niryuu/sni-each-converted huggingface dataset:
Paragraph: In the present studies , we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene , a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical , and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a fulllength cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis , inflammation, fibrin deposition , and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis. 
 Title: Molecular and Functional Analysis of the Human Prothrombinase Gene (HFGL2) and Its Role in Viral Hepatitis
Output: True
Paragraph: Single particle cryo-electron microscopy (cryoEM) is becoming widely adopted as a tool for structural characterization of biomolecules at near-atomic resolution. Vitrification of the sample to obtain a dense distribution of particles within a single field of view remains a major bottleneck for the success of such experiments. Here, we describe a simple and cost-effective method to increase the density of frozenhydrated particles on grids with holey carbon support films. It relies on performing multiple rounds of sample application and blotting prior to plunge freezing in liquid ethane. We show that this approach is generally applicable and significantly increases particle density for a range of samples, such as small protein complexes, viruses and filamentous assemblies. The method is versatile, easy to implement, minimizes sample requirements and can enable characterization of samples that would otherwise resist structural studies using single particle cryoEM. Ó 2017 Elsevier Inc. All rights reserved. Single particle cryo-electron microscopy (cryoEM) is becoming an increasingly important tool in structural biology (Nogales and Scheres, 2015; Cheng et al., 2015) . Due to recent advances in detector efficiency, microscope stability and image processing, the 3D structure of biomolecular complexes spanning a wide range of sizes, from haemoglobin to microtubules and intact viruses, can be reconstructed at (near-) atomic resolution (Bai et al., 2013; Brilot et al.,  
 Title: Vitrification after multiple rounds of sample application and blotting improves particle density on cryo-electron microscopy grids
Output: False
Paragraph: The adhesion of microbial pathogens to host cells is mediated by adhesins. Experimental methods used for characterizing adhesins are time-consuming and demand large resources. The availability of specialized software can rapidly aid experimenters in simplifying this problem. We have employed 105 compositional properties and artificial neural networks to develop SPAAN, which predicts the probability of a protein being an adhesin (P ad ). Results: SPAAN had optimal sensitivity of 89% and specificity of 100% on a defined test set and could identify 97.4% of known adhesins at high P ad value from a wide range of bacteria. Furthermore, SPAAN facilitated improved annotation of several proteins as adhesins. Novel adhesins were identified in 17 pathogenic organisms causing diseases in humans and plants. In the severe acute respiratory syndrome (SARS) associated human corona virus, the spike glycoprotein and nsps (nsp2, nsp5, nsp6 and nsp7) were identified as having adhesin-like characteristics. These results offer new lead for rapid experimental testing. 
 Title: SPAAN: a software program for prediction of adhesins and adhesin-like proteins using neural networks
Output: True
Paragraph: Overcrowding during the yearly Hajj mass gatherings is associated with increased risk of spreading infectious diseases, particularly respiratory diseases. Non-pharmaceutical interventions (e.g., hand hygiene, wearing face masks, social distancing) are known to reduce the spread of respiratory viruses from person to person and are therefore recommended to pilgrims by public health agencies. The implementation of effective public health policies and recommendations involves evaluating the adherence to and effectiveness of these measures in the specific context of the Hajj. This review summarizes the evidence related to the effectiveness of non-pharmaceutical interventions in preventing the spread of respiratory infectious diseases during the Hajj. Overall, although hand hygiene compliance is high among pilgrims, face mask use and social distancing remain difficult challenges. Data about the effectiveness of these measures at the Hajj are limited, and results are contradictory, highlighting the need for future large-scale studies. ª 
 Title: Non-pharmaceutical interventions for the prevention of respiratory tract infections during Hajj pilgrimage
Output: False
Paragraph: Background: Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC), associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV), associated with respiratory disease. Findings: In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3). The three major ORFs of CnBoV3 (NS1, NP1 and VP1) shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. Conclusions: We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal's complex disease remains to be determined. 
 Title: A novel bocavirus in canine liver
Output: False
Paragraph: Infl uenza epidemics occur regularly and prediction of their conversion to pandemics and their impact is diffi cult. Coordination of efforts on a global scale to control or reduce the impact is fraught with potential for under and overreaction. In light of the 1956 pandemic and more recently the SARS and H1N1 pandemics, the public health community took steps toward strengthening global surveillance and a coordinated response in keeping with the continuing memory of the tragedy seen in 1918. The scientifi c, professional, and technical resources of the 21 st century are now advanced far beyond those then available. The H1N1 pandemic which commenced in 2009 progressed differently than predicted; its course was diffi cult to predict with any degree of certainty. Public responses to national immunization programs against the H1N1 virus have been weak. International movement of diseases can lead to creation of new endemic areas and continuous spread such as that which happened with West Nile Fever and Chikungunya. The lessons learned and the public and political responses to each actual or threatened pandemic will serve public health well in dealing with future challenges. 
 Title: Infl uenza pandemics: past, present and future challenges
Output: True
Paragraph: Objective: The aim of this study was to determine the etiology and prevalence of pediatric CAP in Beijing using a real-time polymerase chain reaction (PCR) technique. Methods: Between February 15, 2011 and January 18, 2012, 371 pediatric patients with CAP were enrolled at Beijing Children's Hospital. Sixteen respiratory viruses and two bacteria were detected from tracheal aspirate specimens using commercially available multiplex real-time reverse transcription PCR (RT-PCR) kits. Results: A single viral pathogen was detected in 35.3% of enrolled patients, multiple viruses in 11.6%, and virus/bacteria coinfection in 17.8%. In contrast, only 6.5% of patients had a single bacterial pathogen and 2.2% were infected with multiple bacteria. The etiological agent was unknown for 26.7% of patients. The most common viruses were respiratory syncytial virus (RSV) (43.9%), rhinovirus (14.8%), parainfluenza virus (9.4%), and adenovirus (8.6%). In patients under three years of age, RSV (44.6%), rhinovirus (12.8%), and Streptococcus pneumoniae (9.9%) were the most frequent pathogens. In children aged 3e7 years, S. pneumoniae (38.9%), RSV (30.6%), Haemophilus influenzae (19.4%), and adenovirus (19.4%) were most prevalent. Finally in children over seven years, RSV (47.3%), S. pneumoniae (41.9%), and rhinovirus (21.5%) infections were most frequent. Conclusions: Viral pathogens, specifically RSV, were responsible for the majority of CAP in pediatric patients. However, both S. pneumoniae and H. influenzae contributed as major causes of disease. Commercially available multiplexing real-time PCR allowed for rapid detection of the etiological agent. 
 Title: Detection of respiratory viral and bacterial pathogens causing pediatric community-acquired pneumonia in Beijing using real-time PCR-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Production and Hosting by Elsevier on behalf of KeAi ScienceDirect
Output: False
Paragraph: To reveal the putative cellular factors involved in SARS coronavirus replication, the helicase (Hel, nsp13) of SARS coronavirus was used to screen the cDNA library of rat pulmonary epithelial cells using the yeast two-hybrid system. Positively interacting proteins were further tested using a mammalian cell hybrid system and co-immunoprecipitation in the human A549 cell line, which has been shown to support SARS coronavirus replication. Out of the seven positive clones observed by yeast two-hybrid assay, only the Ddx5 (Asp-Glu-Ala-Asp box polypeptide 5) protein showed specific interaction with SARS-CoV helicase. When expression of DdX5 was knocked down by small interfering RNA (siRNA), SARS coronavirus replication was significantly inhibited in fetal rhesus kidney (FRhK-4) cells. Since Ddx5 is a multifunctional protein that plays important roles in transcriptional regulation, its interaction with SARS coronavirus helicase provides interesting clues for studying virus-host cell interactions in SARS-CoV infections. Electronic supplementary material The online version of this article ( 
 Title: Interaction between SARS-CoV helicase and a multifunctional cellular protein (Ddx5) revealed by yeast and mammalian cell two-hybrid systems
Output: True
Paragraph: Equine coronavirus (ECoV) is considered an enteric pathogen of foals and has only recently been associated with infections in adult horses. Seroprevalence data is needed to better understand the epidemiology of ECoV in adult horses, evaluate diagnostic modalities and develop preventive measures. The objective of this study was to investigate the seroprevalence and selective risk factors for ECoV in 5247 healthy adult horses in the USA, using a recently established and validated IgG enzyme-linked immunosorbent assay. Prevalence factors analysed in this study included geographic region, age, breed, sex and use. A total of 504/5247 horses (9.6%) horses tested seropositive. Geographic region (Mid-West; P = 0.008), breed (Draft horses; P = 0.003) and specific uses of horses (ranch/farm, P = 0.034; breeding use, P = 0.016) were all statistically significant risk factors for seropositivity. 
 Title: Seroprevalence and risk factors for infection with equine coronavirus in healthy horses in the USA
Output: False
Paragraph: The main peptidase (M pro ) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M pro by an aza-peptide epoxide (APE; k inact /K i Z 1900(G400) M K1 s K1 ). The crystal structures of the M pro :APE complex in the space groups C2 and P2 1 2 1 2 1 revealed the formation of a covalent bond between the catalytic Cys145 S g atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M pro in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M pro in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M pro are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M pro in the space group P2 1 . 
 Title: Crystal Structures of the Main Peptidase from the SARS Coronavirus Inhibited by a Substrate-like Aza-peptide Epoxide
Output: False
Paragraph: 1. Data collection. Epidemiological data were collected from a variety of online sources. If we were able to find reports listing numbers of confirmed and suspected cases, we used that information. If the epidemiological curve was available online as a graph, which is the case for data obtained from the CDC (Centers for Disease Control and Prevention) and Eurosurveillance sites, we estimated numbers from the graph and matched the plot of the estimated data with the online source. This can conveniently be done in Excel by plotting our estimated numbers on a graph with a transparent background and superimposing the resulting plot on a copy of the epidemiological curve posted online. The data we used are available online at github.com/ JocelineLega/EpiGro. • Data for the 2014-15 chikungunya outbreak in the PAHO countries and territories were extracted from weekly reports published on the PAHO website (1), for the 71-week period from January 3, 2014 to May 8, 2015. Confirmed (autochthonous + imported) and suspected cases are included in this analysis. Not all countries provided weekly revisions of the total number of reported cases, leading to groups of consecutive data points with equal value. In the calculation of the outbreak growth rate, we use a time unit of one week. We do not compensate for the fact that the 53 rd week of 2014 has only 4 days; since the data are first smoothed and then interpolated, such a variation leads to a change in the instantaneous growth rate that is comparable to the size of uncertainties due to fluctuations in the number of reported cases, and is therefore negligible. Excel files with these data are provided for the Dominican Republic (CHIK Dom Rep.xlsx), Guadeloupe (CHIK Guadeloupe.xlsx), and Dominica (CHIK Dominica.xlsx). 
 Title: DATA-DRIVEN OUTBREAK FORECASTING WITH A SIMPLE NONLINEAR GROWTH MODEL TECHNICAL APPENDICES
Output: False
Paragraph: Donor centers are issuing a growing number of recalls and market withdrawals to hospital transfusion services about blood components. More than 1 in 2,000 units were recalled in the late 1990s in the United States. The most common reason for these notices from donor centers is postdonation donor information. Most of these units had been transfused, and many present a "risk of a risk" (ie, a problem might have been present that might have affected the recipient). A few regulations and standards address recalls in general terms, but transfusion services generally have wide discretion in the management of specific common recall problems. The Food and Drug Administration (FDA) is now including posttransfusion evaluations in its guidelines for emerging infectious threats to the blood supply. We suggest that hospital transfusion services should have standard operating procedures for managing recalls and that the hospital transfusion committee and the quality management program should provide local input or oversight. Using the FDA's categories of donor center biological product deviations, we provide recommendations to consider for when to notify the recipient's physician, after postdonation information is received about a previously transfused blood component. More study of this important everyday issue in transfusion medicine is highly desirable. 
 Title: Managing Recalls and Withdrawals of Blood Components
Output: False
Paragraph: Bats are notorious reservoirs of genetically-diverse and high-profile pathogens, and are playing crucial roles in the emergence and re-emergence of viruses, both in human and in animals. In this report, we identified and characterized previously unknown and diverse genetic clusters of bat coronaviruses in the Atlantic Forest Biome, Brazil. These results highlight the virus richness of bats and their possible roles in the public health. 
 Title: Genetic diversity of bats coronaviruses in the Atlantic Forest hotspot biome, Brazil
Output: False
Paragraph: Background: The recent Ebola Virus Disease (EVD) epidemic that hit some countries in West Africa underscores the need to train front line high-risk health workers on disease prevention skills. Although Ghana did not record (and is yet to) any case, and several health workers have received numerous training schemes, there is no record of any study that assessed preparedness of healthcare workers (HCWS) regarding EVD and any emergency prone disease in Ghana. We therefore conducted a hospital based cross sectional study involving 101 HCWs from two facilities in Kumasi, Ghana to assess the level of preparedness of HCWs to respond to any possible EVD. Methods: We administered a face-to-face questionnaire using an adapted WHO (2015) and CDC (2014) Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. Results: A total 92 (91.09%) HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% (n = 26) considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% (n = 9) could correctly identify the right disinfectant (χ 2 = 28.52, p = 0.001). Conclusion: Our study demonstrates poor knowledge and ill preparedness and unwillingness of many HCWs to attend to EVD. Beyond knowledge acquisition, there is the need for more training from time to time to fully prepare HCWs to handle any possible EVD case. 
 Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana
Output: False
Paragraph: Interferon-γ (IFN-γ) represents one of the most important innate immunity responses in a host to combat infections of many human viruses including human herpesviruses. Human N-myc interactor (Nmi) protein, which has been shown to interact with signal transducer and activator of transcription (STAT) proteins including STAT1, is important for the activation of IFN-γ induced STAT1-dependent transcription of many genes responsible for IFN-γ immune responses. However, no proteins encoded by herpesviruses have been reported to interact with Nmi and inhibit Nmi-mediated activation of IFN-γ immune responses to achieve immune evasion from IFN-γ responses. In this study, we show strong evidence that the UL23 protein of human cytomegalovirus (HCMV), a human herpesvirus, specifically interacts with Nmi. This interaction was identified through a yeast two-hybrid screen and co-immunoprecipitation in human cells. We observed that Nmi, when bound to UL23, was not associated with STAT1, suggesting that UL23 binding of Nmi disrupts the interaction of Nmi with STAT1. In cells overexpressing UL23, we observed (a) significantly reduced levels of Nmi and STAT1 in the nuclei, the sites where these proteins act to induce transcription of IFN-γ stimulated genes, and (b) decreased levels of the induction of the transcription of IFN-γ stimulated genes. UL23-deficient HCMV mutants induced higher transcription of IFN-γ stimulated genes and exhibited lower titers than parental and control revertant viruses expressing functional UL23 in IFN-γ treated cells. Thus, UL23 appears to interact directly with Nmi and inhibit nuclear translocation of Nmi and its associated protein STAT1, leading to a decrease of IFN-γ induced responses and an increase of viral resistance to IFN-γ. Our results further highlight the roles of UL23-Nmi interactions in facilitating PLOS Pathogens | https://doi. 
 Title: Human cytomegalovirus UL23 inhibits transcription of interferon-γ stimulated genes and blocks antiviral interferon-γ responses by interacting with human N-myc interactor protein
Output: True
Paragraph: We utilized one-step multiplex reverse transcription-PCR (RT-PCR) and Luminex xMAP technology to develop a respiratory multiplex liquid-chip assay (rMLA) for China, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Performance of rMLA was evaluated by comparing with real-time RT-PCR. Detection data from clinical specimens showed that the rMLA had diagnostic sensitivities of 97.10% for FluA, 94.59% for FluB, 98.68% for PIV-3, 94.87% for RSV and 95.92% for MPV (No Data for MERS-CoV due to the lack of positive specimens). Data of analytical sensitivities showed that the detection limits of the rMLA assay were 5-25 viral RNA copies per μl for FluA, FluB, PIV-3 and MERS-CoV, approximate to the real-time RT-PCR assay; while the values were 8 and 22copies/μl for MPV and RSV, lower than the real-time RT-PCR(78 and 114 copies/μl respectively). The results indicated that the rMLA is a sensitive, specific detection tool and comparable to real-time RT-PCR, especially suitable for high-throughput detection of respiratory specimens. 
 Title: A multiplex liquid-chip assay based on Luminex xMAP technology for simultaneous detection of six common respiratory viruses
Output: False
Paragraph: Recently it has been reported that a cathepsin B inhibitor, CA-074Me, attenuates ecotropic murine leukemia virus (Eco-MLV) infection in NIH3T3 cells, suggesting that cathepsin B is required for the Eco-MLV infection. However, cathepsin B activity was negative or extremely low in NIH3T3 cells. How did CA-074Me attenuate the Eco-MLV infection? The CA-074Me treatment of NIH3T3 cells inhibited cathepsin L activity, and a cathepsin L specific inhibitor, CLIK148, attenuated the Eco-MLV vector infection. These results indicate that the suppression of cathepsin L activity by CA-074Me induces the inhibition of Eco-MLV infection, suggesting that cathepsin L is required for the Eco-MLV infection in NIH3T3 cells. The CA-074Me treatment inhibited the Eco-MLV infection in human cells expressing the exogenous mouse ecotropic receptor and endogenous cathepsins B and L, but the CLIK148 treatment did not, showing that only the cathepsin L suppression by CLIK148 is not enough to prevent the Eco-MLV infection in cells expressing both of cathepsins B and L, and CA-074Me inhibits the Eco-MLV infection by suppressing both of cathepsins B and L. These results suggest that either cathepsin B or L is sufficient for the Eco-MLV infection. 
 Title: Cathepsin L is required for ecotropic murine leukemia virus infection in NIH3T3 cells
Output: True
Paragraph: which may together contribute to the alleviated lung injury and the attenuation of the virulence of H5N1 virus in mice. Keywords Highly pathogenic H5N1 AIV · PA-X · ALI · Pathogenesis · Mice Abstract PA-X is a novel discovered accessory protein encoded by the PA mRNA. Our previous study demonstrated that PA-X decreases the virulence of a highly pathogenic H5N1 strain A/Chicken/Jiangsu/k0402/2010 in mice. However, the underlying mechanism of virulence attenuation associated with PA-X is still unknown. In this study, we compared two PA-X-deficient mutant viruses and the parental virus in terms of induction of pathology and manipulation of host response in the mouse lung, stimulation of cell death and PA nuclear accumulation. We first found that down-regulated PA-X expression markedly aggravated the acute lung injury of the infected mice early on day 1 post-infection (p.i.). We then determined that loss of PA-X expression induced higher levels of cytokines, chemokines and complement-derived peptides (C3a and C5a) in the lung, especially at early time point's p.i. In addition, in vitro assays showed that the PA-X-deficient viruses enhanced cell death and increased expression of reactive oxygen species (ROS) in mammalian cells. Moreover, we also found that PA nuclear accumulation of the PA-X-null viruses accelerated in MDCK cells. These results demonstrate that PA-X decreases the level of complement components, ROS, cell death and inflammatory response, 
 Title: PA-X-associated early alleviation of the acute lung injury contributes to the attenuation of a highly pathogenic H5N1 avian influenza virus in mice
Output: False
Paragraph: Do stress hormones such as corticosterone enhance bird susceptibility to mosquitoes in ways that enhance rates of coinfection? Does this then enhance pathogen emergence? Interactions between pathogens are often mediated by the hosts immune system [1] . Two recent experimental papers suggest that interactions between the immune system and corticosterone may be important in mediating synergistic interactions between pathogens that enhance rates of co-infection in birds. As part of a long term study on the effect of the bacterial pathogen Mycoplasma gallisepticum in house finches Haemorhous mexicanus, Dana Hawley and her team asked the question to what extent are the stress hormones that are important for energy mobilization and regulation of the immune system influenced by experimental infection with the bacterium M. gallisepticum [2] . They found that corticosterone levels increased after house finches were infected with M. gallisepticum, decreased again to pre-infection levels once the infection was cleared, and that individuals with greater disease severity had the highest corticosterone concentrations. Trying to identify factors that influence West Nile virus transmission, Lynn Martin and his team started from the premise that stress hormones might represent a key link between individual-level of infection, population-levels of parasite transmission, and zoonotic disease risk. They experimentally manipulated zebra finch Taeniopygia guttata stress hormones by implanting corticosterone-filled silastic tubules and examined subsequent feeding preferences, feeding success, and productivity of mosquito vectors [3] . Despite performing more frequent 
 Title: Stress hormones bring birds, pathogens and mosquitoes together HHS Public Access
Output: False
Paragraph: Background. Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. Methods. A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. Results. A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02-4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15-3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. Conclusions. Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease. 
 Title: The Role of Influenza and Parainfluenza Infections in Nasopharyngeal Pneumococcal Acquisition Among Young Children
Output: False
Paragraph: The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics. 
 Title: Sequential Adaptive Mutations Enhance Efficient Vector Switching by Chikungunya Virus and Its Epidemic Emergence
Output: False
Paragraph: Abstraet--A preliminary study was conducted to compare the regional intestinal immune responses of neonatal calves inoculated with virulent or attenuated bovine coronavirus (BCV) to determine the cause of reported vaccine failures. A group of 9 newborn, colostrum-deprived calves was used; two calves were inoculated with attenuated virus, four calves were infected with virulent virus (including one naturally infected calf), and three calves were uninfected controls. Calves inoculated with virulent virus produced higher titers of BCV antibodies in the intestines than those inoculated with the attenuated virus. The failure of the calves to respond to the attenuated virus was apparently due to the inability of the virus to replicate to high titers. Spiral colon, ileum, and jejunum were found to be immunologically distinct; the highest anti-BCV antibody responses were detected in spiral colon, the primary site of infection, and involved all four isotypes of bovine immunoglobulins. The antibody response in ileum was lower than in spiral colon. The immune responses developed slowly in jejunum and were associated primarily with the lgG subtypes. 
 Title: ~ Pergamon ANTIBODY RESPONSES IN SPIRAL COLON, ILEUM, AND JEJUNUM OF BOVINE CORONAVIRUS-INFECTED NEONATAL CALVES
Output: False
Paragraph: Background: Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. Results: Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses. 
 Title: BMC Genomics Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses
Output: False
Paragraph: a b s t r a c t Coronaviruses (CoVs) are an important cause of illness in humans and animals. Most human coronaviruses commonly cause relatively mild respiratory illnesses; however two zoonotic coronaviruses, SARS-CoV and MERS-CoV, can cause severe illness and death. Investigations over the past 35 years have illuminated many aspects of coronavirus replication. The focus of this review is the functional analysis of conserved RNA secondary structures in the 5 and 3 of the betacoronavirus genomes. The 5 350 nucleotides folds into a set of RNA secondary structures which are well conserved, and reverse genetic studies indicate that these structures play an important role in the discontinuous synthesis of subgenomic RNAs in the betacoronaviruses. These cis-acting elements extend 3 of the 5 UTR into ORF1a. The 3 UTR is similarly conserved and contains all of the cis-acting sequences necessary for viral replication. Two competing conformations near the 5 end of the 3 UTR have been shown to make up a potential molecular switch. There is some evidence that an association between the 3 and 5 UTRs is necessary for subgenomic RNA synthesis, but the basis for this association is not yet clear. A number of host RNA proteins have been shown to bind to the 5 and 3 cis-acting regions, but the significance of these in viral replication is not clear. Two viral proteins have been identified as binding to the 5 cis-acting region, nsp1 and N protein. A genetic interaction between nsp8 and nsp9 and the region of the 3 UTR that contains the putative molecular switch suggests that these two proteins bind to this region. 
 Title: The structure and functions of coronavirus genomic 3 and 5 ends
Output: False
Paragraph: Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV), replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs) were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200-300 nm), and ''vesicle packets'' apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virusinduced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this ''replication network'' will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions. Citation: Knoops K, Kikkert M, van den Worm SHE, Zevenhoven-Dobbe JC, van der Meer Y, et al. (2008) SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol 6(9): e226. 
 Title: SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum
Output: False
Paragraph: Recent years have seen several advances in our understanding of immunity to virus infection of the lower respiratory tract, including to influenza virus infection. Here, we review the cellular targets of viruses and the features of the host immune response that are unique to the lungs. We describe the interplay between innate and adaptive immune cells in the induction, expression and control of antiviral immunity, and discuss the impact of the infected lung milieu on moulding the response of antiviral effector T cells. Recent findings on the mechanisms that underlie the increased frequency of severe pulmonary bacterial infections following respiratory virus infection are also discussed. Viruses are highly evolved and ubiquitous pathogens. Although infection with many viruses results in a mild, self-limited disease, other viruses can produce severe and frequently fatal infections. The respiratory tract is a major portal through which viruses enter to initiate infection. Whereas some viruses can initiate infection in the respiratory tract and then disseminate to other sites in the body, other viruses typically remain localized to the respiratory tract, where they replicate and induce tissue injury (see Supplementary information S1 (table)). Various defence mechanisms have evolved in the respiratory tract to prevent and control infection by viruses and other pathogens. The respiratory tract can be divided anatomically into the upper respiratory tract (including the nose, mouth and pharynx) and the lower respiratory tract (which consists of the trachea, bronchi and lungs), with the lymphoid tissue of Waldeyer's ring (including the pharyngeal and palatine tonsils) representing the line of demarcation. Because of the crucial role of the lower respiratory tract in respiration, we limit the focus of this Review to recent advances in our understanding of the host immune response to virus infection at this site. 
 Title: Regulating the adaptive immune response to respiratory virus infection NIH Public Access
Output: True
Paragraph: High temperature only associated with influenza A occurrence. High diurnal temperature range (DTR) causes more influenza A cases. Low DTR causes more influenza B cases. High DTR and low temperature were the key drivers for influenza A and B separately. g r a p h i c a l a b s t r a c t X-axis: The value of climate variable; Y-axis: 2-weeks lagged cumulative relative risk (RR), indicating the number of times more likely to have influenza compared to reference value (Ref); Solid line: RR value; Grey shadow: 95% confidence interval (95% CI). Most previous studies focused on the association between climate variables and seasonal influenza activity in tropical or temperate zones, little is known about the associations in different influenza types in subtropical China. The study aimed to explore the associations of multiple climate variables with influenza A (Flu-A) and B virus (Flu-B) transmissions in Shanghai, China. Weekly influenza virus and climate data (mean temperature (MeanT), diurnal temperature range (DTR), relative humidity (RH) and wind velocity (Wv)) were collected between June 2012 and December 2018. Generalized linear models (GLMs), distributed lag non-linear models (DLNMs) and regression tree models were developed to assess such associations. MeanT exerted the peaking risk of Flu-A at 1.4°C (2-weeks' cumulative relative risk (RR): 14.88, 95% confidence interval (CI): 8.67-23.31) and 25.8°C (RR: 12.21, 95%CI: 6.64-19.83), Flu-B had the peak at 1. 4°C (RR: 26.44,). The highest RR of Flu-A was 23.05 (95%CI: 5.12-88.45) at DTR of 15.8°C, that of Flu-B was 38.25 (95%CI: 15.82-87.61) at 3.2°C. RH of 51.5% had the highest RR of Flu-A (9.98, 95%CI: 4.03-26.28) and Flu-B (4.63, 95%CI: 1.95-11.27). Wv of 3.5 m/s exerted the peaking RR of Flu-A (7.48, 95%CI: 2.73-30.04) and . DTR 12°C and MeanT <22°C were the key drivers for Flu-A and Flu-B, separately. The study found j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l oc a t e / s c i t o t e n v complex non-linear relationships between climate variability and different influenza types in Shanghai. We suggest the careful use of meteorological variables in influenza prediction in subtropical regions, considering such complex associations, which may facilitate government and health authorities to better minimize the impacts of seasonal influenza. 
 Title: The complex associations of climate variability with seasonal influenza A and B virus transmission in subtropical Shanghai, China
Output: False
Paragraph: Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion. Citation: Burkard C, Verheije MH, Wicht O, van Kasteren SI, van Kuppeveld FJ, et al. (2014) Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner. PLoS Pathog 10(11): e1004502. 
 Title: Coronavirus Cell Entry Occurs through the Endo-/ Lysosomal Pathway in a Proteolysis-Dependent Manner
Output: True
Paragraph: Background: The risk of healthcare-acquired infection increases during outbreaks of novel infectious diseases. Emergency department (ED) clinicians are at high risk of exposure to both these and common communicable diseases. Personal protective equipment (PPE) is recommended to protect clinicians from acquiring, or becoming vectors of, infection, yet compliance is typically sub-optimal. Little is known about factors that influence use of PPE-specifically gloves and masks-during routine care in the ED. Methods: This was an ethnographic study, incorporating documentation review, field observations and interviews. The theoretical domains framework (TDF) was used to aid thematic analysis and identify relevant enablers of and barriers to optimal PPE use. Results: Thirty-one behavioural themes were identified that influenced participants' use of masks and gloves. There were significant differences, namely: more reported enablers of glove use vs more barriers to mask use. Reasons included more positive unit culture towards glove use, and lower perception of risk via facial contamination. Conclusion: Emerging infectious diseases, spread (among other routes) by respiratory droplets, have caused global outbreaks. Emergency clinicians should ensure that, as with gloves, the use of masks is incorporated into routine cares where appropriate. Further research which examines items of PPE independently is warranted. (R. Barratt). severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and pandemic influenza A [2]. Healthcareassociated transmission of these viral infections, into previously unaffected communities, was a key feature of the early stages of, for example, SARS in Toronto and MERS in Seoul [3, 4] . A notable feature of both outbreaks was the high proportion of those affected who were healthcare workers, with reports of up to 27% and 57% for MERS and SARS, respectively [5] . First responders and emergency department (ED) clinicians are at high risk of exposure to both common and emerging communicable diseases of high consequence, as they are in close contact with symptomatic patients before a diagnosis is made [5] [6] [7] . For example, ED staff are among 
 Title: ARTICLE IN PRESS G Model Enablers of, and barriers to, optimal glove and mask use for routine care in the emergency department: an ethnographic study of Australian clinicians
Output: True
Paragraph: Serum and CSF specimens from clinically healthy Brown Norway (BN) rats inoculated intracerebrally with corona virus JHM were analysed with respect to the state of the blood-brain barrier (BBB) and the intrathecal synthesis and isoelectric distribution of immunoglobulins (Ig). Increased CSF/serum ratios for Ig in the context of an intact BBB were never seen in the absence of intrathecal synthesis of virus-specific antibodies. Affinity-mediated immunoblot analysis revealed a broad pattern of virus-specific antibodies with embedded clusters of restricted heterogeneity, but no signs of oligoclonal Ig production carrying non-viral specificity. From these data it was concluded that BN rats do control the intracerebral spread of JHM virus effectively by a strong local virus-specific antibody response, thereby preventing a clinically apparent disease. 
 Title: Analysis of the intrathecal humoral immune response in Brown Norway (BN) rats, infected with the murine coronavirus JHM
Output: False