niryuu/sni-each-converted huggingface dataset:
Infectious diseases that are caused by pathogenic microorganisms can spread fast and far, from one person to another, directly or indirectly. Prompt quarantining of the infected from the rest, coupled with contact tracing, has been an effective measure to encounter outbreaks. However, urban life and international travel make containment difficult. Furthermore, the length of incubation periods of some contagious diseases like SARS enable infected passengers to elude health screenings before first symptoms appear and thus to carry the disease further. Detecting and visualizing contact-tracing networks, and immediately identifying the routes of infection, are thus important. We apply information visualization and hidden cluster detection for finding cliques of potentially infected people during incubation. Preemptive control and early quarantine are hence possible by our method. Our prototype Infectious Disease Detection and Quarantine Management System (IDDQMS), which can identify and trace clusters of infection by mining patients' history, is introduced in this paper.
Output: Hidden Cluster Detection for Infectious Disease Control and Quarantine Management
Background: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. Methods: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 -J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. Results: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. Conclusions: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.
Output: Establishing an ICD-10 code based SARI- surveillance in Germany -description of the system and first results from five recent influenza seasons
Background: Serratia marcescens is an important nosocomial pathogen and the characteristic property of resistance conferred by extended-spectrum beta-lactamase or a novel AmpC cephalosporinase was not unusual in Taiwan. This study investigated the trends in antimicrobial resistance in S. marcescens from a nationwide surveillance in Taiwan. Materials and methods: S. marcescens isolates were collected biennially between 2002 and 2010 from medical centers and regional hospitals throughout Taiwan, as part of the Taiwan Surveillance of Antimicrobial Resistance program. Minimal inhibitory concentrations were determined by the Clinical and Laboratory Standards Institute reference broth microdilution method. Results: A total of 403 nonduplicate S. marcescens isolates were collected, mostly from respiratory samples (157, 39.0%), followed by the urinary tract samples (90, 22.3%). Overall, 99.3% isolates were susceptible to imipenem, 93.8% to ceftazidime, 89.2% to minocycline, 87.8% to amikacin, 86.8% to cefepime, 82.9% to aztreonam, 73.2% to ceftriaxone, 72.7% to levofloxacin, 63.8% to ciprofloxacin, 60.8% to trimethoprim/sulfamethoxazole (TMP/SMX), and 59.6% to gentamicin. A significantly increased susceptibility rate after 2004 was observed for the following antibiotics: amikacin (73.8% vs. 97.1%), gentamicin (40.0% vs. 72.4%), ciprofloxacin Journal of Microbiology, Immunology and Infection (2014) 47, 387e393 (53.8% vs. 70.4%), ceftriaxone (53.8% vs. 86.0%), cefepime (74.4% vs. 95.1%), aztreonam (72.5% vs. 89.7%), and TMP/SMX (41.3% vs. 73.7%). Conclusion: In this 8-year study, the susceptibility of S. marcescens to ceftazidime and imipenem remained consistently high in Taiwan. S. marcescens isolates demonstrated relatively higher resistance to ciprofloxacin and levofloxacin, and therefore continued surveillance of antimicrobial resistance, especially for fluoroquinolone, is warranted.
Output: A multicenter surveillance of antimicrobial resistance in Serratia marcescens in Taiwan
is one of the most common causes of acute viral hepatitis in the world with an estimated 20 million infections per year. Although the mortality rate is less than 1% among the general population, pregnant women can have a fatality rate of up to 30%. Additionally, chronic hepatitis E has increasingly become a significant clinical problem in immunocompromised individuals. Effective antivirals against HEV are needed. Areas covered-This review article addresses the current state of knowledge of HEV infections with regard to animal and cell culture model systems that are important for antiviral discovery and testing, our current understanding of the molecular mechanisms of virus replication, our understanding of how each viral protein functions, and areas that can potentially be exploited as therapeutic targets. Expert opinion-Lack of an efficient cell culture system for HEV propagation, the limited knowledge of HEV lifecycle, and the inherent self-limiting infection within the normal populace make the development of new therapeutic agents against HEV challenging. There are many promising therapeutic targets, and the tools for identifying and testing potential antivirals are rapidly evolving. The development of effective therapeutics against HEV in immunocompromised and pregnant patient populations is warranted.
Output: Therapeutic Targets for the Treatment of Hepatitis E Virus Infection HHS Public Access
This document outlines recommendations for physiotherapy management for COVID-19 in the acute hospital setting. It includes: recommendations for physiotherapy workforce planning and preparation; a screening tool for determining requirement for physiotherapy; and recommendations for the selection of physiotherapy treatments and personal protective equipment. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with suspected and/or confirmed COVID-19.
Output: Journal Pre-proof Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations
WHO has listed several priority diseases with epidemic potential for which there are no, or insufficient, medical countermeasures. In response, the Bill & Melinda Gates Foundation (with support from PricewaterhouseCoopers) coordinated subject matter experts to create a preparedness plan for Disease X. Disease X is caused by Pathogen X, an infectious agent that is not currently known to cause human disease, but an aetiologic agent of a future outbreak with epidemic or pandemic potential. We have identified crucial areas for acceleration in medical countermeasure product development and international coordination. We have also reviewed novel platforms and process improvements related to manufacturing, which could revolutionise the response to the next pandemic. Finally, we created several coordination and engagement guides. These guides range from the rational design of an intervention target product profile, to the key facets of vaccine and therapeutic development, to accelerated manufacturing and regulatory mechanisms. In this Personal View, we provide a high-level summary of the outcomes of the medical countermeasure development workstream, intended for a broad audience including academia, medical countermeasure developers, and multilateral coordinating bodies. We hope that they might find this piece useful in prioritising strategic investments and efforts to accelerate medical countermeasure development. We observed that in-depth analyses of clinical trial design, chemistry, manufacturing and control activities, and accelerated regulatory pathways are necessary for shortening the timelines for the product development of medical countermeasures. We intend to cover these topics in future publications.
Output: Personal View Disease X: accelerating the development of medical countermeasures for the next pandemic
Acute viral respiratory infections are the most common infections in humans. Co-infection with different respiratory viruses is well documented but not necessarily well understood. The aim of this study was to utilise laboratory data from the winter season following the 2009 influenza A(H1N1) outbreak to investigate rates of respiratory virus co-infections, virus prevalence in different age groups and temporal variations in virus detection. The Health Protection Agency Public Health Laboratory (HPA PHL) Birmingham, UK, routinely uses polymerase chain reaction (PCR) to detect common respiratory viruses. The results from specimens received for respiratory virus investigations from late September 2009 to April 2010 were analysed. A total of 4,821 specimen results were analysed. Of these, 323 (13.2 %) had co-detections of two viruses, 22 (0.9 %) had three viruses and four (0.2 %) had four viruses. Reciprocal patterns of positive or negative associations between different virus pairs were found. Statistical analysis confirmed the significance of negative associations between influenza A and human metapneumovirus (HMPV), and influenza A and rhinovirus. Positive associations between parainfluenza with rhinovirus, rhinovirus with respiratory syncytial virus (RSV) and adenovirus with rhinovirus, parainfluenza and RSV were also significant. Age and temporal distributions of the different viruses were typical. This study found that the co-detection of different respiratory viruses is not random and most associations are reciprocal, either positively or negatively. The pandemic strain of influenza A(H1N1) was notable in that it was the least likely to be co-detected with another respiratory virus.
Output: Respiratory viral infections during the 2009-2010 winter season in Central England, UK: incidence and patterns of multiple virus co-infections
Secretion of a recombinant protein from the yeast Pichia pastoris requires the presence of a signal peptide at the amino terminus. Maintaining the full amino acid sequence of the signal peptide is thought to be important for proper signal processing and protein secretion. We show that at least for one protein, a synthetic human interferon, the presence of a Gateway recombination site within the signal peptide is fully compatible with high levels of protein secretion. The amino termini of the secreted interferon proteins cloned with Gateway and cloned with restriction enzymes and ligase are identical, and the proteins were highly active in biological assays. Compatibility with Gateway cloning simpliWes construction of plasmids directing secretion of recombinant proteins from P. pastoris.
Output: Gateway cloning is compatible with protein secretion from Pichia pastoris
Human infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than 250,000 confirmed cases as of March 21, 2020. An open-label clinical trial has just concluded, suggesting improved resolution of viremia with use of two existing therapies: hydroxychloroquine (HCQ) as monotherapy, and in combination with azithromycin (HCQ-AZ). [1, 2]. The results of this important trial have major implications for global policy in the rapid scale-up and response to this pandemic. The authors present results with p-values for differences in proportions between the study arms, but their analysis is not able to provide effect size estimates. To address this gap, more modern analytical methods including survival models, have been applied to these data, and show modest to no impact of HCQ treatment, with more significant effects from the HCQ-AZ combination, potentially suggesting a role for co-infections in COVID-19 pathogenesis. The trial of Gautret and colleagues, with consideration of the effect sizes, and p-values from multiple models, does not provide sufficient evidence to support wide-scale rollout of HCQ monotherapy for the treatment of COVID-19; larger randomzied studies should be considered. However, these data do suggest further study of HCQ-AZ combination therapy should be prioritized as rapidly as possible.
Output: QUANTIFYING TREATMENT EFFECTS OF HYDROXYCHLOROQUINE AND AZITHROMYCIN FOR COVID-19: A SECONDARY ANALYSIS OF AN OPEN LABEL NON-RANDOMIZED CLINICAL TRIAL A PREPRINT
This paper characterises a virulent strain (CB/05) of canine coronavirus (CCoV) isolated from the internal organs of pups that had died of a systemic disease without evidence of other common canine pathogens. High viral RNA titres were detected in the internal organs by a real-time RT-PCR assay specific for CCoV type II. Sequence analysis of the 3 end (8.7 kb) of the genomic RNA of strain CB/05 revealed conserved structural as well as non-structural proteins, with the exception of a truncated form of non-structural protein 3b. The exceptional form was due to a 38-nucleotide deletion and a frame shift in ORF3b that introduced an early stop codon. By phylogenetic analysis of the structural proteins, the spike (S) protein was found to cluster with feline coronavirus type II strain 79-1683, whereas, the envelope (E), membrane (M) and nucleocapsid (N) proteins segregated together with the reference strain Purdue of transmissible gastroenteritis virus of swine.
Output: Molecular characterisation of the virulent canine coronavirus CB/05 strain ଝ
Despite intense efforts to develop novel and better tools to identify known viruses and to discover new viruses, establishing etiological roles for viruses in human disease is challenging. In large part, this may be attributed to the high variability of viral species and the difficulties in developing broad-spectrum, yet specific, diagnostic assays. To overcome this problem, a novel method for the detection of viruses is described in the current manuscript. The technique relies on the addition of synthetic oligonucleotides to both termini of RNA fragments in a sequence-dependent manner during first-and second-strand DNA synthesis; these oligonucleotides are used subsequently for amplification of the viral nucleic acids of interest. The recognition of the target sequence by the oligonucleotides is mediated by short (6-8 nt) conserved regions, which facilitates development of broad-spectrum assays. The method has been tested for coronaviruses, although it may be also adopted for other RNA viruses.
Output: HexaPrime: A novel method for detection of coronaviruses
Cameron). Study objective: We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department (ED). Methods: This is a double-blind, randomized, controlled study in a university hospital emergency department (ED) in the New Territories of Hong Kong. Patients older than 17 years and presenting between February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike arthritis were randomized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy. Primary outcome measures were pain scores, time to resolution of symptoms and signs, and adverse effects. Secondary outcome measures were the need for additional acetaminophen and relapse rate. Results: There were 90 patients randomized: 46 patients to the indomethacin group and 44 patients to the prednisolone group. Baseline characteristics, including pain scores, were similar in the 2 groups. Both treatment groups had a similar decrease in pain score in the ED. The mean rate of decrease in pain score with activity for indomethacin was Ϫ1.7Ϯ1.6 (SD) mm per day and for prednisolone was Ϫ2.9Ϯ2.0 (SD) mm per day (mean difference 1.2 mm/day; 95% confidence interval 0.4 to 2.0 mm/day; Pϭ.0026). Although these differences were statistically significant, at no time was the difference in mean pain score greater than 13 mm. Therefore, it is unclear whether these differences are clinically significant. The mean total dose of acetaminophen consumed by the prednisolone group was significantly more than in the indomethacin group (mean 10.3 g, range 1 to 21 g versus mean 6.4 g, range 1 to 21 g). Twenty-nine patients in the indomethacin group and 12 patients in the prednisolone group experienced adverse effects (PϽ.05). The commonest adverse effects in the indomethacin group were nausea, indigestion, epigastric pain, dizziness, and gastrointestinal bleeding (Nϭ5; 11%). None of the patients in the prednisolone group developed gastrointestinal bleeding. The relapse rate for both groups was similar. Conclusion: In the treatment of acute goutlike arthritis, oral prednisolone/acetaminophen combination is as effective as oral indomethacin/acetaminophen combination in relieving pain but is associated with fewer adverse effects.
Output: Comparison of Oral Prednisolone/Paracetamol and Oral Indomethacin/Paracetamol Combination Therapy in the Treatment of Acute Goutlike Arthritis: A Double-Blind, Randomized, Controlled Trial
Objectives: We aimed to develop a prospective prediction tool on CrimeaneCongo haemorrhagic fever (CCHF) to identify geographic regions at risk. The tool could support public health decision-makers in implementation of an effective control strategy in a timely manner. Methods: We used monthly surveillance data between 2004 and 2015 to predict case counts between 2016 and 2017 prospectively. The Turkish nationwide surveillance data set collected by the Ministry of Health contained 10 411 confirmed CCHF cases. We collected potential explanatory covariates about climate, land use, and animal and human populations at risk to capture spatiotemporal transmission dynamics. We developed a structured Gaussian process algorithm and prospectively tested this tool predicting the future year's cases given past years' cases. Results: We predicted the annual cases in 2016 and 2017 as 438 and 341, whereas the observed cases were 432 and 343, respectively. Pearson's correlation coefficient and normalized root mean squared error values for 2016 and 2017 predictions were (0.83; 0.58) and (0.87; 0.52), respectively. The most important covariates were found to be the number of settlements with fewer than 25 000 inhabitants, latitude, longitude and potential evapotranspiration (evaporation and transpiration). Conclusions: Main driving factors of CCHF dynamics were human population at risk in rural areas, geographical dependency and climate effect on ticks. Our model was able to prospectively predict the numbers of CCHF cases. Our proof-of-concept study also provided insight for understanding possible mechanisms of infectious diseases and found important directions for practice and policy to combat against emerging infectious diseases. Ç. Ak, Clin Microbiol Infect 2020;26:123.e1e123.e7
Output: A prospective prediction tool for understanding CrimeaneCongo haemorrhagic fever dynamics in Turkey
Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied. We now report that the agonists trehalose-6,6-dibehenate (TDB), curdlan, and furfurman, which stimulate Dectin-1, Dectin-2, and Mincle, respectively, activate transcription factors (NF-κB, NFAT, and AP-1) to various extents in murine RAW 264.7 macrophages, even though similar pathways are activated. The agonists also elicit differential expression of maturation markers in bone marrow-derived dendritic cells, as well as differential cytokine secretion from these cells and from splenic mononuclear cells. In vivo assays also show that agonists of Dectin-1 and Dectin-2, but not Mincle, induce heavy IgA secretion in intestinal mucosa even when delivered parenterally. Strikingly, this effect appears to be formulation-independent. Collectively, the data suggest that adjuvants based on Dectin-1 and Dectin-2 agonists may significantly improve the efficacy of parenteral vaccines by inducing robust local immune reactions in intestinal mucosa.
Output: Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa
Background: Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. Methods: We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. Results: Dexamethasone-immunosuppressed male mice (6-8 weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥10% weight loss and high clinical scores soon after dexamethasone withdrawal (10 dpi), which warranted euthanasia at 12 dpi. Viral loads in blood and most tissues at 5 dpi were significantly higher than those at 12 dpi (P b 0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45+ and CD8+ inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival). Conclusions: Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment.
Output: Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons
In the current COVID-19 crisis, the US and many countries in the world are suffering acute shortages of modern ventilators to care for desperately ill patients. Since modern ICU ventilators are powerful devices that can deliver very high gas flow rates and pressures, multiple physicians have attempted to ventilate more than one patient on a single ventilatorso-called "vent splitting". Early applications of this approach have utilized simple concatenations of ventilator tubing and T-pieces, to provide flow to more than one patient. Additional approaches using custom flow splitters -sometimes made using 3D printing technologies -have also advanced into the clinic with FDA approval. However, heretofore there has been less progress made on controlling individual ventilatory pressures for patients with severe lung disease. Given the inherent variability and instability of lung compliance amongst patients with COVID-19, there remains an important need to provide a means of extending ventilator usefulness to more than one patient, but in a way that provides more tailored pressures that can be titrated over time. In this descriptive report, we provide the basis for a ventilator circuit that can support two patients with individualized peak inspiratory and end-expiratory pressures. The circuit is comprised of exclusively "off the shelf" materials and is inexpensive to produce. The circuit can be used with typical ICU ventilators, and with anesthesia ventilators used in operating rooms. Inspiratory and end-expiratory pressures for each patient can be titrated over time, without changes for one patient affecting the ventilation parameters of the other patient. Using in-line spirometry, individual tidal volumes can be measured for each patient. This Pressure-Regulated Ventilator Splitting (PReVentS) Yale University protocol operates under a pressure-control ventilatory mode, and may function optimally when patients are not triggering breaths from the ventilator. This method has been tested thus far only in the laboratory with mock lungs, and has not yet been deployed in animals or in patients. However, given the novelty and potential utility of this approach, we deemed it appropriate to provide this information to the broader critical care community at the present time. In coming days and weeks, we will continue to characterize and refine this approach, using large animal models and proof-of-principle human studies.
Output: Pressure-Regulated Ventilator Splitting (PReVentS) - A COVID-19 Response Paradigm from Yale University
Objectives. To assess the beneficial and adverse effects of Xiaoyaosan for depression. Search Strategy. Electronic databases were searched until December 2009. Inclusion Criteria. We included randomized clinical trials testing Xiaoyaosan against placebo, antidepressants, or combined with antidepressants against antidepressants alone. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. Results. 26 randomized trials (involving 1837 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that Xiaoyaosan combined with antidepressants was more effective in comprehensive effect, the score of HAMD and the score of SDS compared with antidepressants alone. Xiaoyaosan was superior to antidepressants for the score of HAMD. However, Xiaoyaosan was not different from placebo for the score of SDS. There was no adverse effects reported in the trials from Xiaoyaosan. Conclusions. Xiaoyaosan appears to be effective on improving symptoms in patients with depression. However, due to poor methodological quality in the majority of included trials, the potential benefit from Xiaoyaosan need to be confirmed in rigorous trials and the design and reporting of trials should follow international standards.
Output: Chinese Herbal Formula Xiao Yao San for Treatment of Depression: A Systematic Review of Randomized Controlled Trials
Necrotizing enterocolitis remains one of the most vexing problems in the neonatal intensive care unit. Risk factors for NEC include prematurity, formula feeding, and inappropriate microbial colonization of the GI tract. The pathogenesis of NEC is believed to involve weakening of the intestinal barrier by perinatal insults, translocation of luminal bacteria across the weakened barrier, an exuberant inflammatory response, and exacerbation of the barrier damage by inflammatory factors, leading to a vicious cycle of inflammation-inflicted epithelial damage. Nitric oxide (NO), produced by inducible NO synthase (iNOS) and reactive NO oxidation intermediates play a prominent role in the intestinal barrier damage by inducing enterocyte apoptosis and inhibiting the epithelial restitution processes, namely enterocyte proliferation and migration. The factors that govern iNOS upregulation in the intestine are not well understood, which hampers efforts in developing NO/iNOS-targeted therapies. Similarly, efforts to identify bacteria or bacterial colonization patterns associated with NEC have met with limited success, because the same bacterial species can be found in NEC and in non-NEC subjects. However, microbiome studies have identified the three important characteristics of early bacterial populations of the GI tract: high diversity, low complexity, and fluidity. Whether NEC is caused by specific bacteria remains a matter of debate, but data from hospital outbreaks of NEC strongly argue in favor of the infectious nature of this disease. Studies in Cronobacter muytjensii have established that the ability to induce NEC is the property of specific strains rather than the species as a whole. Progress in our understanding of the roles of bacteria in NEC will require microbiological experiments and genome-wide analysis of virulence factors. Necrotizing enterocolitis (NEC), a severe inflammation of the small intestine, is the most common and most lethal disease affecting the GI tract of the premature infant. Despite aggressive medical and surgical treatment, the mortality rate for NEC is typically 15%-30% in the very low birth weight neonates and approaches 100% in cases involving pan-necrosis [1, 2] . Unfortunately, the incidence of NEC continues to rise because recent advances in neonatology have resulted in the survival of infants born at 23 weeks gestation [3] .
Output: Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis ☆
Text mining was used to extract technical intelligence from the open source global SARS research literature. A SARS-focused query was applied to the Science Citation Index (SCI) (SCI 2008) database for the period 1998-early 2008. The SARS research literature infrastructure (prolific authors, key journals/institutions/countries, most cited authors/journals/documents) was obtained using bibliometrics, and the SARS research literature technical structure (hierarchical taxonomy) was obtained using computational linguistics/document clustering.
Output: Structure and infrastructure of infectious agent research literature: SARS
Scorpions are well known for their dangerous stings that can result in severe consequences for human beings, including death. Neurotoxins present in their venoms are responsible for their toxicity. Due to their medical relevance, toxins have been the driving force in the scorpion natural compounds research field. On the other hand, for thousands of years, scorpions and their venoms have been applied in traditional medicine, mainly in Asia and Africa. With the remarkable growth in the number of characterized scorpion venom components, several drug candidates have been found with the potential to tackle many of the emerging global medical threats. Scorpions have become a valuable source of biologically active molecules, from novel antibiotics to potential anticancer therapeutics. Other venom components have drawn attention as useful scaffolds for the development of drugs. This review summarizes the most promising candidates for drug development that have been isolated from scorpion venoms.
Output: Scorpion venom components as potential candidates for drug development
Recently, Zika virus (ZIKV) has attracted much attention in consideration of its association with severe neurological complications including fetal microcephaly. However, there are currently no prophylactic vaccines or therapeutic drugs approved for clinical treatments of ZIKV infection. To determine the potential anti-ZIKV inhibitors, we screened a library of clinical drugs with good safety profiles. Erythromycin estolate (Ery-Est), one of the macrolide antibiotics, was found to effectively inhibit ZIKV infection in different cell types and significantly protect A129 mice from ZIKV-associated neurological signs and mortality. Through further investigation, Ery-Est was verified to inhibit ZIKV entry by disrupting the integrity of the viral membrane which resulted in the loss of ZIKV infectivity. Furthermore, Ery-Est also showed inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Thus, Ery-Est may be a promising drug for patients with ZIKV infection, particularly pregnant women.
Output: Erythromycin Estolate Inhibits Zika Virus Infection by Blocking Viral Entry as a Viral Inactivator
Contact history is crucial during an infectious disease outbreak and vital when seeking to understand and predict the spread of infectious diseases in human populations. e transmission connectivity networks of people infected with highly contagious Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia were assessed to identify super-spreading events among the infected patients between 2012 and 2016. Of the 1379 MERS cases recorded during the study period, 321 (23.3%) cases were linked to hospital infection, out of which 203 (14.7%) cases occurred among healthcare workers. ere were 1113 isolated cases while the number of recorded contacts per MERS patient is between 1 (n � 210) and 17 (n � 1), with a mean of 0.27 (SD � 0.76). Five super-important nodes were identified based on their high number of connected contacts worthy of prioritization (at least degree of 5). e number of secondary cases in each SSE varies (range, 5-17). e eigenvector centrality was significantly (p < 0.05) associated with place of exposure, with hospitals having on average significantly higher eigenvector centrality than other places of exposure. Results suggested that being a healthcare worker has a higher eigenvector centrality score on average than being nonhealthcare workers. Pathogenic droplets are easily transmitted within a confined area of hospitals; therefore, control measures should be put in place to curtail the number of hospital visitors and movements of nonessential staff within the healthcare facility with MERS cases.
Output: Network Analysis of MERS Coronavirus within Households, Communities, and Hospitals to Identify Most Centralized and Super-Spreading in the Arabian Peninsula, 2012 to 2016
Used since ancient times especially for the local treatment of pulmonary diseases, lungs and airways are a versatile target route for the administration of both local and systemic drugs. Despite the existence of different platforms and devices for the pulmonary administration of drugs, only a few formulations are marketed, partly due to physiological and technological limitations. Respiratory infections represent a significant burden to health systems worldwide mainly due to intrahospital infections that more easily affect immune-compromised patients. Moreover, tuberculosis (TB) is an endemic infectious disease in many developing nations and it has resurged in the developed world associated with the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. Currently, medicine faces the specter of antibiotic resistance. Besides the development of new anti-infectious drugs, the development of innovative and more efficient delivery systems for drugs that went off patent appears as a promising strategy pursued by the pharmaceutical industry to improve the therapeutic outcomes and to prolong the utilities of their intellectual property portfolio. In this context, nanotechnology-based drug delivery systems (nano-DDS) emerged as a promising approach to circumvent the limitations of conventional formulations and to treat drug resistance, opening the hypothesis for new developments in this area.
Output: Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases ☆
Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea and dehydration in sucking piglets and has a high mortality rate. An immunochromatography (IC) assay, known as a lateral flow test, is a simple device intended to detect the presence of target pathogens. Here, we developed an IC assay that detected PEDV antigens with 96.0% (218/227) sensitivity and 98.5% (262/266) specificity when compared with real-time reverse transcriptase (RT)-PCR using FAM-labeled probes based on sequences from nucleocapsid genes. The detection limits of the real-time RT-PCR and IC assays were 1 × 10 2 and 1 × 10 3 copies, respectively. The IC assay developed herein did not detect non-specific reactions with other viral or bacterial pathogens, and the assay could be stored at 4 • C or room temperature for 15 months without affecting its efficacy. Thus, the IC assay may result in improved PED detection and control on farms, and is a viable alternative to current diagnostic tools for PEDV.
Output: A novel diagnostic approach to detecting porcine epidemic diarrhea virus: The lateral immunochromatography assay
P53 controls the cell cycle arrest and cell apoptosis through interaction with the downstream genes and their signal pathways. To stimulate the investigation into the complicated responses of p53 under the circumstance of ion radiation (IR) in the cellular level, a dynamic model for the p53 stress response networks is proposed. The model can be successfully used to simulate the dynamic processes of generating the double-strand breaks (DSBs) and their repairing, ataxia telangiectasia mutated (ATM) activation, as well as the oscillations occurring in the p53-MDM2 feedback loop.
Output: A dynamic model for the p53 stress response networks under ion radiation
Sixteen monoclonal antibodies (Mcabs) were prepared against infectious bronchitis virus strain M41, all of them reacting with the peplomer protein. One of them, Mcab 13, was able to neutralize the virus and to inhibit hemagglutination. Competition binding assays allowed the definition of five epitopes, designated as A, B, C, D, and E, of which epitopes A and B are overlapping. Furthermore, the binding of Mcab 13 (epitope E) could be enhanced by the addition of Mcabs from group B, C, and D. A dot immunoblot assay was used to analyze the effect of denaturation on antibody recognition of the epitopes. Only the binding of Mcab 13 was affected, indicating that the epitope involved in neutralization and hemagglutination is conformation dependent. The epitopes A to D were highly conserved among IBV strains, while epitope E was specific for strains M41 and D3896. In this last strain, however, this epitope was not involved in neutralization.
Output: Epitopes on the Peplomer Protein of Infectious Bronchitis Virus Strain M41 as Defined by Monoclonal Antibodies
Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.
Output: Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing
Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority of neurological complications and death in young children. While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. Ideally, EV71 specific intravenous immunoglobulins could be developed for targeted treatment of severe cases. To date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of VP1 has been identified. Other enteroviruses have been shown to possess major conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins. Hence, we attempted to isolate such neutralizing antibodies against conformational epitopes for their potential in the treatment of infection as well as differential diagnosis and vaccine optimization. Here we describe a universal neutralizing monoclonal antibody that recognizes a conserved conformational epitope of EV71 which was mapped using escape mutants. Eight escape mutants from different subgenogroups (A, B2, B4, C2, C4) were rescued; they harbored three essential mutations either at amino acid positions 59, 62 or 67 of the VP3 protein which are all situated in the ''knob'' region. The escape mutant phenotype could be mimicked by incorporating these mutations into reverse genetically engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal antibody binding and neutralization activity. This is the first conformational neutralization epitope mapped on VP3 for EV71.
Output: A Novel Universal Neutralizing Monoclonal Antibody against Enterovirus 71 That Targets the Highly Conserved ''Knob'' Region of VP3 Protein
The clinical presentation of severe acute respiratory syndrome (SARS) resembles that of other etiologies of community-acquired pneumonia, making diagnosis difficult. Hematological and biochemical abnormalities, particularly lymphopenia, are common in patients with SARS. Methods. With the use of 2 databases, we compared the ability of the absolute lymphocyte count, absolute neutrophil count, lactate dehydrogenase level, creatine kinase level, alanine aminotransferase level, and serum calcium level at hospital admission to discriminate between cases of SARS and cases of community-acquired pneumonia. The SARS database contained data for 144 patients with SARS from the 2003 Toronto SARS outbreak. The community-acquired pneumonia database contained data for 8044 patients with community-acquired pneumonia from Edmonton, Canada. Patients from the SARS database were matched to patients from the communityacquired pneumonia database according to age, and receiver operating characteristic curves were constructed for each laboratory variable. Results. The areas under the receiver operating characteristic curves (AUCs) demonstrated fair to poor discriminatory ability for all laboratory variables tested except absolute neutrophil count, which had an AUC of 0.80, indicating good discriminatory ability (although there was no cutoff value of the absolute neutrophil count at which reasonable sensitivity or specificity could be obtained). Combinations of any 2 tests did not perform significantly better than did the absolute neutrophil count alone. Conclusions. Routine laboratory tests, including determination of absolute lymphocyte count, should not be used in the diagnosis of SARS or incorporated into current case definitions of SARS. The role of the absolute neutrophil count in SARS diagnosis is likely limited, but it should be assessed further.
Output: Can Routine Laboratory Tests Discriminate between Severe Acute Respiratory Syndrome and Other Causes of Community-Acquired Pneumonia?
Background: Development an effective vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) is urgent and limited information is available on vaccination in nonhuman primate (NHP) model. We herein report of evaluating a recombinant receptor-binding domain (rRBD) protein vaccine in a rhesus macaque model. Methods: Nine monkeys were randomly assigned to high-dose, low-dose and mock groups,which were immunized with different doses of rRBD plus alum adjuvant or adjuvant alone at different time points (0, 8, 25 weeks). Immunological analysis was conducted after each immunisation. Monkeys were challenged with MERS-CoV at 14 days after the final immunisation followed by observation for clinical signs and chest X-rays. Nasal, oropharyngeal and rectal swabs were also collected for analyses. Monkeys were euthanized 3 days after challenge and multiple specimens from tissues were collected for pathological, virological and immunological tests. Conclusion: Robust and sustained immunological responses (including neutralisation antibody) were elicited by the rRBD vaccination. Besides, rRBD vaccination alleviated pneumonia with evidence of reduced tissue impairment and clinical manifestation in monkeys. Furthermore, the rRBD vaccine decreased viral load of lung, trachea and oropharyngeal swabs of monkeys. These data in NHP paves a way for further development of an effective human vaccine against MERS-CoV infection.
Output: Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge ☆-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Streptococcus mutans plays an important role in the development of dental caries in humans by synthesizing adhesive insoluble glucans from sucrose by mutansucrase activity. To explore the anti-cariogenic characteristics of rubusoside (Ru), a natural sweetener component in Rubus suavissimus S. Lee (Rosaceae), we investigated the inhibitory effect of Ru against the activity of mutansucrase and the growth of Streptococcus mutans. Ru (50 mM) showed 97% inhibitory activity against 0.1 U/mL mutansucrase of S. mutans with 500 mM sucrose. It showed competitive inhibition with a K i value of 1.1 ± 0.2 mM and IC 50 of 2.3 mM. Its inhibition activity was due to hydrophobic and hydrogen bonding interactions based on molecular docking analysis. Ru inhibited the growth of S. mutans as a bacteriostatic agent, with MIC and MBC values of 6 mM and 8 mM, respectively. In addition, Ru showed synergistic anti-bacterial activity when it was combined with curcumin. Therefore, Ru is a natural anti-cariogenic agent with antimutansucrase activity and antimicrobial activity against S. mutans.
Output: Anti-cariogenic Characteristics of Rubusoside