niryuu/sni-each-converted huggingface dataset:
Paragraph: The development of safe and effective vaccines for the prevention and control of emerging and neglected infectious diseases is an international priority, as is the development of similar control measures for bioterrorist threats. International standards have been established to ensure the protection of human subjects and the scientific integrity of clinical trial study design and data collection. A general overview of the history of the regulatory guidelines and ethical principles underpinning the vaccine development process is provided, with an emphasis on clinical trials conducted in the United States. 157 The contemporary vaccine development process involves sequential assessment of safety, immunogenicity, and efficacy in phase1, 2, and 3 clinical trials. The process is not always linear or straightforward, and adaptive flexible clinical trial designs can increase the likelihood of a successful outcome. Because the efficacy of vaccines for a number of the diseases discussed in this volume cannot be tested directly in humans, alternative approaches have been developed to address this challenge. The major elements of typical clinical trial protocol are discussed, and a checklist of essential documents supporting the trial is provided. As novel vaccine approaches and technologies emerge, the regulatory and ethical considerations will need to be revisited and adapted to respond to the everchanging landscape. 
 Title: Clinical Trials of Vaccines for Biodefense and Emerging and Neglected Diseases 12 12 Introduction Historical Considerations Regulatory issues Ethical issues Stages of Vaccine Development Overview Pre-IND stage IND stage Phase 1 clinical trials Phase 2 clinical trials Phase 3 clinical trials Phase 4 clinical trials Clinical Trial Protocol Development Background and rationale Objectives and purpose Study design Study population Study agent/interventions Study procedures and evaluations Study schedule Assessment of safety Clinical monitoring Statistical considerations Quality management Ethics/protection of human subjects Data management and record keeping Other considerations II. FUNDAMENTAL ASPECTS OF VACCINOLOGY CLINICAL TRIALS OF VACCINES FOR BIODEFENSE AND EMERGING AND NEGLECTED DISEASES 158
Output: False
Paragraph: Background: Effective influenza pandemic management requires understanding of the factors influencing behavioral changes. We aim to determine the differences in knowledge, attitudes and practices in various different cohorts and explore the pertinent factors that influenced behavior in tropical Singapore. Methods: We performed a cross-sectional knowledge, attitudes and practices survey in the Singapore military from mid-August to early-October 2009, among 3054 personnel in four exposure groups -laboratory-confirmed H1N1-2009 cases, close contacts of cases, healthcare workers, and general personnel. Results: 1063 (34.8%) participants responded. The mean age was 21.4 (SE 0.2) years old. Close contacts had the highest knowledge score (71.7%, p = 0.004) while cases had the highest practice scores (58.8%, p < 0.001). There was a strong correlation between knowledge and practice scores (r = 0.27, p < 0.01) and knowledge and attitudes scores (r = 0.21, p < 0.01). The significant predictors of higher practice scores were higher knowledge scores (p < 0.001), Malay ethnicity (p < 0.001), exposure group (p < 0.05) and lower education level (p < 0.05). The significant predictors for higher attitudes scores were Malay ethnicity (p = 0.014) and higher knowledge scores (p < 0.001). The significant predictor for higher knowledge score was being a contact (p = 0.007). Knowledge is a significant influence on attitudes and practices in a pandemic, and personal experience influences practice behaviors. Efforts should be targeted at educating the general population to improve practices in the current pandemic, as well as for future epidemics. *Between patients, contacts, healthcare workers and general servicemen **Correlation is significant at the 0.05 level (2-tailed) † Correlation is significant at the 0.01 level (2-tailed) † † Corrected for age, sex, education, housing and ethnicity Yap et al. 
 Title: Knowledge, attitudes and practices towards pandemic influenza among cases, close contacts, and healthcare workers in tropical Singapore: a cross-sectional survey
Output: False
Paragraph: Background: Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are two coronaviruses with demonstrated potential to generate significant nosocomial outbreaks. In particular, MERS continues to pose a significant threat in the Middle East since 2012. Currently, no licensed vaccine or drug treatment is available to treat patients infected with either coronavirus. However, there are some MERS vaccines in the preclinical stage of development. We sought to evaluate the potential impact of targeted vaccination strategies for mitigating SARS and MERS outbreaks in healthcare settings using simple mathematical models and detailed historic transmission trees describing the progression of past nosocomial outbreaks of SARS and MERS. Results: Our findings suggest that vaccination strategies targeting patients and healthcare workers, which have been disproportionately affected during past outbreaks, and assuming two vaccination coverage levels at 50 and 75% have the potential to avert nearly 50% or more of MERS or SARS cases. Conclusion: Our modeling results informed by historic outbreak data for SARS and MERS suggest that vaccination strategies targeting patients could be an effective measure to mitigate and prevent outbreaks in the healthcare setting. 
 Title: Evaluating the potential impact of targeted vaccination strategies against severe acute respiratory syndrome coronavirus (SARS- CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks in the healthcare setting
Output: True
Paragraph: Isolation precautions are intended to minimize pathogen transmission and reduce hospital-acquired infections. More recently, the effectiveness of isolation precautions has been questioned because of increasing evidence of risks. These putative downsides are divided into a quantifiable monetary cost (i.e., a literal cost to the system) and clinically important but less easily quantifiable costs (i.e., "costs" to the patient). The authors also briefly review deisolation and alternatives to isolation. The present review is not arguing against appropriate isolation or precautions, simply that the authors consider both risks and benefits and disseminate up-to-date information. Their patient-focused goal is to mitigate risks for those who truly need isolating and to end isolation as soon as it is safe and appropriate to do so. "Isolation is the sum total of wretchedness to a man." Thomas Carlyle (1800s Scottish Philosopher) Hindawi Publishing Corporation 
 Title: Patient Isolation Precautions: Are They Worth It?
Output: False
Paragraph: Background: V(D)J recombination takes place during lymphocyte development to generate a large repertoire of T-and B-cell receptors. Mutations in recombination-activating gene 1 (RAG1) and RAG2 result in loss or reduction of V(D) J recombination. It is known that different mutations in RAG genes vary in residual recombinase activity and give rise to a broad spectrum of clinical phenotypes. Objective: We sought to study the immunologic mechanisms causing the clinical spectrum of RAG deficiency. Methods: We included 22 patients with similar RAG1 mutations (c.519delT or c.368_369delAA) resulting in N-terminal truncated RAG1 protein with residual recombination activity but presenting with different clinical phenotypes. We studied precursor B-cell development, immunoglobulin and T-cell receptor repertoire formation, receptor editing, and B-and T-cell numbers. Results: Clinically, patients were divided into 3 main categories: T 2 B 2 severe combined immunodeficiency, Omenn syndrome, and combined immunodeficiency. All patients showed a block in the precursor B-cell development, low B-and T-cell numbers, normal immunoglobulin gene use, limited B-and T-cell repertoires, and slightly impaired receptor editing. Conclusion: This study demonstrates that similar RAG mutations can result in similar immunobiological effects but different clinical phenotypes, indicating that the level of residual recombinase activity is not the only determinant for clinical outcome. We postulate a model in which the type and moment of antigenic pressure affect the clinical phenotypes of these patients. (J Allergy Clin Immunol 2014;133:1124-33.)  
 Title: Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes
Output: False
Paragraph: Risk communication guidelines widely used in public health are based on the psychometric paradigm of risk, which focuses on risk perception at the level of individuals. However, infectious disease outbreaks and other public health emergencies are more than public health events and occur in a highly charged political, social and economic environment. This study examines other sociological and cultural approaches from scholars such as Ulrich Beck and Mary Douglas for insights on how to communicate in such environments. It recommends developing supplemental tools for outbreak communication to deal with issues such as questions of blame and fairness in risk distribution and audiences who do not accept biomedical explanations of disease. Une traduction en français de ce résumé figure à la fin de l'article. Al final del artículo se facilita una traducción al español. ‫املقالة.‬ ‫لهذه‬ ‫الكامل‬ ‫النص‬ ‫نهاية‬ ‫يف‬ ‫الخالصة‬ ‫لهذه‬ ‫العربية‬ ‫الرتجمة‬ 
 Title: Policy & practice Risk and outbreak communication: lessons from alternative paradigms
Output: False
Paragraph: To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion. Seven days post-permanent ligation, hearts from CD13 knockout (CD13 KO ) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13 KO infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13. Cardiac myocytes of CD13 KO mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling. Conversely, immunohistochemical and flow cytometric analysis of CD13 KO infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking. Accordingly, CD13 KO infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling. In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing. --- 
 Title: CD13 is essential for inflammatory trafficking and infarct healing following permanent coronary artery occlusion in mice
Output: True
Paragraph: The SNP rs12252-C allele alters the function of interferon-induced transmembrane protein-3 increasing the disease severity of influenza virus infection in Caucasians, but the allele is rare. However, rs12252-C is much more common in Han Chinese. Here we report that the CC genotype is found in 69% of Chinese patients with severe pandemic influenza A H1N1/09 virus infection compared with 25% in those with mild infection. Specifically, the CC genotype was estimated to confer a sixfold greater risk for severe infection than the CT and TT genotypes. More importantly, because the risk genotype occurs with such a high frequency, its effect translates to a large population-attributable risk of 54.3% for severe infection in the Chinese population studied compared with 5.4% in Northern Europeans. Interferon-induced transmembrane protein-3 genetic variants could, therefore, have a strong effect of the epidemiology of influenza in China and in people of Chinese descent. 
 Title: ARTICLE Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals
Output: True
Paragraph: 2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus. 
 Title: Structure analysis of the receptor binding of 2019-nCoV
Output: False
Paragraph: The Ebola virus disease outbreak in West Africa and the Middle East Respiratory Syndrome outbreak in the Republic of Korea have given huge impacts in different aspects. Health security is no more a new coinage. Global health security became more realistic in its practical application. In the perspective of global health, it will be helpful to peruse lessons learned from the Ebola outbreak in West Africa and MERS outbreak in Korea. Global Health Security S27 
 Title: Ministry of Health and Welfare
Output: False
Paragraph: Contact precautions are widely recommended to prevent multidrug-resistant organism (MDRO) transmission. However, conflicting data exist regarding their effectiveness. Prior systematic reviews examined contact precautions as part of a larger bundled approach, limiting ability to understand their effectiveness. The aim of this review was to characterize the effectiveness of contact precautions alone against transmission of any MDRO among adult acute care patients. Directed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, comprehensive searches of four electronic scientific literature databases were conducted for studies published in English from January 2004 to June 2014. Studies were included if interventional, original research, evaluating contact isolation precautions against MDRO transmission among inpatients. Searches returned 284 studies, six of which were included in the review. These studies measured four different MDROs with one study showing a reduction in transmission. Whereas studies were of high quality regarding outcome operationalization and statistical analyses, overall quality was moderate to low due to poor intervention description, population characterization and potential biases. Where compliance was measured (N ¼ 4), it presented a threat to validity because it included select parts of the intervention, ranged from 21% to 87%, and was significantly different across study phases (N ¼ 2). The poor quality of evidence on this topic continues to limit interpretation of these data. Hence, this conflicting body of literature does not constitute evidence for or against contact precautions. We recommend that researchers consider power calculation, compliance monitoring, nonequivalent concurrent controls when designing future studies on this topic. 
 Title: Effectiveness of contact precautions against multidrug- resistant organism transmission in acute care: a systematic review of the literature
Output: True
Paragraph: Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe, and Asia1,2 since its re-emergence in Kenya in 2004. The severity of disease and spread of this epidemic virus present a serious public health threat in the absence of vaccines or anti-viral therapies. Here, we describe a novel vaccine that protects against emerging CHIKV infection of non-human primates (NHP). We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from different CHIKV strains. Monkeys immunized with VLPs produced high titer neutralizing antibodies that protected against viremia after high dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, establishing a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans. Chikungunya virus (CHIKV), a mosquito-borne alphavirus in the family Togaviridae, was first isolated in Tanzania in 19523. Infection by this virus in humans is characterized by rash, high fever and, its hallmark feature, severe arthritis that can persist for years1,2. An epidemic strain of CHIKV appeared on Reunion Island in 2005 and has since spread to more than 18 countries4 (see also http://www.cdc.gov/ncidod/dvbid/chikungunya/ CH_GlobalMap.html). Dissemination of this epidemic virus is associated with genetic mutations that facilitate adaptation to a new insect vector, the Asian tiger mosquito, Aedes 
 Title: designed the research studies
Output: True
Paragraph: In this study, we document a case of phenobarbital-induced anticonvulsant hypersensitivity syndrome (AHS), which has been rarely reported in veterinary medicine. A 2-yearold, 5.4 kg, neutered male Russian Blue cat was diagnosed with idiopathic epilepsy and started on phenobarbital treatment. Eight days after initiation of phenobarbital treatment, the cat showed tachypnea and hyperthermia. CBC and serum biochemistry were unremarkable. However, the patient showed high serum amyloid A (SAA). On abdominal ultrasonography, generalized enlargement of abdominal lymph nodes and splenic multiple hypo-echoic nodules, which were consistent with reactive lymphadenopathy were found. The cat was diagnosed with AHS, and phenobarbital was discontinued. After 10 days of cessation, the patient had normal SAA, and clinical signs were resolved. 
 Title: Phenobarbital-induced anticonvulsant hypersensitivity syndrome in a cat
Output: False
Paragraph: The Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS). A large number of HIV-1-related studies are based on three non-human model animals: chimpanzee, rhesus macaque, and mouse. However, the differences in host-HIV-1 interactions between human and these model organisms have remained unexplored. 
 Title: BMC Microbiology CAPIH: A Web interface for comparative analyses and visualization of host-HIV protein-protein interactions
Output: False
Paragraph: We would like to dedicate the article to Dr. Linda Brodsky (1952e2014) who spent her entire professional life at the Women and Children's Hospital of Buffalo working to improve the lives of children with airway disease. We would also like to acknowledge Dr. Brodsky's contribution to the standardization of tonsil size in airway obstruction. Respiratory virus Tonsil Adenoid Sleep-disordered breathing Obstructive sleep apnea Tonsil and adenoid hypertrophy Airway obstruction Recombinant adenovirus a b s t r a c t Background: Airway obstruction due to enlargement of tonsils and adenoids is a common pediatric problem resulting in sleep disordered breathing. The cause for the relatively abnormal growth of tonsils and adenoids is poorly understood. Methods: Non-acutely ill children undergoing tonsillectomy and adenoidectomy (T&A) for various reasons were enrolled prospectively in a study to determine the frequency of asymptomatic respiratory viral infections in each lymphoid tissue and to relate the number and types of virus to the degree of airway obstruction. Molecular techniques were used to detect 9 respiratory viruses while Brodsky scores and measurements of percentages airway obstruction were used to estimate the degree of airway compromise due to the tonsil and adenoid, respectively. Results: Viruses were detected in 70.9% of tonsils and 94.7% of adenoids, p < 0.001. Adenovirus was the most common virus detected at 71.1%. Adenoids had an average of 2.4 viruses compared to 0.92 for tonsils, p < 0.001. Higher Brodsky scores were only associated with EBV in tonsils, p ¼ 0.03, while greater percentages of airway obstruction in the adenoids were associated with adenovirus, EBV, corona virus, parainfluenza virus and rhinovirus, p 0.005. Conclusions: Asymptomatic viral infections are common and directly related to the degree of airway obstruction significantly more often in adenoids than tonsils. 
 Title: The ubiquity of asymptomatic respiratory viral infections in the tonsils and adenoids of children and their impact on airway obstruction
Output: True
Paragraph: The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and 78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003 (9.40 ± 7.83)% to 2004 (3.20 ± 4.78)% (P < 0.001) and remained stable thereafter until 2018 (4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio (FEV 1 /FVC %, t = 2.21, P = 0.04) and mid-flow of maximum expiration (FEF 25%-75% , t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 20.23)% (P = 0.000 2), then declined slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible. Bone Research (2020) 8:8 ; https://doi. 
 Title: Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study
Output: True
Paragraph: We describe an evidence-based approach to enhancing the resilience of healthcare workers in preparation for an influenza pandemic, based on evidence about the stress associated with working in healthcare during the SARS outbreak. SARS was associated with significant long-term stress in healthcare workers, but not with increased mental illness. Reducing pandemic-related stress may best be accomplished through interventions designed to enhance resilience in psychologically healthy people. Applicable models to improve adaptation in individuals include Folkman and Greer's framework for stress appraisal and coping along with psychological first aid. Resilience is supported at an organizational level by effective training and support, development of material and relational reserves, effective leadership, the effects of the characteristics of "magnet hospitals," and a culture of organizational justice. Evidence supports the goal of developing and maintaining an organizational culture of resilience in order to reduce the expected stress of an influenza pandemic on healthcare workers. This recommendation goes well beyond the provision of adequate training and counseling. Although the severity of a pandemic is unpredictable, this effort is not likely to be wasted because it will also support the health of both patients and staff in normal times. 
 Title: Applying the Lessons of SARS to Pandemic Influenza An Evidence-based Approach to Mitigating the Stress Experienced by Healthcare Workers
Output: True
Paragraph: Are pathogens in outdoor air a health issue at present or will they become a problem in the future? A working group called AirPath -Outdoor Environments and Human Pathogens in Air was set up in 2007 at University College London, UK with the aim of opening new discussion and creating a research network to investigate the science and impacts of outdoor pathogens. Our objective in this paper is to review and discuss the following areas: What is the source of human pathogens in outdoor air? What current, developing and future techniques do we need? Can we identify at-risk groups in relation to their activities and environments? How do we prepare for the anticipated challenges of environmental change and new and emerging diseases? And how can we control for and prevent pathogens in outdoor environments? We think that this work can benefit the wider research community and policy makers by providing a concise overview of various research aspects and considerations which may be important to their work. 
 Title: Environmental Health Outdoor environments and human pathogens in air
Output: False
Paragraph: Background. Human bocavirus (HBoV) was recently discovered in children with respiratory tract disease and gastroenteritis. The causative role of HBoV in human gastroenteritis remains uncertain, and, to our knowledge, no previous case-control study has studied the relationship between HBoV and gastroenteritis. Methods. We conducted a case-control study that examined stool samples from 397 children with diarrhea and from 115 asymptomatic control subjects. HBoV was detected using polymerase chain reaction. Real-time polymerase chain reaction was used to quantify the HBoV loads in case and control groups. Common enteric viruses were examined using enzyme-linked immunosorbent assays, polymerase chain reaction, and reverse-transcription polymerase chain reaction. Results. At least 1 viral agent was discovered in 60.2% of cases. HBoV was detected in 14 samples, and 9 were coinfected with either rotavirus (7 of 14 samples) or human calicivirus (2 of 14). Many (8 [57.1%] of 14) of the HBoV infections occurred during September-December 2006. Most (12 [85.7%]) of the HBoV-infected children were 7-18 months of age. The percentage of children with HBoV infection did not differ significantly between case patients and control subjects (3.5% vs. 3.5%), and the statistical analysis did not support a correlation between HBoV infection and more-severe clinical symptoms. The viral load differences between the 2 groups were not statistically significant ( , by log-normal Student's t test). In addition, the VP1/VP2 partial gene of HBoV P p .09 from case patients and control subjects showed minimal sequence variation. A single genetic lineage of HBoV was revealed in persons in China. Despite its high prevalence in stool samples, our study does not support a causative role of HBoV in gastroenteritis. 
 Title: Human Bocavirus in Children Hospitalized for Acute Gastroenteritis: A Case-Control Study
Output: True
Paragraph: Objectives To investigate the occurrence of respiratory pathogens in samples from children with and without respiratory symptoms and to identify whether age and/ or coinfections modify the impact of respiratory pathogens on symptoms. Study design In a prospective longitudinal study, 18 children were sampled biweekly for respiratory pathogens, irrespective of respiratory symptoms. Polymerase chain reaction was performed for 13 respiratory pathogens. Episodes were defined "asymptomatic" if no symptoms of any respiratory tract illness were present between 1 week before and 1 week after sampling. Results A total of 230 samples were collected. In 56% of the symptomatic episodes, a pathogen was detected, compared with 40% of the asymptomatic episodes (P ‫؍‬ .03). Rhinovirus and coronaviruses were most prevalent in both symptomatic and asymptomatic episodes. In the youngest children, 9% of the pathogen-positive episodes were asymptomatic, compared with 36% in the oldest children (P ‫؍‬ .01). Multiple pathogens were found in 17% of the symptomatic episodes and in 3% of the asymptomatic episodes (P ‫؍‬ .02). Respiratory pathogens are frequently detected in samples from children with no respiratory symptoms. Symptomatic cases occurred more often in younger children and with detections of more than 1 respiratory pathogen. (J Pediatr 2009;154:396-400) PCR Polymerase chain reaction RSV Respiratory syncytial virus From the Divisions of Respiratory Diseases (M.vdZ., B.vE., C.vdE.) and Infectious Diseases (T.W.), 
 Title: Respiratory Pathogens in Children with and without Respiratory Symptoms
Output: True
Paragraph: Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDAapproved drug could rapidly be deployed during future outbreaks. Filovirus outbreaks occur sporadically, but with increasing frequency. With no current approved filovirus therapeutics, the 2014 Makona Ebola virus epidemic in Guinea, Sierra PLOS Pathogens | 
 Title: Interferon-γ Inhibits Ebola Virus Infection
Output: True
Paragraph: The demands of structural and functional genomics for large quantities of soluble, properly folded proteins in heterologous hosts have been aided by advancements in the Weld of protein production and puriWcation. Escherichia coli, the preferred host for recombinant protein expression, presents many challenges which must be surmounted in order to over-express heterologous proteins. These challenges include the proteolytic degradation of target proteins, protein misfolding, poor solubility, and the necessity for good puri-Wcation methodologies. Gene fusion technologies have been able to improve heterologous expression by overcoming many of these challenges. The ability of gene fusions to improve expression, solubility, puriWcation, and decrease proteolytic degradation will be discussed in this review. The main disadvantage, cleaving the protein fusion, will also be addressed. Focus will be given to the newly described SUMO fusion system and the improvements that this technology has advanced over traditional gene fusion systems.  
 Title: SUMO fusion technology for diYcult-to-express proteins
Output: False
Paragraph: Background Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. Method Three respiratory clinical samples were tested on welldifferentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air-liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. Results Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). Conclusion We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates. 
 Title: Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses
Output: False
Paragraph: Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 59-end triphosphate-a signature of certain viral and bacterial transcripts-confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNA Phe and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA Phe do not, nor do a variety of base-or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA Phe in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA Leu , which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity. 
 Title: Native Tertiary Structure and Nucleoside Modifications Suppress tRNA's Intrinsic Ability to Activate the Innate Immune Sensor PKR
Output: False
Paragraph: | The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. www.nature.com/reviews/genetics 
 Title: Natural selection and infectious disease in human populations
Output: True
Paragraph: Bovine coronaviruses (BCoVs) isolated in Japan consist of four genetic groups, as determined by phylogenetic analysis using the polymorphic region (aa 456-592) of the S glycoprotein gene. Japanese field isolates of BCoV, reference Kakegawa strain, and vaccine strain 66/H were analyzed for their antigenic properties by indirect immunofluorescence and neutralization testing. There were no significant differences observed among these BCoVs in direct immunofluorescence tests. However, antigenic differences were observed between BCoVs in the neutralization tests, although there was no clear indication of a distinct serotype. A monoclonal antibody, 4H4, against the Kakegawa strain belonging to group 1 lacked significant neutralizing activity for viruses of groups 2, 3, and 4. Therefore, we speculate that the genetic differences between these groups may have altered their antigenicity. Analysis of mutant viruses resistant to neutralization by 4H4 revealed that the antigenic site of the Kakegawa strain maps to amino acid position 284 of the S glycoprotein. This site is not homologous to a known antigenic site (aa 528) of the Quebec strain belonging to group 1, and it is not located in the conformational domain comprising domain I (aa 351-403) and domain II (aa 517-621). This amino acid constitutes a neutralization epitope of BCoV, which is distinct from aa 528 of the Quebec strain. These results indicate antigenic evolution of BCoV between the genetic groups circulating in Japan. 
 Title: Antigenic variation among recent Japanese isolates of bovine coronaviruses belonging to phylogenetically distinct genetic groups
Output: False
Paragraph: Many of the studies on emerging epidemics (such as SARS and pandemic flu) use mass action models to estimate reproductive numbers and the needed control measures. In reality, transmission patterns are more complex due to the presence of various social networks. One level of complexity can be accommodated by considering a community of households. Our study of transmission dynamics in a community of households emphasizes five types of reproductive numbers for the epidemic spread: household-to-household reproductive number, leaky vaccine-associated reproductive numbers, perfect vaccine reproductive number, growth rate reproductive number, and the individual reproductive number. Each of those carries different information about the transmission dynamics and the required control measures, and often some of those can be estimated from the data while others cannot. Simulations have shown that under certain scenarios there is an ordering for those reproductive numbers. We have proven a number of ordering inequalities under general assumptions about the individual infectiousness profiles. Those inequalities allow, for instance, to estimate the needed vaccine coverage and other control measures without knowing the various transmission parameters in the models. Along the way, we've also shown that in choosing between increasing vaccine efficacy and increasing coverage levels by the same factor, preference should go to efficacy. 
 Title: REPRODUCTIVE NUMBERS, EPIDEMIC SPREAD AND CONTROL IN A COMMUNITY OF HOUSEHOLDS
Output: False
Paragraph: Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3-5 days post inoculation (dpi) and in the kidney at 8 dpi, with heavy viral loads at 1-11 and 1-28 dpi, respectively. The expression of mRNAs encoding Toll-like receptor (TLR) 3 and TLR7 were upregulated at 3-8 dpi, and that of TIR-domain-containing adapter-inducing interferon (IFN) β (TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88 (MyD88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor (TRAF) 3 and TRAF6 were upregulated expression in both tissues. Moreover, melanoma differentiation-associated protein 5 (MDA5), laboratory of genetics and physiology 2 (LGP2), stimulator of IFN genes (STING), and mitochondrial antiviral signaling protein (MAVS), as well as TANK binding kinase 1 (TBK1), inhibitor of kappaB kinase (IKK) ԑ, IKKα, IKKβ, IFN regulatory factor (IRF) 7, nuclear factor of kappaB (NF-κB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β (MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally, consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney. 
 Title: Responses of the Toll-like receptor and melanoma differentiation- associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks
Output: False
Paragraph: In 2012, a novel coronavirus (CoV) associated with severe respiratory disease, Middle East respiratory syndrome (MERS-CoV; previously known as human coronavirus-Erasmus Medical Center or hCoV-EMC), emerged in the Arabian Peninsula. To date, 114 human cases of MERS-CoV have been reported, with 54 fatalities. Animal models for MERS-CoV infection of humans are needed to elucidate MERS pathogenesis and to develop vaccines and antivirals. In this study, we developed rhesus macaques as a model for MERS-CoV using intratracheal inoculation. The infected monkeys showed clinical signs of disease, virus replication, histological lesions, and neutralizing antibody production, indicating that this monkey model is suitable for studies of MERS-CoV infection. 
 Title: An Animal Model of MERS Produced by Infection of Rhesus Macaques With MERS Coronavirus
Output: True
Paragraph: Non-PCR-based target amplification technologies, including transcription-mediated amplification (TMA), nucleic acid sequence-based amplification (NASBA), and strand displacement amplification (SDA), are currently the basis for a broad range of clinical infectious-disease molecular diagnostics. These amplification technologies are very sensitive and specific and can be used in combination with traditional end-point or "real-time" detection formats. For several nucleic acid targets, TMA, NASBA, and SDA have certain advantages over PCR-based applications. This two-part article will review the molecular basis of each technology and how the technology has been applied to clinical diagnostic systems. The articles will describe the current testing platforms available, U.S. Food and Drug Administration (FDA)-and non-FDA-approved assays, and availability of analytespecific reagents. In addition, an open-platform system is described that utilizes standardized reagents and methods and allows the user to develop in-house protocols. Finally, applications for the future are discussed. Microbiology Newsletter 122 0196-4399/00 (see frontmatter) 
 Title: Life Beyond PCR: Alternative Target Amplification Technologies for the Diagnosis of Infectious Diseases, Part I *
Output: True
Paragraph: Background: Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak. Methods: In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR. Results: Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm 3 , p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm 3 , p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants. Conclusions: When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment. 
 Title: Bordetella pertussis in infants hospitalized for acute respiratory symptoms remains a concern
Output: True
Paragraph: Highly pathogenic avian H5N1 influenza viruses that are currently circulating in southeast Asia may acquire the potential to cause the next influenza pandemic. A number of alternate approaches are being pursued to generate cross-protective, dose-sparing, safe, and effective vaccines, as traditional vaccine approaches, i.e., embryonated egg-grown, are not immunogenic. We developed a replicationincompetent adenoviral vector-based, adjuvant-and egg-independent pandemic influenza vaccine strategy as a potential alternative to conventional egg-derived vaccines. 
 Title: New Pre-pandemic Influenza Vaccines: An Egg-and Adjuvant- independent Human Adenoviral Vector Strategy Induces Long- lasting Protective Immune Responses in Mice
Output: False