niryuu/sni-each-converted huggingface dataset:
Introduction Surfactant protein D (SP-D) plays an important role in the innate responses against pathogens and its production is altered in lung disorders. Methods We studied the circulating levels of SP-D in 37 patients with acute respiratory distress syndrome due to the A/H1N1 virus infection and in 40 healthy controls. Cox logistic regression models were constructed to explore the association of SP-D levels and risk of death. Results Mortality rate after a 28-day was 32.42 %. Significant higher levels of SP-D were detected in A/H1N1 patients with fatal outcome (p \ 0.05). After adjusting for confounding variables, levels of SP-D C250 ng/mL were associated with increased the risk of death (HR = 8.27, 95 % CI 1.1-64.1, p = 0.043). Conclusions Our results revealed that higher circulating levels of SP-D are associated with higher mortality risk in critically ill A/H1N1 patients. SP-D might be a predictive factor of poor outcomes in viral pneumonia.
Output: Serum Surfactant Protein D (SP-D) is a Prognostic Marker of Poor Outcome in Patients with A/H1N1 Virus Infection
Background: The inflammatory response in pneumococcal infection is primarily driven by immunoreactive bacterial cell wall components [lipoteichoic acid (LTA)]. An acute release of these components occurs when pneumococcal infection is treated with b-lactam antibiotics. Objectives: We hypothesized that non-lytic rifampicin compared with lytic b-lactam antibiotic treatment would attenuate the inflammatory response in patients with pneumococcal pneumonia. Methods: In the PRISTINE (Pneumonia treated with RIfampicin aTtenuates INflammation) trial, a randomized, therapeutic controlled, exploratory study in patients with community-acquired pneumococcal pneumonia, we looked at LTA release and inflammatory and clinical response during treatment with both rifampicin and b-lactam compared with treatment with b-lactam antibiotics only. The trial is registered in the Dutch trial registry, number NTR3751 (European Clinical Trials Database number 2012-003067-22). Results: Forty-one patients with community-acquired pneumonia were included; 17 of them had pneumococcal pneumonia. LTA release, LTA-mediated inflammatory responses, clinical outcomes, inflammatory biomarkers and transcription profiles were not different between treatment groups. The PRISTINE study demonstrated the feasibility of adding rifampicin to b-lactam antibiotics in the treatment of community-acquired pneumococcal pneumonia, but, despite solid in vitro and experimental animal research evidence, failed to demonstrate a difference in plasma LTA concentrations and subsequent inflammatory and clinical responses. Most likely, an inhibitory effect of human plasma contributes to the low immune response in these patients. In addition, LTA plasma concentration could be too low to mount a response via Toll-like receptor 2 in vitro, but may nonetheless have an effect in vivo.
Output: Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial
Platform technologies for the changing need of diagnostics are one of the main challenges in medical device technology. From one point-of-view the demand for new and more versatile diagnostic is increasing due to a deeper knowledge of biomarkers and their combination with diseases. From another point-of-view a decentralization of diagnostics will occur since decisions can be made faster resulting in higher success of therapy. Hence, new types of technologies have to be established which enables a multiparameter analysis at the point-of-care. Within this review-like article a system called Fraunhofer ivD-platform is introduced. It consists of a credit-card sized cartridge with integrated reagents, sensors and pumps and a read-out/processing unit. Within the cartridge the assay runs fully automated within 15-20 minutes. Due to the open design of the platform different analyses such as antibody, serological or DNA-assays can be performed. Specific examples of these three different assay types are given to show the broad applicability of the system.
Output: MINIATURIZATION FOR POINT-OF-CARE ANALYSIS: PLATFORM TECHNOLOGY FOR ALMOST EVERY BIOMEDICAL ASSAY
IgE is a key mediator in allergic disease. Yet, many details of the composition of the humanIgErepertoireare,instrongcontrasttootherantibodyisotypes,poorlydefined. The low levels of human IgE in circulation and the rarity of IgE-producing B cells are important reasons for this lack of knowledge. In this review we summarize current knowledge of these repertoires both in terms of their complexity and activity, knowledgethatdespitethedifficultiesencounteredwhenstudyingthemoleculardetails of human IgE has been acquired in recent years. We also take a look at likely future developments, for instance through improvements in sequencing technology and methodology that allows isolation of additional allergen-specific human antibodies mimicking IgE, as this certainly will support our understanding of human IgE in the contextofhumandiseaseinyearstocome.
Output: The human IgE repertoire
The 39-terminal domain of the most conserved ORF1b in three of the four families of the order Nidovirales (except for the family Arteriviridae) encodes a (putative) 29-O-methyltransferase (29-O-MTase), known as non structural protein (nsp) 16 in the family Coronaviridae and implicated in methylation of the 59 cap structure of nidoviral mRNAs. As with coronavirus transcripts, arterivirus mRNAs are assumed to possess a 59 cap although no candidate MTases have been identified thus far. To address this knowledge gap, we analysed the uncharacterized nsp12 of arteriviruses, which occupies the ORF1b position equivalent to that of the nidovirus 29-O-MTase (coronavirus nsp16). In our in-depth bioinformatics analysis of nsp12, the protein was confirmed to be family specific whilst having diverged much further than other nidovirus ORF1b-encoded proteins, including those of the family Coronaviridae. Only one invariant and several partially conserved, predominantly aromatic residues were identified in nsp12, which may adopt a structure with alternating a-helices and b-strands, an organization also found in known MTases. However, no statistically significant similarity was found between nsp12 and the twofold larger coronavirus nsp16, nor could we detect MTase activity in biochemical assays using recombinant equine arteritis virus (EAV) nsp12. Our further analysis established that this subunit is essential for replication of this prototypic arterivirus. Using reverse genetics, we assessed the impact of 25 substitutions at 14 positions, yielding virus phenotypes ranging from WT-like to non-viable. Notably, replacement of the invariant phenylalanine 109 with tyrosine was lethal. We concluded that nsp12 plays an essential role during EAV replication, possibly by acting as a co-factor for another enzyme.
Output: Arterivirus nsp12 versus the coronavirus nsp16 29-O-methyltransferase: comparison of the C-terminal cleavage products of two nidovirus pp1ab polyproteins
Objective-To assess whether multiplex polymerase chain reaction (mPCR) vs. non-MPCR testing impacts the use of antibiotics, chest radiographs, and isolation precautions. Study design-We retrospectively compared use of antibiotics, chest radiographs, and isolation precautions for patients <18 years old (excluding neonates) hospitalized at a tertiary referral center tested for respiratory pathogens in the emergency department or during the first 2 hospital days, during two periods: Results-Subjects (n=2430) in the MPCR group were older, had more complex chronic conditions, and were admitted to the PICU more often compared with the non-MPCR (n=2349) group. Subjects in the MPCR group had more positive tests (42.4% vs. 14.4%, p<0.01), received fewer days of antibiotics (4 vs. 5 median antibiotic days, p<0.01), fewer chest radiographs performed, (59% vs. 78%, p<0.01), and were placed in isolation longer (20 vs. 0 median isolationhours, p<0.01) compared with the non-MPCR group. In multivariable regression, patients tested with MPCR were less likely to receive antibiotics for ≥2 days (OR 0.5, 95% CI 0.5-0.6), chest radiographs at admission (OR 0.4, 95% CI 0.3-0.4), and more likely to be in isolation for ≥2 days (OR 2.4, 95% CI 2.1-2.8 compared with the non-MPCR group.
Output: Impact of Multiplex Polymerase Chain Reaction Testing for Respiratory Pathogens on Healthcare Resource Utilization for Pediatric Inpatients HHS Public Access
High-throughput molecular profiling and computational biology are changing the face of virology, providing a new appreciation of the importance of the host in viral pathogenesis and offering unprecedented opportunities for better diagnostics, therapeutics and vaccines. Here, we provide a snapshot of the evolution of systems virology, from global gene expression profiling and signatures of disease outcome, to geometry-based computational methods that promise to yield novel therapeutic targets, personalized medicine and adeeper understanding of how viruses cause disease. To realize these goals, pipets and petri dishes need to join forces with the powers of mathematics and computational biology.
Output: SYSTEMS VIROLOGY: HOST-DIRECTED APPROACHES TO VIRAL PATHOGENESIS AND DRUG TARGETING
The current COVID-19 pandemic has led to a dramatic shortage of masks and other personal protective equipment (PPE) in hospitals around the globe [1] . One component of PPE that is in particular demand are disposable N95 face masks. To alleviate this, many methods of N95 mask sterilization have been studied and proposed with the hope of being able to safely reuse masks [2] . Two major considerations must be made when re-sterilizing masks: (1) the sterilization method effectively kills pathogens, penetrating into the fibers of the mask, and (2) the method does not degrade the operational integrity of the N95 filters. We studied Cobalt-60 ( 60 Co) gamma irradiation as a method of effective sterilization without inducing mask degradation. Significant literature exists supporting the use of gamma radiation as a sterilization method, with viral inactivation of SARS-CoV reported at doses of at most 10 kGy [3] , with other studies supporting 5 kGy for many types of viruses [4] . However, concerns have been raised about the radiation damaging the fiber material within the mask, specifically by causing cross-linking of polymers, leading to cracking and degradation during fitting and/or deployment [5, 6] . A set of 3M 8210 and 9105 masks were irradiated using MIT's 60 Co irradiator. Three masks of each type received 0 kiloGray (kGy), 10 kGy and 50 kGy of approximately 1.3 MeV gamma radiation from the circular cobalt sources, at a dose rate of 2.2kGy per hour. Following this sterilization procedure, the irradiated masks passed a OSHA Gerson Qualitative Fit Test QLFT 50 (saccharin apparatus) [7] when donned correctly, performed at the Brigham and Women's Hospital, in a blinded study repeated in triplicate. However, the masks' filtration of 0.3 µm particles was significantly degraded, even at 10 kGy. These results suggest against gamma, and possibly all ionizing radiation, as a method of disposable N95 sterilization. Even more importantly, they argue against using the qualitative fit test alone to assess mask integrity.
Output: DISPOSABLE N95 MASKS PASS QUALITATIVE FIT-TEST BUT HAVE DECREASED FILTRATION EFFICIENCY AFTER COBALT-60 GAMMA IRRADIATION
Since accurate forecasting of tourist arrivals is very important for planning for potential tourism demand and improving the tourism infrastructure, various tourist arrivals forecasting methods have been developed. The purpose of this study is to apply the adaptive network-based fuzzy inference system (ANFIS) model to forecast the tourist arrivals to Taiwan and demonstrate the forecasting performance of this model. Based on the mean absolute percentage errors and statistical results, we can see that the ANFIS model has better forecasting performance than the fuzzy time series model, grey forecasting model and Markov residual modified model. Thus, the ANFIS model is a promising alternative for forecasting the tourist arrivals. We also use the ANFIS model to forecast the monthly tourist arrivals to Taiwan from Japan, Hong Kong and Macao, and the United States.
Output: Forecasting tourist arrivals by using the adaptive network-based fuzzy inference system
Background: During the 2014 West African Ebola Virus Disease (EVD) outbreak, the U.S. Centers for Disease Control and Prevention recommended that all emergency department (ED) patients undergo travel screening for risk factors of importing EVD. Objectives: We sought to determine the overall adherence rate to the recommended travel screening protocol and to identify factors associated with nonadherence to the protocol. Methods: We conducted a multicenter, retrospective analysis of adherence to the travel screening program in an academic hospital and three affiliated community hospitals. A regression model identified patient and hospital factors associated with nonadherence. Results: Of the 147,062 patients included for analysis, 93.7% (n = 137,834) had travel screenings completed. We identified several characteristics of patients that were most likely to be missed by the screening protocol-patients with low English proficiency, patients who arrive via ambulance or helicopter, and patients with more severe illness or injury based on initial triage acuity. Conclusions: These findings should be used to improve adherence to the travel screening protocol for future emerging infectious disease threats. Ó
Output: Original Contributions ADHERENCE TO UNIVERSAL TRAVEL SCREENING IN THE EMERGENCY DEPARTMENT DURING EPIDEMIC EBOLA VIRUS DISEASE
Here, we present a comprehensive in vitro characterization of the excised iterative, bimodular PCP-TE of the gramicidin S synthetase GrsB, which is able to act both as a ligation and a cyclization catalyst. Using the native pentapeptidylthioester substrates, GrsB PCP-TE catalyzes the dimerization and subsequent formation of the decapeptide lactam gramicidin S. Interestingly, the detection of linear decapeptidyl-SNAC as an enzyme-dependent intermediate supports the iterative mechanism in vivo, in which two pentapeptides, one bound as an ester to the active site serine of the TE domain and the second bound as a thioester to the adjacent pan-PCP, are ligated to a decapeptidyl-pan-PCP that subsequently transferred to the adjacent TE domain and cyclized. Moreover, GrsB PCP-TE can handle different substrates length, leading not only to dimerization, but also to trimerization and the formation of different ring sizes.
Output: The Iterative Gramicidin S Thioesterase Catalyzes Peptide Ligation and Cyclization
Infectious salmon anaemia virus (ISAV) is a piscine orthomyxovirus causing a serious disease in farmed Atlantic salmon (Salmo salar L.). The virus surface glycoprotein hemagglutinin-esterase (HE) is responsible for both viral attachment and release. Similarity to bovine and porcine torovirus hemagglutinin-esterase (BToV HE, PToV HE), bovine coronavirus HE (BCoV HE) and influenza C hemagglutinin-esterase-fusion (InfC HEF) proteins were exploited in a computational homology-based structure analysis of ISAV HE. The analysis resolved structural aspects of the protein and identified important features of relevance to ISAV HE activity. By recombinant expression and purification of secretory HE (recHE) proteins, receptorbinding and quantitative analyses of enzymatic activities displayed by ISAV HE molecules are presented for the first time. Three different recHE molecules were constructed: one representing a high virulent isolate, one a low virulent, while in the third a Ser 32 to Ala 32 amino acid substitution was introduced in the enzymatic catalytic site as inferred from the model. The three amino acid differences between the high and low virulent variants, of which two localized to the putative receptor-binding domain and one in the esterase domain, had no impact on receptor-binding or -release activities. In contrast, the Ser 32 amino acid substitution totally abolished enzymatic activity while receptor binding increased, as observed by agglutination of Atlantic salmon red blood cells. This demonstrates the essential role of a serine in the enzyme's catalytic site. In conclusion, structural analysis of ISAV HE in combination with selected recHE proteins gave insights into structure-function relationships and opens up for further studies aiming at dissecting molecular determinants of ISAV virulence.
Output: Structural and functional analysis of the hemagglutinin-esterase of infectious salmon anaemia virus
Arenaviruses and hantaviruses cause severe human disease. Little is known regarding host proteins required for their propagation. We identified human proteins that interact with the glycoproteins (GPs) of a prototypic arenavirus and hantavirus and show that the lectin endoplasmic reticulum (ER)-Golgi intermediate compartment 53 kDa protein (ERGIC-53), a cargo receptor required for glycoprotein trafficking within the early exocytic pathway, associates with arenavirus, hantavirus, coronavirus, orthomyxovirus, and filovirus GPs. ERGIC-53 binds to arenavirus GPs through a lectin-independent mechanism, traffics to arenavirus budding sites, and is incorporated into virions. ERGIC-53 is required for arenavirus, coronavirus, and filovirus propagation; in its absence, GP-containing virus particles form but are noninfectious, due in part to their inability to attach to host cells. Thus, we have identified a class of pathogen-derived ERGIC-53 ligands, a lectin-independent basis for their association with ERGIC-53, and a role for ERGIC-53 in the propagation of several highly pathogenic RNA virus families.
Output: The Intracellular Cargo Receptor ERGIC-53 Is Required for the Production of Infectious Arenavirus, Coronavirus, and Filovirus Particles
Despite many years of research, human DNA vaccines have yet to fulfill their early promise. Over the past 15 years, multiple generations of DNA vaccines have been developed and tested in preclinical models for prophylactic and therapeutic applications in the areas of infectious disease and cancer, but have failed in the clinic. Thus, while DNA vaccines have achieved successful licensure for veterinary applications, their poor immunogenicity in humans when compared with traditional protein-based vaccines has hindered their progress. Many strategies have been attempted to improve DNA vaccine potency including use of more efficient promoters and codon optimization, addition of traditional or genetic adjuvants, electroporation, intradermal delivery and various prime-boost strategies. This review summarizes these advances in DNA vaccine technologies and attempts to answer the question of when DNA vaccines might eventually be licensed for human use. DNA vaccines are composed of a bacterial plasmid that encodes the antigen of interest under the control of a strong eukaryotic promoter, such as CMV intron A. Host cells can be transfected by a variety of routes including injection of the plasmid into the muscle or dermis, or mucosal application. DNA vaccines present a range of advantages (Box 1) over conventional live virus or protein subunit vaccines as they enable the antigen to be expressed by APCs that then process and present epitopes from the antigen on MHC class I and II molecules, thereby inducing cellular immunity. Plasmid preparation is rapid and cost effective when compared with recombinant proteins and does not suffer problems such as improper protein folding. DNA is highly stable and flexible, allowing easy modification of plasmid sequences that may be relevant, for example, during a pandemic, when speed of vaccine design is paramount.
Output: Technologies for enhanced efficacy of DNA vaccines NIH Public Access NIH-PA Author Manuscript Mode of action of DNA vaccines
Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for dissemination, long-term persistence within tissues and virus replication. Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or membrane fusion. These processes play important roles in the mechanisms contributing to the pathogenesis of these agents and in establishing viral genome persistence and latency. Upon viral infection, monocytes respond with an elevated expression of proinflammatory signalling molecules and antiviral responses, as is shown in the case of the influenza, Chikungunya, human herpes and Zika viruses. Human immunodeficiency virus initiates acute inflammation on site during the early stages of infection but there is a shift of M1 to M2 at the later stages of infection. Cytomegalovirus creates a balance between pro-and anti-inflammatory processes by inducing a specific phenotype within the M1/M2 continuum. Despite facilitating inflammation, infected macrophages generally display abolished apoptosis and restricted cytopathic effect, which sustains the virus production. The majority of viruses discussed in this review employ monocytes/macrophages as a repository but certain viruses use these cells for productive replication. This review focuses on viral adaptations to enter monocytes/macrophages, immune escape, reprogramming of infected cells and the response of the host cells.
Output: Molecular Sciences Monocytes and Macrophages as Viral Targets and Reservoirs
Porcine epidemic diarrhea virus (PEDV) targets the intestinal mucosa in pigs. To protect against PEDV invasion, a mucosal vaccine is utilized effectively. In this study, we generated a recombinant adenovirus vaccine encoding the heat-labile enterotoxin B (LTB) and the core neutralizing epitope (COE) of PEDV (rAd-LTB-COE). The fusion protein LTB-COE was successfully expressed by the recombinant adenovirus in HEK293 cells, and the immunogenicity of the vaccine candidate was assessed in BALB/c mice and piglets. Three intramuscular or oral vaccinations with rAd-LTB-COE at two-week intervals induced robust humoral and mucosal immune responses. Moreover, a cell-mediated immune response was promoted in immunized mice, and the neutralizing antibody inhibited both the vaccine strain and the emerging PEDV isolate. Immunization experiments in piglets revealed that rAd-LTB-COE was immunogenic and induced good immune responses in piglets. Further studies are required to evaluate the efficacy of rAd-LTB-COE against a highly virulent PEDV challenge.
Output: Recombinant adenovirus carrying a core neutralizing epitope of porcine epidemic diarrhea virus and heat-labile enterotoxin B of Escherichia coli as a mucosal vaccine
The transmission modes of SARS-coronavirus appear to be through droplet spread, close contact and fomites although air borne transmission has not been ruled out. This clearly places dental personnel at risks as they work in close proximity to their patients employing droplet and aerosol generating procedures. Although the principle of universal precautions is widely advocated and followed throughout the dental community, additional precautionary measures -termed standard precaution may be necessary to help control the spread of this highly contagious disease. Patient assessment should include questions on recent travel to SARS infected areas and, contacts of patients, fever and symptoms of respiratory infections. Special management protocols and modified measures that regulate droplet and aerosol contamination in a dental setting have to be introduced and may include the reduction or avoidance of droplet/aerosol generation, the disinfection of the treatment field, application of rubber dam, pre-procedural antiseptic mouthrinse and the dilution and efficient removal of contaminated ambient air. The gag, cough or vomiting reflexes that lead to the generation of aerosols should also be prevented.
Output: PRACTICE Severe Acute Respiratory Syndrome (SARS) and the GDP. Part II: Implications for GDPs
We investigated the incidences and characteristics of pediatric traumatic injuries requiring emergency department visits, through a complementary approach using both nationwidesample and single-institutional data. Data for children (aged <15 years) identified with traumatic injuries during a 10-year period from the Korean National Health Insurance Sharing Service (n = 35,064 among 10,114,909 randomly sampled cases from the claim records of the National Health Insurance) and the authors' institute (n = 39,228) were retrospectively reviewed. The incidences and characteristics of the injuries were investigated using both datasets; additionally, detailed information regarding the injury environments was investigated using the single-institutional data. The findings were similar across both datasets. The incidence of injuries increased during the study period; the head was most commonly injured, whereas the trunk or proximal extremities were rarely injured; low-energy head injuries accounted for >50% of the cases in children aged <5 years, although the incidences of lowerextremity injuries and fractures increased in older children. Single-institutional data demonstrated that the proportion of indoor playground and trampoline-related injuries increased rapidly during the study period, and outdoor injuries and seasonal variation (with peak incidences in May and June) were more prominent in older children. Based on similarities between both datasets, the detailed results regarding pediatric traumatic injuries obtained from the singleinstitutional data could be generalized nationally with adequate external validity. To prevent traumatic injuries, it may be more effective to wear protective equipment covering the head and distal extremities rather than the trunk or proximal extremities; simple clothing, such as caps, could prevent many injuries in preschoolers. Among older children, safety guidelines for outdoor sports/leisure activities are needed. The increase in pediatric traumatic injuries may be partially explained by the increased availability of indoor playgrounds and installation of trampolines. Stricter adherence to the preventive guidelines is needed. Low-energy injuries (that is, superficial injuries such as abrasions or open wounds such as lacerations) were the most common injury type for children aged <5 years. Although fracture is a rare injury type in young children, it was relatively common in children aged >5 years and became the most common injury type in children aged >11 years (bold font). Data are presented as n (%).
Output: Characteristics and trends of traumatic injuries in children visiting emergency departments in South Korea: A retrospective serial cross-sectional study using both nationwide-sample and single-institutional data
The past decade has seen an explosion in the field of in vitro disease modelling, in particular the development of organoids. These selforganizing tissues derived from stem cells provide a unique system to examine mechanisms ranging from organ development to homeostasis and disease. Because organoids develop according to intrinsic developmental programmes, the resultant tissue morphology recapitulates organ architecture with remarkable fidelity. Furthermore, the fact that these tissues can be derived from human progenitors allows for the study of uniquely human processes and disorders. This article and accompanying poster highlight the currently available methods, particularly those aimed at modelling human biology, and provide an overview of their capabilities and limitations. We also speculate on possible future technological advances that have the potential for great strides in both disease modelling and future regenerative strategies.
Output: Disease modelling in human organoids
Human erythrocytes infected with the malarialparasite Plasmodium falciparum contain flattened membrane lamellae. It has been suggested that the lamellae may be involved in the sorting of malarial proteins to the cytoplasm and the cell membrane of the host erythrocyte. We have previously shown that the lamellae accumulate sphingolipids by virtue of their lipid composition in a manner similar to the trans-Golgi and the trans-Golgi network in mammalian cells. In this paper, we show by immunofluorescence microscopy that a monoclonal antibody to the lamellae labeled a perinuclear organetle that colocalized with WGA and the mannose-6-phosphate receptor in cultured mammalian cells. Immunoelectron microscopy experiments revealed that LWLI labels cisternae of the trans-face and the trans-Golgi network. Western blot analysis of subcellular fractions using LWLI detected a 170 kD protein which is associated with the luminal side of Golgi membranes of rat liver and is conserved in all cell lines studied. Our results indicate that (i) the 170 kD protein is a novel marker of the mammalian trans-Golgi and the trans-Golgi network and (ii) in addition to similarities in their morphological and lipid characteristics, the lamellae induced by P. falciparum in erythrocytes share proteinaceous determinants with the Golgi apparatus of mammalian cells.
Output: Recognition of a 170 kD protein in mammalian Golgi complexes by an antibody against malarial intraerythrocytic lamellae
Background: The Middle Eastern Respiratory Syndrome Coronavirus is a serious and emerging issue in Saudi Arabia and the world. A response was required to reduce possible disease transmission between the hospital and university. College of Nursing academic staff developed a programme in response to the educational and emotional needs of participants. Methods: A MERS-CoV Task Force responded to the rapidly unfolding epidemic. The aim was to find out what nursing staff and nursing students in the college knew about MERS-CoV. While most gaps in knowledge were addressed after an intense information seminar, other learning needs were identified and responded to. The Task Force developed mandatory information sessions for all nursing faculty, students and staff. All staff were informed by email, letters and posters. There are 28 faculty staff, 84 support staff and 480 students in the College of Nursing. The information settings all took place within the College of Nursing, Princess Nourah University, Kingdom of Saudi Arabia. Questionnaires were given to faculty, students and staff to understand their baseline knowledge. After the sessions, faculty, students and staff were asked about what was learned through the sessions, and what educational needs still needed to be addressed. Approval was sought and received by the Ethics Committee for the College of Nursing. Participants completed informed consent forms and the voluntary nature of the study was explained. Results: The total number of people attending the education sessions was133, including 65 students. 18 faculty members attended and 57 support staff. Data was gathered on gaps in participant knowledge and a plan was developed to address the gaps. Policies were established around student participation in clinical and return to work practices for staff with any symptoms. Conclusion: In hospitals there is above average risk for exposure to infectious diseases. Student nurses travel between hospital and university, with the capacity to act as a conduit of pathogens to large, susceptible populations. Nursing colleges must respond thoroughly to protect students and staff and prevent spread of disease into the university community in the midst of an epidemic.
Output: An educational programme for nursing college staff and students during a MERS-coronavirus outbreak in Saudi Arabia
A wide array of wildlife species, including many animals, are used in traditional medicines across many medicinal systems, including in Traditional Chinese Medicine (TCM). Due to over-exploitation and habitat loss, the populations of many animals commonly used in TCM have declined and are unable to meet market demand. A number of measures have been taken to try to reduce the impact that this large and growing market for TCM may have on wild animal species. Consumer preferences and behavior are known to play an important role in the consumption and protection of wild animals used in traditional medicine, and thus are likely to be an important factor in the success of many of these mechanisms-particularly given the significant percentage of TCMs that are over-the-counter products (access to which is not mediated by practitioners). In this study we conducted questionnaires and designed stated preference experiments embodying different simulation scenarios using a random sample of the population in Beijing to elicit individuals' knowledge, perceptions and preferences toward wild or farmed animal materials and their substitutes used in traditional Chinese medicine. We found that respondents had a stated preference for wild materials over farm-raised and other alternatives because they believe that the effectiveness of wildsourced materials is more credible than that of other sources. However, we also found that, although respondents used TCM products, they had a poor understanding of the function or composition of either traditional Chinese medicines or proprietary Chinese medicines (PCM), and paid little attention to the composition of products when making purchasing decisions. Furthermore, awareness of the need for species protection, or "conservation consciousness" was found to play an important role in willingness to accept substitutions for wild animal materials, while traditional animal medicinal materials (TAMs) derived from wellknown endangered species, such as bear bile and tiger bone, show relatively higher substitutability. These results suggest that there is still hope for conservation measures which PLOS ONE | seek to promote a transition to farmed animal, plant and synthetic ingredients and provide clear directions for future social marketing, education and engagement efforts. This study was conducted in Beijing in the summer of 2011. A stratified survey design was chosen to randomly select neighborhoods and households from a sample frame, according to Perception and Preference of Wild Animals in Traditional Medicine PLOS ONE |
Output: Consumption and Protection of Wild Animals Used in Traditional Medicine
Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. and horses vaccinated against a commercially available bacterin. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. Other lipids of interest were triacylglycerols that were only elevated in the serum of infected horses and sphingomyelins that were increased only in the serum of vaccinated horses. This is the first report looking at the equine serum lipidome during leptospiral infection and vaccination.
Output: Lipidomic analysis of immune activation in equine leptospirosis and Leptospira- vaccinated horses
The hnRNP C heterotetramer [(C1 3 )C2] binds RNA polymerase II transcripts in the nucleus, along with other proteins of the core hnRNP complex, and plays an important role in mRNA biogenesis and transport. Infection of HeLa cells with poliovirus causes hnRNP C to re-localize from the nucleus, where it is normally retained during interphase, to the cytoplasm. We have proposed that in the cytoplasm, the protein isoforms of hnRNP C participate in the recognition of viral specific RNAs by the poliovirus replication proteins and/or in the assembly of membrane-bound RNA replication complexes. In SK-OV-3 cells, which express reduced levels of hnRNP C compared to HeLa cells or 293 cells, the kinetics of poliovirus replication are delayed. hnRNP C is also re-localized from the nucleus to the cytoplasm in SK-OV-3 cells infected with poliovirus. Increased expression of hnRNP C in SK-OV-3 cells by transient transfection increases the rate of virus production and overall yield over that seen in mock-transfected cells. We propose that hnRNP C interacts with poliovirus RNA and replication proteins to increase the efficiency of viral genomic RNA synthesis.
Output: Delayed kinetics of poliovirus RNA synthesis in a human cell line with reduced levels of hnRNP C proteins
Streptococcus pneumoniae (S. pneumoniae) and viruses are considered as primary risks of community-acquired pneumonia (CAP), and the effects of co-infection bacterial and virus in the prognosis of patients with severe CAP (SCAP) are poorly described. Therefore, this study is conducted to investigate the regulation of Beclin1-PI3K/AKT axis in reinfection of S. pneumoniae after influenza A virus in mice model of bronchoalveolar lavage fluid (BALF). Samples of sputum and BALF were collected from patients with SCAP for etiological detection. The expression of each gene was determined by RT-qPCR and western blot analysis. Influenza A/PR/8/34 and S. pneumoniae were used to establish the mice model of reinfection pneumonia. The virus quantity, expression levels of inflammatory factors, bacterial load, and myeloperoxidase (MPO) activity were tested. HE staining was applied to observe histopathology of lung tissue. The expression of Beclin1 was downregulated and the PI3K/AKT pathway was activated in viral pneumonia. In vivo experiment, the reinfection of S. pneumoniae following influenza A virus infection increased the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice. In contrast, inhibition of the PI3K/AKT pathway or overexpression of Beclin1 reduced the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice reinfected with S. pneumoniae after influenza A virus infection. Collectively, our study demonstrates that inhibition of the PI3K/AKT signaling pathway or overexpressed Beclin1 alleviates reinfection of S. pneumoniae after influenza A virus infection in SCAP.
Output: Inhibition of the PI3K/AKT Signaling Pathway or Overexpression of Beclin1 Blocks Reinfection of Streptococcus pneumoniae After Infection of Influenza A Virus in Severe Community-Acquired Pneumonia
Land in urban fringe area is the primary source for land supply and development. In Hong Kong (HK), nine new towns have been built in New Territories since 1970s, providing 172.6 km 2 built-up land and large amount of residences for 3.4 million people. However, due to land scarcity, development restriction, and social opposition, New Development Area (NDA), as the small-scale extension of New Town (NT), was designated as one of the main approaches for HK medium and long term land supply. To demonstrate the characteristics of urban fringe land use transitions in Hong Kong, literature review and case study were used in this research. The history of new town development and the scheme of new development areas were introduced firstly. Afterwards, the land use features of NT and NDA were compared and the case of Hung Shui Kiu NDA was illustrated. It is concluded that while housing, infrastructure and facility were the main elements in NTs, employment, vibrancy and environment were suggested to be the new compulsory elements in NDAs integrated to the traditional planning concepts. As for the development approach, lease modification was adopted in NDA to allow private landowners directly develop their land, in addition to the traditional development approach of land resumption in NT. It is suggested to ensure the development of NDA, the proposed development plan should be persuasive to provide the optimal land use distribution as a trade-off among the profits of developers, the interests of local villager, government concern and the provision of land for future residents. Also, community engagement will play a more important role in NDA planning process. Referring to the analysis of urban fringe land use transitions and strategies for planning and development, the study would also be helpful to others growing cities.
Output: Urban fringe land use transitions in Hong Kong: from new towns to new development areas
Purpose of the Review-To discuss recent insights into the relationships between viral respiratory infections and asthma inception in the context of a long-term goal of moving towards prevention strategies for childhood asthma. Recent Findings-There is strong evidence for respiratory syncytial virus (RSV) and human rhinovirus (RV) wheezing illnesses as important risk factors for asthma inception. The mechanisms underlying these relationships have been an intense area of study. Novel approaches for the prevention of virus infections and/or lessening the severity of associated illnesses are at various stages of development, and are important potential tools in efforts aimed at primary and secondary prevention of asthma. Summary-Viral respiratory infections in early life are a major source of morbidity and critical in the development of asthma. Mechanisms by which these infections lead to asthma inception in susceptible individuals are emerging. Further, there are promising potential interventions currently available that should be tested in clinical trials. The goal of prevention of disease inception is clearly on the horizon.
Output: Early Life Viral Infections and the Development of Asthma -A Target for Asthma Prevention?
Phylogenetic trees constructed using predicted amino acid sequences of putative proteins of coronavirus HKU1 (CoV-HKU1) revealed that CoV-HKU1 formed a distinct branch among group 2 coronaviruses. Of the 14 trees from p65 to nsp10, nine showed that CoV-HKU1 was clustered with murine hepatitis virus. From nsp11, the topologies of the trees changed dramatically. For the eight trees from nsp11 to N, seven showed that the CoV-HKU1 branch was the first branch. The codon usage patterns of CoV-HKU1 differed significantly from those in other group 2 coronaviruses. Split decomposition analysis revealed that recombination events had occurred between CoV-HKU1 and other coronaviruses. * These authors contributed equally to the manuscript.
Output: Phylogenetic and recombination analysis of coronavirus HKU1, a novel coronavirus from patients with pneumonia
In this study, 185 nasopharyngeal swabs were tested to compare the sensitivity and specificity of the Luminex NxTAG (NxTAG) Respiratory Pathogen Panel (RPP) Assay with those of the Luminex Respiratory Virus Panel (RVP) Fast Assay v2 and singleplex real-time polymerase chain reaction (PCR). The NxTAG Assay identified at least one infectious agent in 164 (88.7%) of the swabs. In 91 (6.2%) tests with negative results with the RVP Fast Assay v2, a virus was identified by the NxTAG (P b 0.001). With the NxTAG Assay, the detection rates were significantly higher for respiratory syncytial virus (P = 0.003), human metapneumovirus (P b 0.001), human rhinovirus/human enterovirus (P = 0.009) and human adenovirus (P b 0.001). Finally, the NxTAG Assay identified M. pneumoniae in 32 of 44 (72.7%) PCR-positive samples. However, the concordance with real-time PCR results was low for both assays. In conclusion, the results indicate that the NxTAG Assay overcomes some of the limitations of previous Luminex assays, although further studies are needed for a more complete evaluation of the new assay.
Output: Partial comparison of the NxTAG Respiratory Pathogen Panel Assay with the Luminex xTAG Respiratory Panel Fast Assay V2 and singleplex real-time polymerase chain reaction for detection of respiratory pathogens
Introduction: Outbreaks of infectious diseases trigger an increase in scientific research and output. Early in outbreaks, evidence is scarce, but it accumulates rapidly. We are continuously facing new disease outbreaks, including the new coronavirus (SARS-nCoV-2) in December 2019.The objective of this study was to describe the accumulation of evidence during the 2013-2016 Zika virus (ZIKV) outbreak in the Pacific and the Americas related to aetiological causal questions about congenital abnormalities and Guillain-Barré syndrome. Methods: We hypothesised that the temporal sequence would follow a pre-specified order, according to study design. We assessed 1) how long it takes before findings from a specific study design appear, 2) how publication of preprints could reduce the time to publication and 3) how time to publication evolves over time. Results: We included 346 publications published between March 6, 2014 and January 1, 2019. In the 2013--2016 ZIKV outbreak, case reports, case series and basic research studies were published first. Case-control and cohort studies appeared between 400-700 days after ZIKV was first detected in the region of the study origin. Delay due to the publication process were lowest at the beginning of the outbreak. Only 4.6% of the publications was available as preprints. Discussion: The accumulation of evidence over time in new causal problems generally followed a hierarchy. Preprints reduced the delay to initial publication. Our methods can be applied to new emerging infectious diseases.
Output: Emergence of evidence during disease outbreaks: lessons learnt from the Zika virus outbreak
Murine hepatitis viruses provide excellent animal models for the study of virus-induced diseases of the central nervous system and gastrointestinal tract. Several studies have indirectly provided evidence that the spike glycoprotein (S) of these coronaviruses bears determinants for pathogenesis and the induction of protective immunity. In order to directly evaluate the immunogenicity of this protein, it was purified by affinity chromatography with an in vitro neutralizing and in vivo protective monoclonal antibody which immunoprecipitated the 180-kDa spike glycoprotein of the neurotropic A59 strain of murine hepatitis virus (MHV-A59). Mice immunized twice with approximately 1 ag of purified S in Freund's adjuvant developed high titers of neutralizing and fusion inhibiting antibodies, even though the protein was at least partially denaturated after elution from the affinity column. Moreover, these mice were protected from lethal encephalitis when challenged intracerebrally with 10 LDso of MHV-A59. This study provides a direct demonstration of the importance of the coronavirus spike giycoprotein in the induction of a protective immune response. o 1SSoAcademic press. Inc.
Output: Protection from Lethal Coronavirus Infection by Affinity-Purified Spike Glycoprotein of Murine Hepatitis Virus, Strain A59
e Abstract-A long-standing concern for international spread of new, virulent pathogens became a reality with the advent of Severe Acute Respiratory Syndrome (SARS). This respiratory syndrome, caused by a coronavirus, spread rapidly across 30 nations since its first recognition in late 2002. SARS has presented the greatest recent threat to U.S. public health, and has come at a time when purposeful introduction of pathogens by terrorists is also of heightened concern. SARS has forced the international medical establishment to reexamine how best to manage such incidents.
Output: Clinical Communications SARS AND ITS IMPACT ON CURRENT AND FUTURE EMERGENCY DEPARTMENT OPERATIONS