamic development potent protective zikv e diii-specific antibody zk2b10 isolated zikv convalescent individual unbiased repertoire analysis showed dramatic changes usage antibody variable region germline genes however lineage tracing zk2b10 revealed limited somatic hypermutation transient expansion 12 months following onset symptoms ngs-derived germline-like zk2b10 somatic variants neutralized zikv potently protected mice lethal challenge zikv without detectable cross-reactivity dengue virus denv site-directed mutagenesis identified two residues within chain n31 s91 essential functional maturation zk2b10 repertoire lineage features unveiled help elucidate developmental process protective potential e diii-directed antibodies zikv infection  \n",
       "10561                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  zika virus zikv first discovered 1947 africa since sporadic zikv infections humans reported africa asia long time virus mostly unnoticed due mild symptoms low fatality rates however 2015-2016 epidemic central south america millions people infected discovered zikv causes microcephaly babies mothers infected pregnancy examination c proteins zikv shell using disorder predictor pondr vlxt revealed protein contains relatively high disorder levels comparable yellow fever virus yfv hand disorder levels c protein relatively low account low case fatality rate cfr virus contrast virulent yfv characterized high disorder c protein larger variation found percentage intrinsic disorder pid c protein various zikv strains strains african lineage characterized higher pids using vivo vitro experiments laboratories also previously shown strains african origin greater potential inflict higher fetal morbidity strains asian lineage dengue-2 virus denv-2 least potential strong correlations found potential inflict fetal morbidity shell disorder zikv r 2 0 9 denv-2 denv-2 zikv r 2 0 8 strong correlation cfr pid also observed zikv included analysis sets shell proteins variety flaviviruses r 2 0 8 observations potential implications antiviral vaccine development design cancer therapeutics terms developing therapeutic viruses penetrate hard-to-reach organs  \n",
       "10565                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          zika virus zikv mosquito-borne flavivirus almost neglected pathogen introduction americas 2015 responsible threat global health causing great social sanitary alarm due increased virulence rapid spread association severe neurological ophthalmological complications currently specific antiviral therapy zikv available treatments palliative mainly directed toward relief symptoms fever rash administering antipyretics anti-histamines fluids dehydration nevertheless lately search antivirals major aim zikv investigations screening libraries different sources testing natural compounds repurposing drugs known antiviral activity allowed identification several antiviral candidates directed viral structural proteins enzymes cellular elements present updated review current knowledge anti-zikv strategies focusing host-directed antivirals realistic alternative combat zikv infection  \n",
       "10572                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               zoonoses diseases transmitted animals humans posing great threat health life people world according estimations 600 million cases diseases caused contaminated food noted 2010 including almost 350 million caused pathogenic bacteria campylobacter salmonella well yersinia enterocolitica listeria monocytogenes may dwell livestock poultry cattle swine also found wild animals pets fish rodents animals often asymptomatic carriers pathogens excrete faeces thus delivering environment therefore pathogens may invade new individuals well reside vegetables fruits pathogenic bacteria also penetrate food production areas may remain form biofilm covering surfaces machines equipment common occurrence microbes food products well improper careless processing leads common poisonings symptoms foodborne infections may mild sometimes flu-like also may accompanied severe complications even fatal aim paper summarize provide information campylobacteriosis salmonellosis yersiniosis listeriosis aetiological factors diseases along general characteristics pathogens virulence factors reservoirs  \n",
       "\n",
       "[665 rows x 2 columns]"
      ]
     },
     "execution_count": 23,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "symptom = df_y[df_y['Cleaned_Content'].str.contains('symptom')]\n",
    "\n",
    "symptom"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 24,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Number of symptom keywords were found :  665\n"
     ]
    }
   ],
   "source": [
    "symptom_texts = symptom['Cleaned_Content'].values\n",
    "\n",
    "print(\"Number of symptom keywords were found : \",len(symptom_texts))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 25,
   "metadata": {},
   "outputs": [],
   "source": [
    "top_n_words = 50"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 26,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Word</th>\n",
       "      <th>Frequency</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>34</th>\n",
       "      <td>respiratory</td>\n",
       "      <td>840</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>82</th>\n",
       "      <td>virus</td>\n",
       "      <td>678</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>35</th>\n",
       "      <td>infection</td>\n",
       "      <td>656</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>124</th>\n",
       "      <td>patients</td>\n",
       "      <td>605</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>36</th>\n",
       "      <td>symptoms</td>\n",
       "      <td>584</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "            Word  Frequency\n",
       "34   respiratory        840\n",
       "82         virus        678\n",
       "35     infection        656\n",
       "124     patients        605\n",
       "36      symptoms        584"
      ]
     },
     "execution_count": 26,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "tokens = ' '.join(symptom['Cleaned_Content']).split(' ')\n",
    "fd = FreqDist(tokens)\n",
    "word_freq = pd.DataFrame(list(fd.items()), columns = [\"Word\", \"Frequency\"])\\\n",
    ".sort_values(by = 'Frequency', ascending = False)\n",
    "top_50_words = word_freq[:top_n_words]\n",
    "top_50_words.head()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# MY QUESTIONS"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## 1) Find lines that include corona and What is the most frequent words in these specific group."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 27,
   "metadata": {},
   "outputs": [
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       "      <th></th>\n",
       "      <th>Content</th>\n",
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       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>these first authors contributed equally to this article background as of february 29, 2020, nearly 80 thousand confirmed novel coronavirus (sars-cov-2) infection cases had been reported in china. risk factors for transmission remain largely uncharacteri</td>\n",
       "      <td>first authors contributed equally article background february 29 2020 nearly 80 thousand confirmed novel coronavirus sars-cov-2 infection cases reported china risk factors transmission remain largely uncharacteri</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>21</th>\n",
       "      <td>2019 novel coronavirus (2019-ncov) had typical clinical manifestations (fever and cough) ,and presented with characteristic chest ct imaging features (multiple lesions in both lungs, often accompanied by ggo, vascular enlargement and cobblestone/reticular pattern), which are helpful to the radiologist in the early detection and diagnosis of this emerging global health emergency. in addition, changes in these main ct features can indicate development of the disease.</td>\n",
       "      <td>2019 novel coronavirus 2019-ncov typical clinical manifestations fever cough presented characteristic chest ct imaging features multiple lesions lungs often accompanied ggo vascular enlargement cobblestone reticular pattern helpful radiologist early detection diagnosis emerging global health emergency addition changes main ct features indicate development disease</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>22</th>\n",
       "      <td>2019 novel coronavirus (2019-ncov) is a virus identified as the cause of the outbreak of pneumonia first detected in wuhan, china. investigations on the transmissibility, severity, and other features associated with this virus are ongoing. currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. in contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. the main protease of sars-cov is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-ncov, is considered to be an attractive target for drug development. in this study, we have identified 4 small molecular drugs with high binding capacity with sars-cov main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-ncov.</td>\n",
       "      <td>2019 novel coronavirus 2019-ncov virus identified cause outbreak pneumonia first detected wuhan china investigations transmissibility severity features associated virus ongoing currently vaccine therapeutic antibody prevent infection time required develop effective immune strategy pathogen contrast specific inhibitors targeting key protease involved replication proliferation virus effective means alleviate epidemic main protease sars-cov essential life cycle virus showed 96 1 similarity main proteaseof 2019-ncov considered attractive target drug development study identified 4 small molecular drugs high binding capacity sars-cov main protease high-throughput screening based 8 000 clinical drug libraries drugs widely used clinical applications guaranteed safety may serve promising candidates treat infection 2019-ncov</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>25</th>\n",
       "      <td>2019-ncov is a newly identified coronavirus with high similarity to sars-cov. we performed a structural analysis of the receptor binding domain (rbd) of spike glycoprotein responsible for entry of coronaviruses into host cells. the rbds from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. however, 2019-ncov has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in sars-cov. molecular modeling revealed that 2019-ncov rbd has a stronger interaction with angiotensin converting enzyme 2 (ace2). a unique phenylalanine f486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ace2. ace2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. structural analysis suggests that ace2 from these animals can potentially bind rbd of 2019-ncov, making them all possible natural hosts for the virus. 2019-ncov is thought to be transmitted through respiratory droplets. however, since ace2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. finally, antibodies and small molecular inhibitors that can block the interaction of ace2 with rbd should be developed to combat the virus.</td>\n",
       "      <td>2019-ncov newly identified coronavirus high similarity sars-cov performed structural analysis receptor binding domain rbd spike glycoprotein responsible entry coronaviruses host cells rbds two viruses share 72 identity amino acid sequences molecular simulation reveals highly similar ternary structures however 2019-ncov distinct loop flexible glycyl residues replacing rigid prolyl residues sars-cov molecular modeling revealed 2019-ncov rbd stronger interaction angiotensin converting enzyme 2 ace2 unique phenylalanine f486 flexible loop likely plays major role penetration deep hydrophobic pocket ace2 ace2 widely expressed conserved primary structures throughout animal kingdom fish amphibians reptiles birds mammals structural analysis suggests ace2 animals potentially bind rbd 2019-ncov making possible natural hosts virus 2019-ncov thought transmitted respiratory droplets however since ace2 predominantly expressed intestines testis kidney fecal-oral routes transmission also possible finally antibodies small molecular inhibitors block interaction ace2 rbd developed combat virus</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>27</th>\n",
       "      <td>26 previous findings of middle east respiratory syndrome coronavirus (mers-cov)-27 related viruses in bats, and the ability of tylonycteris-batcov hku4 spike protein to utilize 28 mers-cov receptor, human dipeptidyl peptidase 4 hdpp4, suggest a bat ancestral origin of 29 mers-cov. we developed 12 primary bat cell lines from seven bat species, including 30 tylonycteris pachypus, pipistrellus abramus and rhinolophus sinicus (hosts of tylonycteris-31 batcov hku4, pipistrellus-batcov hku5 and sars-related-cov respectively), and tested 32 their susceptibilities to mers-covs, sars-cov and human coronavirus 229e (hcov-229e). 33 five cell lines, including p. abramus and r. sinicus but not t. pachypus cells, were susceptible 34 to human mers-cov emc/2012. however, three tested camel mers-cov strains showed 35 different infectivities, with only two strains capable of infecting three and one cell lines 36 respectively. sars-cov can only replicate in r. sinicus cells, while hcov-229e cannot 37 replicate in any bat cells. bat dipeptidyl peptidase 4 (dpp4) sequences were closely related to 38 those of human and non-human primates but distinct from dromedary dpp4 sequence. critical 39 residues for binding to mers-cov spike protein were mostly conserved in bat dpp4. dpp4 40 was expressed in the five bat cells susceptible to mers-cov, with significantly higher mrna 41 expression levels than those in non-susceptible cells (p=0.0174), supporting that dpp4 42 expression is critical for mers-cov infection in bats. however, overexpression of t. pachypus 43 dpp4 failed to confer mers-cov susceptibility in t. pachypus cells, suggesting other cellular 44 factors in determining viral replication. the broad cellular tropism of mers-cov should 45 prompt further exploration of host diversity of related viruses to identify its ancestral origin. 46 47 all rights reserved. no reuse allowed without permission.</td>\n",
       "      <td>26 previous findings middle east respiratory syndrome coronavirus mers-cov -27 related viruses bats ability tylonycteris-batcov hku4 spike protein utilize 28 mers-cov receptor human dipeptidyl peptidase 4 hdpp4 suggest bat ancestral origin 29 mers-cov developed 12 primary bat cell lines seven bat species including 30 tylonycteris pachypus pipistrellus abramus rhinolophus sinicus hosts tylonycteris-31 batcov hku4 pipistrellus-batcov hku5 sars-related-cov respectively tested 32 susceptibilities mers-covs sars-cov human coronavirus 229e hcov-229e 33 five cell lines including p abramus r sinicus pachypus cells susceptible 34 human mers-cov emc 2012 however three tested camel mers-cov strains showed 35 different infectivities two strains capable infecting three one cell lines 36 respectively sars-cov replicate r sinicus cells hcov-229e cannot 37 replicate bat cells bat dipeptidyl peptidase 4 dpp4 sequences closely related 38 human non-human primates distinct dromedary dpp4 sequence critical 39 residues binding mers-cov spike protein mostly conserved bat dpp4 dpp4 40 expressed five bat cells susceptible mers-cov significantly higher mrna 41 expression levels non-susceptible cells p 0 0174 supporting dpp4 42 expression critical mers-cov infection bats however overexpression pachypus 43 dpp4 failed confer mers-cov susceptibility pachypus cells suggesting cellular 44 factors determining viral replication broad cellular tropism mers-cov 45 prompt exploration host diversity related viruses identify ancestral origin 46 47 rights reserved reuse allowed without permission</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10512</th>\n",
       "      <td>wuhan coronavirus, called 2019-ncov, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by january 30, 2020. currently, there is no effective treatment for this epidemic. however, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. fortunately, the sequence identity of the 2019-ncov protease and that of severe-acute respiratory syndrome virus (sars-cov) is as high as 96.1%. we show that the protease inhibitor binding sites of 2019-ncov and sars-cov are almost identical, which means all potential anti-sars-cov chemotherapies are also potential 2019-ncov drugs. here, we report a family of potential 2019-ncov drugs generated by a machine intelligence-based generative network complex (gnc). the potential effectiveness of treating 2019-ncov by using some existing hiv drugs is also analyzed.</td>\n",
       "      <td>wuhan coronavirus called 2019-ncov newly emerged virus infected 9692 people leads 213 fatalities january 30 2020 currently effective treatment epidemic however viral protease coronavirus well-known essential replication thus effective drug target fortunately sequence identity 2019-ncov protease severe-acute respiratory syndrome virus sars-cov high 96 1 show protease inhibitor binding sites 2019-ncov sars-cov almost identical means potential anti-sars-cov chemotherapies also potential 2019-ncov drugs report family potential 2019-ncov drugs generated machine intelligence-based generative network complex gnc potential effectiveness treating 2019-ncov using existing hiv drugs also analyzed</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10513</th>\n",
       "      <td>wuhan novel coronavirus disease outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading.</td>\n",
       "      <td>wuhan novel coronavirus disease outbreak become global outbreak raised concern scientific community design discover definitive cure deadly virus caused deaths numerous infected people upon infection spreading</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10514</th>\n",
       "      <td>wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus for hubei province. to achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. we excluded those without relevant epidemiological descriptions, working or living in wuhan for a long time, or hard to determine the possible exposure time. we proposed a monte caro simulation approach to estimate the incubation of covid-19 as well as employed nonparametric ways. we also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. all rights reserved. no reuse allowed without permission.</td>\n",
       "      <td>wuhan pneumonia acute infectious disease caused 2019 novel coronavirus hubei province achieve accurate calculation incubation period involved officially confirmed cases clear history exposure time onset excluded without relevant epidemiological descriptions working living wuhan long time hard determine possible exposure time proposed monte caro simulation approach estimate incubation covid-19 well employed nonparametric ways also employed manifold learning related statistical analysis decipher incubation relationships different age gender groups rights reserved reuse allowed without permission</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10578</th>\n",
       "      <td>zoonotic coronaviruses (covs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) 1 . host immune responses to cov are complex and regulated in part through antiviral interferons.</td>\n",
       "      <td>zoonotic coronaviruses covs significant threats global health exemplified recent emergence severe acute respiratory syndrome coronavirus 2 sars-cov-2 1 host immune responses cov complex regulated part antiviral interferons</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10580</th>\n",
       "      <td>zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. in this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated venezuelan equine encephalitis (vee) virus vaccine, strain 3526 (vrp 3526). using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the vrp 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. importantly, packaging under biosafety level 2 (bsl2) conditions distinguishes vrp 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. in addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated vrp approaches. taking these results together, the vrp 3526 platform represents a safe and highly portable system that can be rapidly deployed under bsl2 conditions for generation of candidate vaccines against emerging microbial pathogens. importance while vee virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. in this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. together, the new system represents a highly portable, safe system for use in the context of disease emergence.</td>\n",
       "      <td>zoonotic viruses circulate swarms animal reservoirs emerge human populations causing epidemics adversely affect public health portable safe effective vaccine platforms needed context outbreak emergence situations work report generation characterization alphavirus replicon vaccine platform based non-select agent attenuated venezuelan equine encephalitis vee virus vaccine strain 3526 vrp 3526 using noroviruses coronaviruses model systems demonstrate utility vrp 3526 platform generation recombinant proteins production virus-like particles vivo efficacy vaccine emergent viruses importantly packaging biosafety level 2 bsl2 conditions distinguishes vrp 3526 previously reported alphavirus platforms makes approach accessible majority laboratories around world addition improved outcomes vulnerable aged models well heterologous challenge suggest improved efficacy compared previously attenuated vrp approaches taking results together vrp 3526 platform represents safe highly portable system rapidly deployed bsl2 conditions generation candidate vaccines emerging microbial pathogens importance vee virus replicon particles provide robust established platform antigen expression vaccination utility limited requirement high-containment-level facilities production packaging work utilize attenuated vaccine strain capable use lower biocontainment level retaining capacity wild-type replicon particle importantly new replicon platform provides equal protection aged mice following heterologous challenge distinguishes attenuated replicon platforms together new system represents highly portable safe system use context disease emergence</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
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       "<p>1521 rows × 2 columns</p>\n",
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       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 Content  \\\n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          these first authors contributed equally to this article background as of february 29, 2020, nearly 80 thousand confirmed novel coronavirus (sars-cov-2) infection cases had been reported in china. risk factors for transmission remain largely uncharacteri   \n",
       "21                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 2019 novel coronavirus (2019-ncov) had typical clinical manifestations (fever and cough) ,and presented with characteristic chest ct imaging features (multiple lesions in both lungs, often accompanied by ggo, vascular enlargement and cobblestone/reticular pattern), which are helpful to the radiologist in the early detection and diagnosis of this emerging global health emergency. in addition, changes in these main ct features can indicate development of the disease.   \n",
       "22                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     2019 novel coronavirus (2019-ncov) is a virus identified as the cause of the outbreak of pneumonia first detected in wuhan, china. investigations on the transmissibility, severity, and other features associated with this virus are ongoing. currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. in contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. the main protease of sars-cov is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-ncov, is considered to be an attractive target for drug development. in this study, we have identified 4 small molecular drugs with high binding capacity with sars-cov main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-ncov.   \n",
       "25                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           2019-ncov is a newly identified coronavirus with high similarity to sars-cov. we performed a structural analysis of the receptor binding domain (rbd) of spike glycoprotein responsible for entry of coronaviruses into host cells. the rbds from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. however, 2019-ncov has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in sars-cov. molecular modeling revealed that 2019-ncov rbd has a stronger interaction with angiotensin converting enzyme 2 (ace2). a unique phenylalanine f486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ace2. ace2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. structural analysis suggests that ace2 from these animals can potentially bind rbd of 2019-ncov, making them all possible natural hosts for the virus. 2019-ncov is thought to be transmitted through respiratory droplets. however, since ace2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. finally, antibodies and small molecular inhibitors that can block the interaction of ace2 with rbd should be developed to combat the virus.   \n",
       "27                                                                                                                                                                26 previous findings of middle east respiratory syndrome coronavirus (mers-cov)-27 related viruses in bats, and the ability of tylonycteris-batcov hku4 spike protein to utilize 28 mers-cov receptor, human dipeptidyl peptidase 4 hdpp4, suggest a bat ancestral origin of 29 mers-cov. we developed 12 primary bat cell lines from seven bat species, including 30 tylonycteris pachypus, pipistrellus abramus and rhinolophus sinicus (hosts of tylonycteris-31 batcov hku4, pipistrellus-batcov hku5 and sars-related-cov respectively), and tested 32 their susceptibilities to mers-covs, sars-cov and human coronavirus 229e (hcov-229e). 33 five cell lines, including p. abramus and r. sinicus but not t. pachypus cells, were susceptible 34 to human mers-cov emc/2012. however, three tested camel mers-cov strains showed 35 different infectivities, with only two strains capable of infecting three and one cell lines 36 respectively. sars-cov can only replicate in r. sinicus cells, while hcov-229e cannot 37 replicate in any bat cells. bat dipeptidyl peptidase 4 (dpp4) sequences were closely related to 38 those of human and non-human primates but distinct from dromedary dpp4 sequence. critical 39 residues for binding to mers-cov spike protein were mostly conserved in bat dpp4. dpp4 40 was expressed in the five bat cells susceptible to mers-cov, with significantly higher mrna 41 expression levels than those in non-susceptible cells (p=0.0174), supporting that dpp4 42 expression is critical for mers-cov infection in bats. however, overexpression of t. pachypus 43 dpp4 failed to confer mers-cov susceptibility in t. pachypus cells, suggesting other cellular 44 factors in determining viral replication. the broad cellular tropism of mers-cov should 45 prompt further exploration of host diversity of related viruses to identify its ancestral origin. 46 47 all rights reserved. no reuse allowed without permission.   \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  ...   \n",
       "10512                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               wuhan coronavirus, called 2019-ncov, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by january 30, 2020. currently, there is no effective treatment for this epidemic. however, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. fortunately, the sequence identity of the 2019-ncov protease and that of severe-acute respiratory syndrome virus (sars-cov) is as high as 96.1%. we show that the protease inhibitor binding sites of 2019-ncov and sars-cov are almost identical, which means all potential anti-sars-cov chemotherapies are also potential 2019-ncov drugs. here, we report a family of potential 2019-ncov drugs generated by a machine intelligence-based generative network complex (gnc). the potential effectiveness of treating 2019-ncov by using some existing hiv drugs is also analyzed.   \n",
       "10513                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    wuhan novel coronavirus disease outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading.   \n",
       "10514                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus for hubei province. to achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. we excluded those without relevant epidemiological descriptions, working or living in wuhan for a long time, or hard to determine the possible exposure time. we proposed a monte caro simulation approach to estimate the incubation of covid-19 as well as employed nonparametric ways. we also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. all rights reserved. no reuse allowed without permission.   \n",
       "10578                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   zoonotic coronaviruses (covs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) 1 . host immune responses to cov are complex and regulated in part through antiviral interferons.   \n",
       "10580  zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. in this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated venezuelan equine encephalitis (vee) virus vaccine, strain 3526 (vrp 3526). using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the vrp 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. importantly, packaging under biosafety level 2 (bsl2) conditions distinguishes vrp 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. in addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated vrp approaches. taking these results together, the vrp 3526 platform represents a safe and highly portable system that can be rapidly deployed under bsl2 conditions for generation of candidate vaccines against emerging microbial pathogens. importance while vee virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. in this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. together, the new system represents a highly portable, safe system for use in the context of disease emergence.   \n",
       "\n",
       "                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Cleaned_Content  \n",
       "1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     first authors contributed equally article background february 29 2020 nearly 80 thousand confirmed novel coronavirus sars-cov-2 infection cases reported china risk factors transmission remain largely uncharacteri  \n",
       "21                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           2019 novel coronavirus 2019-ncov typical clinical manifestations fever cough presented characteristic chest ct imaging features multiple lesions lungs often accompanied ggo vascular enlargement cobblestone reticular pattern helpful radiologist early detection diagnosis emerging global health emergency addition changes main ct features indicate development disease  \n",
       "22                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              2019 novel coronavirus 2019-ncov virus identified cause outbreak pneumonia first detected wuhan china investigations transmissibility severity features associated virus ongoing currently vaccine therapeutic antibody prevent infection time required develop effective immune strategy pathogen contrast specific inhibitors targeting key protease involved replication proliferation virus effective means alleviate epidemic main protease sars-cov essential life cycle virus showed 96 1 similarity main proteaseof 2019-ncov considered attractive target drug development study identified 4 small molecular drugs high binding capacity sars-cov main protease high-throughput screening based 8 000 clinical drug libraries drugs widely used clinical applications guaranteed safety may serve promising candidates treat infection 2019-ncov  \n",
       "25                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      2019-ncov newly identified coronavirus high similarity sars-cov performed structural analysis receptor binding domain rbd spike glycoprotein responsible entry coronaviruses host cells rbds two viruses share 72 identity amino acid sequences molecular simulation reveals highly similar ternary structures however 2019-ncov distinct loop flexible glycyl residues replacing rigid prolyl residues sars-cov molecular modeling revealed 2019-ncov rbd stronger interaction angiotensin converting enzyme 2 ace2 unique phenylalanine f486 flexible loop likely plays major role penetration deep hydrophobic pocket ace2 ace2 widely expressed conserved primary structures throughout animal kingdom fish amphibians reptiles birds mammals structural analysis suggests ace2 animals potentially bind rbd 2019-ncov making possible natural hosts virus 2019-ncov thought transmitted respiratory droplets however since ace2 predominantly expressed intestines testis kidney fecal-oral routes transmission also possible finally antibodies small molecular inhibitors block interaction ace2 rbd developed combat virus  \n",
       "27                                                        26 previous findings middle east respiratory syndrome coronavirus mers-cov -27 related viruses bats ability tylonycteris-batcov hku4 spike protein utilize 28 mers-cov receptor human dipeptidyl peptidase 4 hdpp4 suggest bat ancestral origin 29 mers-cov developed 12 primary bat cell lines seven bat species including 30 tylonycteris pachypus pipistrellus abramus rhinolophus sinicus hosts tylonycteris-31 batcov hku4 pipistrellus-batcov hku5 sars-related-cov respectively tested 32 susceptibilities mers-covs sars-cov human coronavirus 229e hcov-229e 33 five cell lines including p abramus r sinicus pachypus cells susceptible 34 human mers-cov emc 2012 however three tested camel mers-cov strains showed 35 different infectivities two strains capable infecting three one cell lines 36 respectively sars-cov replicate r sinicus cells hcov-229e cannot 37 replicate bat cells bat dipeptidyl peptidase 4 dpp4 sequences closely related 38 human non-human primates distinct dromedary dpp4 sequence critical 39 residues binding mers-cov spike protein mostly conserved bat dpp4 dpp4 40 expressed five bat cells susceptible mers-cov significantly higher mrna 41 expression levels non-susceptible cells p 0 0174 supporting dpp4 42 expression critical mers-cov infection bats however overexpression pachypus 43 dpp4 failed confer mers-cov susceptibility pachypus cells suggesting cellular 44 factors determining viral replication broad cellular tropism mers-cov 45 prompt exploration host diversity related viruses identify ancestral origin 46 47 rights reserved reuse allowed without permission  \n",
       "...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    ...  \n",
       "10512                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               wuhan coronavirus called 2019-ncov newly emerged virus infected 9692 people leads 213 fatalities january 30 2020 currently effective treatment epidemic however viral protease coronavirus well-known essential replication thus effective drug target fortunately sequence identity 2019-ncov protease severe-acute respiratory syndrome virus sars-cov high 96 1 show protease inhibitor binding sites 2019-ncov sars-cov almost identical means potential anti-sars-cov chemotherapies also potential 2019-ncov drugs report family potential 2019-ncov drugs generated machine intelligence-based generative network complex gnc potential effectiveness treating 2019-ncov using existing hiv drugs also analyzed  \n",
       "10513                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     wuhan novel coronavirus disease outbreak become global outbreak raised concern scientific community design discover definitive cure deadly virus caused deaths numerous infected people upon infection spreading  \n",
       "10514                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             wuhan pneumonia acute infectious disease caused 2019 novel coronavirus hubei province achieve accurate calculation incubation period involved officially confirmed cases clear history exposure time onset excluded without relevant epidemiological descriptions working living wuhan long time hard determine possible exposure time proposed monte caro simulation approach estimate incubation covid-19 well employed nonparametric ways also employed manifold learning related statistical analysis decipher incubation relationships different age gender groups rights reserved reuse allowed without permission  \n",
       "10578                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       zoonotic coronaviruses covs significant threats global health exemplified recent emergence severe acute respiratory syndrome coronavirus 2 sars-cov-2 1 host immune responses cov complex regulated part antiviral interferons  \n",
       "10580  zoonotic viruses circulate swarms animal reservoirs emerge human populations causing epidemics adversely affect public health portable safe effective vaccine platforms needed context outbreak emergence situations work report generation characterization alphavirus replicon vaccine platform based non-select agent attenuated venezuelan equine encephalitis vee virus vaccine strain 3526 vrp 3526 using noroviruses coronaviruses model systems demonstrate utility vrp 3526 platform generation recombinant proteins production virus-like particles vivo efficacy vaccine emergent viruses importantly packaging biosafety level 2 bsl2 conditions distinguishes vrp 3526 previously reported alphavirus platforms makes approach accessible majority laboratories around world addition improved outcomes vulnerable aged models well heterologous challenge suggest improved efficacy compared previously attenuated vrp approaches taking results together vrp 3526 platform represents safe highly portable system rapidly deployed bsl2 conditions generation candidate vaccines emerging microbial pathogens importance vee virus replicon particles provide robust established platform antigen expression vaccination utility limited requirement high-containment-level facilities production packaging work utilize attenuated vaccine strain capable use lower biocontainment level retaining capacity wild-type replicon particle importantly new replicon platform provides equal protection aged mice following heterologous challenge distinguishes attenuated replicon platforms together new system represents highly portable safe system use context disease emergence  \n",
       "\n",
       "[1521 rows x 2 columns]"
      ]
     },
     "execution_count": 27,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "corona = df_y[df_y['Cleaned_Content'].str.contains('corona')]\n",
    "\n",
    "corona"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 28,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Number of corona keywords were found :  1521\n"
     ]
    }
   ],
   "source": [
    "corona_texts = corona['Cleaned_Content'].values\n",
    "print(\"Number of corona keywords were found : \",len(corona_texts))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 29,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Word</th>\n",
       "      <th>Frequency</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>14</th>\n",
       "      <td>coronavirus</td>\n",
       "      <td>1705</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>65</th>\n",
       "      <td>virus</td>\n",
       "      <td>1692</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>217</th>\n",
       "      <td>respiratory</td>\n",
       "      <td>1444</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>238</th>\n",
       "      <td>mers-cov</td>\n",
       "      <td>1164</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>16</th>\n",
       "      <td>infection</td>\n",
       "      <td>1154</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "            Word  Frequency\n",
       "14   coronavirus       1705\n",
       "65         virus       1692\n",
       "217  respiratory       1444\n",
       "238     mers-cov       1164\n",
       "16     infection       1154"
      ]
     },
     "execution_count": 29,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "top_n_words = 50\n",
    "\n",
    "tokens = ' '.join(corona['Cleaned_Content']).split(' ')\n",
    "fd = FreqDist(tokens)\n",
    "word_freq = pd.DataFrame(list(fd.items()), columns = [\"Word\", \"Frequency\"])\\\n",
    ".sort_values(by = 'Frequency', ascending = False)\n",
    "top_50_words = word_freq[:top_n_words]\n",
    "top_50_words.head()\n",
    "\n"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## 2) Find diet.txt and get the data... What is the most frequent words in these specific group."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 30,
   "metadata": {},
   "outputs": [],
   "source": [
    "read_text=open('diet.txt','r')\n",
    "\n",
    "diet=read_text.read().lower()\n",
    "\n",
    "diet=diet.split()\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 31,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>word</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>oregano</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>sage</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>basil</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>fennel</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>garlic</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>65</th>\n",
       "      <td>glukan</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>66</th>\n",
       "      <td>flexseed</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>67</th>\n",
       "      <td>stress</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>68</th>\n",
       "      <td>alchol</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>69</th>\n",
       "      <td>sugar</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>70 rows × 1 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "        word\n",
       "0    oregano\n",
       "1       sage\n",
       "2      basil\n",
       "3     fennel\n",
       "4     garlic\n",
       "..       ...\n",
       "65    glukan\n",
       "66  flexseed\n",
       "67    stress\n",
       "68    alchol\n",
       "69     sugar\n",
       "\n",
       "[70 rows x 1 columns]"
      ]
     },
     "execution_count": 31,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "dietdf = pd.DataFrame(diet, columns = ['word'])\n",
    "\n",
    "dietdf"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 32,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Word</th>\n",
       "      <th>Frequency</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>9</th>\n",
       "      <td>echinacea</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>lemon</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>25</th>\n",
       "      <td>water</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10</th>\n",
       "      <td>sambucus</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18</th>\n",
       "      <td>vitamin</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "         Word  Frequency\n",
       "9   echinacea          2\n",
       "5       lemon          2\n",
       "25      water          2\n",
       "10   sambucus          2\n",
       "18    vitamin          2"
      ]
     },
     "execution_count": 32,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "tokens = ' '.join(dietdf['word']).split(' ')\n",
    "fd = FreqDist(tokens)\n",
    "word_freq = pd.DataFrame(list(fd.items()), columns = [\"Word\", \"Frequency\"])\\\n",
    ".sort_values(by = 'Frequency', ascending = False)\n",
    "top_50_words = word_freq[:top_n_words]\n",
    "top_50_words.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  }
 ],
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