niryuu/sni-each-converted huggingface dataset:
Seventy-two human and 72 bovine faecal specimens were tested for rotavirus by polyacrylamide gel electrophoresis (PAGE). four commercial enzyme-linked immunosorbent assay (ELISA) kits (RotaScreen, Wellcozyme, Rotazyme II and IDEIA) and two latex agglutination (LA) kits (RotaScreen and Wellcome). Specimens which were negative by PAGE but positive by one or more of the kits were further examined by direct and immuno-electron microscopy (DEM and IEM). If also negative by DEM and IEM the kit result was considered to be a false positive. Three kits (RotaScreen and IDEIA ELISAs and RotaScreen LA) had specificity and sensitivity greater than 90% on the human specimens but only two (RotaScreen ELISA and LA) had specificity and sensitivity over 80% on the bovine specimens. These kits can therefore be used with reasonable confidence for rotavirus diagnosis. but none of them has any advantage over PAGE other than speed.
Output: Comparison of six commercial kits for the diagnosis of rotavirus infection in man and calves
currently under evaluation as a human immunodeficiency virus (HIV)-1 vaccine vector. The most compelling reasons to develop rVSV as a vaccine vector include a very low seroprevalence in humans, the ability to infect and robustly express foreign antigens in a broad range of cells, and vigorous growth in continuous cell lines used for vaccine manufacture. Numerous preclinical studies with rVSV vectors expressing antigens from a variety of human pathogens have demonstrated the versatility, flexibility, and potential efficacy of the rVSV vaccine platform. When administered to nonhuman primates (NHPs), rVSV vectors expressing HIV-1 Gag and Env elicited robust HIV-1specific cellular and humoral immune responses, and animals immunized with rVSV vectors expressing simian immunodeficiency virus (SIV) Gag and HIV Env were protected from AIDS after challenge with a pathogenic SIV/HIV recombinant. However, results from an exploratory neurovirulence study in NHPs indicated that these prototypic rVSV vectors might not be adequately attenuated for widespread use in human populations. To address this safety concern, a variety of different attenuation strategies, designed to produce a range of further attenuated rVSV vectors, are currently under investigation. Additional modifications of further attenuated rVSV vectors to upregulate expression of HIV-1 antigens and coexpress molecular adjuvants are also being developed in an effort to balance immunogenicity and attenuation.
Output: Recombinant vesicular stomatitis virus as an HIV-1 vaccine vector
Although clinical ethicists are becoming more prevalent in healthcare settings, their required training and education have not been clearly delineated. Most agree that training and education are important, but their nature and delivery remain topics of debate. One option is through completion of a clinical ethics fellowship. In this paper, the first four fellows to complete a newly developed fellowship program discuss their experiences. They describe the goals, structure, participants and activities of the fellowship. They identify key elements for succeeding as a clinical ethicist and sustaining a clinical ethics program. They critically reflect upon the challenges faced in the program. The one-year fellowship provided real-time clinical opportunities that helped them to develop the necessary knowledge and skills, gain insight into the role and scope of practice of clinical ethicists and hone valuable character traits. The fellowship enabled each of the fellows to assume confidently and competently a position as a clinical ethicist upon completion.
Output: Clinical education of ethicists: the role of a clinical ethics fellowship
Pathogenicity islands (PAIs), a distinct type of genomic island (GI), play important roles in the rapid adaptation and increased virulence of pathogens. 89K is a newly identified PAI in epidemic Streptococcus suis isolates that are related to the two recent largescale outbreaks of human infection in China. However, its mechanism of evolution and contribution to the epidemic spread of S. suis 2 remain unknown. In this study, the potential for mobilization of 89K was evaluated, and its putative transfer mechanism was investigated. We report that 89K can spontaneously excise to form an extrachromosomal circular product. The precise excision is mediated by an 89K-borne integrase through site-specific recombination, with help from an excisionase. The 89K excision intermediate acts as a substrate for lateral transfer to non-89K S. suis 2 recipients, where it reintegrates sitespecifically into the target site. The conjugal transfer of 89K occurred via a GI type IV secretion system (T4SS) encoded in 89K, at a frequency of 10 -6 transconjugants per donor. This is the first demonstration of horizontal transfer of a Gram-positive PAI mediated by a GI-type T4SS. We propose that these genetic events are important in the emergence, pathogenesis and persistence of epidemic S. suis 2 strains.
Output: GI-type T4SS-mediated horizontal transfer of the 89K pathogenicity island in epidemic Streptococcus suis serotype 2m mi_7553 1670..1683
Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta-1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta-1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. Conclusion: Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.
Output: A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
The carbohydrate binding profile of the red algal lectin KAA-2 from Kappaphycus alvarezii was evaluated by a centrifugal ultrafiltration-HPLC method using pyridylaminated oligosaccharides. KAA-2 bound exclusively to high mannose type N-glycans, but not to other glycans such as complex type, hybrid type, or the pentasaccharide core of N-glycans. This lectin exhibited a preference for an exposed a1-3 Man on a D2 arm in a similar manner to Eucheuma serra agglutinin (ESA-2), which shows various biological activities, such as anti-HIV and anti-carcinogenic activity. We tested the anti-influenza virus activity of KAA-2 against various strains including the recent pandemic H1N1-2009 influenza virus. KAA-2 inhibited infection of various influenza strains with EC 50 s of low nanomolar levels. Immunofluorescence microscopy using an anti-influenza antibody demonstrated that the antiviral activity of KAA-2 was exerted by interference with virus entry into host cells. This mechanism was further confirmed by the evidence of direct binding of KAA-2 to a viral envelope protein, hemagglutinin (HA), using an ELISA assay. These results indicate that this lectin would be useful as a novel antiviral reagent for the prevention of infection.
Output: High mannose-specific lectin (KAA-2) from the red alga Kappaphycus alvarezii potently inhibits influenza virus infection in a strain-independent manner
Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors. Genetic or pharmacologic inhibition of either pathway alone, but not together, selectively killed PI3K mutant tumor cells in an mTOR-dependent manner. The expression of ribosomal and proteasomal components was significantly up-regulated in primary human colorectal tumors harboring PI3K pathway activation. Importantly, a PI3K SL gene signature containing the top hits of the SL genes identified in our metaanalysis robustly predicted overall patient survival in colorectal cancer, especially among patients with tumors with an activated PI3K pathway. These results suggest that disruption of protein turnover homeostasis via ribosome or proteasome inhibition may be a novel treatment strategy for PI3K mutant human tumors.
Output: Functional genomics reveals that tumors with activating phosphoinositide 3-kinase mutations are dependent on accelerated protein turnover
Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009-2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged <5 years (89.1%, 932/1046), particularly young infants aged <1 year (43.3%, 453/1046), represented the highest proportion of patients with RSV infections. In contrast, older adults aged !60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature !38˚C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial PLOS ONE | drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact. Clinical and Epidemiologic Characteristics of RSV Infections PLOS ONE |
Output: Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory- Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study a11111 OPEN ACCESS
Background: Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that caused an outbreak in south China in 2003. The cause of SARS was identified as a novel coronavirus (CoV). The existence of asymptomatic seroconvertors and the detection of the SARS-CoV RNA in plasma during the course of infection all suggest that SARS could, as least theoretically, be transmitted by transfusion. An estimate of the risk of SARS transmission through blood transfusion will contribute to decisions concerning blood safety monitoring and may be useful in the design of strategies to decrease the risk of transfusion-transmitted infections. Study design and methods: Case onset dates from the 2003 Shenzhen SARS epidemic and investigational results from Taiwan on viremia in humans are used to estimate the number of cases that were viremic throughout the epidemic. Estimates of the asymptomatic-to-clinically confirmed SARS-CoV infection ratio, the proportion of asymptomatic infections reported in a seroprevalence survey in Hongkong, and the population size of Shenzhen are used to infer the SARS-CoV transfusion-transmission risk. Statistical resampling methods are used. Results: Based on data from Shenzhen, Hongkong and Taiwan, the maximum and mean risk (per million) of SARS-CoV transmission from donors in Shenzhen were estimated as 23.57 (95% CI: 6.83-47.69) and 14.11 (95% CI: 11.00-17.22), respectively. The estimated risk peaked on April 02, 2003. Conclusions: Although there are currently no confirmed reports of the transmission of SARS-CoV from asymptomatic individuals, recent research data indicate that transfusion-transmitted SARS-CoV is at least theoretically possible. Although the risk is low, with its rapid spread of the disease, appearance of alarmingly high infectivity and high fatality rate, public health authorities need to consider strategies for blood donor recruitment and virus inactivation during an epidemic to further ensure blood safety.
Output: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003
To ensure the safety of wastewater reuse for irrigation of food crops and drinking water pathogenic viruses must be reduced to levels that pose no significant risk. To achieve this goal minimum reduction of viruses by treatment trains have been suggested. For use of edible crops a 6-log reduction and for production of potable drinking water a 12-log reduction has been suggested. These reductions were based on assuming infective virus concentrations of 10 5 to 10 6 per liter. Recent application of molecular methods suggests that some pathogenic viruses may be occurring in concentrations of 10 7 to 10 9 per liter. Factors influencing these levels include the development of molecular methods for virus detection, emergence of newly recognized viruses, decrease in per capita water use due to conservation measures, and outbreaks. Since neither cell culture nor molecular methods can assess all the potentially infectious virus in wastewater conservative estimates should be used to assess the virus load in untreated wastewater. This review indicates that an additional 2-to 3-log reduction of viruses above current recommendations may be needed to ensure the safety of recycled water. Information is needed on peak loading of viruses. In addition, more virus groups need to be quantified using better methods of virus quantification, including more accurate methods for measuring viral infectivity in order to better quantify risks from viruses in recycled water.
Output: How much reduction of virus is needed for recycled water: A continuous changing need for assessment?
One sentence summary: A systematic review and meta-analysis of randomised clinical trials investigating antimicrobial prophylaxis or metaphylaxis against naturally occurring bovine respiratory disease. Editor: Edmundo Calva ABSTRACT A distinct difference between veterinary and human medicine is the routine use of antimicrobial mass medications (prophylaxis, metaphylaxis) to healthy individuals. The need for antimicrobial mass medications is based on beliefs that group/s of animals will contract a bacterial disease (i.e. morbidity) and/or die (i.e. mortality). Bovine respiratory disease (BRD) represents the major indication for cattle antimicrobials worldwide. The objectives were to perform a systematic review and meta-analysis of randomised controlled clinical trials (RCTs) for naturally occurring BRD investigating antimicrobial prophylaxis/metaphylaxis to prevent morbidity/mortality. In total, 58 publications met the inclusion criteria summarizing 169 individual RCTs, spanning 50 years . Antimicrobial prophylaxis and metaphylaxis demonstrated moderate, yet highly variable relative risk reductions in BRD morbidity. These were dependent on the antimicrobial classes used, dependent on metaphylaxis definition, BRD attack rates and duration of the RCTs. Best relative risk reductions were from broad-spectrum critically important antimicrobials, or combinations. BRD prophylaxis/metaphylaxis represents major antimicrobial consumption for highly variable short-term gains in absolute risk reduction of morbidity/mortality. Despite widespread use of prevention products, the need for antimicrobial mass medications should be re-evaluated since the underlying problem is more likely the segmented infrastructure of the feedlot and veal calf industries compared to the disease itself.
Output: Do antimicrobial mass medications work? A systematic review and meta-analysis of randomised clinical trials investigating antimicrobial prophylaxis or metaphylaxis against naturally occurring bovine respiratory disease
Objective. To implement a learner-led, discussion-based course aimed at exposing second-year pharmacy learners to the study of emerging infectious diseases from a global health perspective and to assess the role and importance of pharmacists in the management of disease outbreaks. Design. Learners examined literature pertinent to an emerging infectious disease in a 3-credit, discussionbased course and participated in peer discussion led by a designated learner. Instructional materials included journal articles, audio-visual presentations, documentaries, book chapters, movies, newspaper/ magazine articles, and other materials. Learning outcomes were measured based on the ability of learners to perform critical thinking and analysis, communicate with their peers, and participate in class discussions. Assessment. The course was offered to 2 consecutive cohorts consisting of 14 and 16 learners, respectively. Overall, every learner in the first cohort achieved a final grade of A for the course. In the second cohort, the overall grade distribution consisted of grades of A, B, and C for the course. Learner evaluations indicated that the active-learning, discussion-based environment significantly enhanced interest in the topic and overall performance in the course. Conclusion. The elective course on emerging infectious diseases provided in-depth exposure to disease topics normally not encountered in the pharmacy curriculum. Learners found the material and format valuable, and the course enhanced their appreciation of infectious diseases, research methodology, critical thinking and analysis, and their roles as pharmacists.
Output: TEACHERS' TOPICS A Learner-led, Discussion-based Elective on Emerging Infectious Disease
Nonstructural protein 15 (nsp15), also called endoribonuclease, is a gene product of open reading frame 1b (ORF 1b) in coronaviruses. It is an important enzyme in the transcription/replication process involved in discontinuous negative-strand RNA synthesis. In this work, mutants of nsp15 from Human coronavirus 229E (HCoV-229E) were made based on structural analysis of the homologous nsp15s in Severe acute respiratory syndrome coronavirus (SARS-CoV) and Mouse hepatitis virus (MHV). The I26A/N52A mutant of nsp15 was overexpressed, purified and crystallized, and this mutant led to a trimeric form rather than hexamers or monomers. Crystals of trimeric nsp15 were obtained by the hanging-drop vapour-diffusion method using polyethylene glycol as a precipitant and diffracted to 2.5 Å resolution. The crystals belonged to space group C222 1 , with unit-cell parameters a = 85.9, b = 137.5, c = 423.1 Å , = = = 90 . Acta Cryst. (2015).
Output: Crystallization and preliminary X-ray crystallographic analysis of a nonstructural protein 15 mutant from Human coronavirus 229E
Viral infections are leading causes of both upper and lower airway acute illness in all age groups of healthy persons, and have also been implicated in the acute exacerbations of chronic respiratory disorders like asthma and COPD. Human rhinovirus, respiratory syncytial virus, influenza virus and coronavirus have been considered as the most important respiratory pathogens and relatively little attention has been paid to the role of parainfluenza viruses (hPIVs). Human parainfluenza viruses are single-stranded RNA viruses belonging to the paramyxovirus family that may evoke lower respiratory infections in infants, children and immunocompromised individuals. Among nonimmune compromised adults, hPIV infection typically causes mild disease manifested as upper respiratory tract symptoms and is infrequently associated with severe croup or pneumonia. Moreover, hPIV infection may be associated with viral exacerbations of chronic airway diseases, asthma or COPD or chronic rhinosinusitis. In this review, we summarized the basic epidemiology and immunology of hPIVs and addressed the more recent data implicating the role of parainfluenza viruses in the exacerbation of chronic airway disorders. After respiratory syncytial virus, hPIVs are the second most common causes of acute respiratory tract infections among children aged <5 years, possibly accounting for up to 17% of hospitalizations [5] . Although age-specific rates of lower respiratory tract infections vary significantly in different populations, the medical burden of hPIVs is similar to that of RSV infection in children [6] . Serological surveys have indicated that 60% of the children are infected with hPIV-3 by 2 years of age, and this
Output: ASTHMA (WJ CALHOUN AND V ORTEGA, SECTION EDITORS) The Role of Human Parainfluenza Virus Infections in the Immunopathology of the Respiratory Tract
Non-coding ribonucleic acid (RNA) has without a doubt captured the interest of biomedical researchers. The ability to screen the entire human genome with high-throughput sequencing technology has greatly enhanced the identification, annotation and prediction of the functionality of non-coding RNAs. In this review, we discuss the current landscape of non-coding RNA research and quantitative analysis. Non-coding RNA will be categorized into two major groups by size: long non-coding RNAs and small RNAs. In long non-coding RNA, we discuss regular long non-coding RNA, pseudogenes and circular RNA. In small RNA, we discuss miRNA, transfer RNA, piwi-interacting RNA, small nucleolar RNA, small nuclear RNA, Y RNA, single recognition particle RNA, and 7SK RNA. We elaborate on the origin, detection method, and potential association with disease, putative functional mechanisms, and public resources for these non-coding RNAs. We aim to provide readers with a complete overview of non-coding RNAs and incite additional interest in non-coding RNA research.
Output: Current Research on Non-Coding Ribonucleic Acid (RNA)
As the global COVID-19 pandemic escalates there is a need within radiation oncology to work to support our patients in the best way possible. Measures are required to reduce infection spread between patients and within the workforce. Departments need contingency planning to create capacity and continue essential treatments despite a reduced workforce. The #radonc community held an urgent online journal club on Twitter in March 2020 to discuss these issues and create some consensus on crucial next steps. There were 121 global contributors. This document summarises these discussions around themes of infection prevention, rationalisation of workload and working practice in the presence of infection.
Output: COVID-19: Global radiation oncology's targeted response for pandemic preparedness-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/)
Medicinal plants have been used worldwide for centuries to maintain health and to treat diseases, more so chronic diseases. However, adulteration and use of spurious materials as substitutes have become a major concern for users and industry for reasons of safety and efficacy. Therefore, authentication of medicinal plants is of utmost importance. Morphological, anatomical, chemical and DNA markers solve the problem by differentiating the genuine material from the adulterants, substitutes and spurious drugs. DNA markers use nucleotide sequences to identify species; it takes preference over the other two markers being not age dependent, tissue specific and having a higher discriminating power. Therefore, characterization of plants with such markers is an ideal approach for identification of medicinal plant species and populations/varieties of the same species. Availability of certified taxonomic specimens in herbaria is certainly required for unambiguous confirmation through final visual comparison and analysis.
Output: Authentication of medicinal plants by DNA markers
RLadyBug is an S4 package for the simulation, visualization and estimation of stochastic epidemic models in R. Maximum likelihood and Bayesian inference can be performed to estimate the parameters in a susceptible-exposed-infectious-recovered (SEIR) model, which is a stochastic model for describing a single outbreak of an infectious disease. The package is thus one step towards statistical software supporting parameter estimation, calculation of confidence intervals and hypothesis testing for transmission models.
Output: RLadyBug-An R package for stochastic epidemic models
Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done.
Output: molecules Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples
Background: Epidemiological interventions aim to control the spread of infectious disease through various mechanisms, each carrying a different associated cost. Methodology: We describe a flexible statistical framework for generating optimal epidemiological interventions that are designed to minimize the total expected cost of an emerging epidemic while simultaneously propagating uncertainty regarding the underlying disease model parameters through to the decision process. The strategies produced through this framework are adaptive: vaccination schedules are iteratively adjusted to reflect the anticipated trajectory of the epidemic given the current population state and updated parameter estimates. Conclusions: Using simulation studies based on a classic influenza outbreak, we demonstrate the advantages of adaptive interventions over non-adaptive ones, in terms of cost and resource efficiency, and robustness to model misspecification.
Output: A Statistical Framework for the Adaptive Management of Epidemiological Interventions
Background: Early administration of appropriate antimicrobials has been correlated with a better prognosis in bacteremic patients, but a research highlighting a comparison of the adverse impact of inappropriate empirical antibiotic therapy between patient with Gram-positive and Gram-negative bacteremia is insufficient. Methods: In a retrospective cohort study, adults with communityonset monomicrobial bacteremia during the 6-year period were enrolled. Clinical information was retrieved from medical records, using a predetermined case record form. Antimicrobial susceptibility was determined by the disk diffusion method, based on performance standards of the Clinical Laboratory Standard Institute in 2016. A propensity-score-matched analysis was performed to control for the baseline characteristics at bacteremia onset between the Gram-positive and Gram-negative groups. The propensity score was calculated by the independent predictors of 28-day crude mortality recognized by a multivariable logistic regression model. Results: The total 2,053 adults (Gram-positive, 566 patients and Gram-negative, 1,487) presenting with community-onset monomicrobial bacteremia between the six-year period were recruited. Bacteremia severity (a Pitt bacteremia score) at onset and initial manifestation was different between two groups. On the basis of seven independent predictors of 28-day mortality recognized by the multivariate regression.566 of the 1,487 patients in the Gramnegative group were matched to 566 patients in the Gram-positive group with the closest propensity scores. After appropriate propensity-score matching, no significant differences were observed in baseline characteristics and patient outcomes between the two groups, in terms of age, bacteremia severity, major comorbidities, comorbidity severity, and 28-day mortality.
Output: P1-BT01 Comparing the effects of inappropriate empirical antibiotic therapy on mortality in adults with community-onset gram- positive and gram-negative bacteremia
The coronavirus, mouse hepatitis virus strain A59 (MHV), expresses a chymotrypsin-like cysteine proteinase (3CLpro) within the gene 1 polyprotein. The MHV 3CLpro is similar to the picornavirus 3C proteinases in the relative location of confirmed catalytic histidine and cysteine residues and in the predicted use of Q/(S, A, G) dipeptide cleavage sites. However, less is known concerning the participation of aspartic acid or glutamic acid residues in catalysis by the coronavirus 3Clike proteinases or of the precise coding sequence of 3CLpro within the gene 1 polyprotein. In this study, aspartic acid residues in MHV 3CLpro were mutated and the mutant proteinases were tested for activity in an in vitro trans cleavage assay. MHV 3CLpro was not inactivated by substitutions at Asp 3386 (D53) or Asp 3398 (D65), demonstrating that they were not catalytic residues. MHV 3CLpro was able to cleave at a glutamine-glycine (QG 3607-8 ) dipeptide within the 3CLpro domain upstream from the predicted carboxy-terminal QS 3635-6 cleavage site of 3CLpro. The predicted full-length 3CLpro (S 3334 to Q 3635 ) had an apparent mass of 27 kDa, identical to the p27 3CLpro in cells, whereas the truncated proteinase (S 3334 to Q 3607 ) had an apparent mass of 24 kDa. This 28-amino-acid carboxy-terminal truncation of 3CLpro rendered it inactive in a trans cleavage assay. Thus, MHV 3CLpro was able to cleave at a site within the putative full-length proteinase, but the entire predicted 3CLpro domain was required for activity. These studies suggest that the coronavirus 3CL-proteinases may have a substantially different structure and catalytic mechanism than other 3C-like proteinases. ᭧ 1997 Academic Press
Output: Determinants of Mouse Hepatitis Virus 3C-like Proteinase Activity
Background: Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care. Methods: From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture. Results: A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Nonimmunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321). Conclusions: Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.
Output: Viral Infection Is Not Uncommon in Adult Patients with Severe Hospital-Acquired Pneumonia
Immunomics research uses in silico epitope prediction, as well as in vivo and in vitro approaches. We inoculated BALB/c (H2 d ) mice with 17DD yellow fever vaccine to investigate the correlations between approaches used for epitope discovery: ELISPOT assays, binding assays, and prediction software. Our results showed a good agreement between ELISPOT and binding assays, which seemed to correlate with the protein immunogenicity. PRED BALB/c prediction software partially agreed with the ELISPOT and binding assay results, but presented low specificity. The use of prediction software to exclude peptides containing no epitopes, followed by high throughput screening of the remaining peptides by ELISPOT, and the use of MHC-biding assays to characterize the MHC restrictions demonstrated to be an efficient strategy. The results allowed the characterization of 2 MHC class I and 17 class II epitopes in the envelope protein of the YF virus in BALB/c (H2 d ) mice.
Output: Comprehensive analysis of T cell epitope discovery strategies using 17DD yellow fever virus structural proteins and BALB/c (H2 d ) mice model
Background: Respiratory syncytial virus (RSV), human Rhinovirus (HRV) and human Metapneumo Virus (HMPV) are important viral pathogens causing acute respiratory tract infections in the hospitalized patients. Sensitive and accurate detection of RSV, HRV and HMPV is necessary for clinical diagnosis and treatment. Results: A locked nucleic acid (LNA)-based multiplex closed one-tube nested real-time RT-PCR (mOTNRT-PCR) assay was developed for simultaneous detection of RSV, HRV and HMPV. The sensitivity, specificity, reproducibility and clinical performance of mOTNRT-PCR were evaluated and compared with individual real time PCR (RT-qPCR) assay using clinical samples. The analytical sensitivity of mOTNRT-PCR assay was 5 copies/reaction for RSV, HRV and HMPV, respectively, and no cross-reaction with other common respiratory viruses was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.51 to 3.67%. Of 398 nasopharyngeal aspirates samples tested, 109 (27.39%), 150 (37.69%) and 44 (11.06%) were positive for RSV, HRV and HMPV, respectively, whereas 95 (23.87%), 137 (34.42%) and 38 (9.55%) were positive for RSV, HRV and HMPV, respectively, by individual RT-qPCR assay. Thirty three samples that were positive by mOTNRT-PCR but negative by RT-qPCR were confirmed as true positives by sequencing using reported traditional two-step nested PCR assay. Conclusion: mOTNRT-PCR assay reveals extremely higher sensitivity than that of RT-qPCR assay for detecting RSV, HRV and HMPV in clinical settings.
Output: A multiplex one-tube nested real time RT- PCR assay for simultaneous detection of respiratory syncytial virus, human rhinovirus and human metapneumovirus
Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is formed by two or more phenylpropanoid units. Lignans possess diverse pharmacological properties, including their antiviral activities that have been reported in recent years. This review discusses the distribution of lignans in nature according to their structural classification, and it provides a comprehensive summary of their antiviral activities. Among them, two types of antiviral lignans-podophyllotoxin and bicyclol, which are used to treat venereal warts and chronic hepatitis B (CHB) in clinical, serve as examples of using lignans for antivirals-are discussed in some detail. Prospects of lignans in antiviral drug discovery are also discussed.
Output: molecules Lignans and Their Derivatives from Plants as Antivirals
The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.
Output: Potent Inhibition of Junín Virus Infection by Interferon in Murine Cells
Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.
Output: Evolution and Variation of the SARS-CoV Genome
Background: In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.
Output: Send Orders for Reprints to reprints@benthamscience.ae Cellular Antiviral Factors that Target Particle Infectivity of HIV-1
Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens. Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens. At least one pathogen was molecularly detected in pigs at 63 (61.8%) exhibitions. Influenza A virus was most prevalent and was detected in 498 (17.4%) samples. Influenza D virus was detected in two (0.07%) samples. More than one pathogen was detected in 165 (5.8%) samples. Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.
Output: Assessing exhibition swine as potential disseminators of infectious disease through the detection of five respiratory pathogens at agricultural exhibitions
The bovine enteric calici-like virus, Newbury agent 1 (NA1) was characterised to determine if it is a member of the Caliciviridae and to establish its antigenic relationship to the established bovine enteric calicivirus Newbury agent 2 (NA2). Solid phase immune electron microscopy (SPIEM) allowed quantification of NA1 virions and identification of faecal samples with optimal virus levels. NA1 particles were 36.6 nm in diameter, had an indefinite surface structure resembling that of human small round structured viruses (SRSVs), and a buoyant density of 1.34 g ml 31 . A single capsid protein of 49.4 kDa was detected by Western blotting in purified NA1 preparations prepared from post-infection but not pre-infection faecal samples and with post-but not pre-infection sera. NA1 was antigenically unrelated to the bovine enteric calicivirus NA2 by SPIEM. These properties were consistent with classification of NA1 within the Caliciviridae but demonstrated heterogeneity in the capsid composition of bovine enteric caliciviruses. ß
Output: Characterisation of the bovine enteric calici-like virus, Newbury agent 1
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. An Pediatr (Barc). 2006;65(3):205-10 205 ORIGINALES Papel del rinovirus en las infecciones respiratorias en niños hospitalizados Antecedentes El rinovirus se considera un agente causal de cuadros catarrales banales, sin embargo se ha descrito como un agente inductor de exacerbaciones asmáticas en adultos y niños mayores. En nuestro medio no se ha descrito el papel del rinovirus en infecciones respiratorias de niños hospitalizados. Objetivos Describir las infecciones confirmadas por rinovirus en niños hospitalizados por infección respiratoria en un hospital de segundo nivel. We performed a prospective descriptive study in children admitted to hospital with fever or respiratory tract infection and with a positive isolation of rhinovirus in nasopharyngeal washings between September 2004 and July 2005. Virological diagnosis was made with direct immunofluorescent assay and/or reverse transcription-polymerase chain reaction in specimens obtained from nasopha-Estudio parcialmente financiado por el Fondo de Investigaciones Sanitarias. FIS N.º 98/0310. Correspondencia: Dra. C. Calvo Rey. Viento, 5, 5.º A. 28760 Tres Cantos. Madrid. España. Correo electrónico: ccalvo@mi.madritel.es Recibido en noviembre de 2005. Aceptado para su publicación en marzo de 2006. Calvo Rey C, et al. Rinovirus en las infecciones respiratorias en niños hospitalizados 206 An Pediatr (Barc). 2006;65(3):205-10 ryngeal washings. The clinical characteristics of the patients were analyzed. There were 76 children with rhinovirus infection, representing 25 % of admissions in 304 children with fever or respiratory tract infection. Rhinovirus was the second most frequent viral agent identified after respiratory syncytial virus (RSV) (29.9 % of admissions). Fifty-four children (71.1 %) were under 2 years of age. The most frequent clinical diagnoses were recurrent wheezing in 60.5 %, bronchiolitis in 23.7 %, pneumonia in 7.9 %, and upper respiratory tract infection in 5.3 %. Fever > 38°C was present in 57.9 % of the patients and radiologic infiltrate was found in 23.7 %. Oxygen saturation less than 95 % was found in 43.4 % of the patients. Of 22 children aged more than 2 years, a diagnosis of asthmatic crisis was made in 21. Rhinoviruses were frequently identified in hospitalized children with respiratory tract disease and were the second most common viruses after RSV. In our series, it was the most frequent cause of recurrent wheezing in hospitalized children and the second most common cause in infants.
Output: ROLE OF RHINOVIRUS IN RESPIRATORY TRACT INFECTIONS IN HOSPITALIZED CHILDREN Background
Background: Dengue is a major public health problem in the tropics and sub-tropics, but the disease is less known to non-dengue-endemic countries including in Northeast Asia. However, an unexpected dengue outbreak occurred in 2014 in Japan. Given that autochthonous (domestic) dengue cases had not been reported for the past 70 years in Japan, this outbreak was highly unusual and suggests that several environmental factors might have changed in a way that favors vector mosquitoes in the Northeast Asian region. Methods: A Climate Risk Factor (CRF) index, as validated in previous work, was constructed using climate and nonclimate factors. This CRF index was compared to the number of reported dengue cases in Tokyo, Japan where the outbreak was observed in 2014. In order to identify high-risk areas, the CRF index was further estimated at the 5 km by 5 km resolution and mapped for Japan and South Korea. Results: The high-risk areas determined by the CRF index corresponded well to the provinces where a high number of autochthonous cases were reported during the outbreak in Japan. At the provincial-level, high-risk areas for dengue fever were the Eastern part of Tokyo and Kanakawa, the South-Eastern part of Saitama, and the North-Western part of Chiba. While a relatively small number of high-risk areas were identified in South Korea compared with Japan, the highrisk areas in South Korea include popular tourist destinations where international visitors have been increasing. Conclusion: The recent dengue outbreak in Japan may signal that the two adjacent non-dengue-endemic countries are also exposed to the risk of temporal and sporadic behavior of dengue fever. It is critical to understand potential high-risk areas for future outbreaks and to set up appropriate prevention activities at the governmental-level.
Output: The threat of climate change to non- dengue-endemic countries: increasing risk of dengue transmission potential using climate and non-climate datasets