niryuu/sni-each-converted huggingface dataset:
Main point: Hydroxychloroquine was found to be more potent than chloroquine at inhibiting SARS-CoV-2 in vitro. Hydroxychloroquine sulfate 400 mg given twice daily for 1 day, followed by 200 mg twice daily for 4 more days is recommended to treat SARS-CoV-2 infection. Abstract Background. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods. The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug's safety profile. Results. Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Hydroxychloroquine was found to be more potent than chloroquine to 4 / 25 inhibit SARS-CoV-2 in vitro.
Output: In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Dilated cardiomyopathy (DCM) is a prevalent heart muscle disease characterized by impaired contractility and dilation of the ventricles. Recent clinical research suggests that cardiotropic viruses are important environmental pathogenic factors in human DCM, which may therefore be considered as a chronic viral cardiomyopathy. All virus-positive DCM patients thus come into the focus of virological research and should be considered for antiviral strategies. Interferon-β therapy has been shown to mediate virus elimination in patients with adenovirus or coxsackievirus persistence. We discuss here several possible new molecular targets for patients infected with cardiotropic viruses in (1) the cellular virus uptake system, (2) virus-induced cellular signaling pathways, and (3) interactions between virus-encoded proteins with important cellular target proteins. The potential of these approaches in the setting of a chronic viral infection is significantly different from that in an acute viral infection. Specific problems encountered in a chronic situation and possible solutions are discussed.
Output: 6 New Therapeutics Targets in Chronic Viral Cardiomyopathy
Tumor-infiltrating immune cells can impact tumor growth and progression. The inhibitory CD200 receptor (CD200R) suppresses the activation of myeloid cells and lack of this pathway results in a reduction of tumor growth, conversely a tumorigenic effect of CD200R triggering was also described. Here we investigated the role of CD200R activation in syngeneic mouse tumor models. We showed that agonistic CD200R antibody reached tumors, but had no significant impact on tumor growth and minor effect on infiltration of immune myeloid cells. These effects were reproduced using two different anti-CD200R clones. In contrast, we showed that CD200-deficiency did decrease melanoma tumor burden. The presence of either endogenous or tumor-expressed CD200 restored the growth of metastatic melanoma foci. On the basis of these findings, we conclude that blockade of the endogenous ligand CD200 prevented the tumorigenic effect of CD200R-expressing myeloid cells in the tumor microenvironment, whereas agonistic anti-CD200R has no effect on tumor development.
Output: The pro-tumor effect of CD200 expression is not mimicked by agonistic CD200R antibodies
Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual fi gure of almost 60 000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-eff ective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations.
Output: Current status of rabies and prospects for elimination
Background. Experimental inoculation is an important tool for common cold and asthma research. Producing rhinovirus (RV) inocula from nasal secretions has required prolonged observation of the virus donor to exclude extraneous pathogens. We produced a RV-A16 inoculum using reverse genetics and determined the dose necessary to cause moderate colds in seronegative volunteers. Methods. The consensus sequence of RV-A16 from a previous inoculum was cloned, and inoculum virus was produced using reverse genetics techniques. After safety testing, volunteers were inoculated with either RV-A16 (n = 26) or placebo (n = 10), Jackson cold scores were recorded, and nasal secretions were tested for shedding of RV-A16 ribonucleic acid. Results. The reverse genetics process produced infectious virus that was neutralized by specific antisera and had a mutation rate similar to conventional virus growth techniques. The 1000 median tissue culture infectious dose (TCID 50 ) dose produced moderate colds in most individuals with effects similar to that of a previously tested conventional RV-A16 inoculum. Conclusions. Reverse genetics techniques produced a RV-A16 inoculum that can cause clinical colds in seronegative volunteers, and they also serve as a stable source of virus for laboratory use. The recombinant production procedures eliminate the need to derive seed virus from nasal secretions, thus precluding introduction of extraneous pathogens through this route.
Output: Development of a Rhinovirus Inoculum Using a Reverse Genetics Approach
Sustained adaptive immunity to pathogens provides effective protection against infections, and effector cells located at the site of infection ensure rapid response to the challenge. Both are essential for the success of vaccine development. To explore new vaccination approach against Mycobacterium tuberculosis (M.tb) infection, we have shown that Rv3615c, identified as ESX-1 substrate protein C of M.tb but not expressed in BCG, induced a dominant Th1-type response of CD4 + T cells from patients with tuberculosis pleurisy, which suggests a potential candidate for vaccine development. But subcutaneous immunization with Rv3615c induced modest T-cell responses systemically, and showed suboptimal protection against virulent M.tb challenge at the site of infection. Here, we use a mouse model to demonstrate that intranasal immunization with Rv3615c induces sustained capability of adaptive CD4 + T-and B-cell responses in lung parenchyma and airway. Rv3615c contains a dominant epitope of mouse CD4 + T cells, Rv3615c 41-50 , and elicits CD4 + T-cell response with an effector-memory phenotype and multi-Th1-type cytokine coexpressions. Since T cells resident at mucosal tissue are potent at control of infection at early stage, our data show that intranasal immunization with Rv3615c promotes a sustained regional immunity to M.tb, and suggests a potency in control of M.tb infection. Our study warranties a further investigation of Rv3615c as a candidate for development of effective vaccination against M.tb infection. adaptive immunity, CD4, intranasal, mucosal, Mycobacterium tuberculosis, Rv3615c, Th1
Output: Intranasal immunization with Mycobacterium tuberculosis Rv3615c induces sustained adaptive CD4 + T-cell and antibody responses in the respiratory tract
The roles of intracellular second messengers in interferon-y (IFN-'t)-induced Ia antigen (Ag) expression by astroglia and microglia were examined. Ia Ag on both glia types was induced by IFN-~,. Reagents known to increase intracellular cAMP or activate intracellular protein kinase C (PKC) reduced IFN-3,-induced Ia Ag expression by astroglia. In contrast, increasing intracellular cAMP had no suppressive effect on Ia Ag expression by microglia. These results indicate (1) cAMP and PKC negatively regulate IFN-3,-induced Ia expression on astroglia, and (2) Ia expression is regulated differentially in astroglia vs. microglia. These findings may explain the frequent observation of Ia ÷ microglia (or macrophages) but not astroglia in various neurodegenerative diseases.
Output: Differential suppression of interferon-7-induced Ia antigen expression on cultured rat astroglia and microglia by second messengers
Background: Developing methods to reconstruct transmission histories for viral outbreaks could provide critical information to support locating sources of disease transmission. Phylogenetic methods used to measure the degree of relatedness among sequenced viral samples have proven useful in identifying potential outbreak sources. The complex nature of infectious disease, however, makes it difficult to assign a rigorously defined quantitative confidence value assessing the likelihood of a true direct transmission event using genetic data alone. Results: A new method is presented to calculate a confidence value assessing the likelihood of a transmission event using both phylogenetic inference and limited knowledge of incubation and infectious duration times. The method is applied to simulations of a foot and mouth disease (FMD) outbreak to demonstrate how the combination of both phylogenetic and epidemiology data can be used to strengthen the assessment of the likelihood of direct transmission over methods using just phylogenetic data or infection timing data alone. The method is applied to a previous FMD outbreak to identify areas where over confidence in previously inferred direct transmission may exist. Conclusion: Combining knowledge from viral evolution and epidemiology within a single integrated transmission inference framework is an important approach to assess the potential likelihood of transmission events and makes clear how specific features of a virus' spread through the course of an outbreak will directly determine the potential for confidence in inferred host transmission links. Background Developing methods to protect against RNA virus outbreaks in the face of constantly changing disease dynamics remains one of the great public health challenges of our time. One small piece of this problem involves determining the host-pathogen transmission history to identify an outbreak's origin. In recent cases such as the 2003 SARS outbreak [1, 2], H5N1 influenza [3] infection in humans and Marburgvirus [4], phylogenetic inference has been used to help identify potential outbreak sources. Typically, a collection of sequences from candidate related sources are compared to infer transmission links between the most closely related sequences. These methods have been used beyond the public health domain to provide evidence in HIV [5, 6] and other forensic investigations [7] to help infer when a suspect is involved in infecting a victim. P (δ, σ|M ) rather than P (δ|M ). This reflects the desire to estimate the probability of observing the genetic relation δ in conjunction with infection related timing values for the transmission hypothesis M . The σ parameter values are motivated by a SEIR type infection concept [22], which describes a host in one of four 5 . CC-BY-ND 4.0 International license is made available under a
Output: Mapping a viral phylogeny onto outbreak trees to improve host transmission inference
Asthma is a common and debilitating disease that has substantially increased in prevalence in Western Societies in the last 2 decades. Respiratory tract infections by respiratory syncytial virus (RSV) and rhinovirus (RV) are widely implicated as common causes of the induction and exacerbation of asthma. These infections in early life are associated with the induction of wheeze that may progress to the development of asthma. Infections may also promote airway inflammation and enhance T helper type 2 lymphocyte (Th2 cell) responses that result in exacerbations of established asthma. The mechanisms of how RSV and RV induce and exacerbate asthma are currently being elucidated by clinical studies, in vitro work with human cells and animal models of disease. This research has led to many potential therapeutic strategies and, although none are yet part of clinical practise, they show much promise for the prevention and treatment of viral disease and subsequent asthma.
Output: Understanding the mechanisms of viral induced asthma: New therapeutic directions
Herbal formulas from traditional Chinese medicines (TCMs) have been extensively used in clinics as effective therapies, but it is still a great challenge to demonstrate the scientific basis for their therapeutic effects at the level of molecular biology. By taking a classic herbal formula (Yu Ping Feng decoction, YPF) as an example, this study developed a novel network pharmacology based method to identify its potential therapeutic targets. First, this study constructed a "targets-(pathways)-targets" (TPT) network in which targets of YPF were connected by relevant pathways; then, this network was decomposed into separate modules with strong internal connections; lastly, the propensity of each module toward different diseases was assessed by a contribution score. On the basis of a significant association between network modules and therapeutic diseases validated by chi-square test (p-value < 0.001), this study identified the network module with the strongest propensity toward therapeutic diseases of YPF. Further, the targets with the highest centrality in this module are recommended as YPF's potential therapeutic targets. By integrating the complicated "multi-targetsmulti-pathways-multi-diseases" relationship of herbal formulas, the method shows promise for identifying its potential therapeutic targets, which could contribute to the modern scientific illustration of TCMs' traditional clinical applications. Understanding the scientific basis and therapeutic mechanisms of herbal formulas from traditional Chinese medicines (TCMs) is essential since they play a vital role in complementary and alternative therapies in clinical practice to cure diseases or restore the whole-body balance; additionally, they provide a rich source for drug discovery. Owing to the complexity of the constituents in TCMs, reductionism, which individually considers each ingredient, cannot adequately explain the effects generated by an entire formula, and therefore faces several challenges comprehending and illustrating the mechanisms of herbal formulas. With the rapid development of bioinformatics, a combined attempt based on system/network biology and polypharmacology has created a new paradigm called network pharmacology (NP). In recent years, NP has been proposed as a promising approach for understanding herbal formulas 1,2 and predicting potential new drugs or targets 3-5 . To some extent, NP-based research on the underlying therapeutic mechanisms of herbal formulas has been well-accepted 6,7 and accounts for the strong compatibility of different scales of systems. A distinct advantage of network analysis is that it can excavate underlying information from multilevel interactions, especially when dealing with big data. Yu Ping Feng (YPF) decoction, a classic herbal formula, has been used in clinics to treat various diseases, such as respiratory tract infection 8,9 , nosocomial pneumonia 10 , chronic bronchitis 11 , and perennial allergic rhinitis 12,13 .
Output: A network pharmacology-based approach to analyse potential targets of traditional herbal formulas: An example of Yu Ping Feng decoction OPEN
The effect of 100 separate viral infections of the respiratory tract on pulmonary function was evaluated prospectively over an eight-year period in 84 patients with chronic obstructive pulmonary diseases and in eight normal subjects. Some viral infections were associated with small acute declines in forced vital capacity and/or I-sec forced expiratory volume of 25-300 ml. These declines were detectable only during the 9Q-day period after infection. The greatest abnormalities of pulmonary function followed infections with influenza virus, and the mean acute changes in I-sec forced expiratory volume (-118.5 ml) were significantly greater than expected (-15.2 ml; P = 0.03). Smaller, statistically insignificant declines followed infections with parainfluenza virus, rhinovirus, adenovirus, and respiratory syncytial virus, and no changes were detectable after infections with coronavirus, herpes simplex virus, Mycoplasma pneumoniae, and Haemophilus influenzae. Long-term effects of influenza or other viral infections on the course of chronic obstructive pulmonary disease were not detected in this study population. The hypothesis that viral infections of the respiratory tract may contribute to progressive deterioration of airway function in patients with chronic bronchitis, emphysema, and other chronic obstructive pulmonary diseases (COPD) has intrigued investigators for several years [1] [2] [3] [4] [5] . Evidence supporting this hypothesis includes the well-documented association between viral infections and acute exacerbations of bronchitis in patients with COPD [5] [6] [7] [8] [9] [10] [11] [12] , as well as the recent reports that transient alterations in the function of small airways may occur in normal adults after acute viral infections of the respiratory tract [13] [14] [15] [16] [17] [18] [19] .
Output: Effect of Viral Infections on Pulmonary Function in Patients with Chronic Obstructive Pulmonary Diseases
The first responders of human antiviral immunity are components of the intrinsic immune response that reside within each and every one of our cells. This cell-autonomous arsenal consists of nucleic acid sensors and antiviral effectors strategically placed by evolution to detect and restrict invading viruses. While some factors are present at baseline to allow for constant surveillance of the cell interior, others are upregulated by cytokines (such as interferons) that signal a viral infection underway in neighboring cells. In this review, we highlight the multiple roles played by the interferoninduced transmembrane (IFITM) proteins during viral infection, with focuses on IFITM3 and HIV-1. Moreover, we discuss the cellular pathways in which IFITM proteins are intertwined and the various functions they have been ascribed outside the context of infection. While appreciated as broadly-acting, potent restriction factors that prevent virus infection and pathogenesis in cell culture and in vivo, questions remain regarding their precise mode of action and importance in certain viral contexts. Continued efforts to study IFITM protein function will further cement their status as critical host determinants of virus susceptibility and prioritize them in the development of new antiviral therapies.
Output: More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins
New habitat-based models for spread of hantavirus are developed which account for interspecies interaction. Existing habitat-based models do not consider interspecies pathogen transmission, a primary route for emergence of new infectious diseases and reservoirs in wildlife and man. The modeling of interspecies transmission has the potential to provide more accurate predictions of disease persistence and emergence dynamics. The new models are motivated by our recent work on hantavirus in rodent communities in Paraguay. Our Paraguayan data illustrate the spatial and temporal overlap among rodent species, one of which is the reservoir species for Jabora virus and others which are spillover species. Disease transmission occurs when their habitats overlap. Two mathematical models, a system of ordinary differential equations (ODE) and a continuous-time Markov chain (CTMC) model, are developed for spread of hantavirus between a reservoir and a spillover species. Analysis of a special case of the ODE model provides an explicit expression for the basic reproduction number, ℛ 0 , such that if ℛ 0 < 1, then the pathogen does not persist in either population but if ℛ 0 > 1, pathogen outbreaks or persistence may occur. Numerical simulations of the CTMC model display sporadic disease incidence, a new behavior of our habitat-based model, not present in other models, but which is a prominent feature of the seroprevalence data from Paraguay. Environmental changes that result in greater habitat overlap result in more encounters among various species that may lead to pathogen outbreaks and pathogen establishment in a new host.
Output: Author manuscript; available in PMC
The primary step for efficient control of viral diseases is the development of simple, rapid, and sensitive virus detection. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been used to detect viral RNA molecules because of its simplicity and high sensitivity for a number of viruses. RT-LAMP for the detection of Potato virus X (PVX) was developed and compared with conventional reverse transcription polymerase chain reaction (RT-PCR) to demonstrate its advantages over RT-PCR. RT-LAMP reactions were conducted with or without a set of loop primers since one out of six primers showed PVX specificity. Based on real-time monitoring, RT-LAMP detected PVX around 30 min, compared to 120 min for RT-PCR. By adding a fluorescent reagent during the reaction, the extra step of visualization by gel electrophoresis was not necessary. RT-LAMP was conducted using simple inexpensive instruments and a regular incubator to evaluate whether RNA could be amplified at a constant temperature instead of using an expensive thermal cycler. This study shows the potential of RT-LAMP for the diagnosis of viral diseases and PVX epidemiology because of its simplicity and rapidness compared to RT-PCR.
Output: The Plant Pathology Journal Development of a Rapid Detection Method for Potato virus X by Reverse Tran- scription Loop-Mediated Isothermal Amplification
Background: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap. Methods: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging diseases, from 2003 to the end of June 2009. The timeliness gap was calculated as the difference in days between the report release dates of the matching outbreaks in the WHO and ProMED-mail systems. Civil liberties scores were collected as indicators of the transparency of each country. The Human Development Index and data indicating the density of physicians and nurses were collected to reflect countries' development and health workforce statuses. Then, logistic regression was performed to determine the correlation between the timeliness gap and civil liberties, human development, and health workforce status, controlling for year. The reporting timeliness gap for avian flu and H1N1 outbreaks significantly decreased after 2003. On average, reports were posted 4.09 (SD = 7.99) days earlier by ProMED-mail than by the WHO. Countries with partly free (OR = 5.77) and free civil liberties scores (OR = 10.57) had significantly higher likelihoods of longer timeliness gaps than non-free countries. Similarly, countries with very high human development status had significantly higher likelihoods of longer timeliness gaps than countries with middle or low human development status (OR = 5.30). However, no association between the timeliness gap and health workforce density was found. The study found that the adoption of IHR 2005, which contributed to countries' awareness of the importance of timely reporting, had a significant impact in improving the reporting timeliness gap. In addition, the greater the civil liberties in a country (e.g., importance of freedom of the media), the longer the timeliness gap.
Output: Is the reporting timeliness gap for avian flu and H1N1 outbreaks in global health surveillance systems associated with country transparency?
Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed. coronavirus / experimental infection / FECV / persistence / cat
Output: Pathogenic characteristics of persistent feline enteric coronavirus infection in cats
Enhancing citizens' and communities' resilience is critical to adapt successfully to ongoing challenges faced by communities, as well as acute shocks resulting from disasters. While significant progress has been made in this area, several research and practice gaps remain. A crucial next step to advance resilience is the development of a resilience-oriented workforce. This narrative review examines existing literature to determine key components of a resilience-oriented workforce, with a focus on organizational structures, training and education, and leadership models. Reviewed articles spanned a variety of study types, including needs assessments of existing workforce, program evaluations, and reviews/commentaries. A resilience-oriented workforce spans many disciplines and training programs will need to reflect that. It requires a collaborative organizational model that promotes information sharing structures. Leadership models should foster a balance between workforce autonomy and operation as a collective entity. Optimal strategies to develop a resilience-oriented workforce have yet to be realized and future research will need to collect and synthesize data to promote and evaluate the growth of this field.
Output: Beyond Disaster Preparedness: Building a Resilience-Oriented Workforce for the Future
Poland has implemented the influenza surveillance system called Sentinel as of 2004. The system consists of both epidemiological and virological surveillance. It is an important tool for monitoring the situation in the entire country, coordinated by the National Influenza Center situated at the National Institute of Public Health-National Institute of Hygiene (NIPH-NIH) in Warsaw, Poland. In the 2015/2016 epidemic season, more than 1600 samples were tested in the Sentinel System, of which 38.6% were positive. The samples were evaluated in seven age-groups: 0-4, 5-9, 10-14, 15-25, 26-44, 45-64, and over 65 years of age. Significant differences were reported in the number of confirmed cases of infection caused by influenza and influenza-like viruses, depending on the age-group. The highest number of confirmed cases of infections was reported for the age range of 26-44 years, accounting for 30% of the total. In each age-group, the presence of infection caused by influenza-like viruses, collectively accounting for only 3.8% of all positive tests, was also confirmed. Weekly reports generated by the Sentinel System enable to determine and control a current influenza activity in the country, which is of essential importance in case of the emergence of a new strain with a pandemic potential.
Output: The Sentinel System as the Main Influenza Surveillance Tool
Objective: Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI. Results: Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36-100% and 98.35-100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.
Output: Phylogenic analysis of human bocavirus detected in children with acute respiratory infection in Yaounde, Cameroon
Background: An ongoing outbreak of mystery pneumonia in Wuhan was caused by coronavirus disease 2019 . The infectious disease has spread globally and become a major threat to public health. We aim to investigate the ultra-high-resolution CT (UHR-CT) findings of imported COVID-19 related pneumonia from the initial diagnosis to early-phase follow-up. Methods: This retrospective study included confirmed cases with early-stage COVID-19 related pneumonia imported from the epicenter. Initial and early-phase follow-up UHR-CT scans (within 5 days) were reviewed for characterizing the radiological findings. The normalized total volumes of ground-glass opacities (GGOs) and consolidations were calculated and compared during the radiological follow-up by artificial-intelligence-based methods. Results: Eleven patients (3 males and 8 females, aged 32-74 years) with confirmed COVID-19 were evaluated. Subpleural GGOs with inter/intralobular septal thickening were typical imaging findings. Other diagnostic CT features included distinct margins (8/11, 73%), pleural retraction or thickening (7/11, 64%), intralesional vasodilatation (6/11, 55%). Normalized volumes of pulmonary GGOs (p=0.003) and consolidations (p=0.003) significantly increased during the CT follow-up. The abnormalities of GGOs with peripleural distribution, consolidated areas, septal thickening, pleural involvement and intralesional vasodilatation on UHR-CT indicate the diagnosis of COVID-19. COVID-19 cases could manifest significantly progressed GGOs and consolidations with increased volume during the early-phase CT follow-up.
Output: Ultra-High-Resolution CT Follow-Up in Patients with Imported Early-Stage
Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This organism is unique in that it causes proliferation of infected enterocytes, resulting in thickening of the intestinal epithelium, most often the small intestine. This disease affects mainly weanling foals and causes fever, lethargy, peripheral edema, diarrhea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinemia, thickening of segments of the small intestinal wall observed on abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in feces. The epidemiology and genetic basis for pathogenesis for this disease is beginning to be elucidated. Phenotypic traits, genomic features, and gene expression profiles during L. intracellularis infection in vitro and in vivo are presented. In addition, this article reviews the epidemiology, pathological and clinicopathological findings, diagnosis, and control of EPE. ß
Output: Lawsonia intracellularis infection and proliferative enteropathy in foals
Bovine norovirus (BNoV) has emerged as a viral pathogen that causes a gastrointestinal illness and diarrhea in cattle. Despite its worldwide distribution, very little information is known about BNoV in Africa. In this study, BNoV was detected in 27.6% (8/29) of tested fecal materials, collected from sporadic cases of diarrheic calves, using the reverse transcription-polymerase chain reaction (RT-PCR) and primers that target RNA dependent RNA polymerase gene. Additionally, one primer pair was designed to flank the BNoV-VP2 (small capsid protein) gene for molecular analysis. Study VP2 sequences were phylogenetically-related to BNoV-GIII.2 (Newbury2-like) genotype, which is highly prevalent all over the world. However, they were separated within the cluster and one strain (41FR) grouped with recombinant GIII.P1/GIII.2 strains. Compared to reference VP2 sequences, 14 amino acid substitution mutations were found to be unique to our strains. The study confirms that BNoV is currently circulating among diarrheic calves of Egypt and also characterizes its ORF3 (VP2) genetically. The status of BNoV should be continuously evaluated in Egypt for effective prevention and control. T 1 The BNoV-RdRp targeting primers were used in one step RT-PCR for the purpose of BNoV detection. 2 The BNoV-VP2 targeting primers were used in one step RT-PCR for the purpose of sequencing and molecular analysis. 3 F; forward (sense) primer, R; reverse (antisense) primer. 4 The VP2 specific primers were designed based on the GenBank reference sequence (Bo/Newbury2/1976/UK/ AF097917).
Output: Phylogeny of bovine norovirus in Egypt based on VP2 gene
Infectious disease outbreaks often have consequences beyond human health, including concern among the population, economic instability, and sometimes violence. A warning system capable of anticipating social disruptions resulting from disease outbreaks is urgently needed to help decision makers prepare appropriately. We designed a system that operates in near real-time to identify and predict social response. Over 150,000 Internet-based news articles related to outbreaks of 16 diseases in 72 countries and territories were provided by HealthMap. These articles were automatically tagged with indicators of the disease activity and population reaction. An anomaly detection algorithm was implemented on the population reaction indicators to identify periods of unusually severe social response. Then a model was developed to predict the probability of these periods of unusually severe social response occurring in the coming week, 2 and 3 weeks. This model exhibited remarkably strong performance for diseases with substantial media coverage. For country-disease pairs with a median of 20 or more articles per year, the onset of social response in the next week was correctly predicted over 60% of the time, and 87% of weeks were correctly predicted. Performance was weaker for diseases with little media coverage, and, for these diseases, the main utility of our system is in identifying social response when it occurs, rather than predicting when it will happen in the future. Overall, the developed near real-time prediction approach is a promising step toward developing predictive models to inform responders of the likely social consequences of disease spread. This research was funded by Defense Threat Reduction Agency (www.dtra.mil) contact HDTRA1-12-C-0061.
Output: Predicting social response to infectious disease outbreaks from internet-based news streams
Introduction: Acute respiratory infections (ARI) result in substantial annual morbidity among military personnel and decrease operational readiness. Herein, we summarize the research efforts of the Infectious Disease Clinical Research Program (IDCRP) related to ARIs. Methods: The ARI Research Area of the IDCRP was established in response to the 2009 emergence of pandemic influenza A/H1N1. That year, IDCRP investigators deployed the ARI Consortium Natural History Study (ARIC NHS), a multi-centered, longitudinal observational study to assess etiology, epidemiology, and clinical characteristics of influenza-like illness (ILI) and severe acute respiratory infections (SARI) in the U.S. military. The success of this initial effort spurred implementation of several new initiatives. These include the FluPlasma trial, designed to evaluate the efficacy of hyperimmune anti-influenza plasma for the treatment of severe influenza; the self-administered live-attenuated influenza vaccine (SNIF) trial, which assessed the immunogenicity and acceptance of a self-administered live-attenuated influenza vaccine in military personnel; the Study to Address Threats of ARI in Congregate Military Populations (ATARI), a prospective study of ILI transmission, etiology and epidemiology in recruits; and the Flu Breath Test (FBT) study, a preliminary study of exhaled volatile organic compounds (VOC) in influenza patients. In addition, the InFLUenza Patient-Reported Outcome (FLU-PRO) survey, a daily diary to measure influenza symptoms during clinical trials, was developed. Lastly, the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study, a two-year randomized trial designed to compare the effectiveness of the three types of licensed vaccines, launched in Fall 2018. Results: The on-going ARIC NHS has enrolled over 2000 ILI and SARI cases since its inception, providing data on burden and clinical manifestations of ARI in military personnel and their families. The FluPlasma 2 trial concluded subject enrollment in 2018. Preliminary results from ATARI study show a high frequency of respiratory viruses circulating during the first two weeks of recruit training. Based on assessment of FLU-PRO responses, which were found to be reliable and reproducible, the survey may be a useful tool in clinical trials and epidemiological studies. The Flu Breath Study will complete enrollment in 2019. Findings from PAIVED are intended to provide evidence needed for assessing influenza vaccination policy in the military. Conclusions: The ARI burden in the armed services remains significant every year and the threat is dynamic given emergent and evolving threats, such as influenzas. With strong successes to date, future initiatives of the ARI Research Area will focus on interventional studies, ARI transmission dynamics in congregate military settings, and determinants of risk of pandemic influenza and other emergent respiratory viruses.
Output: The Acute Respiratory Infection Consortium: A Multi-Site, Multi-Disciplinary Clinical Research Network in the Department of Defense
Pandemic 2009 H1N1 is normally susceptible to oseltamivir, but variants harboring the H275Y (CAC → TAC) mutation exhibit resistance. We describe the use of a combined reverse-transcription polymerase chain reaction (RT-PCR)/pyrosequencing approach to identify the H275 residue. A total of 223 specimens were tested with this method: 216 randomly selected clinical specimens positive for 2009 H1N1 and 7 cell-culture supernatants from the Centers for Disease Control and Prevention (CDC; 4 resistant, 3 susceptible 2009 H1N1 strains). The assay detected H275Y in 1 clinical respiratory sample (0.5%) and all 4 oseltamivir-resistant strains from the CDC; the remaining 215 clinical and 3 susceptible CDC specimens were wild-type. Sanger sequencing confirmed the results for 50 of 50 selected isolates. The RT-PCR/pyrosequencing method was highly specific, producing no amplicons or valid sequences from samples containing non-H1N1 viruses or bacteria. Our findings suggest that this method provides a rapid tool for H275Y detection, with high sensitivity and potential benefit for patient care.
Output: Reverse-transcription polymerase chain reaction/pyrosequencing to characterize neuraminidase H275 residue of influenza A 2009 H1N1 virus for rapid and specific detection of the viral oseltamivir resistance marker in a clinical laboratory
Previous studies have shown that bats are reservoirs of a large number of viruses, many of which cause illness and mortality in humans and other animals. However, these batassociated pathogens cause little, if any, clinicopathology in bats. This long-term adaptation should be reflected somewhat in the immune system. Toll-like receptors (TLRs) are the first line of immune defense against pathogens in vertebrates. Therefore, this study focuses on the selection of TLRs involved in virus recognition. The coding sequences of TLR3, TLR7, TLR8, and TLR9 were sequenced in ten bats. The selection pressure acting on each gene was also detected using branch-and site-specific methods. The results showed that the ancestor of bats and certain other bat sublineages evolved under positive selection for TLR7, TLR8, and TLR9. The highest proportion of positive selection occurred in TLR9, followed by TLR8 and TLR7. All of the positively selected sites were located in the leucine-rich repeat (LRR) domain, which implied their important roles in pathogen recognition. However, TLR3 evolved under negative selection. Our results are not in line with previous studies which identified more positively selected sites in TLR8 in mammalian species. In this study, the most positively selected sites were found in TLR9. This study encompassed more species that were considered natural reservoirs of viruses. The positive selection for TLR7, TLR8, and TLR9 might contribute to the adaptation of pathogen-host interaction in bats, especially in bat TLR9.
Output: Selective evolution of Toll-like receptors 3, 7, 8, and 9 in bats
Cylindrical protein scaffolds are thought to stabilize membrane tubules, preventing membrane fission. In contrast, Snead et al. find that when scaffold proteins assemble, bulky disordered domains within them become acutely concentrated, generating steric pressure that destabilizes tubules, driving fission. Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysinrvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of BAR domains in isolation, the current paradigm is that they polymerize into cylindrical scaffolds that stabilize lipid tubules, preventing membrane fission. But in nature BAR domains are often part of multi-domain proteins that contain large intrinsically-disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domaincontaining proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data challenge the idea that cellular membranes adopt the curvature of BAR scaffolds, suggesting instead that the ability to concentrate disordered domains is the key requirement for membrane remodeling and fission by BAR domain-containing proteins. All rights reserved. No reuse allowed without permission.
Output: BAR scaffolds drive membrane fission by crowding disordered domains
Fifty-five volunteers treated with either intranasal recombinant interferon (rIFN; 2 x 10 6 IV/day) or placebo for 15 days were exposed to coronavirus by direct intranasal inoculation on the eighth day of treatment. Symptom scores were recorded, and cultures of virus were taken daily for all volunteers for seven days after inoculation. Nineteen (73%) of the 26 placebo recipients met symptom-score criteria for a cold, compared with 12 (41070) of the IFN recipients (P = .02). The mean nasal symptom scores in the placebo and IFN groups were 9.2 and 5.4, respectively (P = .03), and the mean total symptom scores in the two groups were 23.2 and 9.4, respectively (P = .003). The mean number of days with a total symptom score >4 was 1.6 in the placebo recipients and 0.5 in the rIFN recipients (P = .02). Prophylactic intranasal rIFN effectively shortened the duration and reduced the severity of coronavirus cold symptoms.
Output: Prevention of Experimental Coronavirus Colds with Intranasal (l-2b Interferon
Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged as a causative agent of severe respiratory disease in humans. Here, we constructed recombinant modified vaccinia virus Ankara (MVA) expressing full-length MERS-CoV spike (S) protein (MVA-MERS-S). The genetic stability and growth characteristics of MVA-MERS-S make it a suitable candidate vaccine for clinical testing. Vaccinated mice produced high levels of serum antibodies neutralizing MERS-CoV. Thus, MVA-MERS-S may serve for further development of an emergency vaccine against MERS-CoV.
Output: Middle East Respiratory Syndrome Coronavirus Spike Protein Delivered by Modified Vaccinia Virus Ankara Efficiently Induces Virus-Neutralizing Antibodies
When type III interferon (IFN-l; also known as interleukin-28 and IL-29) was discovered in 2003, its antiviral function was expected to be analogous to that of type I IFNs (IFN-a and IFN-b) via the induction of IFN-stimulated genes (ISGs). Although IFN-l stimulates expression of antiviral ISGs preferentially in cells of epithelial origin, recent studies have defined additional antiviral mechanisms in other cell types and tissues. Viral infection models using mice lacking IFN-l signaling and SNP associations with human disease have expanded our understanding of the contribution of IFN-l to the antiviral response at anatomic barriers and the immune response beyond these barriers. In this review, we highlight recent insights into IFN-l functions, including its ability to restrict virus spread into the brain and to clear chronic viral infections in the gastrointestinal tract. We also discuss how IFN-l modulates innate and adaptive immunity, autoimmunity, and tumor progression and its possible therapeutic applications in human disease.
Output: Interferon-l: Immune Functions at Barrier Surfaces and Beyond
To analyze the impact of different patterns of migration flow in two cities, Hefei and Shenzhen, on the epidemic and disease control of Coronavirus Disease 2019 , in order to provide insight for making differentiated controlling policies. Hefei and Shenzhen between January 19 and February 11, 2020, from data officially published by the provincial and municipal Centers for Disease Control and Prevention (CDC). From these data we calculated basic reproduction number R0 to reflect the rate of spread of COVID-19 in these cities. Aggregated data of population migration during the same period was extracted from Baidu Migration. The change of R0 in the two cites were analyzed and compared. Spearman correlation analysis between R0 and population inflow from epidemic focus were performed.
Output: Association of Population migration and Coronavirus Disease 2019 epidemic control