niryuu/sni-each-converted huggingface dataset:
Paragraph: Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity. 
 Title: Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?
Output: True
Paragraph: Orange JS, Du W and Falsey AR (2015) Therapeutic immunoglobulin selected for high antibody titer to RSV also contains high antibody titers to other respiratory viruses. Specific antibodies against infections most relevant to patients with primary immunodeficiency diseases are not routinely evaluated in commercial polyclonal immunoglobulin preparations. A polyclonal immunoglobulin prepared from plasma of donors having high neutralizing antibody titers to respiratory syncytial virus (RSV) was studied for the presence of antibody titers against seven additional respiratory viruses. While donors were not selected for antibody titers other than against RSV, the immunoglobulin preparation had significantly higher titers to 6 of 7 viruses compared to those present in 10 commercially available therapeutic immunoglobulin products (p ≤ 0.01 to p ≤ 0.001). To consider this as a donor-specific attribute, 20 random donor plasma samples were studied individually and identified a significant correlation between the RSV antibody titer and other respiratory virus titers: donors with high RSV titers were more likely to have higher titers to other respiratory viruses. These findings suggest either some humoral antiviral response bias or more frequent viral exposure of certain individuals. 
 Title: Therapeutic immunoglobulin selected for high antibody titer to RSV also contains high antibody titers to other respiratory viruses
Output: False
Paragraph: Background: Infectious disease surveillance is a process the product of which reflects both actual disease trends and public awareness of the disease. Decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities are all influenced by the information environment, which changes constantly. Biases are therefore imbedded in surveillance systems; these biases need to be characterized to provide better situational awareness for decision-making purposes. Our goal is to develop a statistical framework to characterize influenza surveillance systems, particularly their correlation with the information environment. Methods: We identified Hong Kong influenza surveillance data systems covering healthcare providers, laboratories, daycare centers and residential care homes for the elderly. A Bayesian hierarchical statistical model was developed to examine the statistical relationships between the influenza surveillance data and the information environment represented by alerts from HealthMap and web queries from Google. Different models were fitted for non-pandemic and pandemic periods and model goodness-of-fit was assessed using common model selection procedures. Results: Some surveillance systemsespecially ad hoc systems developed in response to the pandemic flu outbreakare more correlated with the information environment than others. General practitioner (percentage of influenza-like-illness related patient visits among all patient visits) and laboratory (percentage of specimen tested positive) seem to proportionally reflect the actual disease trends and are less representative of the information environment. Surveillance systems using influenza-specific code for reporting tend to reflect biases of both healthcare seekers and providers. Conclusions: This study shows certain influenza surveillance systems are less correlated with the information environment than others, and therefore, might represent more reliable indicators of disease activity in future outbreaks. Although the patterns identified in this study might change in future outbreaks, the potential susceptibility of surveillance data is likely to persist in the future, and should be considered when interpreting surveillance data. 
 Title: Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data
Output: True
Paragraph: The receptors for the hemagglutinating encephalomyelitis virus (HEV, a porcine coronavirus) on chicken erythrocytes were analyzed and compared to the receptors for bovine coronavirus (BCV) and influenza C virus. Evidence was obtained that HEV requires the presence of N-acetyl-9-0-acetylneuraminic acid (Neu5,9Ac,) on the cell surface for agglutination of erythrocytes as has been previously shown for BCV and influenza C virus: (i) Incubation of red blood cells with sialate 9-0acetylesterase, the receptor-destroying enzyme of influenza C virus, rendered the erythrocytes resistant against agglutination by each of the three viruses; (ii) Human erythrocytes which are resistant to agglutination by HEV acquire receptors for HEV after resialylation with Neu5,9Ac,. Sialylation of red 'blood cells with limiting amounts of sialic acid indicated that strain JHB/1/66 of influenza C virus requires less Neu5,9Ac, for agglutination of erythrocytes than the two coronaviruses, both of which were found to be similar in their reactivity with Neu5,9Ac,-containing receptors. 
 Title: Hemagglutinating encephalomyelitis virus attaches to IV-acetyl-9-O-acetylneuraminic acid-containing receptors on erythrocytes: comparison with bovine coronavirus and influenza C virus
Output: False
Paragraph: Background: Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis. To detect RVF virus (RVFV) infection, indirect immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme linked immunosorbent assays (ELISAs) which utilize recombinant RVFV nucleocapsid (RVFV-N) protein as assay antigen, have reportedly been used, however, there is still a need to develop more sensitive and specific methods of detection. Methods: RVFV-N protein was expressed in Escherichia coli (E. coli) and purified by histidine-tag based affinity chromatography. This recombinant RVFV-N (rRVFV-N) protein was then used as antigen to develop an IgG sandwich ELISA and IgM capture ELISAs for human sera. Ninety six serum samples collected from healthy volunteers during the RVF surveillance programme in Kenya in 2013, and 93 serum samples collected from RVF-suspected patients during the 2006-2007 RVF outbreak in Kenya were used respectively, to evaluate the newly established rRVFV-N protein-based IgG sandwich ELISA and IgM capture ELISA systems in comparison with the inactivated virus-based ELISA systems. Results: rRVFV-N protein-based-IgG sandwich ELISA and IgM capture ELISA for human sera were established. Both the new ELISA systems were in 100% concordance with the inactivated virus-based ELISA systems, with a sensitivity and specificity of 100%. Conclusions: Recombinant RVFV-N is a safe and affordable antigen for RVF diagnosis. Our rRVFV-N-based ELISA systems are safe and reliable tools for diagnosis of RVFV infection in humans and especially useful in large-scale epidemiological investigation and for application in developing countries. 
 Title: Comparison of enzyme-linked immunosorbent assay systems using rift valley fever virus nucleocapsid protein and inactivated virus as antigens
Output: True
Paragraph: The avian influenza virus H5N1 and the 2009 swine flu H1N1 are potentially serious pandemic threats to human health, and air travel readily facilitates the spread of infectious diseases. However, past studies have not yet incorporated the effects of air travel on the transmission of influenza in the construction of mathematical epidemic models. Therefore, this paper focused on the human-to-human transmission of influenza, and investigated the effects of air travel activities on an influenza pandemic in a small-world network. These activities of air travel include passengers' consolidation, conveyance and distribution in airports and flights. Dynamic transmission models were developed to assess the expected burdens of the pandemic, with and without control measures. This study also investigated how the small-world properties of an air transportation network facilitate the spread of influenza around the globe. The results show that, as soon as the influenza is spread to the top 50 global airports, the transmission is greatly accelerated. Under the constraint of limited resources, a strategy that first applies control measures to the top 50 airports after day 13 and then soon afterwards to all other airports may result in remarkable containment effectiveness. As the infectiousness of the disease increases, it will expand the scale of the pandemic, and move the start time of the pandemic ahead. 
 Title: Transmission and control of an emerging influenza pandemic in a small-world airline network
Output: False
Paragraph: A reversed passive hemagglutination (I~PHA) method was developed for the detection of bovine eoronavirus in fecal specimens. Sheep erythrocytes fixed with glutaraldehyde, and then treated with tannic acid were coated with anti-bovine coronavirus rabbit antibodies purified by affinity chromatography using bovine eoronavirus linked to Sepharose 4B. The RPHA test was carried out by a microtiter method. Erythrocytes coated with purified specific antibodies were agglutinated by bovine coronavirus, but not by bovine rotavirus or enterovirus. The reaction was inhibited by antiserum to bovine coronavirus, confirming the specificity of the reaction. The I~PIIA test detected bovine coronavirus in 13 of 22 fecal specimens (59 per cent), from natural cases of diarrhea, while the positive rates were only 14 per cent (3/22) and 22 per cent (5/22) for immunofluorescent staining of primary cultures of calf kidney cells infected with the specimens, and immune electron microscopy respectively. The advantages of the I~PHA method are its simplicity, high sensitivity and rapidity. 
 Title: Archives of Virology Detection of Bovine Coronavirus in Feces by Reversed Passive Hemagglutination
Output: True
Paragraph: Background. Precision public health is a state-of-the-art concept in public health research and its application in health care. Application of information technology in field of epidemiology paves the way to its transformation to digital epidemiology. A geospatial epidemiological model was simulated to estimate the spread of Ebola virus disease after a hypothetical outbreak in India. Methods. It was a simulation study based on SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. Simulation was done in Spatiotemporal Epidemiological Modeler (STEM). Epidemiological profile of Ebola virus, that transmitted throughout the Sierra Leon in 2014-2016, was fitted into the SEIR deterministic compartment model designed for India. 
 Title: A Simulation Study on Hypothetical Ebola Virus Transmission in India Using Spatiotemporal Epidemiological Modeler (STEM): A Way towards Precision Public Health
Output: False
Paragraph: Stable major histocompatibility complex (MHC) class I molecules at the cell surface consist of three separate, noncovalently associated components: the class I heavy chain, the b 2 -microglobulin light chain, and a presented peptide. These three components are assembled inside cells via complex pathways involving many other proteins that have been studied extensively. Correct formation of disulfide bonds in the endoplasmic reticulum is central to this process of MHC class I assembly. For a single specific peptide to be presented at the cell surface for possible immune recognition, between hundreds and thousands of peptide-containing precursor polypeptides are required, so the overall process is relatively inefficient. To increase the efficiency of antigen presentation by MHC class I molecules, and for possible therapeutic purposes, single-chain molecules have been developed in which the three, normally separate components have been joined together via flexible linker sequences in a single polypeptide chain. Remarkably, these single-chain MHC class I molecules fold up correctly, as judged by functional recognition by cells of the immune system, and more recently by X-ray crystallographic structural data. This review focuses on the interesting properties and potential of this new type of engineered MHC class I molecule. Antioxid. Redox Signal. 15, 645-655. 
 Title: Properties and Applications of Single-Chain Major Histocompatibility Complex Class I Molecules
Output: True
Paragraph: Background: Nucleoli are composed of possibly several thousand different proteins and represent the most conspicuous compartments in the nucleus; they play a crucial role in the proper execution of many cellular processes. As such, nucleoli carry out ribosome biogenesis and sequester or associate with key molecules that regulate cell cycle progression, tumorigenesis, apoptosis and the stress response. Nucleoli are dynamic compartments that are characterized by a constant flux of macromolecules. Given the complex and dynamic composition of the nucleolar proteome, it is challenging to link modifications in nucleolar composition to downstream effects. Results: In this contribution, we present quantitative immunofluorescence methods that rely on computer-based image analysis. We demonstrate the effectiveness of these techniques by monitoring the dynamic association of proteins and RNA with nucleoli under different physiological conditions. Thus, the protocols described by us were employed to study stress-dependent changes in the nucleolar concentration of endogenous and GFP-tagged proteins. Furthermore, our methods were applied to measure de novo RNA synthesis that is associated with nucleoli. We show that the techniques described here can be easily combined with automated high throughput screening (HTS) platforms, making it possible to obtain large data sets and analyze many of the biological processes that are located in nucleoli. Conclusions: Our protocols set the stage to analyze in a quantitative fashion the kinetics of shuttling nucleolar proteins, both at the single cell level as well as for a large number of cells. Moreover, the procedures described here are compatible with high throughput image acquisition and analysis using HTS automated platforms, thereby providing the basis to quantify nucleolar components and activities for numerous samples and experimental conditions. Together with the growing amount of information obtained for the nucleolar proteome, improvements in quantitative microscopy as they are described here can be expected to produce new insights into the complex biological functions that are orchestrated by the nucleolus. 
 Title: Computer-based fluorescence quantification: a novel approach to study nucleolar biology
Output: True
Paragraph: A tryptophan-rich octapeptide, C8 (Ac-Trp-Glu-Asp-Trp-Val-Gly-Trp-Ile-NH 2 ), modelled on the membrane-proximal external region of the feline immuno-deWciency virus (FIV) gp36 glycoprotein ectodomain, exhibits potent antiviral activity against FIV. A mechanism has been proposed by which the peptide, being positioned on the surface of the cell membrane, inhibits its fusion with the virus. In the present work, peptide-lipid interactions of C8 with dimyristoyl phosphatidylcholine liposomes are investigated using electron spin resonance spectroscopy of spin-labelled lipids. Three other peptides, obtained from modiWcations of C8, have also been investigated, in an attempt to clarify the essential molecular features of the interactions involving the tryptophan residues. The results show that C8 adsorbs strongly on the bilayer surface. Membrane binding requires not only the presence of the Trp residues in the sequence, but also their common orientation on one side of the peptide that is engendered by the WX 2 WX 2 W motif. Membrane interaction correlates closely with peptide antiviral activity, indicating that the membrane is essential in stabilizing the peptide conformation that will be able to inhibit viral infection. 
 Title: Interaction of short modiWed peptides deriving from glycoprotein gp36 of feline immunodeWciency virus with phospholipid membranes
Output: True
Paragraph: Healthcare-associated infections Purpose of review Environmental surfaces in healthcare facilities, particularly in a patient room, are a critical pathway for healthcare-associated pathogen transmission. Despite well-established guides and recommendations regarding environmental surface cleaning and disinfection, there are several challenges in resource-limited settings. This viewpoint article will discuss the practice of environmental cleaning in resource-limited settings including challenges and relationship between environment and healthcare-associated infections in this setting and outlines pre-requisites to overcome these challenges. Recent findings Despite several barriers and challenges, environmental cleaning is a crucial component to help reduce transmission of healthcare-associated infections and multidrug-resistant pathogens as well as emerging infectious disease-associated pathogens in resource-limited settings. However, there is a need to develop a multi-modal strategy together with a mechanism for monitor and feedback to improve the practices of environmental cleaning in resource-limited settings. Summary Additional researches on the barriers and implementation gaps and the role of collaborative network as well as how to apply technology would provide significant insights on the practices of environmental cleaning in resource-limited settings. 
 Title: Environmental Cleaning in Resource-Limited Settings
Output: False
Paragraph: Objective: To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. Methods: Residents $65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. Results: 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20-0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03-2.78) were predictive of respiratory viral infection. In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection. 
 Title: Immune Biomarkers Predictive of Respiratory Viral Infection in Elderly Nursing Home Residents
Output: True
Paragraph: The semi-Markov process often provides a better framework than the classical Markov process for the analysis of events with multiple states. The purpose of this paper is twofold. First, we show that in the presence of right censoring, when the right end-point of the support of the censoring time is strictly less than the right end-point of the support of the semi-Markov kernel, the transition probability of the semi-Markov process is nonidentifiable, and the estimators proposed in the literature are inconsistent in general. We derive the set of all attainable values for the transition probability based on the censored data, and we propose a nonparametric inference procedure for the transition probability using this set. Second, the conventional approach to constructing confidence bands is not applicable for the semi-Markov kernel and the sojourn time distribution. We propose new perturbation resampling methods to construct these confidence bands. Different weights and transformations are explored in the construction. We use simulation to examine our proposals and illustrate them with hospitalization data from a recent cancer survivor study. Multi-state stochastic processes provide a convenient framework for the analysis of event history data (Andersen et al., 1993; Commenges, 1999; Andersen and Keiding, 2002) . The semi-Markov model is a generalization of the classical homogeneous Markov model. It is preferred in many practical applications because it accommodates the dependence of transitions between states on the state durations (Andersen, Esbjerg, and Sorensen, 2000; Kang and Lagakos, 2007) . Suppose {S(t):t ≥ 0} is a finite-state stochastic process with state space ℰ = {1,…, r}. Denote its sequence of consecutive states by {J m :m = 0, 1, 2,…}, and let the corresponding transition times be {T m :m = 0, 1,…}. Without loss of generality, we assume T 0 = 0. Let X m = T m − T m−1 be the sojourn time of the mth transition. Then {S(t):t ≥ 0} is a homogeneous 
 Title: Estimation with Right-Censored Observations Under A Semi- Markov Model
Output: False
Paragraph: Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelopecoated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10 8 copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10 9 copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10 10 copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10 9 copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses. 
 Title: Sublingual Immunization of Trivalent Human Papillomavirus DNA Vaccine in Baculovirus Nanovector for Protection against Vaginal Challenge
Output: True
Paragraph: Multiple sclerosis (MS) is an inflammatory, demyelinating, central nervous system disease mediated by myelin-specific T cells. Environmental triggers that cause a breakdown of myelinspecific T cell tolerance are unknown. We found that CD8 + myelin basic protein (MBP)-specific T cell tolerance can be broken and autoimmunity induced by infection with a virus that does not express MBP cross-reactive epitopes and does not depend on bystander activation. Instead, the virus activated dual T cell receptor (TCR)-expressing T cells capable of recognizing both MBP and viral antigens. These results demonstrate the importance of dual TCR T cells in autoimmunity and suggest a mechanism by which a ubiquitous viral infection could trigger autoimmunity in a subset of infected individuals, as hypothesized in the etiology of MS. Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) that affects more than one million people worldwide. It is believed to be an autoimmune disease in which exposure of genetically predisposed individuals to environmental factors triggers a breakdown in T cell tolerance to myelin antigens. The specific types of myelin-specific T cells that contribute to the pathogenesis of MS are not known. Most studies have focused on the pathogenic role of myelin-specific CD4 + T cells because of the relatively strong association of MS susceptibility with major histocompatibility complex (MHC) class II alleles. In addition, CD4 + T cells are the primary effector T cells in experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS. However, there has been increasing recognition of the potential importance of CD8 + T cells in the pathogenesis of MS. CD8 + T cells typically outnumber CD4 + T cells in acute and chronic lesions in MS patients, and the CD8 + T cell subset exhibits more evidence of antigen-driven activation compared to CD4 + T cells in the CNS and blood of MS patients1, 2. The frequency of CNS antigen-specific CD8 + , but not CD4 + , using Power SYBR Green PCR Master Mix (Applied Biosystems). Tcra V α gene primers and a C α primer have been previously described50. Reactions were run in duplicate, and samples were normalized to the internal β actin control. All P values were calculated with a two-tailed Student's t-test. 
 Title: Viral Infection Triggers Central Nervous System Autoimmunity Via Activation of Dual TCR-Expressing CD8 + T Cells HHS Public Access Author manuscript
Output: False
Paragraph: Cardiotoxicity is a well-known side effect of doxorubicin (DOX), but the mechanisms leading to this phenomenon are still not completely clear. Prediction of drug-induced dysfunction onset is difficult and is still largely based on detection of cardiac troponin (cTn), a circulating marker of heart damage. In the last years, several investigations focused on the possible involvement of microRNAs (miRNAs) in DOX-induced toxicity in vitro, with contrasting results. Recently, several groups employed animal models to mimic patient's condition, investigate the biological pathways perturbed by DOX, and identify diagnostic markers of cardiotoxicity. We reviewed the results from several studies investigating cardiac miRNAs expression in rodent models of DOX-treatment. We also discussed the data from two publications indicating the possible use of circulating miRNA as biomarkers of DOX-induced cardiotoxicity. Unfortunately, limited information was derived from these studies, as selection methods of candidate-miRNAs and heterogeneity in cardiotoxicity assessment greatly hampered the novelty and robustness of the findings. Nevertheless, at least one circulating miRNA, miR-1, showed a good potential as early biomarker of drug-mediated cardiac dysfunction onset. The use of animal models to investigate DOX-induced cardiotoxicity surely helps narrowing the gap between basic research and clinical practice. Despite this, several issues, including selection of relevant miRNAs and less-than-optimal assessment of cardiotoxicity, greatly limited the results obtained so far. Nonetheless, the association of patients-based studies with the use of preclinical models may be the key to address the many unanswered questions regarding the pathophysiology and early detection of cardiotoxicity. 
 Title: Role of microRNAs in doxorubicin-induced cardiotoxicity: an overview of preclinical models and cancer patients
Output: True
Paragraph: Deubiquitylating enzymes or DUBs are a class of enzymes that selectively remove the polypeptide posttranslational modifi cation ubiquitin from a number of substrates. Approximately 100 DUBs exist in human cells and are involved in key regulatory cellular processes, which drive many disease states, making them attractive therapeutic targets. Several aspects of DUB biology have been studied through genetic knock-out or knock-down, genomic, or proteomic studies. However, investigation of enzyme activation and regulation requires additional tools to monitor cellular and physiological dynamics. A comparison between genetic ablation and dominant-negative target validation with pharmacological inhibition often leads to striking discrepancies. Activity probes have been used to profi le classes of enzymes, including DUBs, and allow functional and dynamic properties to be assigned to individual proteins. The ability to directly monitor DUB activity within a native biological system is essential for understanding the physiological and pathological role of individual DUBs. We will discuss the evolution of DUB activity probes, from in vitro assay development to their use in monitoring DUB activity in cells and in animal tissues, as well as recent progress and prospects for assessing DUB inhibition in vivo. 
 Title: Chapter 26 Monitoring Target Engagement of Deubiquitylating Enzymes Using Activity Probes: Past, Present, and Future
Output: False
Paragraph: Graphical Abstract Highlights d Binding to all influenza A subtypes neutralizing seasonal and pandemic strains d Utilizes a rare VH (VH6-1) and carries a low level of somatic mutations d Highly conserved epitope encompassing fusion peptide and hydrophobic groove d Superior therapeutic window compared to oseltamivir in animals Correspondence zhuq@medimmune.com (Q.Z.), john.skehel@crick.ac.uk (J.J.S.) In Brief Identification of a human monoclonal antibody that reacts effectively with all influenza A hemagglutinin subtypes paves the way for developing immunotherapy for people infected with the flu virus. Accession Numbers 5JW5 5JW4 5JW3 KX398429 KX398468 SUMMARY Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans. 
 Title: Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes Article Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes
Output: True
Paragraph: A rapid one-step reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay targeting the pol-integrase gene was developed to detect human immunodeficiency virus type 1 (HIV-1) group M. This HIV-1 RT-LAMP assay is simple and rapid, and amplification can be completed within 35 min under isothermal conditions at 60 • C. The 100% detection limit of HIV-1 RT-LAMP was determined using a standard strain (WHO HIV-1 [97/656]) in octuplicate and found to be 120 copies/ml. The RT-LAMP assay was evaluated for use for clinical diagnosis using plasma samples collected from 57 HIV-1-infected and 40 uninfected individuals in Cameroon, where highly divergent HIV-1 strains are prevalent. Of the 57 samples from infected individuals, 56 harbored group-M HIV-1 strains, such as subtypes A, B, G, F2, and circulating recombinant forms (CRFs) 01, 02, 09, 11, 13; all were RT-LAMP positive. One sample harboring group-O HIV-1 and the 40 HIV-1-uninfected samples were RT-LAMP negative. These findings indicate that HIV-1 RT-LAMP can detect HIV-1 group-M RNA from plasma samples rapidly and with high sensitivity and specificity. These data also suggest that this RT-LAMP assay can be useful for confirming HIV diagnosis, particularly in resource-limited settings. 
 Title: Rapid detection of human immunodeficiency virus type 1 group M by a reverse transcription-loop-mediated isothermal amplification assay
Output: True
Paragraph: Advances in biological sciences have outpaced regulatory and legal frameworks for biosecurity. Simultaneously, there has been a convergence of scientific disciplines such as synthetic biology, data science, advanced computing and many other technologies, which all have applications in health. For example, advances in cybercrime methods have created ransomware attacks on hospitals, which can cripple health systems and threaten human life. New kinds of biological weapons which fall outside of traditional Cold War era thinking can be created synthetically using genetic code. These convergent trajectories are dramatically expanding the repertoire of methods which can be used for benefit or harm. We describe a new risk landscape for which there are few precedents, and where regulation and mitigation are a challenge. Rapidly evolving patterns of technology convergence and proliferation of dual-use risks expose inadequate societal preparedness. We outline examples in the areas of biological weapons, antimicrobial resistance, laboratory security and cybersecurity in health care. New challenges in health security such as precision harm in medicine can no longer be addressed within the isolated vertical silo of health, but require cross-disciplinary solutions from other fields. Nor can they cannot be managed effectively by individual countries. We outline the case for new cross-disciplinary approaches in risk analysis to an altered risk landscape. Keywords Biosecurity · Cybersecurity · Terrorism · Disasters · Health intelligence Advances in biological sciences have occurred at a faster rate than changes in regulatory and legal frameworks for biosecurity. An equally profound change is the convergence of concepts and methods from scientific disciplines that were previously distinct and siloed. Innovations in genomics, synthetic biology, big data, computing science and many other technologies have applications in health and medicine. Equally important, these convergent trajectories are dramatically expanding the repertoire of dual-use technologies-those which can be harnessed for benefit or harm to humanity. Collectively, these trends are shaping a new landscape for systematic risk analysis, for which there are 
 Title: Converging and emerging threats to health security
Output: False
Paragraph: The infection by the new coronavirus (SARS-CoV-2) has taken the dimension of a pandemic, affecting more than 160 countries in a few weeks. In Colombia, despite the implementation of the rules established by the national government, exists an elevate concern both for mortality and for the limited capacity of the health system to respond effectively to the needs of patients infected. For Colombia, assuming a case fatality rate among people infected with SARS-CoV-2 of 0.6% (average data from the information reported for Latin American countries for March 18) (Table 1) , the number of deaths, in one or two weeks, could be 16 and 243, respectively. These estimates differ markedly from those documented in countries such as Spain and Italy, in which COVID-19 case fatality rates exceed 8% (case of Italy) and from the percentage of patients who have required intensive care, which has ranged from 9% to 11% of patients in Mediterranean European countries. These differences could be explained due to: a) the percentage of the population at risk (individuals older than 60 years); b) a higher epidemiological exposure to viral respiratory infections associated with more frequent exposure to them, due to geographic and climatic conditions; c) less spread of the virus by location in the tropical zone; and d) earlier preventive measures to contain the spread of SARS-CoV-2 infection. Therefore, it is possible to establish that the situation in this country will be different from in European Mediterranean and that Colombia could have different endpoints from Spain and Italy. * Corresponding author. Street 67 # 53 -108 Office 2-118, 
 Title: COVID-19 in Colombia endpoints. Are we different, like Europe?
Output: False
Paragraph: Waddlia chondrophila, an obligate intracellular bacterium of the Chlamydiales order, is considered as an agent of bovine abortion and a likely cause of miscarriage in humans. Its role in respiratory diseases was questioned after the detection of its DNA in clinical samples taken from patients suffering from pneumonia or bronchiolitis. To better define the role of Waddlia in both miscarriage and pneumonia, a tool allowing large-scale serological investigations of Waddlia seropositivity is needed. Therefore, enriched outer membrane proteins of W. chondrophila were used as antigens to develop a specific ELISA. After thorough analytical optimization, the ELISA was validated by comparison with micro-immunofluorescence and it showed a sensitivity above 85% with 100% specificity. The ELISA was subsequently applied to human sera to specify the role of W. chondrophila in pneumonia. Overall, 3.6% of children showed antibody reactivity against W. chondrophila but no significant difference was observed between children with and without pneumonia. Proteomic analyses were then performed using mass spectrometry, highlighting members of the outer membrane protein family as the dominant proteins. The major Waddlia putative immunogenic proteins were identified by immunoblot using positive and negative human sera. The new ELISA represents an efficient tool with high throughput applications. Although no association with pneumonia and Waddlia seropositivity was observed, this ELISA could be used to specify the role of W. chondrophila in miscarriage and in other diseases. 
 Title: Undressing of Waddlia chondrophila to enrich its outer membrane proteins to develop a new species-specific ELISA
Output: True
Paragraph: Background: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ,TNF-α and IL-10 for their associations with SARS. Results: IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility. Conclusion: IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility. 
 Title: BMC Infectious Diseases The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome
Output: True
Paragraph: Ubiquitin (Ub) and the ubiquitin-like modifier interferon stimulated gene 15 (ISG15) participate in the host defense of viral infections. Viruses, including the Severe Acute Respiratory Syndrome human coronavirus (SARS hCoV), have co-opted Ub/ISG15-conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub/ISG15conjugated host proteins. Here, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle Eastern Respiratory Syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that similar to SARS PLpro, MERS PLpro is both a deubiquitinating and a deISGylating enzyme. Further analysis of the intrinsic deubiquitinating enzyme (DUB) activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, while SARS PLpro prefers to cleave Lys48-linked polyUb chains. Second, MERS PLpro cleaves polyUb chains in a "mono-distributive" manner (one Ub at a time), and SARS PLpro prefers to cleave K48-linked poly-Ub chains by sensing a di-Ub moiety as a minimal recognition element using a "di-distributive" cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses. 
 Title: SARS hCoV papain-like protease is a unique Lys48 linkage- specific di-distributive deubiquitinating enzyme HHS Public Access
Output: True
Paragraph: The viral ribonucleoprotein complex of human immunodeficiency virus-1 (HIV-1) associates with the viral Envelope (Env) to form infectious virions. While Env and Gag are known to migrate to lipid microdomains, their stoichiometry and specificity of interaction is not known. Here, we analyze the association of different viral glycoproteins, HIV Env and Ebola GP, with HIV-1 Gag protein co-expressed in the same cell. Though these two viral spikes were both expressed, each associated independently with Gag and gave rise to two distinct virion populations, each with a spike of a single type. Confocal imaging demonstrated that HIV Env 89.6 and Ebola GP localized to distinct lipid raft microdomains within the same cell, where each associated with distinct Gag particles. Similar Env localization was observed in HIV-infected T cells, where ~14 percent of Env was associated with Gag during productive infection. Together, these data suggest that a single Gag complex associates "quantally" with an individual lipid raft microdomain to assemble functional virions during infection. 
 Title: Quantal formation of lentiviruses in cells: segregation of viral glycoproteins to lipid rafts that associate individually with HIV-1 Capsids
Output: True
Paragraph: Objective: We examined the relationship between hospital structural characteristics and system-level activities for patient safety and infection control, for use in designing an incentive structure to promote patient safety. Methods: This study utilized a questionnaire to collect institutional data about hospital infrastructure and volume of patient safety activities from all 1039 teaching hospitals in Japan. The patient safety activities were focused on meetings and conferences, internal audits, staff education and training, incident reporting and infection surveillance. Generalized linear modeling was used. Results: Of the 1039 hospitals surveyed, 418 (40.2%) hospitals participated. The amount of activities significantly increased by over 30% in hospitals with dedicated patient safety and infection control full-time staff (P < 0.001 and P < 0.01, respectively). High profit margins also predicted the increase of patient safety programs (P < 0.01). Perceived lack of administrative leadership was associated with reduced volume of activities (P < 0.05), and the economic burden of safety programs was found to be disproportionately large for small hospitals (P < 0.05). Conclusions: Hospitals with increased resources had greater spread of patient safety and infection control activities. To promote patient safety programs in hospitals, it is imperative that policy makers require the assignment of dedicated full-time staff to patient safety. Economic support for hospitals will also be required to assure that safety programs are sustainable. 
 Title: Factors associated with system-level activities for patient safety and infection control
Output: True
Paragraph: Respiratory viral infections cause mild to severe diseases, such as common cold, bronchiolitis and pneumonia and are associated with substantial burden for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human in vitro models are mandatory. MucilAir™, a human standardized air-liquid interface 3D airway epithelial culture holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules. The objective of this study was to test the relevance of such a model for the discovery and validation of antiviral drugs. Fully differentiated 3D nasal epithelium cultures were inoculated with picornaviruses, a coronavirus and influenza A viruses in the absence or in the presence of reference antiviral drugs. Results showed that, rupintrivir efficiently inhibits the replication of respiratory picornaviruses in a dose dependent manner and prevents the impairment of the mucociliary clearance. Similarly, oseltamivir reduced the replication of influenza A viruses in a dose dependent manner and prevented the impairment of the epithelial barrier function and cytotoxicity until 4 days of infection. In addition we found that Rhinovirus B14, C15 and influenza A(H1N1) induce significant increase of β Defensins 2 and Cathelicidin release with different time course. These results reveal that a large panel of epithelial functions is modified upon viral infection and validate MucilAir™ as a pertinent tool for pre-clinical antiviral drug testing. 
 Title: Antiviral drug screening by assessing epithelial functions and innate immune responses in human 3D airway epithelium model
Output: True
Paragraph: The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th , 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented. 
 Title: An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov)-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Output: True