title: The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome

text: We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 90° kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold.


title: The determination of treatment effect of chitosan oligosaccharide in lambs with experimentally cryptosporidiosis

text: Abstract In this study, it was aimed to investigate the efficacy of chitosan oligosaccharide administrations in different doses of experimental infected lambs with Cryptosporidium parvum. 32 male lambs were used in the study and the lambs were divided into 4 groups with 8 lambs in each group. Groups 1, 2 and 3, twice a day, were administered chitosan oligosaccharide at a dose of 100, 500, and 1000 mg/kg for 7 days, respectively, with milk replacer. In group 4, lambs with cryptosporidiosis were subjected to normal feeding as control without drug administration. Clinical examinations of lambs were made before treatment (day 0) and on days 1, 3, 5 and 7 after treatment and 5 ml of blood was collected from vena jugularis for blood analysis of all lambs. Weight changes of lambs were recorded at 0, 7, 14, and 21 days. Stool specimens were collected pre-treatment (day 0) and on days 1, 3, 5, 7, 14 and 21 post-treatment to determine oocyst excretion of lambs with cryptosporidiosis. Lambs with a mean oocyte counts >10 after stool examination were included to the treatment. Changes in clinical hematology, blood gases and biochemical parameters were observed during the course of treatment, but these changes were limited. Weight loss was observed at 7th day according to 0th day the lambs with experimental cryptosporidiosis but gradually weight increase was observed at 14th and 21st days and these changes were similar in all groups. Oocyst excretion decreased in all groups during treatment. According to 0th day, there was a significant (p < 0.05) decrease in oocyte excretions in the third day in group 1 and 2, and in day 5 in the group 3 and 4. Significant changes (p < 0.05) were observed in oocyst excretions on the third and fifth days among the groups. As a result, in lambs with experimental cryptosporidiosis, chitosan oligosaccharide improved in clinical signs and stool character shorter than the positive control group and the administration of chitosan oligosaccharide at doses of 100, 500 and 1000 mg/kg for 7 days significantly reduced oocyst excretion but not enough to remove cryptosporidiosis completely.


title: An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus

text: Passive serotherapy can confer immediate protection against microbial infection, but methods to rapidly generate human neutralizing monoclonal antibodies are not yet available. We have developed an improved method for Epstein-Barr virus transformation of human B cells. We used this method to analyze the memory repertoire of a patient who recovered from severe acute respiratory syndrome coronavirus (SARS-CoV) infection and to isolate monoclonal antibodies specific for different viral proteins, including 35 antibodies with in vitro neutralizing activity ranging from 10(−8)M to 10(−11)M. One such antibody confers protection in vivo in a mouse model of SARS-CoV infection. These results show that it is possible to interrogate the memory repertoire of immune donors to rapidly and efficiently isolate neutralizing antibodies that have been selected in the course of natural infection. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1080) contains supplementary material, which is available to authorized users.


title: Visualizing the invisible: class excursions to ignite children’s enthusiasm for microbes

text: We have recently argued that, because microbes have pervasive – often vital – influences on our lives, and that therefore their roles must be taken into account in many of the decisions we face, society must become microbiology‐literate, through the introduction of relevant microbiology topics in school curricula (Timmis et al. 2019. Environ Microbiol 21: 1513‐1528). The current coronavirus pandemic is a stark example of why microbiology literacy is such a crucial enabler of informed policy decisions, particularly those involving preparedness of public‐health systems for disease outbreaks and pandemics. However, a significant barrier to attaining widespread appreciation of microbial contributions to our well‐being and that of the planet is the fact that microbes are seldom visible: most people are only peripherally aware of them, except when they fall ill with an infection. And it is disease, rather than all of the positive activities mediated by microbes, that colours public perception of ‘germs’ and endows them with their poor image. It is imperative to render microbes visible, to give them life and form for children (and adults), and to counter prevalent misconceptions, through exposure to imagination‐capturing images of microbes and examples of their beneficial outputs, accompanied by a balanced narrative. This will engender automatic mental associations between everyday information inputs, as well as visual, olfactory and tactile experiences, on the one hand, and the responsible microbes/microbial communities, on the other hand. Such associations, in turn, will promote awareness of microbes and of the many positive and vital consequences of their actions, and facilitate and encourage incorporation of such consequences into relevant decision‐making processes. While teaching microbiology topics in primary and secondary school is key to this objective, a strategic programme to expose children directly and personally to natural and managed microbial processes, and the results of their actions, through carefully planned class excursions to local venues, can be instrumental in bringing microbes to life for children and, collaterally, their families. In order to encourage the embedding of microbiology‐centric class excursions in current curricula, we suggest and illustrate here some possibilities relating to the topics of food (a favourite pre‐occupation of most children), agriculture (together with horticulture and aquaculture), health and medicine, the environment and biotechnology. And, although not all of the microbially relevant infrastructure will be within reach of schools, there is usually access to a market, local food store, wastewater treatment plant, farm, surface water body, etc., all of which can provide opportunities to explore microbiology in action. If children sometimes consider the present to be mundane, even boring, they are usually excited with both the past and the future so, where possible, visits to local museums (the past) and research institutions advancing knowledge frontiers (the future) are strongly recommended, as is a tapping into the natural enthusiasm of local researchers to leverage the educational value of excursions and virtual excursions. Children are also fascinated by the unknown, so, paradoxically, the invisibility of microbes makes them especially fascinating objects for visualization and exploration. In outlining some of the options for microbiology excursions, providing suggestions for discussion topics and considering their educational value, we strive to extend the vistas of current class excursions and to: (i) inspire teachers and school managers to incorporate more microbiology excursions into curricula; (ii) encourage microbiologists to support school excursions and generally get involved in bringing microbes to life for children; (iii) urge leaders of organizations (biopharma, food industries, universities, etc.) to give school outreach activities a more prominent place in their mission portfolios, and (iv) convey to policymakers the benefits of providing schools with funds, materials and flexibility for educational endeavours beyond the classroom.


title: Blood-Borne Pathogens: A Canadian Blood Services Centre for Innovation Symposium

text: Abstract Testing donations for pathogens and deferring selected blood donors have reduced the risk of transmission of known pathogens by transfusion to extremely low levels in most developed countries. Protecting the blood supply from emerging infectious threats remains a serious concern in the transfusion medicine community. Transfusion services can employ indirect measures such as surveillance, hemovigilance, and donor questioning (defense), protein-, or nucleic acid based direct testing (detection), or pathogen inactivation of blood products (destruction) as strategies to mitigate the risk of transmission-transmitted infection. In the North American context, emerging threats currently include dengue, chikungunya, and hepatitis E viruses, and Babesia protozoan parasites. The 2003 SARS and 2014 Ebola outbreaks illustrate the potential of epidemics unlikely to be transmitted by blood transfusion but disruptive to blood systems. Donor-free blood products such as ex vivo generated red blood cells offer a theoretical way to avoid transmission-transmitted infection risk, although biological, engineering, and manufacturing challenges must be overcome before this approach becomes practical. Similarly, next generation sequencing of all nucleic acid in a blood sample is currently possible but impractical for generalized screening. Pathogen inactivation systems are in use in different jurisdictions around the world, and are starting to gain regulatory approval in North America. Cost concerns make it likely that pathogen inactivation will be contemplated by blood operators through the lens of health economics and risk-based decision making, rather than in zero-risk paradigms previously embraced for transfusable products. Defense of the blood supply from infectious disease risk will continue to require innovative combinations of surveillance, detection, and pathogen avoidance or inactivation.


title: Chapter 27 Practical Considerations in Virtual Screening and Molecular Docking

text: Abstract Molecular docking has become an important common component of the drug discovery toolbox, and its relative low-cost implications and perceived simplicity of use has stimulated an everincreasing popularity within academic communities. The inherent “garbage-in-garbage-out” defect of molecular docking, however, leads a lot of researchers to dedicate countless hours to the identification of hit compounds that later prove to be inactive. Several considerations that can greatly improve the success and enrichment of true bioactive hit compounds are commonly overlooked at the initial stages of a molecular docking study. This chapter will cover several of these considerations, including protonation states, active site waters, separating actives from decoys, consensus docking and molecular mechanics generalized-Born/surface area (MM-GBSA) rescoring, and incorporation of pharmacophoric constraints, in an attempt to clarify what is, in fact, very complicated and inherent difficulties of a structure-based drug design study.


title: Reflecting upon vulnerable and dependent bodies during the COVID‐19 crisis

text: This paper is a short narrative on how feminism helped me find a balance in my life and how this balance has been disrupted with the Covid‐19 crisis. I reflect on how this crisis is showing our vulnerabilities as human beings. This crisis reflects how our bodies depend on each other, moving away from the dominant patriarchal ontology that perceives bodies as being independent (Butler, 2016). I reflect on how this crisis is letting the most vulnerable in situations of survival because the infrastructures (Butler, 2016) that support our bodies are not functioning. At the same time, this crisis is providing visibility to certain occupations that are dominated by issues of race, class and gender. These occupations are being at least temporarily rehabilitated to their central position in society. We are living a time where we could show, through our teaching, possible resistance to the neoliberal ontology that captured humanity.


title: Porcine epidemic diarrhea: a review of current epidemiology and available vaccines

text: Porcine epidemic diarrhea virus (PEDV), an Alphacoronavirus in the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. PEDV can also cause diarrhea, agalactia, and abnormal reproductive cycles in pregnant sows. Although PEDV was first identified in Europe, it has resulted in significant economic losses in many Asian swine-raising countries, including Korea, China, Japan, Vietnam, and the Philippines. However, from April 2013 to the present, major outbreaks of PEDV have been reported in the United States, Canada, and Mexico. Moreover, intercontinental transmission of PEDV has increased mortality rates in seronegative neonatal piglets, resulting in 10% loss of the US pig population. The emergence and re-emergence of PEDV indicates that the virus is able to evade current vaccine strategies. Continuous emergence of multiple mutant strains from several regions has aggravated porcine epidemic diarrhea endemic conditions and highlighted the need for new vaccines based on the current circulating PEDV. Epidemic PEDV strains tend to be more pathogenic and cause increased death in pigs, thereby causing substantial financial losses for swine producers. In this review, we described the epidemiology of PEDV in several countries and present molecular characterization of current strains. We also discuss PEDV vaccines and related issues.


It’s True Even in a Pandemic: Children are Not Merely Little Adults


title: Estimation of the Probability of Reinfection With COVID-19 by the Susceptible-Exposed-Infectious-Removed-Undetectable-Susceptible Model

text: BACKGROUND: With the sensitivity of the polymerase chain reaction test used to detect the presence of the virus in the human host, the worldwide health community has been able to record a large number of the recovered population. OBJECTIVE: The aim of this study was to evaluate the probability of reinfection in the recovered class and the model equations, which exhibits the disease-free equilibrium state for the coronavirus disease. METHODS: The model differential equation was evaluated for the disease-free equilibrium for the case of reinfection as well as the existence and stability criteria for the disease, using the model proportions. This evaluation shows that the criteria for a local or worldwide asymptotic stability with a basic reproductive number (R(0)=0) were satisfied. Hence, there is a chance of no secondary reinfections from the recovered population, as the rate of incidence of the recovered population vanishes (ie, B=0). RESULTS: With a total of about 900,000 infected cases worldwide, numerical simulations for this study were carried out to complement the analytical results and investigate the effect that the implementation of quarantine and observation procedures has on the projection of further virus spread. CONCLUSIONS: As shown by the results, the proportion of the infected population, in the absence of a curative vaccination, will continue to grow worldwide; meanwhile, the recovery rate will continue slowly, which means that the ratio of infection rate to recovery rate will determine the death rate that is recorded. Most significant for this study is the rate of reinfection by the recovered population, which will decline to zero over time as the virus is cleared clinically from the system of the recovered class.


title: Effect of lockdown amid COVID-19 pandemic on air quality of the megacity Delhi, India

text: Abstract Amid the COVID-19 pandemic, a nationwide lockdown is imposed in India initially for three weeks from 24th March to 14th April 2020 and extended up to 3rd May 2020. Due to the forced restrictions, pollution level in cities across the country drastically slowed down just within few days which magnetize discussions regarding lockdown to be the effectual alternative measures to be implemented for controlling air pollution. The present article eventually worked on this direction to look upon the air quality scenario amidst the lockdown period scientifically with special reference to the megacity Delhi. With the aid of air quality data of seven pollutant parameters (PM10, PM2.5, SO2, NO2, CO, O3 and NH3) for 34 monitoring stations spread over the megacity we have employed National Air Quality Index (NAQI) to show the spatial pattern of air quality in pre and during-lockdown phases. The results demonstrated that during lockdown air quality is significantly improved. Among the selected pollutants, concentrations of PM10 and PM2.5 have witnessed maximum reduction (>50%) in compare to the pre-lockdown phase. In compare to the last year (i.e. 2019) during the said time period the reduction of PM10 and PM2.5 is as high as about 60% and 39% respectively. Among other pollutants, NO2 (−52.68%) and CO (−30.35%) level have also reduced during-lockdown phase. About 40% to 50% improvement in air quality is identified just after four days of commencing lockdown. About 54%, 49%, 43%, 37% and 31% reduction in NAQI have been observed in Central, Eastern, Southern, Western and Northern parts of the megacity. Overall, the study is thought to be a useful supplement to the regulatory bodies since it showed the pollution source control can attenuate the air quality. Temporary such source control in a suitable time interval may heal the environment.


Negotiating Inequality: Disruption and COVID‐19 in the United States


title: Chapter 14 The use of host factors in microbial forensics

text: Abstract Advances have been made in the forensic analysis of microbes and toxins. An underdeveloped and underutilized area in microbial forensics is how the host interacts with microorganisms in a way that provides unique signatures for forensic use. For forensic purposes, an immediate goal is to distinguish a potential victim and innocent person from a perpetrator, and to distinguish between a naturally acquired or intentional infection. Principal methods that are sufficiently developed are characterization of the humoral immune response to microbial antigens including vaccine-induced immunity and detection of antibiotics that may be present in a possible perpetrator. This chapter presents central elements of the host response in a simplified fashion and describes a representative example, which, in the appropriate context, has a high potential of providing evidence that may aid an investigation to distinguish a perpetrator from a victim. This chapter also presents information about the immune system so that the interested reader can have a fuller understanding of the immune response in general.


title: Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial

text: BACKGROUND: Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described in Saudi Arabia. MERS-CoV poses a significant risk to public health security because of an absence of currently available effective countermeasures. We aimed to assess the safety and immunogenicity of the candidate simian adenovirus-vectored vaccine expressing the full-length spike surface glycoprotein, ChAdOx1 MERS, in humans. METHODS: This dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial was done at the Centre for Clinical Vaccinology and Tropical Medicine (Oxford, UK) and included healthy people aged 18–50 years with negative pre-vaccination tests for HIV antibodies, hepatitis B surface antigen, and hepatitis C antibodies (and a negative urinary pregnancy test for women). Participants received a single intramuscular injection of ChAdOx1 MERS at three different doses: the low-dose group received 5 × 10(9) viral particles, the intermediate-dose group received 2·5 × 10(10) viral particles, and the high-dose group received 5 × 10(10) viral particles. The primary objective was to assess safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited, unsolicited, and serious adverse events after vaccination. The secondary objective was to assess the cellular and humoral immunogenicity of ChAdOx1 MERS, measured by interferon-γ-linked enzyme-linked immunospot, ELISA, and virus neutralising assays after vaccination. Participants were followed up for up to 12 months. This study is registered with ClinicalTrials.gov, NCT03399578. FINDINGS: Between March 14 and Aug 15, 2018, 24 participants were enrolled: six were assigned to the low-dose group, nine to the intermediate-dose group, and nine to the high-dose group. All participants were available for follow-up at 6 months, but five (one in the low-dose group, one in the intermediate-dose group, and three in the high-dose group) were lost to follow-up at 12 months. A single dose of ChAdOx1 MERS was safe at doses up to 5 × 10(10) viral particles with no vaccine-related serious adverse events reported by 12 months. One serious adverse event reported was deemed to be not related to ChAdOx1 MERS. 92 (74% [95% CI 66–81]) of 124 solicited adverse events were mild, 31 (25% [18–33]) were moderate, and all were self-limiting. Unsolicited adverse events in the 28 days following vaccination considered to be possibly, probably, or definitely related to ChAdOx1 MERS were predominantly mild in nature and resolved within the follow-up period of 12 months. The proportion of moderate and severe adverse events was significantly higher in the high-dose group than in the intermediate-dose group (relative risk 5·83 [95% CI 2·11–17·42], p<0·0001) Laboratory adverse events considered to be at least possibly related to the study intervention were self-limiting and predominantly mild in severity. A significant increase from baseline in T-cell (p<0·003) and IgG (p<0·0001) responses to the MERS-CoV spike antigen was observed at all doses. Neutralising antibodies against live MERS-CoV were observed in four (44% [95% CI 19–73]) of nine participants in the high-dose group 28 days after vaccination, and 19 (79% [58–93]) of 24 participants had antibodies capable of neutralisation in a pseudotyped virus neutralisation assay. INTERPRETATION: ChAdOx1 MERS was safe and well tolerated at all tested doses. A single dose was able to elicit both humoral and cellular responses against MERS-CoV. The results of this first-in-human clinical trial support clinical development progression into field phase 1b and 2 trials. FUNDING: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research.


Questions raised by COVID‐19 case descriptions


title: Graphene-Based Strategies in Liquid Biopsy and in Viral Diseases Diagnosis

text: Graphene-based materials are intriguing nanomaterials with applications ranging from nanotechnology-related devices to drug delivery systems and biosensing. Multifunctional graphene platforms were proposed for the detection of several typical biomarkers (i.e., circulating tumor cells, exosomes, circulating nucleic acids, etc.) in liquid biopsy, and numerous methods, including optical, electrochemical, surface-enhanced Raman scattering (SERS), etc., have been developed for their detection. Due to the massive advancements in biology, material chemistry, and analytical technology, it is necessary to review the progress in this field from both medical and chemical sides. Liquid biopsy is considered a revolutionary technique that is opening unexpected perspectives in the early diagnosis and, in therapy monitoring, severe diseases, including cancer, metabolic syndrome, autoimmune, and neurodegenerative disorders. Although nanotechnology based on graphene has been poorly applied for the rapid diagnosis of viral diseases, the extraordinary properties of graphene (i.e., high electronic conductivity, large specific area, and surface functionalization) can be also exploited for the diagnosis of emerging viral diseases, such as the coronavirus disease 2019 (COVID-19). This review aimed to provide a comprehensive and in-depth summarization of the contribution of graphene-based nanomaterials in liquid biopsy, discussing the remaining challenges and the future trend; moreover, the paper gave the first look at the potentiality of graphene in COVID-19 diagnosis.


title: Chapter 11 Systems Virology Why everybody wants to measure everything

text: Abstract Virologists have long known that viral pathogenesis must be studied from the standpoint of both the virus and the host. Nevertheless, given its relative simplicity, studying the virus has always been more tractable. As outlined in the previous chapters, virus-centric approaches have yielded a tremendous amount of information about viral genetics, viral replication cycles, and host and tissue tropisms. Along the way have come insights into host innate and adaptive immune responses and the many ways in which viruses antagonize these responses while exploiting other cellular processes to their advantage. The sequencing of the human genome, however, dramatically changed the field of viral pathogenesis. Virologists are now able to move beyond virus-centric or single-gene approaches and instead investigate the host response to infection on a genome-wide scale. In this chapter, we focus on the insights into viral pathogenesis that are provided by examining the host transcriptional response, including the dynamics of innate and acquired immunity, diagnostic signatures, and the identification of targets for antiviral drugs.


The Sexual and Reproductive Health of Adolescents and Young Adults During the COVID‐19 Pandemic


title: A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy Results

text: A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.


title: Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

text: The devastating Ebola virus (EBOV) outbreak in West Africa in 2013–2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens.


title: An original design of remote robot-assisted intubation system

text: The success rate of pre-hospital endotracheal intubation (ETI) by paramedics is lower than physicians. We aimed to establish a remote robot-assisted intubation system (RRAIS) and expected it to improve success rate of pre-hospital ETI. To test the robot’s feasibility, 20 pigs were intubated by direct laryngoscope or the robot system. Intubation time, success rate, airway complications were recorded during the experiment. The animal experiment showed that participants achieved a higher success rate in absolute numbers by the robot system. In summary, we have successfully developed a remote robot-assisted intubation system. It is promising for RRAIS to improve the success rate of pre-hospital ETI and change the current rescue model.


title: Computational Sequence Analysis of Mammalian Reovirus Proteins

text: In the present study, computer-assisted searches for sequence similarities were performed with amino acid sequences from mammalian reovirus proteins. These analysis revealed that many proteins of reovirus are partially similar to known viral or cellular proteins. Consensus sequences have been identified that are in accordance with already suspected functions of reovirus proteins. The analysis has also revealed unexpected similarities of some reovirus proteins with specific classes of proteins which sequences are present in the databases. This could suggest yet unidentified activities for some of the reovirus proteins.


title: Analytic solution of the SEIR epidemic model via asymptotic approximant

text: An analytic solution is obtained to the SEIR Epidemic Model. The solution is created by constructing a single second-order nonlinear differential equation in [Formula: see text] and analytically continuing its divergent power series solution such that it matches the correct long-time exponential damping of the epidemic model. This is achieved through an asymptotic approximant (Barlow et al., 2017) in the form of a modified symmetric Padé approximant that incorporates this damping. The utility of the analytical form is demonstrated through its application to the COVID-19 pandemic.


title: Planning for a pandemic: Mitigating risk to radiation therapy service delivery in the COVID‐19 era

text: The novel coronavirus (COVID‐19) has rapidly impacted all of our lives following its escalation to pandemic status on 11 March 2020. Government guidelines and restrictions implemented to mitigate the risk of COVID‐19 community transmission have forced radiation therapy departments to promptly adjust to the significant impact on our ability to deliver best clinical care. The inherent nature of our tri‐partied professions relies heavily on multidisciplinary teamwork and patient–clinician interactions. Teamwork and patient interaction are critical to the role of a radiation therapist. The aim of this paper is to describe the experience of the Peter MacCallum Cancer Centre’s (Peter Mac) radiation therapy services during the preliminary stages of the COVID‐19 pandemic in minimising risk to patients, staff and our clinical service. Four critical areas were identified in developing risk mitigation strategies across our service: (a) Workforce planning, (b) Workforce communication, (c) Patient safety and wellbeing, and (d) Staff safety and wellbeing. Each of these initiatives had a focus on continuum of clinical care, whilst minimising risk of cross infection for our radiation therapy workforce and patients alike. Initiatives included, but were not limited to, establishing COVID‐Eclipse clinical protocols, remote access to local applications, implementation of Microsoft Teams, personal protective equipment (PPE) guidelines and virtual ‘Division of Radiation Oncology’ briefing/updates. The COVID‐19 pandemic has dictated change in conventional radiation therapy practice. It is hoped that by sharing our experiences, the radiation therapy profession will continue to learn, adapt and navigate this period together, to ensure optimal outcomes for ourselves and our patients.


title: Partial RdRp sequences offer a robust method for Coronavirus subgenus classification

text: The recent reclassification of the Riboviria, and the introduction of multiple new taxonomic categories including both subfamilies and subgenera for coronaviruses (family Coronaviridae, subfamily Orthocoronavirinae) represents a major shift in how official classifications are used to designate specific viral lineages. While the newly defined subgenera provide much-needed standardisation for commonly cited viruses of public health importance, no method has been proposed for the assignment of subgenus based on partial sequence data, or for sequences that are divergent from the designated holotype reference genomes. Here, we describe the genetic variation of a partial region of the coronavirus RNA-dependent RNA polymerase (RdRp), which is one of the most used partial sequence loci for both detection and classification of coronaviruses in molecular epidemiology. We infer Bayesian phylogenies from more than 7000 publicly available coronavirus sequences and examine clade groupings relative to all subgenus holotype sequences. Our phylogenetic analyses are largely coherent with genome-scale analyses based on designated holotype members for each subgenus. Distance measures between sequences form discrete clusters between taxa, offering logical threshold boundaries that can attribute subgenus or indicate sequences that are likely to belong to unclassified subgenera both accurately and robustly. We thus propose that partial RdRp sequence data of coronaviruses is sufficient for the attribution of subgenus-level taxonomic classifications and we supply the R package, “MyCoV”, which provides a method for attributing subgenus and assessing the reliability of the attribution. The analysis of polymerase chain reaction amplicons derived from biological samples is the most common modern method for detection and classification of infecting viral agents, such as Coronaviruses. Recent updates to the official standard for taxonomic classification of Coronaviruses, however, may leave researchers unsure as to whether the viral sequences they obtain by these methods can be classified into specific viral taxa due to variations in the sequences when compared to type strains. Here, we present a plausible method for defining genetic dissimilarity cut-offs that will allow researchers to state which taxon their virus belongs to and with what level of certainty. To assist in this, we also provide the R package ‘MyCoV’ which classifies user generated sequences.


title: Status presens of antiviral drugs and strategies: Part II: RNA VIRUSES (EXCEPT RETROVIRUSES)

text: More than 40 compounds have been formally licensed for clinical use as antiviral drugs, and half of these are used for the treatment of HIV infections. The others have been approved for the therapy of herpesvirus (HSV, VZV, CMV), hepadnavirus (HBV), hepacivirus (HCV) and myxovirus (influenza, RSV) infections. New compounds are in clinical development or under preclinical evaluation, and, again, half of these are targeting HIV infections. Yet, quite a number of important viral pathogens (i.e. HPV, HCV, hemorrhagic fever viruses) remain in need of effective and/or improved antiviral therapies.


How the coronavirus pandemic has affected the clinical management of Philadelphia-negative chronic myeloproliferative neoplasms in Italy—a GIMEMA MPN WP survey


title: RadioGraphics Update: Radiographic and CT Features of Viral Pneumonia

text: Editor’s Note.—Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics. Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article.


Concealed SARS-CoV-2 interstitial pneumonia unmasked by infarct-like acute myocarditis


title: Surveillance of respiratory viruses in the outpatient setting in rural coastal Kenya: baseline epidemiological observations

text: Background: Endemic and seasonally recurring respiratory viruses are a major cause of disease and death globally. The burden is particularly severe in developing countries. Improved understanding of the source of infection, pathways of spread and persistence in communities would be of benefit in devising intervention strategies. Methods: We report epidemiological data obtained through surveillance of respiratory viruses at nine outpatient health facilities within the Kilifi Health and Demographic Surveillance System, Kilifi County, coastal Kenya, between January and December 2016. Nasopharyngeal swabs were collected from individuals of all ages presenting with acute respiratory infection (ARI) symptoms (up to 15 swabs per week per facility) and screened for 15 respiratory viruses using real-time PCR. Paediatric inpatient surveillance at Kilifi County Hospital for respiratory viruses provided comparative data. Results: Over the year, 5,647 participants were sampled, of which 3,029 (53.7%) were aged <5 years. At least one target respiratory virus was detected in 2,380 (42.2%) of the samples; the most common being rhinovirus 18.6% (1,050), influenza virus 6.9% (390), coronavirus 6.8% (387), parainfluenza virus 6.6% (371), respiratory syncytial virus (RSV) 3.9% (219) and adenovirus 2.7% (155). Virus detections were higher among <5-year-olds compared to older children and adults (50.3% vs 32.7%, respectively; χ (2)(1) =177.3, P=0.0001). Frequency of viruses did not differ significantly by facility (χ (2)(8) =13.38, P=0.072). However, prevalence was significantly higher among inpatients than outpatients in <5-year-olds for RSV (22.1% vs 6.0%; χ (2)(1) = 159.4, P=0.0001), and adenovirus (12.4% vs 4.4%, χ (2)(1) =56.6, P=0.0001). Conclusions: Respiratory virus infections are common amongst ARI outpatients in this coastal Kenya setting, particularly in young children. Rhinovirus predominance warrants further studies on the health and socio-economic implications. RSV and adenovirus were more commonly associated with severe disease. Further analysis will explore epidemiological transmission patterns with the addition of virus sequence data.


title: Ready or Not, Patients Will Present: Improving Urban Pandemic Preparedness

text: Over the past century, society has achieved great gains in medicine, public health, and health-care infrastructure, particularly in the areas of vaccines, antibiotics, sanitation, intensive care and medical technology. Still, despite these developments, infectious diseases are emerging at unprecedented rates around the globe. Large urban centers are particularly vulnerable to communicable disease events, and must have well-prepared response systems, including on the front-line level. In November 2018, the United States’ largest municipal health-care delivery system, New York City Health + Hospitals, hosted a half-day executive-level pandemic response workshop, which sought to illustrate the complexity of preparing for, responding to, and recovering from modern-day infectious diseases impacting urban environments. Attendees were subjected to a condensed, plausible, pandemic influenza scenario and asked to simulate the high-level strategic decisions made by leaders by internal (eg, Chief Medical Officer, Chief Nursing Officer, and Legal Affairs) and external (eg, city, state, and federal public health and emergency management entities) partners across an integrated system of acute, postacute, and ambulatory sites, challenging players to question their assumptions about managing the consequences of a highly pathogenic pandemic.


title: Medical and microbiological problems arising from airborne infection in hospitals

text: Abstract The practical importance and frequency of airborne nosocomial infections has been a matter of dispute for many years. This is because most of the pathogens acquired in hospitals are able to use various different routes of infecting the patient's body so that it may be difficult or even impossible to prove an individual infection to be airborne. Only microbes such as Streptococcus pyogenes, Neisseria meningitidis, Corynebacterium diphtheriae, Mycobacterium tuberculosis, or certain respiratory viruses that are known to be predominantly transmitted by droplet infection from infected persons or healthy carriers, have been accepted to be the cause of airborne nosocomial infections. Other pathogens such as legionellae, pseudomonads or clostridia may be distributed in the hospital environment via an insufficient or defective air-conditioning system, with or without humidification. The assessment of indirect airborne infections caused by infective particles derived from dust which has settled on furniture or the floor or which has been introduced to the hospital environment by shoes, open windows, building works or potted indoor plants is much more difficult. Many Gram-positive bacteria such as Staphylococcus aureus, mycobacteria, nocardiae, and endospores of clostridia and bacilli, as well as the reproductive elements of fungi do remain viable and infective in dry dust and may therefore infect patients when the dust is disturbed. In contrast to nosocomial infections due to Gram-negative bacteria, against which most preventive measures have been concentrated in the past and which are usually not airborne in origin, it appears that the possibility of direct or indirect transmission of hospital pathogens by air has been underestimated. When other routes of nosocomial infections are well controlled, airborne infections may gain more practical importance in hospitals.


title: 15 Cleaning and decontamination of the healthcare environment

text: Abstract: Evidence is accumulating for the role of cleaning in controlling hospital infections. Hospital pathogens such as meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), norovirus, multi-resistant Gram-negative bacilli and Clostridium difficile persist in the healthcare environment for considerable lengths of time. Cleaning with both detergent and disinfectant-based regimens help control these pathogens in both routine and outbreak situations. The most important transmission risk comes from organisms on frequently handled items because hand contact with a contaminated site could deliver a pathogen to a patient. Cleaning practices should be tailored to clinical risk, near-patient areas and hand-touch-sites and scientifically evaluated for all surfaces and equipment in today’s hospitals.


title: Chemo-enzymatic synthesis of C-9 acetylated sialosides

text: Abstract A chemo-enzymatic synthesis of [(5-acetamido-9-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonic acid)-(2→3)-O-(β-d-galactopyranosyl)-(1→3)-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)]-l-serine acetate (1) has been accomplished by a regioselective chemical acetylation of Neu5Ac (2) to give 9-O-acetylated sialic acid 3, which was enzymatically converted into CMP-Neu5,9Ac2 (4) employing a recombinant CMP-sialic acid synthetase from Neisseria meningitis [EC 2.7.7.43]. The resulting compound was then employed for the enzymatic glycosylation of the C-3′ hydroxyl of chemically prepared glycosylated amino acid 10 using recombinant rat α-(2→3)-O-sialyltransferase expressed in Spodooptera frugiperda [EC 2.4.99.4] to give, after deprotection of the N α-benzyloxycarbonyl (CBz)-protecting group of serine, target compound 1. The N α-CBz-protected intermediate 11 can be employed for the synthesis of glycolipopeptides for immunization purposes.


title: Chapter 9 Nutraceuticals in Alternative and Underutilized Fruits as Functional Food Ingredients: Ancient Species for New Health Needs

text: Abstract A diet containing high levels of fruit has been associated with a lowered risk of chronic diseases as, in addition to their vitamin and mineral content, they also contain various compounds with health-protective effects, in particular antioxidant and antiinflammatory compounds. Wild plant species are of interest to the food industry because of their ability to replace synthetic chemicals and nutraceuticals; however, the nutritional, economical, and sociocultural values of some neglected and underutilized natural resources have not yet been fully exploited. Some of these less well-known and underutilized fruits, which have the potential to provide novel sources of health-promoting agents, are presented in this chapter (i.e., Asimina triloba (L.) Dunal, Crataegus azarolus L., Lycium barbarum L., Morus nigra L., and Amelanchier canadensis (L.) Medicus). Underutilized fruits could represent an opportunity for growers to gain access to these special markets where consumers place emphasis on high contents of nutrients that are capable of preventing degenerative diseases. The development of specific horticultural models for nutraceutical fruit production could be an interesting opportunity to obtain a highly standardized raw material for fresh or derived products.


title: Atypical skin manifestations during immune checkpoint blockage in COVID19-infected lung cancer patients

text: Abstract A new coronavirus, named SARS-CoV-2 by the World Health Organization (WHO), has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, China. As of mid-April 2020, this virus has affected more than 180 countries and territories, infecting more than 1,650,000 individuals and causing over 100.000 deaths. With ≈20 million new cases per year globally, cancer affects a significant portion of the population. Individuals affected by cancer are more susceptible to infections due to coexisting chronic diseases (cardiovascular, pulmonary and diabetes), overall poor health status, and systemic immunosuppressive states caused by both cancer and anticancer treatments. As a consequence, patients with malignancies, and especially with lung cancer who develop COVID19 experience more difficult outcomes. A recent multicenter study developed by the Hubei Anti-Cancer Association also documented that lung cancer patients had an increased risk of death, ICU requirement, risk of presenting severe or critical symptoms, and use of invasive mechanical ventilation. Here we present two representative cases of patients with lung cancer and COVID19 without respiratory compromise and with atypical and severe skin manifestations, findings that could be influenced by the chronic use of anti-PD1 antibodies.


Considerations for Management of Longitudinal Melanonychia During the COVID-19 Pandemic: An International Perspective


title: Strategies for the prevention and management of coronavirus disease 2019

text: Early protection, early identification, early diagnosis, and early isolation are crucial to combat with Covid-19 outbreaks


title: Multiplex semi-nested RT-PCR with exogenous internal control for simultaneous detection of bovine coronavirus and group A rotavirus

text: Abstract Neonatal calf diarrhea is a multi-etiology syndrome of cattle and direct detection of the two major agents of the syndrome, group A rotavirus and Bovine coronavirus (BCoV) is hampered by their fastidious growth in cell culture. This study aimed at developing a multiplex semi-nested RT-PCR for simultaneous detection of BCoV (N gene) and group A rotavirus (VP1 gene) with the addition of an internal control (mRNA ND5). The assay was tested in 75 bovine feces samples tested previously for rotavirus using PAGE and for BCoV using nested RT-PCR targeted to RdRp gene. Agreement with reference tests was optimal for BCoV (kappa=0.833) and substantial for rotavirus detection (kappa=0.648). the internal control, ND5 mRNA, was detected successfully in all reactions. Results demonstrated that this multiplex semi-nested RT-PCR was effective in the detection of BCoV and rotavirus, with high sensitivity and specificity for simultaneous detection of both viruses at a lower cost, providing an important tool for studies on the etiology of diarrhea in cattle.


title: The rubella virus E2 and E1 spike glycoproteins are targeted to the Golgi complex

text: Rubella virus (RV) has been reported to bud from intracellular membranes in certain cell types. In this study the intracellular site of targeting of RV envelope E2 and E1 glycoproteins has been investigated in three different cell types (CHO, BHK-21 and Vero cells) transfected with a cDNA encoding the two glycoproteins. By indirect immunofluorescence, E2 and E1 were localized to the Golgi region of all three cell types, and their distribution was disrupted by treatment with BFA or nocodazole. Immunogold labeling demonstrated that E2 and E1 were localized to Golgi cisternae and indicated that the glycoproteins were distributed across the Golgi stack. Analysis of immunoprecipitates obtained from stably transfected CHO cells revealed that E2 and E1 become endo H resistant and undergo sialylation without being transported to the cell surface. Transport of RV glycoproteins to the Golgi complex was relatively slow (t1/2 = 60-90 min). Coprecipitation experiments indicated that E2 and E1 form a heterodimer in the RER. E1 was found to fold much more slowly than E2, suggesting that the delay in transport of the heterodimer to the Golgi may be due to the slow maturation of E1 in the ER. These results indicate that RV glycoproteins behave as integral membrane proteins of the Golgi complex and thus provide a useful model to study targeting and turnover of type I membrane proteins in this organelle.


The inaugural workshop “Deep Sequencing in Infectious Diseases: Immune and Pathogen Repertoires for the Improvement of Patient Outcomes” was held in Singapore on 13–14 October 2016. The aim of the workshop was to discuss the latest trends in using high-throughput sequencing, bioinformatics, and allied technologies to analyze immune and pathogen repertoires and their interplay within the host, bringing together key international players in the field and Singapore-based researchers and clinician-scientists. The focus was in particular on the application of these technologies for the improvement of patient diagnosis, prognosis and treatment, and for other broad public health outcomes. The presentations by scientists and clinicians showed the potential of deep sequencing technology to capture the coevolution of adaptive immunity and pathogens. For clinical applications, some key challenges remain, such as the long turnaround time and relatively high cost of deep sequencing for pathogen identification and characterization and the lack of international standardization in immune repertoire analysis.


title: Comparison of Different Tests to Diagnose Feline Infectious Peritonitis

text: Clinical data from 488 cats (1979–2000) with histopathologically confirmed feline infectious peritonitis (FIP) and 620 comparable controls were evaluated retrospectively to assess the value of several diagnostic tests frequently used in the evaluation of cats with suspected FIP. Diagnostic utility of serum albumin to globulin ratio for the diagnosis of FIP was greater than of the utility of serum total protein and ‐/‐globulin concentrations. Diagnostic utility of these variables was higher when performed on effusion. On effusion, positive and negative predictive values of Rivalta's test, a test that distinguishes between exudates and transudates (0.86 and 0.97), anti‐coronavirus antibody detection (0.90 and 0.79), and immunofluorescence staining of coronavirus antigen in macrophages (1.00 and 0.57) were investigated. The positive and negative predictive values of presence of anti‐coronavirus antibodies were 0.44 and 0.90, respectively, antibody concentrations (1:1,600) were 0.94 and 0.88, presence of immune complexes measured by a competitive enzyme‐linked immunosorbent assay were 0.67 and 0.84, and detection of viral RNA by serum reverse‐transcrip‐tase polymerase chain reaction (RT‐PCR) were 0.90 and 0.47. Effusion RT‐PCR was performed in 6 cats; it was positive in all 5 cats with FIP and negative in the cat with another disease. Diagnostic assays on the fluid in cats with body effusion had good predictive values. Definitive diagnosis of FIP on the basis of measurement of various variables in serum was not possible. Serum tests can only be used to facilitate the decision for more invasive diagnostic methods.


title: Sometimes Sperm Whales (Physeter macrocephalus) Cannot Find Their Way Back to the High Seas: A Multidisciplinary Study on a Mass Stranding

text: BACKGROUND: Mass strandings of sperm whales (Physeter macrocephalus) remain peculiar and rather unexplained events, which rarely occur in the Mediterranean Sea. Solar cycles and related changes in the geomagnetic field, variations in water temperature and weather conditions, coast geographical features and human activities have been proposed as possible causes. In December 2009, a pod of seven male sperm whales stranded along the Adriatic coast of Southern Italy. This is the sixth instance from 1555 in this basin. METHODOLOGY/PRINCIPAL FINDINGS: Complete necropsies were performed on three whales whose bodies were in good condition, carrying out on sampled tissues histopathology, virology, bacteriology, parasitology, and screening of veins looking for gas emboli. Furthermore, samples for age determination, genetic studies, gastric content evaluation, stable isotopes and toxicology were taken from all the seven specimens. The animals were part of the same group and determined by genetic and photo-identification to be part of the Mediterranean population. Causes of death did not include biological agents, or the “gas and fat embolic syndrome”, associated with direct sonar exposure. Environmental pollutant tissue concentrations were relatively high, in particular organochlorinated xenobiotics. Gastric content and morphologic tissue examinations showed a prolonged starvation, which likely caused, at its turn, the mobilization of lipophilic contaminants from the adipose tissue. Chemical compounds subsequently entered the blood circulation and may have impaired immune and nervous functions. CONCLUSIONS/SIGNIFICANCE: A multi-factorial cause underlying this sperm whales' mass stranding is proposed herein based upon the results of postmortem investigations as well as of the detailed analyses of the geographical and historical background. The seven sperm whales took the same “wrong way” into the Adriatic Sea, a potentially dangerous trap for Mediterranean sperm whales. Seismic surveys should be also regarded as potential co-factors, even if no evidence of direct impact has been detected.


title: Resident viruses and their interactions with the immune system

text: The human body is colonized with a diverse resident microflora that includes viruses. Recent studies of metagenomes have begun to characterize the composition of the human ‘virobiota’ and its associated genes (the ‘virome’), and have fostered the emerging field of host-virobiota interactions. In this Perspective, we explore how resident viruses interact with the immune system. We review recent findings that highlight the role of the immune system in shaping the composition of the virobiota and consider how resident viruses may impact host immunity. Finally, we discuss the implications of virobiota–immune system interactions for human health.


title: An inflammatory cytokine signature helps predict COVID-19 severity and death

text: The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-, and IL-1{beta} in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF- levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF- serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF- levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF- levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.


title: Beneficial effects of probiotics in upper respiratory tract infections and their mechanical actions to antagonize pathogens

text: Probiotics are live micro‐organisms with beneficial effects on human health, which have the ability to counteract infections at different locations of the body. Clinical trials have shown that probiotics can be used as preventive and therapeutic agents in upper respiratory tract infections (URTIs) and otitis. Their mechanical properties allow them to aggregate and to compete with pathogens for nutrients, space and attachment to host cells. Consequently, they can directly antagonize pathogens and thus exert beneficial effects without directly affecting the metabolism of the host. An overview of the probiotics with such traits, tested up to date in clinical trials for the prevention or treatment of URTIs and otitis, is presented in this review. Their mechanical properties in the respiratory tract as well as at other locations are also cited. Species with interesting in vitro properties towards pharyngeal cells or against common respiratory pathogens have also been included. The potential safety risks of the cited species are then discussed. This review could be of help in the screening of probiotic strains with specific mechanical properties susceptible to have positive effects in clinical trials against URTIs.


title: Effect of COVID-19 Epidemic on Delay of Diagnosis and Treatment Path for Patients with Nasopharyngeal Carcinoma

text: INTRODUCTION: 2019 novel coronavirus disease (COVID-19) outbreaks have been occurring in China and other countries in the world. To prevent further spread of the disease, restrictions of population flow from the government and measures to reduce virus transmission from hospitals may lead to the delay of diagnosis and treatment in patients with nasopharyngeal carcinoma (NPC). METHODS: All NPC patients with radiotherapy indications were included from 20 weekdays before (group A) and after (group B) January 31, 2020, when the institute began to take measures against COVID-19. The waiting intervals of each step and variation from the diagnosis and treatment path of NPC between two groups were compared. RESULTS: Significant differences were found between the group A and group B in the median waiting days for pathological biopsy (5 vs 15, P=0.012), radiotherapy immobilization and simulation (3.5 vs 16.5, P<0.001), validation of position and plan (20 vs 61, P<0.001) and initiation of radiotherapy (28 vs 36, P=0.005). During the waiting period of radiotherapy, 32.4% of the NPC patients received an additional one cycle of chemotherapy to the original treatment strategy. CONCLUSION: The prevalence of COVID-19 caused delay in the diagnosis and treatment of NPC patients to a certain extent. Additional chemotherapy could be considered to counteract the effect of treatment delay. More specific measures should be taken to balance the risk of delayed diagnosis and treatment of NPC and infection of COVID-19.


title: The effects of governmental and individual predictors on COVID‐19 protective behaviors in China: a path analysis model

text: The outbreak of the COVID‐19 pandemic has plunged the world into a crisis. To contain the crisis, it is essential to build full cooperation between the government and the public. However, it is unclear which governmental and individual factors are the determinants and how they interact on protective behaviors against COVID‐19. To resolve this issue, this study built a multiple mediation model and found government emergency public information as detailed pandemic information and positive risk communication had more important impacts on protective behaviors than rumor refutation and supplies. Moreover, governmental factors could indirectly affect protective behaviors through individual factors such as perceived efficacy, positive emotions, and risk perception. These findings suggest that systematic intervention programs for governmental factors need to be integrated with individual factors to finally achieve effective prevention and control of the COVID‐19 pandemic among the public. This article is protected by copyright. All rights reserved.


title: Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: Recommendations from the Spanish Menopause Society, Sociedad Española de Ginecología y Obstetricia and Sociedad Española de Trombosis y Hemostasia

text: Abstract COVID-19 is associated with a systemic inflammatory response with activation of coagulation in symptomatic patients. The possibility of coagulopathies in peri- and postmenopausal women taking estrogen therapies makes it necessary to consider antithrombotic strategies, such as the use of low molecular weight heparins (LMWH) at specific prophylactic or treatment doses for each individual case, depending on the risk factors that each woman presents. For such reasons, a panel of experts from various Spanish scientific societies has met to develop usage recommendations for managing menopausal women taking menopausal hormone therapy (MHT) or combined hormonal contraception (CHC) during the COVID-19 pandemic.


title: Plasma medicine: Opportunities for nanotechnology in a digital age

text: Advances in digital technologies have opened new opportunities for creating more reliable, time‐ and cost‐effective, safer and mobile methods of diagnosing, managing and treating diseases. A few examples of advanced nano‐ and digital technologies are already FDA‐approved for diagnosing and treating diseases. Plasma treatment is still emerging as a new healthcare technology, but it is showing a strong potential for treatment of many diseases including cancers and antimicrobial‐resistant infections, with little or no adverse side effects. Here, we argue that with the ever‐increasing complex healthcare challenges facing communities, including the ongoing COVID‐19 pandemic, it is critical to consider combining unique properties of emerging healthcare technologies into a single multimodal treatment modality that could lead to unprecedented healthcare benefits. In this article, we focus on the healthcare opportunities created by establishing a nexus between plasma, nano‐ and digital technologies. We argue that the combination of plasma, nano‐ and digital technologies into a single multimodal healthcare package may significantly improve patient outcomes and comfort, and reduce the economic burden on community healthcare, as well as alleviate many problems related to overcrowded healthcare systems.


title: Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

text: The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies.


Contact Tracing to Manage COVID19 Spread – Balancing Personal Privacy and Public Health


title: Health seeking behaviors of patients with acute respiratory infections during the outbreak of novel coronavirus disease 2019 in Wuhan, China

text: We conducted two surveys to evaluate the health-seeking behaviors of individuals with acute respiratory infections (ARI) during the COVID-19 outbreak in Wuhan, China. Among 351 participants reporting ARI (10.3%, 351/3,411), 36.5% sought medical assistance. Children were more likely to seek medical assistance than other age groups (66.1% vs. 28.0%-35.1%).


title: Could influenza transmission be reduced by restricting mass gatherings? Towards an evidence-based policy framework

text: Abstract Introduction Mass gatherings (MG) may provide ideal conditions for influenza transmission. The evidence for an association between MG and influenza transmission is reviewed to assess whether restricting MG may reduce transmission. Methods Major databases were searched (Pubmed, EMBASE, Scopus, CINAHL), producing 1706 articles that were sifted by title, abstract, and full-text. A narrative approach was adopted for data synthesis. Results Twenty-four papers met the inclusion criteria, covering MG of varying sizes and settings, and including 9 observational studies, 10 outbreak reports, 4 event reports, and a quasi-experimental study. There is some evidence that certain types of MG may be associated with increased risk of influenza transmission. MG may also “seed” new strains into an area, and may instigate community transmission in a pandemic. Restricting MGs, in combination with other social distancing interventions, may help reduce transmission, but it was not possible to identify conclusive evidence on the individual effect of MG restriction alone. Evidence suggests that event duration and crowdedness may be the key factors that determine the risk of influenza transmission, and possibly the type of venue (indoor/outdoor). Conclusion These factors potentially represent a basis for a policy-making framework for MG restrictions in the event of a severe pandemic.


title: The genetic code as expressed through relationships between mRNA structure and protein function

text: Structured RNA elements within messenger RNA often direct or modulate the cellular production of active proteins. As reviewed here, RNA structures have been discovered that govern nearly every step in protein production: mRNA production and stability; translation initiation, elongation, and termination; protein folding; and cellular localization. Regulatory RNA elements are common within RNAs from every domain of life. This growing body of RNA-mediated mechanisms continues to reveal new ways in which mRNA structure regulates translation. We integrate examples from several different classes of RNA structure-mediated regulation to present a global perspective that suggests that the secondary and tertiary structure of RNA ultimately constitutes an additional level of the genetic code that both guides and regulates protein biosynthesis.


title: Life Trajectories, Biomedical Evidence, and Lessons for Policies

text: Here I compare two types of evidence that have recently emerged from the literature. This Commentary is a contribution to the Frontiers Research Topic on social disparities in aging, and aims to draw attention to the novel connections that link social disparities, the biological capital of individuals, and policy strategies. The biological capital (as defined in the paper), accrued since conception by individuals, in turn affects their social, cultural, and economic capitals, and thus creates a positive feedback loop. In a large network funded by the European Commission, Lifepath, we have shown that the determinants of health inequalities start in early life and cumulate throughout the life-course. For example, exposure to adverse childhood experiences (ACEs) influences the likelihood of later in life health effects, including poor aging. In this paper I compare two types of evidence that have recently emerged from the literature. One addresses the role of early vs. late exposures to risk factors for aging and mortality, including ACEs, using e.g., microsimulation models. The second type of evidence, provided in a recent document of the WHO European Regional Office, is based on the analysis of five broad determinants of health inequalities and eight different macroeconomic policies to tackle such inequalities. Six of the policies, if enacted, have the potential to reduce inequalities in the short term by increasing public expenditure on housing and community amenities, increasing expenditure on labor market policies, reducing income inequality, increasing social protection expenditure, reducing unemployment, and/or reducing out-of-pocket payments for health. Both of these lines of evidence suggest that there are ample opportunities for policy interventions. I also discuss the need for analytical methods to bridge the two types of analyses (biomedical and macroeconomic), i.e., fill the gap between analyses based on individual determinants of health inequalities and those based on societal determinants, to help create more effective policy-making. Also, I propose that before launching large projects to reduce health inequalities, well-designed experiments must be conducted to test their efficacy. These experiments, though, are challenging when addressing social policies, in consideration of ethical constraints and timescales.


title: A digital embrace to blunt the curve of COVID19 pandemic

text: Digital health, virtual care, telehealth, and telemedicine are all terms often used interchangeably to refer to the practice of care delivered from a distance. Because virtual care collapses the barriers of time and distance, it is ideal for providing care that is patient-centered, lower cost, more convenient and at greater productivity. All these factors make virtual care tools indispensable elements in the COVID19 response. In this perspective, we offer implementation guidance and policy insights relevant to the use of virtual care tools to meet the challenges of the COVID19 pandemic.


title: Institutional Preparedness to Prevent Future Middle East Respiratory Syndrome Coronavirus-Like Outbreaks in Republic of Korea

text: A year has passed since the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea. This 2015 outbreak led to a better understanding of healthcare infection control. The first Korean patient infected by Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was diagnosed on May 20, 2015, after he returned from Qatar and Bahrain. Thereafter, 186 Korean people were infected with the MERS-CoV in a short time through human-to-human transmission. All these cases were linked to healthcare settings, and 25 (13.5 %) infected patients were healthcare workers. Phylogenetic analysis suggested that the MERS-CoV isolate found in the Korean patient was closely related to the Qatar strain, and did not harbor transmission efficiency-improving mutations. Nevertheless, with the same infecting virus strain, Korea experienced the largest MERS-CoV outbreak outside the Arabian Peninsula, primarily due to the different characteristics of population density and the healthcare system. We aimed to review the epidemiological features and existing knowledge on the Korean MERS outbreak, and suggest methods to prevent future epidemics.


Illicit drug use and harms in Australia in the context of COVID‐19 and associated restrictions: Anticipated consequences and initial responses


Cardiac Surgery and the COVID-19 Pandemic: What We Know, What We Don’t Know, and What We Need to Do


Interhospital Transfer of Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Preliminary Considerations From the Emilia-Romagna Experience


Reply to “Liver tests abnormalities in COVID-19: trick or treat?”


title: Igniting Change: Supporting the Well-Being of Academicians Who Practice and Teach Critical Care

text: Academicians who maintain a critical care clinical practice encounter numerous stressors, especially during the COVID-19 pandemic, which can influence well-being. This article provides historical perspectives on the stressors inherent in working in the critical care environment as well as the stressors of working in the academic environment. It proposes the application of the synergy model as a framework to help improve the well-being of academicians who practice and teach critical care. The most valuable strategy to improve professional well-being is for organizations to take a systems approach. The article focuses on approaches that are potentially within each individual’s control.


title: Review of Health Systems of the Middle East and North Africa Region

text: This article is an updated version of the previous edition article by Francisca Ayodeji Akala, volume 4, pp. 542–553, © 2008, Elsevier Inc.


title: Chikungunya resurgence in the Maldives and risk for importation via tourists to Europe in 2019–2020: A GeoSentinel case series

text: BACKGROUND: Chikungunya virus (CHIKV) is an arthropod-borne virus mainly transmitted in tropical areas by Aedes spp. mosquitoes. It has been responsible for small-to-large outbreaks in temperate areas including southern Europe and North America. Past outbreaks in 2006 on the islands of Maldives, as well as on other islands in the Indian Ocean and in Southeast Asia, demonstrated for the first time the capacity of CHIKV to disseminate through travel and transcontinental commerce, and revealed the major socio-economic impact of CHIKV epidemics. Recently, CHIKV has been circulating in highly touristic areas including the Maldives, where 1,736 cases were notified by the Health Protection Agency during 2019. CASE SERIES: Among EuroTravNet/GeoSentinel patient records, eight CHIKV-confirmed cases imported the Maldives to France, Germany, Denmark, Italy and Spain were identified between February 2019 and February 2020; exceeding the total number of CHIKV infections travel-acquired in Maldives reported to this surveillance network during the previous 10 years. CONCLUSIONS: The prevention and control of CHIKV introduction into naïve areas colonised by competent vectors is crucial. CHIKV outbreaks must be detected and reported in a timely manner. This must lead to adapted health information for international travellers and to prompt management of suspected imported cases. Conversely, travellers make for excellent sentinels and increased reports of imported cases might reflect a change in the level of endemicity or even herald an outbreak. Feedback to the local health authorities and matching this with local epidemiological surveillance data may lead to health benefits for the local population.


title: Skin signs resembling vascular acrosyndromes during the COVID‐19 outbreak in Italy

text: We have read with great interest Dr Estébanez article regarding the case of a 28-year-old woman affected by COVID-19, presenting confluent erythematous-yellowish papules at both heels. After three days, the lesions persisted and became hardened erythematous plaques.


title: Current pharmacological treatments for COVID‐19: What's next?

text: Since December 2019 SARS‐Cov‐2 was found responsible for the disease COVID‐19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID‐19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID‐19, focusing on their antiviral, immune‐modulatory and/or anti‐inflammatory actions. Where available, data from clinical trials involving patients with COVID‐19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID‐19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID‐19 and reducing its symptoms and complications.


Distant learning of BLS amid the COVID-19 pandemic: Influence of the outbreak on lay trainees’ willingness to attempt CPR, and the motivating effect of the training


title: The economics of Africa's floriculture air-cargo supply chain

text: This article examines the economics of Africa's emerging air cargo supply chains, taking floriculture as a case study. Floriculture is an important employer, and earner of foreign exchange for several regions of central/southern and eastern Africa including more recently Ethiopia. Air transportation often plays a critical role when the supply-chain involves high-value, non-durable, relatively light-weight, and compact consignments such as flowers, and geographically when regions are difficult to access by other trunk modes. The success of air cargo chains, however, depend as much on the quality of surface modes serving various “last mile” access and egress functions, as well as efficient nodal interchange points and the availability of suitable airport and airline capacity. The last, because of the important role of belly-hold space, includes consideration of passenger as well as cargo specific services. To meet the needs of Africa's floriculture sector, a variety of supply-chain models have emerged that embrace air and surface links, as well as storage at various points in the chain. The paper considers the nature of these chains, the reason d'être for their structures, and their limitations.


title: Clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to SARS-CoV-2 infection

text: Abstract Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.


title: Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles

text: Abstract A series of thiazole clubbed 1,3,4-oxadiazole derivatives (5a–l) have been synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. Synthesized compounds were evaluated for their antimicrobial and cytotoxic activities. The results indicated that, compounds 5c and 5i exhibited the most potent antibacterial activity. Compound 5f was found to be the most potent antifungal agent. The structure activity relationship revealed that the presence of electron withdrawing groups at para position of phenyl ring remarkably enhanced the antibacterial activity of synthesized compounds. Further, the results of preliminary MTT cytotoxicity studies on HeLa cells suggested that potent antimicrobial activity of 5b, 5c, 5f, 5h and 5i is accompanied by low cytotoxicity.


Toxicologic and comparative clinical pathology externship scholarships broaden clinical pathology resident training opportunities


title: Respiratory tract infection-related healthcare utilisation in children with Down’s syndrome

text: PURPOSE: Children with Down’s syndrome (DS) are prone to respiratory tract infections (RTIs) due to anatomical variation, immune system immaturity and comorbidities. However, evidence on RTI-related healthcare utilisation, especially in primary care, is incomplete. In this retrospective cohort study, we use routinely collected primary and secondary care data to quantify RTI-related healthcare utilisation in children with DS and matched controls without DS. METHODS: Retrospective cohort study of 992 children with DS and 4874 matched controls attending English general practices and hospitals as identified in Clinical disease research using LInked Bespoke studies and Electronic health Records (CALIBER) from 1997 to 2010. Poisson regression was used to calculate consultation, hospitalisation and prescription rates, and rate ratios. Wald test was used to compare risk of admission following consultation. The Wilcoxon rank–sum test was used to compare length of stay by RTI type and time-to-hospitalisation. RESULTS: RTI-related healthcare utilisation is significantly higher in children with DS than in controls in terms of GP consultations (adjusted RR 1.73; 95% CI 1.62–1.84), hospitalisations (adjusted RR 5.70; 95% CI 4.82–6.73), and antibiotic prescribing (adjusted RR 2.34; 95% CI 2.19–2.49). Two percent of children with DS presenting for an RTI-related GP consultation were subsequently admitted for an RTI-related hospitalisation, compared to 0.7% in controls. CONCLUSIONS: Children with DS have higher rates of GP consultations, hospitalisations and antibiotic prescribing compared to controls. This poses a significant burden on families. Further research is recommended to characterise healthcare behaviours and clinical decision-making, to optimise care for this at risk group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s15010-020-01408-5) contains supplementary material, which is available to authorized users.


title: Global Access to Handwashing: Implications for COVID-19 Control in Low-Income Countries

text: BACKGROUND: Low-income countries have reduced health care system capacity and are therefore at risk of substantially higher COVID-19 case fatality rates than those currently seen in high-income countries. Handwashing is a key component of guidance to reduce transmission of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic. Prior systematic reviews have indicated the effectiveness of handwashing to reduce transmission of respiratory viruses. In low-income countries, reduction of transmission is of paramount importance, but social distancing is challenged by high population densities and access to handwashing facilities with soap and water is limited. OBJECTIVES: Our objective was to estimate global access to handwashing with soap and water to inform use of handwashing in the prevention of COVID-19 transmission. METHODS: We utilized observational surveys and spatiotemporal Gaussian process regression modeling in the context of the Global Burden of Diseases, Injuries, and Risk Factors Study to estimate access to a handwashing station with available soap and water for 1,062 locations from 1990 to 2019. RESULTS: Despite overall improvements from 1990 {33.6% [95% uncertainty interval (UI): 31.5, 35.6] without access} to 2019, globally in 2019, 2.02 (95% UI: 1.91, 2.14) billion people, 26.1% (95% UI: 24.7, 27.7) of the global population, lacked access to handwashing with available soap and water. More than 50% of the population in sub-Saharan Africa and Oceania were without access to handwashing in 2019, and in eight countries, 50 million or more persons lacked access. DISCUSSION: For populations without handwashing access, immediate improvements in access or alternative strategies are urgently needed, and disparities in handwashing access should be incorporated into COVID-19 forecasting models when applied to low-income countries. https://doi.org/10.1289/EHP7200


title: Clinical characteristics and viral etiologies of outpatients with acute respiratory infections in Huzhou of China: a retrospective study

text: BACKGROUND: Viruses are commonly found in patients with acute respiratory infections (ARIs). However, the viral etiologies and clinical characteristics of outpatients with ARIs are poorly understood in China. Here, we identified the viral etiologies in outpatients with ARIs in Huzhou, China. RESULTS: Our results indicated that of 426 outpatients, 246 were positive for viruses. Of them, 221 were positive for a single virus, including influenza A, which comprised H3N2 (28.5%) and pandemic H1N1 (2009) (19.0%), enterovirus (10.4%), and influenza B (8.6%). Other single viruses were detected at less than 8.0%. Twenty-five patients were positively coinfected with two viruses. The prevalent viruses in coinfections were rhinovirus and H3N2 virus (28.0%). Viruses were major pathogens in young children (< 5 years) (75.0%). Coinfections were prevalent in older adults (11.9%) and young children (9.5%). Virus-positive outpatients presented higher temperatures and more sore throat, fatigue and shortness of breath than virus-negative outpatients. ARIs and most virus detections peaked during the winter, but enteroviruses emerged between April and September. CONCLUSION: Viruses are major agents of ARIs among outpatients in Huzhou, China. There was a variation in the distribution of viruses across different age groups and seasons. These findings are beneficial for planning prevention and treatment services for outpatients with ARIs.


title: Genome-wide analysis of codon usage bias in Bovine Coronavirus

text: BACKGROUND: Bovine coronavirus (BCoV) belong to the genus Betacoronavirus of the family Coronaviridae. BCoV are widespread around the world and cause enteric or respiratory infections among cattle, leading to important economic losses to the beef and dairy industry worldwide. To study the relation of codon usage among viruses and their hosts is essential to understand host-pathogen interaction, evasion from host’s immune system and evolution. METHODS: We performed a comprehensive analysis of codon usage and composition of BCoV. RESULTS: The global codon usage among BCoV strains is similar. Significant differences of codon preferences in BCoV genes in relation to codon usage of Bos taurus host genes were found. Most of the highly frequent codons are U-ending. G + C compositional constraint and dinucleotide composition also plays a role in the overall pattern of BCoV codon usage. CONCLUSIONS: The results of these studies revealed that mutational bias is a leading force shaping codon usage in this virus. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0780-y) contains supplementary material, which is available to authorized users.


title: Genetic Variation of the Human α-2-Heremans-Schmid Glycoprotein (AHSG) Gene Associated with the Risk of SARS-CoV Infection

text: Genetic background may play an important role in the process of SARS-CoV infection and SARS development. We found several proteins that could interact with the nucleocapsid protein of the SARS coronavirus (SARS-CoV). α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. Cytochrome P450 Family 3A (CYP4F3A) is an ω-oxidase that inactivates Leukotriene B4 (LTB4) in human neutrophils and the liver. We investigated the association between the polymorphisms of these two inflammation-associated genes and SARS development. The linkage disequilibrium (LD) maps of these two genes were built with Haploview using data on CHB+JPT (version 2) from the HapMap. A total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study, after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR] 2.42; 95% confidence interval [CI] 1.30-4.51); rs4917 (AOR 1.84; 95% CI 1.02-3.34); and rs3794987 (AOR 2.01; 95% CI 1.10–3.68). To further validate the association, the ten tag SNPs were genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30–2.04) was found to be associated with SARS susceptibility. The combined analysis of the two studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR 1.70; 95% CI 1.37–2.09). The statistical analysis of the rs2248690 genotype data among the patients and healthy controls in the HCW cohort, who were all similarly exposed to the SARS virus, also supported the findings. Further, the SNP rs2248690 affected the transcriptional activity of the AHSG promoter and thus regulated the AHSG serum level. Therefore, our study has demonstrated that the AA genotype of rs2268690, which leads to a higher AHSG serum concentration, was significantly associated with protection against SARS development.


title: Contaminant source identification within a building: Toward design of immune buildings

text: Abstract The level of protection of a building against the intentional or accidental release of chemical agents is crucial. Both scenarios could endanger life and safety of the buildings occupants. Equipping buildings with appropriate chemical sensors can alert the building occupants about the contaminant release. The readings of these sensors can be employed to trace the location of release, and help to take the appropriate actions to minimize the casualties. However, only a limited number of them can be installed due to their initial and operating cost. Moreover, there is no information about the source strength, release time and possible source location. This paper reports the development of a methodology to identify the source location using sensors reading from limited locations. The methodology uses the artificial neural network (ANN) as a statistical analysis integrated with a multi-zone airborne contaminant transport model, CONTAM. To evaluate the applicability of this method, the contaminant dispersion within a building was modeled and the results were integrated to an ANN for the source identification. The prediction made by the trained ANN was then evaluated by predicting the source of the contaminant in 40 extra cases, which had not been seen by the network during the training session. The model was able to predict the source location in more than 90% of the cases when the building was monitored by three or more sensors. The results show that the method can be used to help building designers decide the optimum configuration of the sensors required for a space based on the accuracy level of the source detection.


2020 International Year of the Midwife – an unexpected challenge


A24 Application of large-scale sequencing and data analysis to research on emerging infectious diseases


title: Influence of Breed Size, Age, Fecal Quality, and Enteropathogen Shedding on Fecal Calprotectin and Immunoglobulin A Concentrations in Puppies During the Weaning Period

text: BACKGROUND: Fecal calprotectin and immunoglobulin A (IgA) are markers of intestinal inflammation and immunity in adult dogs. HYPOTHESIS: Fecal calprotectin and IgA concentrations in puppies are not influenced by fecal moisture in puppies but by enteropathogen shedding. ANIMALS: Three hundred and twenty‐four puppies. METHODS: Fecal consistency was assessed by gross examination. Fecal moisture was evaluated before and after lyophilization. Canine parvovirus and coronavirus were detected in feces by qPCR and qRT‐PCR respectively. Giardia intestinalis antigen was quantified by ELISA. The standard McMaster flotation technique was used to detect eggs and oocysts in feces. Fecal calprotectin and IgA concentrations were quantified by in‐house radioimmunoassays. RESULTS: For each marker (IgA and calprotectin), a strong positive correlation was observed between concentration in fresh feces and concentration in fecal dry matter. 75.6% of the puppies were found to be infected by at ≥1 of the enteropathogens evaluated. Fecal calprotectin concentration was significantly influenced by age (P = .001), with higher concentrations in younger puppies, but not by viral (P = .863) or parasitic infection (P = .791). Fecal IgA concentration was significantly influenced by enteropathogen shedding (P = .01), with a lower fecal IgA concentration in puppies shedding at ≥1 enteropathogen compared to puppies without any enteropathogen shedding, but not by age. CONCLUSIONS: Fecal calprotectin and IgA are of no diagnostic value to detect presence of enteropathogens in clinically healthy puppies or puppies with abnormal feces, but could help to better understand the maturation of digestive tract.


title: Nature's patterns, unlocked with AI

text: Smart software could predict the next invasive plant species or disease outbreak


title: Viral otitis media

text: Acute otitis media (AOM) and viral upper respiratory tract infections (URIs) represent the two most common diseases affecting the human population, and account for substantial patient morbidity and health care costs. Epidemiologic and experimental studies suggest that URIs play a causal role in the pathogenesis of AOM. Specifically, viruses can either invade the middle ear (ME) space and invoke an inflammatory response that culminates in ME effusion formation and consequent symptoms, or URIs might cause eustachian-tube dysfunction, resulting in negative ME pressures and subsequent ME effusion (hydrops ex vacuo theory). The events responsible for the inflammatory response of the human ME following viral exposure have not been well characterized. Although many prophylactic and therapeutic interventions have been evaluated for the treatment of AOM, the information on virusspecific interventions is sparse. In this article, the epidemiology, pathogenesis, diagnosis, and management of viral otitis media are reviewed.