niryuu/sni-each-converted huggingface dataset:
1) Seroepidemiological analysis of influenza pandemics (1986 -2003) in Shizuoka Prefecture and all Japan revealed differences in geographical, annual, seasonal, and age distributions. (2) For 17 years, the pandemics generally began at the 50th week every year showing over 1.0 patient/clinic, reached the peak at 5th week the following year, and ended over 10 -15th week. Two big A/H3N2 pandemics were seen in 1989/1990 and 1997/1998 seasons, claiming over 1 million patients in Japan. (3) As herald strains, A/H3N2 strains (A/Sydney-like) were found in October 1999, and B strains (B/Victoria-and B/Yamagata-like) were detected in July and November 1998 and, in August and December 2000 in Shizuoka. B/Shizuoka/1/98 strain was registered internationally as a vaccine-recommended strain. (4) A/H3N2 and B viruses were detected in 55 -78% of flu patients (almost under 10 years) with encephalopathy in 1999/2000 and 78 -91% in 2000/ 2001 by MDCK and reverse transcription polymerase chain reaction (RT-PCR) methods. (5) High hemagglutination inhibition (HI) titers over 40 in 250 persons were shown against A/Sydney/5/97 (H3N2), A/Yokohama/8/98 (H3N2), A/Panama/2007/99 (H3N2) and A/Moscow/10/99 (H1N1) strains, while low titers showed against A/Beijing/262/95 (H1N1) and A/New Caledonia/20/99 (H1N1), and B/Beijing/243/97, B/Shangdong/7/97 and B/Yamanashi/106/98 strains in 1998 -2000. (6) In anti-HA titers against A/H3N2, A/H1N1 and B subtypes, clear generation gaps were observed between children (0 -19 years), adults (20 -59 years) and old men (over 60 years). (7) The pandemics are dependent on host immunity (acquired and vaccinated) and climatic conditions (low temperature, low humidity and limited rainfall), considering highly pathogenic avian influenza (HPAI) viruses (A/H5N1, A/H7N7) like severe acute respiratory syndrome (SARS) corona virus in 2002 -
Output: Seroepidemiological analysis of influenza pandemics in Shizuoka Prefecture and all Japan
A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, Müller et al. described several important differences between the two viruses [M. A. Müller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor -2 (hACE2) . These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions. Citation Perlman S, Zhao J. 2013. Human coronavirus EMC is not the same as severe acute respiratory syndrome coronavirus. mBio 4(1):e00002-13.
Output: Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Cómo citar este artículo: Reina J, et al. Etiología viral de las exacerbaciones de los pacientes con enfermedad pulmonar obstructiva crónica en la época invernal. Med Clin (Barc). 2019. https://doi.
Output: ARTICLE IN PRESS G Model
Biological risk relates to a broad spectrum of possible scenarios, that can be classified in three categories: natural occurring, unintended and deliberate. The prevention and management of such events require dedicated measures at national and international level, in terms of biosafety and biosecurity: an optimized intervention can minimize the probability of occurrence, but also adverse short-term (i.e.: number of casualties, population reaction…) and long-term (i.e.: chronic illnesses, ecological changes, trades drop…) consequences. Natural scenarios include common, emerging/re-emerging and chronic infectious diseases: they are caused by biological agents, which can be normally present in the communities, as acute or chronic pathologies, or suddenly appear, causing new or uncommon syndromes. In particular, a lot of environmental and human factors can influence emerging and re-emerging diseases: for example, urbanization and people mobility facilitate microorganisms spread, while climate changes are likely to induce a relocation of pathogens vectors. Unintended events are usually due to research and diagnostic activities: laboratories are the places where biological agents are handled and a lack in Biosafety measures or negligence can result in accidental release; the so called Laboratory Acquired Infections represent the main consequence, since they cause pathologies in the laboratory workers, but could be also transmitted in the population. Deliberate use of biological agents is strictly related to terroristic activities: microorganisms are very suitable for this purpose, since they are hidden and can easily spread. The present chapter summarizes the main characteristics of biological Alessandro Mancon and Davide Mileto equally contributed to this work.
Output: The Global Threats from Naturally Occurring Infectious Diseases
The presence and consistent expression of the genes encoding the human papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours presents the opportunity for an immunotherapeutic approach for control of the disease. This report describes the construction and characterisation of a recombinant vaccinia virus designed to express modtfied forms of the E6 and E7 proteins from HPV16 and HPVl8, the viruses most commonly associated with cervical cancer. The recombinant virus (designated TA-HPV) was based on the Wyeth vaccine strain of vaccinia, and was shown to express the desired gene products. Studies in mice indicated that the recombinant virus was less neurovirulent than the parental virus and was capable of inducing an HPV-spectftc CTL response. This pre-clinical evaluation has provided a basis for the initiation of human trials in cervical cancer patients. Copyright 0 1996 Elsevier Science Ltd.
Output: Construction and characterisation of a recombinant vaccinia virus expressing human papillomavirus proteins for immunotherapy of cervical cancer
The aim of the study was assessment of the usefulness of multiplex real-time PCR tests in the diagnostic and therapeutic process in children hospitalized due to pneumonia and burdened with comorbidities. Methods. The study group included 97 children hospitalized due to pneumonia at the Karol Jonscher Teaching Hospital in Poznań, in whom multiplex real-time PCR tests (FTD respiratory pathogens 33; fast-track diagnostics) were used. Results. Positive test results of the test were achieved in 74 patients (76.3%). The average age in the group was 56 months. Viruses were detected in 61 samples (82% of all positive results); bacterial factors were found in 29 samples (39% of all positive results). The presence of comorbidities was established in 90 children (92.78%). On the basis of the obtained results, 5 groups of patients were established: viral etiology of infection, 34 patients; bacterial etiology, 7 patients; mixed etiology, 23 patients; pneumocystis, 9 patients; and no etiology diagnosed, 24 patients. Conclusions. Our analysis demonstrated that the participation of viruses in causing severe lung infections is significant in children with comorbidities. Multiplex real-time PCR tests proved to be more useful in establishing the etiology of pneumonia in hospitalized children than the traditional microbiological examinations.
Output: Assessment of the Usefulness of Multiplex Real-Time PCR Tests in the Diagnostic and Therapeutic Process of Pneumonia in Hospitalized Children: A Single-Center Experience
Modelers published thoughtful articles after the 2003 SARS crisis, but had limited if any real-time impact on the global response and may even have inadvertently contributed to a lingering misunderstanding of the means by which the epidemic was controlled. The impact of any intervention depends on its efficiency as well as efficacy, and efficient isolation of infected individuals before they become symptomatic is difficult to imagine. Nonetheless, in exploring the possible impact of quarantine, the product of efficiency and efficacy was varied over the entire unit interval. Another mistake was repeatedly fitting otherwise appropriate gamma distributions to times to event regardless of whether they were stationary or not, particularly onset-isolation intervals whose progressive reduction evidently contributed to SARS control. By virtue of their unknown biology, newly-emerging diseases are more challenging than familiar human scourges. Influenza, for example, recurs annually and has been modeled more thoroughly than any other infectious disease. Moreover, models were integrated into preparedness exercises, during which working relationships were established that bore fruit during the 2009 A/H1N1 pandemic. To provide the most accurate and timely advice possible, especially about the possible impact of measures designed to control diseases caused by novel human pathogens, we must appreciate the value and difficulty of policy-oriented modeling. Effective communication of insights gleaned from modeling SARS will help to ensure that policymakers involve modelers in future outbreaks of newly-emerging infectious diseases. Accordingly, we illustrate the increasingly timely care-seeking by which, together with increasingly accurate diagnoses and effective isolation, SARS was controlled via heuristic arguments and descriptive analyses of familiar observations. Published by Elsevier B.V.
Output: Modeling and public health emergency responses: Lessons from SARS
Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsVencapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.
Output: Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles
Coronaviruses (CoVs) have caused outbreaks of deadly pneumonia in humans since the beginning of the 21st century. The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and was responsible for an epidemic that spread to five continents with a fatality rate of 10% before being contained in 2003 (with additional cases reported in 2004). The Middle-East respiratory syndrome coronavirus (MERS-CoV) emerged in the Arabian Peninsula in 2012 and has caused recurrent outbreaks in humans with a fatality rate of 35%. SARS-CoV and MERS-CoV are zoonotic viruses that crossed the species barrier using bats/palm civets and dromedary camels, respectively. No specific treatments or vaccines have been approved against any of the six human coronaviruses, highlighting the need to investigate the principles governing viral entry and cross-species transmission as well as to prepare for zoonotic outbreaks which are likely to occur due to the large reservoir of CoVs found in mammals and birds. Here, we review our understanding of the infection mechanism used by coronaviruses derived from recent structural and biochemical studies.
Output: Structural insights into coronavirus entry
A mandatory step in the formation of an infectious retroviral particle is the acquisition of its envelope glycoprotein (Env). This step invariably occurs by Env positioning itself in the host membrane at the location of viral budding and being incorporated along with the host membrane into the viral particle. In some ways, this step of the viral life cycle would appear to be imprecise. There is no specific sequence in Env or in the retroviral structural protein, Gag, that is inherently required for the production of an infectious Env-containing particle. Additionally, Env-defective proviruses can efficiently produce infectious particles with any of a number of foreign retroviral Env glycoproteins or even glycoproteins from unrelated viral families, a process termed pseudotyping. However, mounting evidence suggests that Env incorporation is neither passive nor random. Rather, several redundant mechanisms appear to contribute to the carefully controlled process of Env acquisition, many of which are apparently used by a wide variety of enveloped viruses. This review presents and discusses the evidence for these different mechanisms contributing to incorporation.
Output: Mechanisms for Env Glycoprotein Acquisition by Retroviruses
The envelope of hepatitis B virus (HBV), containing the L, M, and S proteins, is essential for virus entry and maturation. For direct visualization of HBV, we determined whether envelope assembly could accommodate the green fluorescent protein (GFP). While the Cterminal addition of GFP to S trans-dominant negatively inhibited empty envelope particle secretion, the N-terminal GFP fusion to S (GFP.S) was co-integrated into the envelope, giving rise to fluorescent particles. Microscopy and topogenesis analyses demonstrated that the proper intracellular distribution and folding of GFP.S, required for particle export were rescued by interprotein interactions with wild-type S. Thereby, a dual location of GFP, inside and outside the envelope, was observed. GFP.S was also efficiently packaged into the viral envelope, and these GFP-tagged virions retained the capacity for attachment to HBV receptor-positive cells in vitro. Together, GFP-tagged virions should be suitable to monitor HBV uptake and egress in live hepatocytes. D 2004 Elsevier Inc. All rights reserved.
Output: Functional incorporation of green fluorescent protein into hepatitis B virus envelope particles
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease , but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. : medRxiv preprint Patients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.
Output: Virologic and clinical characteristics for prognosis of severe COVID-19: a retrospective observational study in Wuhan, China
Background: One of the most commonly applied protectotype vaccination protocol against infectious bronchitis (IB) in broiler chickens in the EU is simultaneous or alternate use of Ma5 and 4/91 vaccine strains. After IB vaccination and infection, systemic and upper respiratory tract (URT), humoral and cell-mediated immunity (CMI), are stimulated. The level of this stimulation correlates with the level of protection against IB. Results: We've investigated the development of URT and systemic, cell-mediated and humoral immunity in commercial broiler chickens vaccinated with Ma5 and/or 4/91 strains at hatch day. We've demonstrated that the group vaccinated with Ma5 and 4/91 strain simultaneously developed the most desirable immunity which reflects the level of CD8 + T cells stimulation in spleen and Harderian gland, as well as the level of IgA and IgY in URT washings and serum and their cross-reactivity with 7 IBV strains. Conclusions: Although we did not demonstrate directly why Ma5 + 4/91 protocol is so efficient it seems that it combines the benefits of monovalent vaccination with either Ma5 or 4/91 and while Ma5 seems to stimulate CMI more efficiently, the 4/91 strain generates a wider spectrum of immune system cross-reactivity and higher URT IgA production.
Output: Immunological aspects of the efficiency of protectotype vaccination strategy against chicken infectious bronchitis
Glycyrrhetinic acid (GA) is a major constituent of the herb Glycyrrhiza glabra, and many of its derivatives demonstrate a broad spectrum of antiviral activities. In the current study, 18 water-soluble b-cyclodextrin (CD)-GA conjugates, in which GA was covalently coupled to the primary face of b-CD using 1,2,3-triazole moiety along with varying lengths of linker, were synthesized via copper-catalyzed azide-alkyl cycloaddition reaction. Benefited from the attached b-CD moiety, all these conjugates showed lower hydrophobicity (AlogP) compared with their parent compound GA. With the exception of per-O-methylated b-CD-GA conjugate (35), all other conjugates showed no significant cytotoxicity to MDCK cells, and these conjugates were then screened against A/WSN/33 (H1N1) virus using the cytopathic effect assay. The preliminary results indicated that six conjugates showed promising antiviral activity, and the C-3 and C-30 of GA could tolerate some modifications. Our findings suggested that GA could be used as a lead compound for the development of potential anti-influenza virus agents.
Output: Synthesis and structure-activity relationship studies of water-soluble b-cyclodextrin-glycyrrhetinic acid conjugates as potential anti-influenza virus agents
This paper presents a label-free affinity-based capacitive biosensor using interdigitated electrodes. Using an optimized process of DNA probe preparation to minimize the effect of contaminants in commercial thiolated DNA probe, the electrode surface was functionalized with the 24-nucleotide DNA probes based on the West Nile virus sequence (Kunjin strain). The biosensor has the ability to detect complementary DNA fragments with a detection limit down to 20 DNA target molecules (1.5 aM range), making it suitable for a practical point-of-care (POC) platform for low target count clinical applications without the need for amplification. The reproducibility of the biosensor detection was improved with efficient covalent immobilization of purified single-stranded DNA probe oligomers on cleaned gold microelectrodes. In addition to the low detection limit, the biosensor showed a dynamic range of detection from 1 mL À 1 to 10 5 mL À 1 target molecules (20 to 2 million targets), making it suitable for sample analysis in a typical clinical application environment. The binding results presented in this paper were validated using fluorescent oligomers.
Output: A sensitive DNA capacitive biosensor using interdigitated electrodes
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.
Output: Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy
During RNA viruses's replication, double-stranded RNA (dsRNA) is normally produced and induce host innate immune response. Most of gene activation due cytokine mediated but which are due to methylation mediated is still unknown. In the study, DNA methylome was integrated with our previous transcriptome data to investigate the differentially methylated regions and genes using MeDIP-chip technology. We found that the transcriptional expressions of 15, 37 and 18 genes were negatively related with their promoter DNA methylation levels in the cells treated by PolyI:C, Aza-CdR, as well as PolyI:C plus Aza-CdR, respectively, compared with the untreated cells. GO analysis revealed hypo-methylated genes (BNIP3L and CDK9) and a hyper-methylated gene (ZC3HAV1) involved in the host response to viral replication. Our results suggest that these novel genes targeted by DNA methylation can be potential markers relevant to virus replication and host innate immune response to set up a medical model of infectious diseases. PolyI:C treated cells (P < 0.05) [2] . Out of these DEGs, eighteen are Abbreviations: PK15, porcine kidney epithelial cell line; dsRNA, double-stranded RNA; PolyI:C, a synthetic viral-like dsRNA analogplolyinosinic: polycyticdylic acid; Aza-CdR, DNA methyltransferases inhibitor 5-aza-2′-deoxycytidine; P, PK15 cells extracellular treatment with PolyI:C; A, PK15 cells treated with Aza-CdR; P+A, PK15 cells treated with PolyI:C followed by the addition of Aza-
Output: Identification of DNA methylation regulated novel host genes relevant to inhibition of virus replication in porcine PK15 cell using double stranded RNA mimics and DNA methyltransferase inhibitor
Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies-either where volunteers are infected with a disease or where existing cases are recruited-in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens-influenza and norovirus-as well as Ebola virus disease.
Output: Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry
Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved "self-eating" mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed.
Output: The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection
We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5-6.4, 6.5-7.4, 7.5-8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007-2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis. Abbreviations: ESRD = end-stage renal disease, TA-SUA = time-averaged serum uric acid.
Output: Lower serum uric acid level predicts mortality in dialysis patients
The heptad repeats 1 and 2 of SARS-CoV spike, termed HR1 and HR2, play critical roles in viral entry. Moreover, HR1 and HR2 derived free peptides are inhibitors of SARS-CoV entry. In this work we used circular dichroism to show that HR2 helix formation is induced at pH 5, the pH of the endosome. In addition, we demonstrate that the HR2 helix is further stabilized at physiological ionic strengths. Together, these observations provide new insight into the mechanism of SARS-CoV entry and suggest that HR2 may be an attractive target for therapeutic intervention.
Output: The SARS-CoV heptad repeat 2 exhibits pH-induced helix formation
Invasive aspergillosis of the lungs and the central nervous system and Legionella pneumophilia serotype 1 infection of the lungs were diagnosed in a 22-month old child during inpatient induction treatment for T-lymphoblastic leukemia. Environmental investigations i.e. samples from the hospital water system did not reveal any Legionella. The patient may have been exposed to waterborne pathogens despite terminal water filtration due to a technical device to release residual tap water from the hose after showering. A sodium chloride nose spray was found to be contaminated with the A. fumigatus isolate of the patient.
Output: Nosocomial legionellosis and invasive aspergillosis in a child with T-lymphoblastic leukemia
Given the potential for laboratory-associated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infections, we must know which cell lines are susceptible to the virus. We investigated 21 cell lines routinely used for virus isolation or research. After infection with SARS-CoV, cells were observed for cytopathic effects, and quantitative real-time polymerase chain reaction was used to measure ongoing viral replication. An indirect immunofluorescence assay was also used as a confirmatory test. The study identified 10 new cell lines capable of supporting the replication of SARS-CoV and confirmed the susceptibility of 4 cell lines previously reported. This study shows that SARS-CoV can be isolated in several cell lines commonly used for diagnostic or research purposes. It also shows that SARS-CoV can achieve high titers in several cell lines, sometimes in the absence of specific cytopathic effects.
Output: SARS-associated Coronavirus Replication in Cell Lines SARS-associated Coronavirus Replication in Cell Lines
Objective To describe the epidemiology and clinical impact of respiratory viruses in a neonatal intensive care unit (NICU). Study design We conducted a retrospective observational study of infants with respiratory viruses detected by multiplex reverse-transcriptase PCR from May 2012 to May 2017. The proportion of symptomatic vs. asymptomatic infants and associated morbidity were assessed. The association of infection prevention and control (IP&C) strategies and transmission was ascertained. Results Respiratory viruses were detected in 83 infants representing 86 unique episodes during which infants remained asymptomatic in 15 (17%). Of the 71 symptomatic episodes, only 45% were associated with increased respiratory and/or nutritional support. Rhinovirus/enteroviruses were most common (69%) and involved nine of 12 transmission events. IP&C strategies including restricting visitors <12 years of age and screening exposed infants were associated with decreased transmission rates. Conclusions NICU patients can be asymptomatic carriers of respiratory viruses. Identification of such infants is important to prevent transmission in the NICU. * Lisa Saiman
Output: Impact of respiratory viruses in the neonatal intensive care unit
Background: In this work we predict enzyme function at the level of chemical mechanism, providing a finer granularity of annotation than traditional Enzyme Commission (EC) classes. Hence we can predict not only whether a putative enzyme in a newly sequenced organism has the potential to perform a certain reaction, but how the reaction is performed, using which cofactors and with susceptibility to which drugs or inhibitors, details with important consequences for drug and enzyme design. Work that predicts enzyme catalytic activity based on 3D protein structure features limits the prediction of mechanism to proteins already having either a solved structure or a close relative suitable for homology modelling. In this study, we evaluate whether sequence identity, InterPro or Catalytic Site Atlas sequence signatures provide enough information for bulk prediction of enzyme mechanism. By splitting MACiE (Mechanism, Annotation and Classification in Enzymes database) mechanism labels to a finer granularity, which includes the role of the protein chain in the overall enzyme complex, the method can predict at 96% accuracy (and 96% micro-averaged precision, 99.9% macro-averaged recall) the MACiE mechanism definitions of 248 proteins available in the MACiE, EzCatDb (Database of Enzyme Catalytic Mechanisms) and SFLD (Structure Function Linkage Database) databases using an off-the-shelf K-Nearest Neighbours multi-label algorithm.
Output: From sequence to enzyme mechanism using multi-label machine learning
Glycyrrhiza glabra L. has become an endangered medicinal plant due to the unabated extraction of glycyrrhizin. Glycyrrhizin is a triterpenoid saponin that is a root centric secondary metabolite having numerous pharmacological properties, such as anti-inflammatory, immunomodulatory, antiallergic, antiulcer, and is found to be effective even against HIV. Harvesting of the roots for high value glycyrrhizin destroys the whole plant causing existential threat to the plant itself and consequent damage to biodiversity. The present study establishes that hairy root cultures of G. glabra, using an optimized elicitor, can dramatically enhance focused production of glycyrrhizin at a much faster pace year-round without causing destruction of the plant. Hairy root cultures of G. glabra were developed using the Agrobacterium rhizogenes A4 strain. The glycyrrhizin content was enhanced using different biotic and abiotic elicitors, for example, PEG (polyethylene glycol), CdCl 2 , cellulase, and mannan at different concentrations and durations. PEG at 1% concentration enhanced the yield of glycyrrhizin up to 5.4fold after 24 h of exposure, whereas 200 µg mL −1 cellulase enhanced glycyrrhizin yield to 8.6-fold after 7 days of treatment. Mannan at 10 mg L −1 concentration enhanced the production of glycyrrhizin up to 7.8-fold after 10 days of stress. Among different antioxidant enzymes, SOD activity was significantly enhanced under drought, cellulase and mannan stress. This identification of elicitors can result in abundant supply of valuable glycyrrhizin to meet broad spectrum demand through commercial production without endangering G. glabra L.
Output: Elicitation Enhanced the Yield of Glycyrrhizin and Antioxidant Activities in Hairy Root Cultures of Glycyrrhiza glabra L
Recent years have seen several advances in our understanding of immunity to virus infection of the lower respiratory tract, including to influenza virus infection. Here, we review the cellular targets of viruses and the features of the host immune response that are unique to the lungs. We describe the interplay between innate and adaptive immune cells in the induction, expression and control of antiviral immunity, and discuss the impact of the infected lung milieu on moulding the response of antiviral effector T cells. Recent findings on the mechanisms that underlie the increased frequency of severe pulmonary bacterial infections following respiratory virus infection are also discussed. Viruses are highly evolved and ubiquitous pathogens. Although infection with many viruses results in a mild, self-limited disease, other viruses can produce severe and frequently fatal infections. The respiratory tract is a major portal through which viruses enter to initiate infection. Whereas some viruses can initiate infection in the respiratory tract and then disseminate to other sites in the body, other viruses typically remain localized to the respiratory tract, where they replicate and induce tissue injury (see Supplementary information S1 (table)). Various defence mechanisms have evolved in the respiratory tract to prevent and control infection by viruses and other pathogens. The respiratory tract can be divided anatomically into the upper respiratory tract (including the nose, mouth and pharynx) and the lower respiratory tract (which consists of the trachea, bronchi and lungs), with the lymphoid tissue of Waldeyer's ring (including the pharyngeal and palatine tonsils) representing the line of demarcation. Because of the crucial role of the lower respiratory tract in respiration, we limit the focus of this Review to recent advances in our understanding of the host immune response to virus infection at this site.
Output: Regulating the adaptive immune response to respiratory virus infection NIH Public Access
CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation have cosponsored these guidelines for preventing opportunistic infections (OIs) among hematopoietic stem cell transplant (HSCT) recipients. The guidelines were drafted with the assistance of a working group of experts in infectious diseases, transplantation, and public health. For the purposes of this report, HSCT is defined as any transplantation of blood-or marrow-derived hematopoietic stem cells, regardless of transplant type (i.e., allogeneic or autologous) or cell source (i.e., bone marrow, peripheral blood, or placental or umbilical cord blood). Such OIs as bacterial, viral, fungal, protozoal, and helminth infections occur with increased frequency or severity among HSCT recipients. These evidence-based guidelines contain information regarding preventing OIs, hospital infection control, strategies for safe living after transplantation, vaccinations, and hematopoietic stem cell safety. The disease-specific sections address preventing exposure and disease for pediatric and adult and autologous and allogeneic HSCT recipients. The goal of these guidelines is twofold: to summarize current data and provide evidence-based recommendations regarding preventing OIs among HSCT patients. The guidelines were developed for use by HSCT recipients, their household and close contacts, transplant and infectious diseases physicians, HSCT center personnel, and public health professionals. For all recommendations, prevention strategies are rated by the strength of the recommendation and the quality of the evidence supporting the recommendation. Adhering to these guidelines should reduce the number and severity of OIs among HSCT recipients.
Output: Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients Recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation
Background: People 65 years or older are at greater risk of serious complications from the seasonal influenza compared with young. To promote elderly people's behavioral compliance toward influenza prevention, the aim of the current project is to develop, implement, and evaluate a theory-based low-administration-cost intervention building on a leading psychological theory, the Health Action Process Approach (HAPA). The target group is Hong Kong Chinese elderly people aged 65 or older who rarely or never adopt any preventive actions. This project will be conducted in three phases over 24 months. In phase 1, intervention program will be developed building on the HAPA theoretical framework which comprises both the initiation and maintenance of influenza prevention behaviors. In phase 2, intervention will be implemented and evaluated using a randomized controlled trial, including: (a) behavior initiation only, (b) behavior initiation + behavior maintenance, and (c) control group. Both the initiation and maintenance components will comprise weekly-delivered telephone-based individual intervention sessions in 3 months. In phase 3, outcome evaluation of behavioral and psychological variables and process evaluation will be conducted. The effectiveness of the intervention will be analyzed using a series of linear mixed models on each behavioral and psychological outcome variable. Structural equation modelling will be used to test the hypothesized theoretical sequence in the HAPA model. Discussion: The proposed project is expected to design theory-based intervention materials to promote the influenza prevention behaviors in Hong Kong elderly people and provide information on its effectiveness and the potential changing mechanism of behavior initiation and maintenance.
Output: Promoting influenza prevention for elderly people in Hong Kong using health action process approach: study protocol
More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low-and middleincome countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a 'One Health' approach.
Output: Rabies elimination research: juxtaposing optimism, pragmatism and realism
A protocol for obtaining small amounts of highly pure virus preparations starting from reduced volumes (<5 ml) of infected tissue culture supernatants is described. This procedure was adapted to the study of transmissible gastroenteritis coronavirus (TGEV) protein composition and RNA encapsidation. This protocol relies on virion capture by monoclonal antibodies specific for a virion membrane protein. These antibodies were bound to protein A-coated ELISA wells armed with rabbit anti-mouse IgG antibodies. As an example, the purification of 35 S-labelled TGEV virions was performed. The quality of virus preparations was assessed by quantifying common contaminating RNAs by real-time RT-PCR. The most critical factors influencing the purity degree are analysed and discussed.
Output: Immunopurification applied to the study of virus protein composition and encapsidation
Caveolin-1 (Cav-1) isoforms, including Cav-1α and Cav-1β, were identified as integral membrane proteins and the major components of caveolae. Cav-1 proteins are highly conserved during evolution from Caenorhabditis elegans to human and are capable of interacting with many signaling molecules through their caveolin scaffolding domains to regulate the activities of multiple signaling pathways. Thus, Cav-1 plays crucial roles in the regulation of cellular proliferation, differentiation and apoptosis in a cell-specific and contextual manner. In addition, Cav-1 is essential for embryonic development of vertebrates owing to its regulation of BMP, Wnt, TGF-β and other key signaling molecules. Moreover, Cav-1 is mainly expressed in terminally differentiated cells and its abnormal expression is often associated with human diseases, such as tumor progression, cardiovascular diseases, fibrosis, lung regeneration, and diseases related to virus. In this review, we will further discuss the potential of Cav-1 as a target for disease therapy and multiple drug resistance.
Output: New glimpses of caveolin-1 functions in embryonic development and human diseases
Much evidence supports the notion that angiotensin II (Ang II), the central product of the renin-angiotensin system (RAS), may play a central role not only in the etiology of hypertension but also in the pathophysiology of cardiovascular diseases in humans. Ang II, via the Ang II type 1 receptor, directly causes cellular phenotypic changes and cell growth, regulates the gene expression of various bioactive substances, and activates multiple intracellular signaling cascades in cardiac myocytes and fibroblasts, as well as vascular endothelial and smooth muscle cells. Recently, new factors have been discovered, such as angiotensin-converting enzyme 2, angiotensin-(1-7), and its receptor Mas. This section summarizes the current knowledge about the broad RAS in the pathophysiology of cardiac hypertrophy and remodeling, heart failure, vascular thickening, and atherosclerosis. Handbook of Biologically Active Peptides. http://dx.
Output: Angiotensin II Peptides
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory illness with a case fatality rate (CFR) of 35,5%. The highest number of MERS-CoV cases are from Saudi-Arabia, the major worldwide hotspot for this disease. In the absence of neither effective treatment nor a ready-to-use vaccine and with yet an incomplete understanding of its epidemiological cycle, prevention and containment measures can be derived from mathematical models of disease epidemiology. We constructed 2-strain models to predict past outbreaks in the interval 2012-2016 and derive key epidemiological information for Macca, Madina and Riyadh. We approached variability in infection through three different disease incidence functions capturing social behavior in response to an epidemic (e.g. Bilinear, BL; Non-monotone, NM; and Saturated, SAT models). The best model combination successfully anticipated the total number of MERS-CoV clinical cases for the 2015-2016 season and accurately predicted both the number of cases at the peak of seasonal incidence and the overall shape of the epidemic cycle. The evolution in the basic reproduction number (R 0 ) warns that MERS-CoV may easily take an epidemic form. The best model correctly captures this feature, indicating a high epidemic risk (1�R 0 �2,5) in Riyadh and Macca and confirming the alleged co-circulation of more than one strain. Accurate predictions of the future MERS-CoV peak week, as well as the number of cases at the peak are now possible. These results indicate public health agencies should be aware that measures for strict containment are urgently needed before new epidemics take off in the region. There is currently no way to anticipate MERS-CoV epidemic outbreaks and strategies for disease prediction and containment are largely undermined by the limited knowledge of its epidemiological cycle. Not an effective treatment nor a vaccine for MERS-CoV exist to date. Instead, using three two-strain mathematical models that incorporate human social behavior as different disease incidence functions (e.g. bilinear, non-monotone and PLOS Neglected Tropical Diseases | https://doi.
Output: A realistic two-strain model for MERS-CoV infection uncovers the high risk for epidemic propagation