niryuu/sni-each-converted huggingface dataset:
An outbreak of a novel coronavirus, named CoVID-19, was first reported in China on 31 December 2019. As of 9 February 2020, cases have been reported in 25 countries, including probable cases of human-to-human transmission in England. We adapted an existing national-scale metapopulation model to capture the spread of CoVID-19 in England and Wales. We used 2011 census data to capture population sizes and population movement, together with parameter estimates from the current outbreak in China. We predict that a CoVID-19 outbreak will peak 126 to 147 days (~4 months) after the start of person-to-person transmission in England and Wales in the absence of controls, assuming biological parameters remain unchanged. Therefore, if person-to-person transmission persists from February, we predict the epidemic peak would occur in June. The starting location has minimal impact on peak timing, and model stochasticity varies peak timing by 10 days. Incorporating realistic parameter uncertainty leads to estimates of peak time ranging from 78 days to 241 days after person-to-person transmission has been established. Seasonal changes in transmission rate substantially impact the timing and size of the epidemic peak, as well as the total attack rate. We provide initial estimates of the potential course of CoVID-19 in England and Wales in the absence of control measures. These results can be refined with improved estimates of epidemiological parameters, and permit investigation of control measures and cost effectiveness analyses. Seasonal changes in transmission rate could shift the timing of the peak into winter months, which will have important implications for health-care capacity planning.
Output: A spatial model of CoVID-19 transmission in England and Wales: early spread and peak timing
The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring. Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calciumphosphate. We have analysed the role of the milk protein a-casein by inactivating the corresponding gene in mice. Absence of a-casein protein significantly curtails secretion of other milk proteins and calcium-phosphate, suggesting a role for a-casein in the establishment of casein micelles. In contrast, secretion of albumin, which is not synthesized in the mammary epithelium, into milk is not reduced. The absence of a-casein also significantly inhibits transcription of the other casein genes. a-Casein deficiency severely delays pup growth during lactation and results in a life-long body size reduction compared to control animals, but has only transient effects on physical and behavioural development of the pups. The data support a critical role for a-casein in casein micelle assembly. The results also confirm lactation as a critical window of metabolic programming and suggest milk protein concentration as a decisive factor in determining adult body weight.
Output: Milk Lacking a-Casein Leads to Permanent Reduction in Body Size in Mice
h i g h l i g h t s • We obtained a spatial epidemic model with logistic growth. • Using multiple-scale analysis, we present amplitude equations. • There are different types of stationary patterns. • Reaction diffusion epidemic systems have rich dynamics. Mathematical models are very useful in analyzing the spread and control of infectious diseases which can be used to predict the developing tendency of the infectious disease, determine the key factors and to seek the optimum strategies of disease control. As a result, we investigated the pattern dynamics of a spatial epidemic model with logistic growth. By using amplitude equation, we found that there were different types of stationary patterns including spotted, mixed, and stripe patterns, which mean that spatial motion of individuals can form high density of diseases. The obtained results can be extended in other related fields, such as vegetation patterns in ecosystems.
Output: Physica A Dynamics of an epidemic model with spatial diffusion
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious 24 disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a 25 high fatality rate. Currently, no specific vaccine or treatment has been approved for this 26 disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-27 displayed antibody library that was constructed from a patient who recovered from SFTS 28 virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope 29 glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in 30 vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 31 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass 32 spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn 33 glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a 34 conformational alteration that is critical for cell membrane fusion between the virus and host 35 cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 36 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 37 247 of 272 reported SFTSV isolates previously reported. Together, these data suggest that 38 Ab10 has potential to be developed into a therapeutic agent that could protect against more 39 than 90% of reported SFTSV isolates. 40 41
Output: An anti-Gn glycoprotein antibody from a convalescent patient potently 2 inhibits the infection of severe fever with thrombocytopenia syndrome virus
The UBA domain is a conserved sequence motif among polyubiquitin binding proteins. For the first time, we demonstrate a systematic, high throughput approach to identification of UBA domain-interacting proteins from a proteome-wide perspective. Using the rabbit reticulocyte lysate in vitro expression cloning system, we have successfully identified eleven proteins that interact with p62's UBA domain, and the majority of the eleven proteins are associated with neurodegenerative disorders, such as Alzheimer's disease. Therefore, p62 may play a novel regulatory role through its UBA domain. Our approach provides an easy route to the characterization of UBA domain interacting proteins and its application will unfold the important roles that the UBA domain plays.
Output: A Method to Identify p62's UBA Domain Interacting Proteins
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by SFTS virus and characterized by a high case fatality rate. Currently, there is no effective therapy for the disease. While the administration of ribavirin does not improve the case fatality rate or viral load in patient blood, it can inhibit viral infection in vitro. Methods: Vero cells were pre-treated with interferons (IFNs) α, β, and γ alone and in combination with ribavirin drugs and inoculated with SFTS virus. Three days later, supernatants were harvested and subjected to virus titration. An unpaired t-test was used for statistical analysis of the drugs' effects. Results: While the effects of IFNγ at high concentrations were slightly weaker than those of the other IFNs, all IFNs showed dose-dependent inhibitory effects. The combined usage of IFNs with ribavirin at 90 % effective concentrations showed large inhibitory effects, with over a 3 log 10 reduction in viral titers. The combined usage of one of type-I/II IFNs with ribavirin drastically reduced SFTS virus infection and therefore may be useful in the treatment of SFTS.
Output: Combination effects of ribavirin and interferons on severe fever with thrombocytopenia syndrome virus infection
Hepatitis C virus (HCV) is a small, enveloped RNA virus that is often capable of establishing a persistent infection, which may lead to chronic liver disease, cirrhosis, hepatocellular carcinoma, and eventually death. For more than 20 years, hepatitis C patients have been treated with interferon-alpha (IFN-α). Current treatment usually consists of polyethylene glycol-conjugated IFN-α that is combined with ribavirin, but even the most advanced IFN-based therapies are still ineffective in eliminating the virus from a large proportion of individuals. Therefore, a better understanding of the IFN-induced innate immune response is urgently needed. By using selectable self-replicating RNAs (replicons) and, more recently, recombinant full-length genomes, many groups have tried to elucidate the mechanism(s) by which IFNs inhibit HCV replication. This chapter attempts to summarize the current state of knowledge in this interesting field of HCV research.
Output: Interferon-Induced Effector Proteins and Hepatitis C Virus Replication
We have recently identified a rare subpopulation of lung colony cells with the characteristics of pulmonary stem cells, and discovered that stem cell colonies grew preferentially on type I collagen films in a serum-free medium. In order to further optimize culture conditions and determine stem cell growth in relation to microenvironments (including the stroma, medium and nanostructures of type I collagen films), both primary and pre-sorted stem cells were cultured on the type I collagen films with controllable degree of polymerization and film thickness, as confirmed by an atomic force microscope and surface profiler. We found that in a primary culture, the spreading of stromal cells is greatly restrained and both the size and number of colonies are significantly reduced on highly polymerized collagen films. In contrast, in a pre-sorted stem cell culture without stromal cells, the intrinsic stem cell properties and cell number are independent of the degree of collagen polymerization. Our results indicate that the nanostructures of type I collagen films primarily affect stem colony formation through the collagene stroma interactions. In those cases, collagen film thickness shows no effect on colony formation.
Output: The influence of collagen film nanostructure on pulmonary stem cells and collagenestromal cell interactions
Background/Aims: Interferon and ribavirin combination therapy for chronic hepatitis C induces a low response rate in human immunodeficiency virus (HIV) infected patients. To assess the impact of intensification of interferon administration and of the addition of amantadine on the efficacy and safety of standard anti-hepatitis C virus (HCV) treatment in HIV-infected patients. Methods: Multicentre, prospective, open-label, randomized, phase III clinical trial. Eighty co-infected patients were randomized to receive ribavirin 800 -1000 mg/day in combination with, group A: interferon alpha2a 3 MIU thrice weekly; group B: IFNa2a 3 MIU daily, plus amantadine 200 mg/day; treatment duration was 24 -48 weeks according to HCV genotype. Results: Forty-one patients were randomized in group A and 39 in group B. Intention-to-treat analysis showed a sustained virological response, defined as HCV-RNA negativization, 6 months after stopping treatment in 22% of patients from group A and 13% from group B (P > 0.05). The lack of a 2-log drop in HCV-RNA levels after 12 weeks of treatment showed a 100% predictive value of lack of sustained response. Conclusions: Amantadine addition and interferon intensification do not improve the low efficacy of combination of interferon alfa plus ribavirin in HIV/HCV co-infected patients. Patients with no early virologic response did not have any probability of sustained response. q
Output: A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients q
Hypokalemic paralysis is a medical emergency due to the risks of cardiac arrhythmia, respiratory failure, and rhabdomyolysis. Besides supplementing patients with KCl to hasten recovery, the astute physician must search for the underlying cause to avoid missing a treatable and curable disorder. We report on an elderly Korean man who presented with marked limb paralysis, myalgias, and mild hypertension. He had prostate cancer treated with orchiectomy and hormone therapy 2 years previously. The major biochemical abnormalities were hypokalemia (K + : 1.7 mmol/l) associated with high renal K + wasting and metabolic alkalosis (HCO 3 : 42.6 mmol/l). Low plasma renin activity, low aldosterone concentration, and normal cortisol concentration pointed to a state of pseudohyperaldosteronism. While reviewing his drug history, the patient revealed he had been consuming eight packs (100 ml/pack) of a Korean herbal tonic daily to treat his prostate cancer for the past 2 months. A significant amount of glycyrrhizic acid (0.23 mg/ml), an active ingredient of licorice, was detected in the tonic. Discontinuation of the herbal tonic along with KCl supplementation achieved recovery in 2 weeks. As many complementary/alternative medicines for cancer contain licorice, this must be kept in mind as a cause of hypokalemia in cancer patients.
Output: A hidden cause of hypokalemic paralysis in a patient with prostate cancer
Purpose To study the levels of perceived threat, perceived severity, perceived vulnerability, response efficacy, and selfefficacy for severe acute respiratory syndrome (SARS) and eight other diseases in five European and three Asian countries. Method A computer-assisted phone survey was conducted among 3,436 respondents. The questionnaire focused on perceived threat, vulnerability, severity, response efficacy, and self-efficacy related to SARS and eight other diseases. Results Perceived threat of SARS in case of an outbreak in the country was higher than that of other diseases. Perceived vulnerability of SARS was at an intermediate level and perceived severity was high compared to other diseases. Perceived threat for SARS varied between countries in Europe and Asia with a higher perceived severity of SARS in Europe and a higher perceived vulnerability in Asia. Response efficacy and self-efficacy for SARS were higher in Asia compared to Europe. In multiple linear regression analyses, country was strongly associated with perceived threat. Conclusions The relatively high perceived threat for SARS indicates that it is seen as a public health risk and offers a basis for communication in case of an outbreak. The strong association between perceived threat and country and different regional patterns require further research.
Output: Perceived Threat, Risk Perception, and Efficacy Beliefs Related to SARS and Other (Emerging) Infectious Diseases: Results of an International Survey
SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates ofthe virus were completely sequenced. To explore the genesis of SARS-ON, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Our results show that all SARS-CoV isolates were clustered into a clique and previously identified coronaviruses formed the other clique. Meanwhile, the three groups of coronaviruses depart from each other clearly in our tree that is consistent with the results of prevenient papers. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. The topology map also shows that the 12 SARS-CoV isolates may be divided into two groups determined by the association with the SARS-CoV from the Hotel M in Hong Kong that may give some information about the infectious relationship of the SARS.
Output: Phylogeny of SARS-CoV as inferred from complete genome comparison
Antiviral roles of natural killer (NK) cell subsets were examined in C57BL/6 mice infected with murine cytomegalovirus (MCMV) and other viruses, including lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and mouse hepatitis virus (MHV). Each virus vigorously induced an NK cell infiltrate into the peritoneal cavity and liver, causing some redistributions of NK cell subsets defined by monoclonal antibody (mAb) directed against Ly49A, C/I, D, and G2. Striking results were seen with a mAb (1F8) reactive with the positively signaling molecule Ly49H, present in MCMV-resistant C57BL/6 mice. mAb 1F8 also stains Ly49 C and I, but exclusion of those reactivities with mAb 5E6, which recognizes Ly49 C and I, indicated that Ly49H ϩ cells infiltrated the peritoneal cavity and liver and were particularly effective at synthesizing interferon ␥ . Depletion of 1F8 ϩ but not 5E6 ϩ cells in vivo by mAb injections enhanced MCMV titers by 20-1,000-fold in the spleen and approximately fivefold in the liver. Titers of LCMV or VV were not enhanced. These anti-MCMV effects were attributed to prototypical NK1.1 ϩ CD3 Ϫ NK cells and not to NK1.1 ϩ CD3 ϩ "NK/T" cells. This is the first evidence that control of a virus infection in vivo is mediated by a distinct NK cell subset.
Output: Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49H
A series of doubly flexible nucleoside analogues were designed based on the acyclic sugar scaffold of acyclovir and the flex-base moiety found in the fleximers. The target compounds were evaluated for their antiviral potential and found to inhibit several coronaviruses. Significantly, compound 2 displayed selective antiviral activity (CC 50 > 3x EC 50 ) towards human coronavirus (HCoV)-NL63 and Middle East respiratory syndrome-coronavirus, but not severe acute respiratory syndrome-coronavirus. In the case of HCoV-NL63 the activity was highly promising with an EC 50 < 10 μM and a CC 50 > 100 μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.
Output: Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity Graphical abstract HHS Public Access Author manuscript
This chapter is focused on the development and use of acoustic wave biosensor platforms for the detection of bacteria, specifically those based on the thickness shear mode (TSM) resonator. We demonstrated the mechanical and electrical implications of bacterial positioning at the solid-liquid interface of a TSM biosensor and presented a model of the TSM with bacteria attached operating as coupled oscillators. The experiments and model provide an understanding of the nature of the signals produced by acoustic wave devices when they are used for testing bacteria. The paradox of "negative mass" could be a real threat to the interpretation of experimental results related to the detection of bacteria. The knowledge of the true nature of "negative mass" linked to the strength of bacteria attachment will contribute significantly to our understanding of the results of "weighing bacteria." The results of this work can be used for bacterial detection and control of processes of bacterial settlement, bacterial colonization, biofilm formation, and bacterial infection in which bacterial attachment plays a role.
Output: Acoustic Wave (TSM) Biosensors: Weighing Bacteria
In recent years, several emerging zoonotic vector-borne infections with potential impact on human health have been identified in Europe, including tularaemia, caused by Francisella tularensis. This remarkable pathogen, one of the most virulent microorganisms currently known, has been detected in increasingly new settings and in a wide range of wild species, including lagomorphs, rodents, carnivores, fish and invertebrate arthropods. Also, a renewed concern has arisen with regard to F. tularensis: its potential use by bioterrorists. Based on the information published concerning the latest outbreaks, the aim of this paper is to review the main features of the agent, its biology, immunology and epidemiology. Moreover, special focus will be given to zoonotic aspects of the disease, as tularaemia outbreaks in human populations have been frequently associated with disease in animals.
Output: Tularaemia: A challenging zoonosis
A 31 year old male with a history of diabetes mellitus type 1 and recent skin infection of the neck (for which he underwent incision and drainage and levofloxacin treatment) presented to the emergency department with a three day history of fever, cough productive of bloody sputum, and shortness of breath. He had recently returned from a trip to Asia. He was tachycardic but normotensive and had an oxygen saturation of 93 % on 3 L nasal cannula. WBC count was 21.8 K/UL with 90 % neutrophils, BUN and creatinine were 8 mg/dL and 1.0 mg/dL, respectively, and glucose >350 mg/dL. Suspicion of cavitary pneumonia on chest radiograph was confirmed by computed tomography (Fig. 20.1 ).
Output: Community Acquired Pneumonia Principles of Management Site-of-Care Decisions Patients admitted to the ICU with severe community-acquired pneumonia (CAP) generally fall into one of two categories: (1) those whose
Despite garnering minimal attention from the medical community overall, olfaction is indisputably critical in the manner in which we as humans interact with our surrounding environment. As the initial anatomical structure in the olfactory pathway, the nasal airway plays a crucial role in the transmission and perception of olfactory stimuli. The goal of this chapter is to provide a comprehensive overview of olfactory disturbances as it pertains to the sinonasal airway. This comprises an in-depth discussion of clinically relevant nasal olfactory anatomy and physiology, classification systems of olfactory disturbance, as well as the various etiologies and pathophysiologic mechanisms giving rise to this important disease entity. A systematic clinical approach to the diagnosis and clinical workup of olfactory disturbances is also provided in addition to an extensive review of the medical and surgical therapeutic modalities currently available.
Output: Diseases of the nasal cavity
Vaxign is the first web-based vaccine design system that predicts vaccine targets based on genome sequences using the strategy of reverse vaccinology. Predicted features in the Vaxign pipeline include protein subcellular location, transmembrane helices, adhesin probability, conservation to human and/or mouse proteins, sequence exclusion from genome(s) of nonpathogenic strain(s), and epitope binding to MHC class I and class II. The precomputed Vaxign database contains prediction of vaccine targets for > 70 genomes. Vaxign also performs dynamic vaccine target prediction based on input sequences. To demonstrate the utility of this program, the vaccine candidates against uropathogenic Escherichia coli (UPEC) were predicted using Vaxign and compared with various experimental studies. Our results indicate that Vaxign is an accurate and efficient vaccine design program.
Output: Methodology Report Vaxign: The First Web-Based Vaccine Design Program for Reverse Vaccinology and Applications for Vaccine Development
To circumvent limitations of poor antigen presentation and immunogenicity of DNA vaccines that target induction of CD8 + T cell immunity, we have generated single chain MHC I trimers (MHC I SCTs) composed of a single polypeptide chain with a linear composition of antigenic peptide, β2microglobulin, and heavy chain of a MHC class I molecule connected by flexible linkers. Because of its pre-assembled nature, the SCT presents enhanced expression and presentation of the antigenic peptide/MHC complexes at the cell surface. Furthermore, DNA vaccination with a plasmid DNA encoding an SCT incorporating an immunodominant viral epitope elicited protective CD8 + T cell responses against lethal virus infection. To extend these findings, here we tested the efficacy of SCT DNA vaccines against bacterial infections. In a mouse infection model of Listeria monocytogenes, the SCT DNA vaccine encoding H-2K d and the immunodominant peptide LLO 91-99 generated functional primary and memory peptide-specific CD8 + T cells that confer partial protection against L. monocytogenes infection. DNA immunization of K d /LLO 91-99 SCTs generated functional memory CD8 + T cells independently of CD4 + T cells, although the expression of cognate or non-cognate CD4 + helper T cell epitopes further enhanced the protective efficacy of SCTs. Our study further demonstrates that the SCT serves as a potent platform for DNA vaccines against various infectious diseases.
Output: Single Chain MHC I trimer-based DNA vaccines for protection against Listeria monocytogenes infection
To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases.
Output: viruses How Polyomaviruses Exploit the ERAD Machinery to Cause Infection
Respiratory pathogens are thought to be involved in the pathogenesis and exacerbations of asthma at all ages; however, little is known about the airway microbiome in the elderly. Aim of the study: To identify respiratory pathogens in the induced sputum (IS) of elderly asthmatics, and to determine the association between pathogens and the markers of asthma activity. Material and methods: Twenty-nine subjects with stable asthma, 15 above 65 years of age and 14 aged 30-49 years, underwent clinical evaluation, fractional exhaled nitric oxide measurement, and sputum induction. Pathogens were detected by multiplex reverse transcription polymerase chain reaction. The periostin concentration of IS supernatants was measured by enzyme-linked immunosorbent assay. Serum eosinophil cationic protein and total IgE levels were measured by ImmunoCAP. Conclusions: Despite the existence of differences in some clinical and inflammatory characteristics of asthma between elderly and non-elderly asthmatics, the pathogen detection rates in the IS from the two groups are similar.
Output: The profile of respiratory pathogens in induced sputum of elderly and non-elderly asthmatics
Background: Viral respiratory infection has long been known to influence the occurrence of asthma exacerbations. Over the last 20 years much effort has been put into clarifying the role that viral respiratory infections play in the eventual development of asthma. Scope of review: In this review we give a general background of the role of viruses in the processes of asthma exacerbation and asthma induction. We review recent additions to the literature in the last 3 years with particular focus on clinical and epidemiologic investigations of influenza, rhinovirus, bocavirus, respiratory syncytial virus, and metapneumovirus. Major conclusions: The development of asthma emerges from a complex interaction of genetic predisposition and environmental factors with viral infection likely playing a significant role in the effect of environment on asthma inception. This article is part of a Special Issue entitled: Biochemistry of Asthma. General significance: Further understanding of the role that viruses play in asthma exacerbation and inception will contribute to decreased asthma morbidity in the future. This article is part of a Special Issue entitled: Biochemistry of Asthma.
Output: Viruses and asthma ☆
Background: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea. Case presentation: A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm 3 . A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm 3 . Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up. Conclusion: This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.
Output: A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean patient successfully treated with clarithromycin
Because outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) might reemerge, identifying antiviral compounds is of key importance. Previously, we showed that the cellular factor TNF-␣ converting enzyme (TACE), activated by the spike protein of SARS-CoV (SARS-S protein), was positively involved in viral entry, implying that TACE is a possible target for developing antiviral compounds. To demonstrate this possibility, we here tested the effects of TACE inhibitors on viral entry. In vitro and in vivo data revealed that the TACE inhibitor TAPI-2 attenuated entry of both pseudotyped virus expressing the SARS-S protein in a lentiviral vector backbone and infectious SARS-CoV. TAPI-2 blocked both the SARS-S protein-induced shedding of angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV, and TNF-␣ production in lung tissues. Since the downregulation of ACE2 by SARS-S protein was proposed as an etiological event in the severe clinical manifestations, our data suggest that TACE antagonists block SARS-CoV infection and also attenuate its severe clinical outcome.
Output: TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds
Objective: In cases of community acquired pneumonia (CAP), it has been known that blood cultures have low yields and rarely affect clinical outcomes. Despite many studies predicting the likelihood of bacteremia in CAP patients, those results have been rarely implemented in clinical practice, and use of blood culture in CAP is still increasing. This study evaluated impact of implementing a previously derived and validated bacteremia prediction rule. Methods: In this registry-based before and after study, we used piecewise regression analysis to compare the blood culture rate before and after implementation of the prediction rule. We also compared 30-day mortality, emergency department (ED) length of stay, time-interval to initial antibiotics after ED arrival, and any changes to the antibiotics regimen as results of the blood cultures. In subgroup analysis, we compared two groups (with or without the use of the prediction rule) after implementation period, using propensity score matching. Results: Following the implementation, the blood culture rate declined from 85.5% to 78.1% (P = 0.003) without significant changes in 30-day mortality and antibiotics regimen. The interval to initial antibiotics (231 min vs. 221 min, P = 0.362) and length of stay (1019 min vs. 954 min, P = 0.354) were not significantly changed. In subgroup analysis, the group that use the prediction rule showed 25 min faster antibiotics initiation (P = 0.002) and 48 min shorter length of stay (P = 0.007) than the group that did not use the rule. Conclusion: Implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30-day mortality and antibiotics regimen.
Output: Original Contribution
Acute respiratory infections (ARI) are a major cause of morbidity worldwide. 1 Some of the earliest studies to describe the epidemiology of these infections were household cohort studies. [2] [3] [4] [5] [6] [7] The largest of these were conducted in Seattle, Washington and Tecumseh, Michigan in the 1960s and 1970s 6,7 and they provided information on the relative frequency, seasonality and symptomatic characteristics of ARI shortly after many respiratory viruses were first identified. 7 Given that the role of household structure in seasonal incidence and transmission of respiratory viruses was the primary objective, an individual's longitudinal history of infection was not a major focus. Indeed, during the first phase of the Tecumseh Study of Respiratory Illness, households were maintained on report for only 1 year, and then gradually replaced so that the entire community could be represented over time. 8 These historical studies relied on cell culture for virus identification, a method that requires specimens to be processed quickly and is considerably less sensitive than current molecular methods. 9 For this reason, the Tecumseh study and others relied extensively on serodiagnosis of influenza infection using twice yearly blood specimens. 10 It was not possible to time infections in those who only were serologically positive, limiting the ability to do robust analyses of transmission patterns. 11 With current molecular techniques, it has become much easier to identify a broad range of agents of respiratory infection. This allows documentation of infection, co-infection and subsequent re-infection. Collecting specimens within a short time from the onset of symptoms still maximizes the likelihood of accurate and timely identification of viruses associated with a respiratory illness for studies of transmission and vaccine effectiveness. Collection of regular blood specimens continues to be valuable as well, for both virus identification and for analysis of serologic correlates of protection. The Household Influenza Vaccine Evaluation (HIVE) Study is an ongoing prospective household cohort study that began in 2010. The HIVE Study was based on the original Tecumseh Study of Respiratory Illness 6 with several key modifications to illness surveillance and to laboratory methods for identification of respiratory viruses. While respiratory virus infections in general could be studied, the primary objective was to estimate the effectiveness of influenza vaccines using a cohort design for comparison with studies using the testnegative design (TND). Under the TND, specimens are collected from participants who meet a respiratory illness case V C The Author(s)
Output: Data Resource Profile Data resource profile: Household Influenza Vaccine Evaluation (HIVE) Study Data resource basics
A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved. Therefore, therapeutic agents that protect the CNS are warranted. In both animal models as well as human patients with MS, T cell entry into the CNS is generally considered the initiating inflammatory event. In order to assess if a drug protects the CNS, any potential effects on immune cell infiltration or proliferation in the periphery must be ruled out. This protocol describes how to determine whether CNS protection observed after drug intervention is a consequence of attenuating CNS-infiltrating immune cells or blocking death of CNS cells during inflammatory insults. The ability to examine MS treatments that are protective to the CNS during inflammatory insults is highly critical for the advancement of therapeutic strategies since current treatments reduce, but do not completely eliminate, relapses (i.e., immune cell infiltration), leaving the CNS vulnerable to degeneration.
Output: Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Timely detection of an inhalational anthrax outbreak is critical for clinical and public health management. Syndromic surveillance has received considerable investment, but little is known about how it will perform relative to routine clinical case finding for detection of an inhalational anthrax outbreak. We conducted a simulation study to compare clinical case finding with syndromic surveillance for detection of an outbreak of inhalational anthrax. After simulated release of 1 kg of anthrax spores, the proportion of outbreaks detected first by syndromic surveillance was 0.59 at a specificity of 0.9 and 0.28 at a specificity of 0.975. The mean detection benefit of syndromic surveillance was 1.0 day at a specificity of 0.9 and 0.32 days at a specificity of 0.975. When syndromic surveillance was sufficiently sensitive to detect a substantial proportion of outbreaks before clinical case finding, it generated frequent false alarms.
Output: Evaluating Detection of an Inhalational Anthrax Outbreak Detecting an Inhalational Anthrax Outbreak Emerging Infectious Diseases • www Detecting an Inhalational Anthrax Outbreak Emerging Infectious Diseases • www
Global climate change is expected to affect the frequency, intensity and duration of extreme water-related weather events such as excessive precipitation, floods, and drought. We conducted a systematic review to examine waterborne outbreaks following such events and explored their distribution between the different types of extreme water-related weather events. Four medical and meteorological databases (Medline, Embase, GeoRef, PubMed) and a global electronic reporting system (ProMED) were searched, from 1910 to 2010. Eighty-seven waterborne outbreaks involving extreme water-related weather events were identified and included, alongside 235 ProMED reports. Heavy rainfall and flooding were the most common events preceding outbreaks associated with extreme weather and were reported in 55 . 2 % and 52 . 9% of accounts, respectively. The most common pathogens reported in these outbreaks were Vibrio spp. (21 . 6%) and Leptospira spp. (12 . 7 %). Outbreaks following extreme water-related weather events were often the result of contamination of the drinking-water supply (53 . 7 %). Differences in reporting of outbreaks were seen between the scientific literature and ProMED. Extreme water-related weather events represent a risk to public health in both developed and developing countries, but impact will be disproportionate and likely to compound existing health disparities. The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>. The written permission of Cambridge University Press must be obtained for commercial re-use.
Output: SYSTEMATIC REVIEW Extreme water-related weather events and waterborne disease
T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection. Our studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection. T cell immunoglobulin mucin domain-1 (TIM-1) is one of a number of phosphatidylserine (PS) receptors that mediate clearance of apoptotic bodies by binding PS on the surface of dead or dying cells. Enveloped viruses mimic apoptotic bodies by exposing PS on the outer leaflet of the viral membrane. While TIM-1 has been shown to serve as an adherence factor/receptor for filoviruses in tissue culture, limited studies have investigated the role of TIM-1 as a receptor in vivo. Here, we sought to determine if TIM-1 was critical for Ebola virus glycoprotein-mediated infection using a BSL2 model virus. We demonstrate that loss of TIM-1 expression results in decreased virus load late during infection and significantly reduced virus-elicited mortality. These findings provide evidence that TIM-1 serves as an important receptor for Ebola virus in vivo. Blocking TIM-1/EBOV interactions may be effective antiviral strategy to reduce viral load and pathogenicity at late times of EBOV infection. TIM-1 enhances Ebola virus pathogenesis PLOS Neglected Tropical Diseases | https://doi.org/10.
Output: TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis
A replicon-based DNA vaccine encoding VP2 gene of canine parvovirus (CPV) was developed by cloning CPV-VP2 gene into a replicon-based DNA vaccine vector (pAlpha). The characteristics of a replicon-based DNA vaccine like, self-amplification of transcripts and induction of apoptosis were analyzed in transfected mammalian cells. When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched repliconbased DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. The virus neutralization antibody and lymphocyte proliferative responses were higher than conventional CPV DNA vaccine and commercial CPV vaccine. These results indicated that DNA-launched repliconbased CPV DNA vaccine was effective in inducing both CPV-specific humoral and cellular immune responses and can be considered as effective alternative to conventional CPV DNA vaccine and commercial CPV vaccine. Crown
Output: Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs
A wide range of RNA viruses use programmed À1 ribosomal frameshifting for the production of viral fusion proteins. Inspection of the overlap regions between ORF1a and ORF1b of the SARS-CoV genome revealed that, similar to all coronaviruses, a programmed À1 ribosomal frameshift could be used by the virus to produce a fusion protein. Computational analyses of the frameshift signal predicted the presence of an mRNA pseudoknot containing three double-stranded RNA stem structures rather than two. Phylogenetic analyses showed the conservation of potential three-stemmed pseudoknots in the frameshift signals of all other coronaviruses in the GenBank database. Though the presence of the three-stemmed structure is supported by nuclease mapping and two-dimensional nuclear magnetic resonance studies, our findings suggest that interactions between the stem structures may result in local distortions in the A-form RNA. These distortions are particularly evident in the vicinity of predicted A-bulges in stems 2 and 3. In vitro and in vivo frameshifting assays showed that the SARS-CoV frameshift signal is functionally similar to other viral frameshift signals: it promotes efficient frameshifting in all of the standard assay systems, and it is sensitive to a drug and a genetic mutation that are known to affect frameshifting efficiency of a yeast virus. Mutagenesis studies reveal that both the specific sequences and structures of stems 2 and 3 are important for efficient frameshifting. We have identified a new RNA structural motif that is capable of promoting efficient programmed ribosomal frameshifting. The high degree of conservation of three-stemmed mRNA pseudoknot structures among the coronaviruses suggests that this presents a novel target for antiviral therapeutics. Citation: Plant EP, Pérez-Alvarado GC, Jacobs JL, Mukhopadhyay B, Hennig M, et al. (2005) A three-stemmed mRNA pseudoknot in the SARS coronavirus frameshift signal. PLoS Biol 3(6): e172.
Output: A Three-Stemmed mRNA Pseudoknot in the SARS Coronavirus Frameshift Signal
The deduced 2 protein sequence from the S3 gene segment of a novel turkey reovirus, designated NC98, isolated from the bursa of birds exhibiting poult enteritis and mortality syndrome was determined. The isolate, serologically distinct from other avian reoviruses, was isolated in turkey embryo kidney cells and RNA was purified for cDNA synthesis. Oligonucleotide primers were designed based on conserved avian S3 nucleotide sequence data. The NC98 S3 open reading frame comprised 1101 base pairs and encoded 366 amino acids with a predicated molecular mass of 40.5 kDa. Although the S3 nucleotide sequence from several chicken isolates share at least 86% identity, they share only 64% with the NC98 turkey isolate. Interestingly, the S3 nucleotide sequence from a muscovy duck reovirus shares 55% identity with NC98 and 53% identity with chicken isolates. As observed in other avian reovirus 2 protein sequences, a zinc-binding motif and double-stranded RNA binding domain were found within the predicted amino acid sequence of NC98. Phylogenetic analysis of the deduced 2 sequence demonstrated that NC98 separated as a distinct virus relative to other avian strains. The results of this study indicate that NC98 is a novel turkey reovirus that shares limited genomic sequence identity to isolates of chicken and duck origin and should be considered a separate virus species within subgroup 2 of the Orthoreovirus genus.
Output: Sequence Analysis of the S3 Gene from a Turkey Reovirus
A B S T R A C T DC-SIGN, a human C-type lectin, is involved in the transmission of many enveloped viruses. Here we report the cloning and characterization of the cDNA and gene encoding porcine DC-SIGN (pDC-SIGN). The full-length pDC-SIGN cDNA encodes a type II transmembrane protein of 240 amino acids. Phylogenetic analysis revealed that pDC-SIGN, together with bovine, canis and equine DC-SIGN, are more closely related to mouse SIGNR7 and SIGNR8 than to human DC-SIGN. pDC-SIGN has the same gene structure as bovine, canis DC-SIGN and mouse SIGNR8 with eight exons. pDC-SIGN mRNA expression was detected in pig spleen, thymus, lymph node, lung, bone marrow and muscles. pDC-SIGN protein was found to express on the surface of monocyte-derived macrophages and dendritic cells, alveolar macrophages, lymph node sinusoidal macrophage-like, dendritic-like and endothelial cells but not of monocytes, peripheral blood lymphocytes or lymph node lymphocytes. A BHK cell line stably expressing pDC-SIGN binds to human ICAM-3 and ICAM-2 immunoadhesins in a calcium-dependent manner, and enhances the transmission of porcine reproductive and respiratory syndrome virus (PRRSV) to target cells in trans. The results will help better understand the biological role(s) of DC-SIGN family in innate immunity during the evolutionary process. ß
Output: Porcine DC-SIGN: Molecular cloning, gene structure, tissue distribution and binding characteristics §