title: A diagnostic model for coronavirus disease 2019 (COVID-19) based on radiological semantic and clinical features: a multi-center study

text: OBJECTIVES: Rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19) is critical during the epidemic. We aim to identify differences in CT imaging and clinical manifestations between pneumonia patients with and without COVID-19, and to develop and validate a diagnostic model for COVID-19 based on radiological semantic and clinical features alone. METHODS: A consecutive cohort of 70 COVID-19 and 66 non-COVID-19 pneumonia patients were retrospectively recruited from five institutions. Patients were divided into primary (n = 98) and validation (n = 38) cohorts. The chi-square test, Student’s t test, and Kruskal-Wallis H test were performed, comparing 1745 lesions and 67 features in the two groups. Three models were constructed using radiological semantic and clinical features through multivariate logistic regression. Diagnostic efficacies of developed models were quantified by receiver operating characteristic curve. Clinical usage was evaluated by decision curve analysis and nomogram. RESULTS: Eighteen radiological semantic features and seventeen clinical features were identified to be significantly different. Besides ground-glass opacities (p = 0.032) and consolidation (p = 0.001) in the lung periphery, the lesion size (1–3 cm) is also significant for the diagnosis of COVID-19 (p = 0.027). Lung score presents no significant difference (p = 0.417). Three diagnostic models achieved an area under the curve value as high as 0.986 (95% CI 0.966~1.000). The clinical and radiological semantic models provided a better diagnostic performance and more considerable net benefits. CONCLUSIONS: Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. A model composed of radiological semantic and clinical features has an excellent performance for the diagnosis of COVID-19. KEY POINTS: • Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. • A diagnostic model for COVID-19 was developed and validated using radiological semantic and clinical features, which had an area under the curve value of 0.986 (95% CI 0.966~1.000) and 0.936 (95% CI 0.866~1.000) in the primary and validation cohorts, respectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06829-2) contains supplementary material, which is available to authorized users.


title: Posttraumatic Stress after SARS

text: Posttraumatic stress disorder (PTSD) can arise in patients with medical illness. We used 2 Chinese self-report measures to examine features of PTSD, anxiety, and depression in 131 survivors of severe acute respiratory syndrome at 1 month and 3 months after discharge from the hospital. Risk factors associated with psychological distress were identified.


title: Column-free purification and coating of SpyCatcher protein on ELISA wells generates universal solid support for capturing of SpyTag-fusion protein from the non-purified condition

text: • Spy Tag-Protein covalent interaction is rapid and specific method for protein immobilization. • By utilization of Non-Chromatographic method and SpyCatcher protein it is possible rapidly develop a universal solid support for SpyTag protein purification. • This method is highly simple and applicable to other proteins.


title: How integration of global omics-data could help preparing for pandemics – a scent of influenza

text: Pandemics caused by novel emerging or re-emerging infectious diseases could lead to high mortality and morbidity world-wide when left uncontrolled. In this perspective, we evaluate the possibility of integration of global omics-data in order to timely prepare for pandemics. Such an approach requires two major innovations. First, data that is obtained should be shared with the global community instantly. The strength of rapid integration of simple signals is exemplified by Google’s(TM) Flu Trend, which could predict the incidence of influenza-like illness based on online search engine queries. Second, omics technologies need to be fast and high-throughput. We postulate that analysis of the exhaled breath would be a simple, rapid and non-invasive alternative. Breath contains hundreds of volatile organic compounds that are altered by infection and inflammation. The molecular fingerprint of breath (breathprint) can be obtained using an electronic nose, which relies on sensor technology. These breathprints can be stored in an online database (a “breathcloud”) and coupled to clinical data. Comparison of the breathprint of a suspected subject to the breathcloud allows for a rapid decision on the presence or absence of a pathogen.


title: Tear biomarkers for keratoconus

text: Keratoconus is a progressive corneal thinning, ectatic condition, which affects vision. Recent advances in corneal topography measurements has helped advance proper diagnosis of this condition and increased research and clinical interests in the disease etiopathogenesis. Considerable progress has been achieved in understanding the progression of the disease and tear fluid has played a major role in the progress. This review discusses the importance of tear fluid as a source of biomarker for keratoconus and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease. Expanding knowledge of the tear proteome, lipidome and metabolome opened up new avenues to study keratoconus and to identify probable prognostic or diagnostic biomarkers for the disease. A multidimensional approach of analyzing tear fluid of patients layering on proteomics, lipidomics and metabolomics is necessary in effectively decoding keratoconus and thereby identifying targets for its treatment.


title: Intestinal Surgery

text: A wide variety of disorders affecting the intestinal tract in cattle may require surgery. Among those disorders the more common are: intestinal volvulus, jejunal hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus. Although general principles of intestinal surgery can be applied, cattle has anatomical and behavior particularities that must be known before invading the abdomen. This article focuses on surgical techniques used to optimize outcomes and discusses specific disorders of small intestine. Diagnoses and surgical techniques presented can be applied in field conditions.


title: A pathway for targeting soluble misfolded proteins to the yeast vacuole

text: We have evaluated the fate of misfolded protein domains in the Saccharomyces cerevisiae secretory pathway by fusing mutant forms of the NH2-terminal domain of lambda repressor protein to the secreted protein invertase. The hybrid protein carrying the wild-type repressor domain is mostly secreted to the cell surface, whereas hybrid proteins with amino acid substitutions that cause the repressor domain to be thermodynamically unstable are retained intracellularly. Surprisingly, the retained hybrids are found in the vacuole, where the repressor moiety is degraded by vacuolar proteases. The following observations indicate that receptor-mediated recognition of the mutant repressor domain in the Golgi lumen targets these hybrid fusions to the vacuole. (a) The invertase-repressor fusions, like wild-type invertase, behave as soluble proteins in the ER lumen. (b) Targeting to the vacuole is saturable since overexpression of the hybrids carrying mutant repressor increases the fraction of fusion protein that appears at the cell surface. (c) Finally, deletion of the VPS10 gene, which encodes the transmembrane Golgi receptor responsible for targeting carboxypeptidase Y to the vacuole, causes the mutant hybrids to be diverted to the cell surface. Together these findings suggest that yeast have a salvage pathway for degradation of nonnative luminal proteins by receptor- mediated transport to the vacuole.


title: Coronavirus Transcription Mediated by Sequences Flanking the Transcription Consensus Sequence

text: Abstract In our studies of murine coronavirus transcription, we continue to use defective interfering (DI) RNAs of mouse hepatitis virus (MHV) in which we insert a transcription consensus sequence in order to mimic subgenomic RNA synthesis from the nondefective genome. Using our subgenomic DI system, we have studied the effects of sequences flanking the MHV transcription consensus sequence on subgenomic RNA transcription. We obtained the following results. (i) Insertion of a 12-nucleotide-long sequence including the UCUAAAC transcription consensus sequence at different locations of the DI RNA resulted in different efficiencies of subgenomic DI RNA synthesis. (ii) Differences in the amount of subgenomic DI RNA were defined by the sequences that flanked the 12-nucleotide-long sequence and were not affected by the location of the 12-nucleotide-long sequence on the DI RNA. (iii) Naturally occurring flanking sequences of intergenic sequences at gene 6–7, but not at genes 1–2 and 2–3, contained a transcription suppressive element(s). (iv) Each of three naturally occurring flanking sequences of an MHV genomic cryptic transcription consensus sequence from MHV gene 1 also contained a transcription suppressive element(s). These data showed that sequences flanking the transcription consensus sequence affected MHV transcription.


title: Adapting IAPT services to support frontline NHS staff during the Covid-19 pandemic: the Homerton Covid Psychological Support (HCPS) pathway

text: The Coronavirus (Covid-19) pandemic is exerting unprecedented pressure on NHS Health and Social Care provisions, with frontline staff, such as those of critical care units, encountering vast practical and emotional challenges on a daily basis. Although staff are being supported through organisational provisions, facilitated by those in leadership roles, the emergence of mental health difficulties or the exacerbation of existing ones amongst these members of staff is a cause for concern. Acknowledging this, academics and healthcare professionals alike are calling for psychological support for frontline staff, which not only addresses distress during the initial phases of the outbreak but also over the months, if not years, that follow. Fortunately, mental health services and psychology professional bodies across the United Kingdom have issued guidance to meet these needs. An attempt has been made to translate these sets of guidance into clinical provisions via the recently established Homerton Covid Psychological Support (HCPS) pathway delivered by Talk Changes (Hackney & City IAPT). This article describes the phased, stepped-care and evidence-based approach that has been adopted by the service to support local frontline NHS staff. We wish to share our service design and pathway of care with other Improving Access to Psychological Therapies (IAPT) services who may also seek to support hospital frontline staff within their associated NHS Trusts and in doing so, lay the foundations of a coordinated response. KEY LEARNING AIMS: (1).. To understand the ways staff can be psychologically and emotionally impacted by working on the frontline of disease outbreaks. (2).. To understand the ways in which IAPT services have previously supported populations exposed to crises. (3).. To learn ways of delivering psychological support and interventions during a pandemic context based on existing guidance and research.


Food Delivery Service During Social Distancing: Proactively Preventing or Potentially Spreading Coronavirus Disease–2019?


A case of goggle‐mask‐related impetigo at the time of the COVID‐19 pandemic


title: Current Perspective of Antiviral Strategies against COVID-19

text: [Image: see text] COVID-19 was declared a pandemic by the World Health Organization on March 11, 2020. This novel coronavirus disease, caused by the SARS-CoV-2 virus, has resulted in severe and unprecedented social and economic disruptions globally. Since the discovery of COVID-19 in December 2019, numerous antivirals have been tested for efficacy against SARS-CoV-2 in vitro and also clinically to treat this disease. This review article discusses the main antiviral strategies currently employed and summarizes reported in vitro and in vivo efficacies of key antiviral compounds in use.


title: Innate Resistance to Flavivirus Infections and the Functions of 2′-5′ Oligoadenylate Synthetases

text: Mouse susceptibility to experimental infections with flaviviruses is significantly influenced by a cluster of genes on chromosome 5 encoding a family of proteins with enzymatic properties, the 2′–5′ oligoadenylate synthetases (OAS). Positional cloning of the locus in question has revealed that susceptibility of laboratory inbred strains to this class of virus is associated with a nonsense mutation in the gene encoding the OAS1B isoform. Analysis of the molecular structure of the cluster in different mammalian species including human indicates that the cluster is extremely polymorphic with a highly variable number of genes and pseudogenes whose functions are not yet completely established. Although still preliminary, a few recent observations also substantiate a possible role for OAS1 in human susceptibility to viral infections (West Nile virus, SARS, etc.) and its possible involvement in some other diseases such as type 1 diabetes and multiple sclerosis. Finally, convergent observations indicate that the molecules encoded by the 2′–5′ OAS cluster might be involved in other fundamental cellular functions such as cell growth and differentiation, gene regulation, and apoptosis.


title: Translational simulation for rapid transformation of health services, using the example of the COVID-19 pandemic preparation

text: Healthcare simulation has significant potential for helping health services to deal with the COVID-19 pandemic. Rapid changes to care pathways and processes needed for protection of staff and patients may be facilitated by a translational simulation approach—diagnosing changes needed, developing and testing new processes and then embedding new systems and teamwork through training. However, there are also practical constraints on running in situ simulations during a pandemic—the need for physical distancing, rigorous infection control for manikins and training equipment and awareness of heightened anxiety among simulation participants. We describe our institution’s simulation strategy for COVID-19 preparation and reflect on the lessons learned—for simulation programs and for health services seeking to utilise translational simulation during and beyond the COVID-19 pandemic. We offer practical suggestions for a translational simulation strategy and simulation delivery within pandemic constraints. We also suggest simulation programs develop robust strategies, governance and relationships for managing change within institutions—balancing clinician engagement, systems engineering expertise and the power of translational simulation for diagnosing, testing and embedding changes.


title: Respiratory Diseases of Rodents and Rabbits

text: This article is written to provide differential diagnostic help for the practitioner who suspects respiratory disease in rodents or rabbits. The authors are laboratory animal veterinarians who work with rodents and rabbits on a herd health basis but also have considerable experience dealing with individual mice, rats, guinea pigs, hamsters, gerbils, and rabbits. The article presents descriptions of the presentation, pathology, treatment, and control of the primary respiratory pathogens of these species, along with an explanation of conditions that may confuse the diagnostic efforts. The article also mentions reported pathogens of secondary importance and provides extensive references.


title: ER stress, autophagy, and RNA viruses

text: Endoplasmic reticulum (ER) stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR), which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host's defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment.


title: Antigenic analysis of feline coronaviruses with monoclonal antibodies (MAbs): Preparation of MAbs which discriminate between FIPV strain 79-1146 and FECV strain 79-1683

text: Abstract We prepared 31 monoclonal antibodies (MAbs) against either FIPV strain 79-1146 or FECV strain 79-1683, and tested them for reactivity with various coronaviruses by indirect flourescent antibody assay (IFA). Sixteen MAbs which reacted with all of the 11 strains of feline coronaviruses, also reacted with canine coronavirus (CCV) and transmissible gastroenteritis virus (TGEV). In many of them, the polypeptide specifity was the recognition of transmembrane (E1) protein of the virus. We succeeded in obtaining MAbs which did not react with eight strains FIPV Type I viruses (showing cell-associated growth) but reacted with FIPV Type II (79-1146, KU-1) and/or FECV Type II (79-1683) viruses (showing non-cell associated growth). These MAbs also reacted with CCV or TGEV. These MAbs recognized peplomer (E2) glycoprotein, and many antigenic differences were found in this E2 protein. These results suggest that FIPV Type II and FECV Type II viruses are antigenically closer to TGEV or CCV than to FIPV Type I viruses. Furthermore, the MAb prepared in this study has enabled discrimination between FIPV strain 79-1146 and FECV strain 79-1683, which was thought to be impossible by the previous serological method.


Ventiladores mecánicos de emergencia para la Covid-19


Fabricated data – should we quarantine? A novel tool for risk assessment is proposed


title: The contributions of allergic sensitization and respiratory pathogens to asthma inception

text: Of the chronic diseases affecting grade-school children, asthma is the most common and accounts for the greatest number of school days missed. Moreover, it can influence family dynamics and function in other ways, and unfortunately, it can also be associated with mortality, particularly in the inner-city environments of the United States. Thus understanding factors that lead to its development in early life is essential in developing strategies aimed at primary prevention. Two risk factors that have been identified by a number of investigators include the development of allergic sensitization and wheezing respiratory tract illnesses caused by viruses and bacteria, either alone or in combination. Both of these factors appear to exert their influences within the first few years of life, such that asthma becomes established before the child enters grade school at age 5 to 6 years. Therefore, because both allergic sensitization and viral and bacterial illnesses can occur in children who do not have asthma, it is paramount to identify genetic and environmental factors that activate, interact with, and/or direct the immune system and components of the respiratory tract along pathways that allow asthma to become established and expressed clinically.


title: The Transmembrane Oligomers of Coronavirus Protein E

text: We have tested the hypothesis that severe acute respiratory syndrome (SARS) coronavirus protein E (SCoVE) and its homologs in other coronaviruses associate through their putative transmembrane domain to form homooligomeric α-helical bundles in vivo. For this purpose, we have analyzed the results of molecular dynamics simulations where all possible conformational and aggregational space was systematically explored. Two main assumptions were considered; the first is that protein E contains one transmembrane α-helical domain, with its N- and C-termini located in opposite faces of the lipid bilayer. The second is that protein E forms the same type of transmembrane oligomer and with identical backbone structure in different coronaviruses. The models arising from the molecular dynamics simulations were tested for evolutionary conservation using 13 coronavirus protein E homologous sequences. It is extremely unlikely that if any of our assumptions were not correct we would find a persistent structure for all the sequences tested. We show that a low energy dimeric, trimeric and two pentameric models appear to be conserved through evolution, and are therefore likely to be present in vivo. In support of this, we have observed only dimeric, trimeric, and pentameric aggregates for the synthetic transmembrane domain of SARS protein E in SDS. The models obtained point to residues essential for protein E oligomerization in the life cycle of the SARS virus, specifically N15. In addition, these results strongly support a general model where transmembrane domains transiently adopt many aggregation states necessary for function.


title: Is it ethical to be a ‘whistleblower’ during COVID‐19 pandemic? Ethical challenges confronted by health care workers in China

text: Should health care workers (HCWs) tell the truth? The answer seems definite to be yes since every medical and nursing staff has taken an oath to the Hippocratic Oath or Nightingale Florence Pledge that only integrity and honesty deserve the trust of patients and commitment of saving life. HCWs who work within the medical system in normal times should follow biomedical ethics, and their primary responsibility is to safeguard the health rights and interests of individual patients.


title: Immunomodulatory activity accompanying chicken egg yolk immunoglobulin Y

text: Abstract Immunity transfer from a mother to the newborn does not depend exclusively on immunoglobulins. Peptides, which are characterized by immunoregulatory properties that accompany IgG2, known as proline- rich polypeptide complex (PRP), have been discovered for the first time in ovine colostrum. In this report we present new data showing that some immunoregulatory peptides associated with the main immunoglobulin class, IgY, are also present in the avian immune system. Cytokine-inducing activity of particular fractions obtained from ovine colostrum, IgG+ (IgG2 containing PRP), IgG− (IgG2 free of PRP), and purified PRP, was compared with that of crude egg yolk IgY (IgY+), additionally purified egg yolk IgY (IgY−), and polypeptides accompanying IgY named Yolkin (Y), using an ex vivo model of whole human blood cells. It was shown that both IgG+ fraction and PRP, but not IgG−, stimulated the whole blood cells to release tumor necrosis factor-α and interleukin-1β cytokines. Similar experiments performed with hen's egg IgY preparations showed that IgY+ and Y samples showed higher cytokine-inducing activity than samples additionally purified with the use of size exclusion chromatography (IgY−). The IgY+ at a dose of 100 μg was even more active than the positive lipopolysaccharide control. It was also found that Y is able to stimulate macrophage cell line J774.2 to release nitric oxide. The results obtained suggest that IgY, the main chicken immunoglobulin fraction, is accompanied by additional polypeptides and plays a role of a transporter of biologically active substances, which was observed in the case of colostral IgG.


title: Inducible Bronchus-Associated Lymphoid Tissue Elicited by a Protein Cage Nanoparticle Enhances Protection in Mice against Diverse Respiratory Viruses

text: BACKGROUND: Destruction of the architectural and subsequently the functional integrity of the lung following pulmonary viral infections is attributable to both the extent of pathogen replication and to the host-generated inflammation associated with the recruitment of immune responses. The presence of antigenically disparate pulmonary viruses and the emergence of novel viruses assures the recurrence of lung damage with infection and resolution of each primary viral infection. Thus, there is a need to develop safe broad spectrum immunoprophylactic strategies capable of enhancing protective immune responses in the lung but which limits immune-mediated lung damage. The immunoprophylactic strategy described here utilizes a protein cage nanoparticle (PCN) to significantly accelerate clearance of diverse respiratory viruses after primary infection and also results in a host immune response that causes less lung damage. METHODOLOGY/PRINCIPAL FINDINGS: Mice pre-treated with PCN, independent of any specific viral antigens, were protected against both sub-lethal and lethal doses of two different influenza viruses, a mouse-adapted SARS-coronavirus, or mouse pneumovirus. Treatment with PCN significantly increased survival and was marked by enhanced viral clearance, accelerated induction of viral-specific antibody production, and significant decreases in morbidity and lung damage. The enhanced protection appears to be dependent upon the prior development of inducible bronchus-associated lymphoid tissue (iBALT) in the lung in response to the PCN treatment and to be mediated through CD4+ T cell and B cell dependent mechanisms. CONCLUSIONS/SIGNIFICANCE: The immunoprophylactic strategy described utilizes an infection-independent induction of naturally occurring iBALT prior to infection by a pulmonary viral pathogen. This strategy non-specifically enhances primary immunity to respiratory viruses and is not restricted by the antigen specificities inherent in typical vaccination strategies. PCN treatment is asymptomatic in its application and importantly, ameliorates the damaging inflammation normally associated with the recruitment of immune responses into the lung.


title: Projecting the Target Quantity of Medical Staff in Taiwan’s Administrative Regions by the Theory of Carrying Capacity

text: As physicians and nurses are the main medical staff in any healthcare system, an appropriate medical workforce distribution is crucial for an aging society. This study thus applies the theory of carrying capacity and the given demand side to explore the carrying capacity, carrying efficiency, and potential adjustment ratio of medical staff in Taiwan’s administrative regions by using the data envelopment analysis (DEA) approach in which a lower carrying efficiency implies a higher shortage ratio. The main findings are as follows. (i) The carrying efficiency of Taiwan’s medical staff is weakening year by year, while the carrying efficiency of the country’s nurses is lower than that of physicians. (ii) The outlying islands of Taiwan have a more serious shortage of physicians and nurses than the main island. (iii) The central government should encourage more physicians and nurses to work in regions with a low carrying efficiency.


title: Are your hands clean enough for point-of-care electrolyte analysis?

text: Summary Aim To investigate clinically significant analytical interference in point-of-care electrolyte analysis caused by contamination of blood specimens with hand disinfectant. Methods Six different hand hygiene products were added separately to heparinised blood samples in varying amounts as contaminant. The contaminated samples were analysed by three different blood gas and electrolyte analysers for assessing interference on measured whole blood sodium and potassium concentrations. Results There were significant analytical interferences caused by hand hygiene product contamination that varied depending on the combination of disinfectant and analyser. Small amounts of Microshield Antibacterial Hand Gel contamination caused large increases in measured sodium concentration. Such effect was much greater compared with the other five products tested, and started to occur at much lower levels of contamination. There was a trend towards lower sodium results in blood samples contaminated with Hexol Antiseptic Lotion (Hexol), the hand hygiene product that we used initially. Apart from AiE Hand Sanitizer, all the other hand disinfectants, especially Hexol, significantly elevated the measured potassium concentration, particularly when a direct ion-selective electrode method was used for measurement. Conclusion Hand disinfectant products can significantly interfere with blood electrolyte analysis. Proper precautions must be taken against contamination since the resultant errors can adversely affect the clinical management of patients.


The International Health Regulations and beyond


Tomar o no tomar «decisiones en caliente» respecto al tratamiento de la infección por SARS-CoV-2


title: Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic virus that causes severe respiratory disease in humans with a case fatality rate close to 40%, but for which no vaccines are available. Here, we evaluated the utility of ChAdOx1, a promising replication-deficient simian adenovirus vaccine vector platform with an established safety profile in humans and dromedary camels, for MERS-CoV vaccine development. Using a transgenic lethal BALB/c MERS-CoV mouse model we showed that single dose intranasal or intramuscular immunisation with ChAdOx1 MERS, encoding full-length MERS-CoV Spike glycoprotein, is highly immunogenic and confers protection against lethal viral challenge. Immunogenicity and efficacy were comparable between immunisation routes. Together these data provide support for further evaluation of ChAdOx1 MERS vaccine in humans and dromedary camels, the animal reservoir of infection.


title: Viruses are prevalent in non-ventilated hospital-acquired pneumonia

text: Abstract Background Hospital-acquired pneumonia arising in non-ventilated patients (NVHAP) is traditionally thought to be caused by bacteria, and little is known about viral etiologies in this syndrome. We sought to describe the prevalence of viruses causing NVHAP and to determine factors independently associated with the isolation of a virus. Methods We identified patients with NVHAP over one year and reviewed their cultures to determine etiologies. Patients with a viral process were compared to those with either negative cultures or a bacterial infection to determine variables independently associated with the recovery of a virus. Results Among 174 cases, cultures were positive in 46.0%, with viruses identified in 22.4%. Bacterial pathogens arose 23.6% of subjects. The most common viruses included rhinovirus, influenza, and parainfluenza. We noted no seasonality in the isolation of viral organisms, and most cases of viral NVHAP developed after more than a week length of stay (LOS). Outcomes in viral NVHAP were similar to those with bacterial NVHAP. Patients with viral and bacterial NVHAP were generally similar. Two variables were independently associated with isolation of a virus: a history of coronary artery disease (adjusted odds ratio: 5.16, 95% CI: 1.14–22.44) and a LOS of greater than 10 days prior to NVHAP diagnosis (adjusted odds ratio: 2.97, 95% CI: 1.35–6.51). As a screening test for a virus, neither had a good sensitivity or specificity. Conclusions Viruses represent a common cause of NVHAP. Clinicians should consider viral diagnostic testing in NVHAP, as this may represent a means to enhance antimicrobial stewardship.


title: The importance of the minimum dosage necessary for UVC decontamination of N95 respirators during the COVID‐19 pandemic

text: The World Health Organization (WHO) recently released a press report highlighting the severe shortage of personal protective equipment (PPE) that is endangering healthcare workers worldwide during the COVID-19 pandemic.1 To meet this urgent need, healthcare institutions across the world have begun to utilize the germicidal properties of ultraviolet C (UVC) to decontaminate N95 respirators so that they can be reused.2 It is clearly crucial that the dose of UVC delivered is sufficient to kill any viable SARS-CoV-2, the causative virus of the COVID-19 pandemic, that may be present on the respirators.


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title: Psychothérapie institutionnelle en situation de confinement: adaptation du cadre en hôpital de jour.Vers une institution mentale virtuelle

text: Résumé Dans le contexte de l’épidémie du virus SARS-Cov-2, l’Unité de Soins Ambulatoires du Centre Hospitalier Universitaire de Toulouse, qui proposait des soins psychothérapiques institutionnels pour des personnes présentant des pathologies psychiatriques sévères et/ou invalidantes, a fermé ses portes aux patients le 16 mars 2020. Cet article vise à documenter les aménagements nécessaires au cadre de soin dans cette période extraordinaire. En effet, l’équipe a dû annoncer aux patients de rester chez eux et de respecter des règles de distanciation sociale. Paradoxe incontournable quand notre travail consiste précisément à dé-confiner, à relier, à être au contact. Rencontres en présence, ateliers collectifs et médiations suspendus ; l’enjeu a été pour nous de mettre au jour ce qui d’un soin psychothérapique institutionnel des psychoses est irréductible ou essentiel. Ces modifications du cadre de soin seront décrites sous les termes de l’édification d’une institution mentale virtuelle, basée sur un cadre tordu par la distance mais non aboli, des consultations téléphoniques ouvrant à un imaginaire psychopathologique spéculatif mais pas désincarné et enfin un objet-blog comme quasi-matérialisation d’un espace virtuel. Cette expérience a amené l'équipe de l’Unité de Soins Ambulatoires à radicaliser les tenants de l’institution pour la maintenir dans son plus simple appareil : une arborescence virtuelle de l’institution mentale. En effet, il y a un préalable à ce qui se crée virtuellement, les interactions entre soignants et patients préexistent. Cette institution mentale virtuelle maintient le cadre qui structure notre projet de soin institutionnel, donc son lien avec l’avant et ce qui sera l’après du confinement. Pour ce faire nous avons mené une analyse « sur le vif » des aménagements concrets de notre dispositif thérapeutique à partir de regards croisés : phénoménologique, systémique et psychodynamique. Abstract Within the context of the SARS-Cov-2 virus epidemic, the Ambulatory Care Unit of the Toulouse University Hospital Center, offering institutional psychotherapeutic care to people with severe and/or disabling psychiatric pathologies, closed its doors to patients on the 16th of March 2020. This article aims to document the necessary adjustments to the care setting during this extraordinary period. As it was, the team had to tell patients to stay at home and to respect rules of social distancing. An inescapable paradox when our work consists precisely in de-confining, connecting, being in contact with each other. Face-to-face meetings, group workshops, the array of our mediations were suspended; the challenge for us was to bring to light what is irreducible or essential in the institutional psychotherapeutic care for psychoses, what must remain active through the confinement. These modifications of the psychotherapeutic setting will be described in terms of constructing a virtual mental institution, based on a setting twisted by the distance but not abolished, telephone consultations opening up to a speculative but not disembodied psychopathological imaginary, and finally a blog as a quasi-materialization of a virtual space. This experience led the team of the Ambulatory Care Unit to radicalize the institution to keep it in its simplest apparatus: a virtual tree structure of the mental institution. The prior interactions between caregivers and patients have been translated (and thus re-created) virtually. As to respect their singular aspects, as well as their fundamental belonging to the collective that supports our institution. This virtual mental institution can therefore maintain the framework that structures our institutional care project, and can link the before and what will be the after of the confinement. For this study, we have conducted an "on-the-spot" analysis of the concrete arrangements of our therapeutic setting from an interdisciplinary perspective: phenomenological, systemic and psychodynamic.


title: Strategies for prevention and control of the 2019 novel coronavirus disease in the department of kidney transplantation

text: To summarize measures for the prevention and control of the 2019 novel coronavirus disease (COVID‐19) in the department of kidney transplantation. We retrospectively analyzed the clinical data of outpatients and inpatients in the department of kidney transplantation from January 20 to March 1, 2020, and followed up the in‐home kidney transplant recipients and those waiting for kidney transplantation through the Internet platform. Our department had formulated detailed prevention and control measures, mainly including kidney transplant outpatient management, kidney transplantation ward management, management of kidney transplant surgery, dialysis management of patients waiting for kidney transplantation, personal protection of medical staff, and follow‐up management of discharged patients after kidney transplantation. During the epidemic period, there were no COVID‐19 cases among 68 outpatient examined kidney transplant recipients, 32 hospitalized kidney transplant recipients, 19 patients waiting for kidney transplantation in hospital, and 30 medical staff. There were no COVID‐19 cases among 160 follow‐up recipients after kidney transplantation and 60 patients waiting for kidney transplantation. During the epidemic period, we implemented strict prevention and control measures and adjusted working methods and procedures to ensure safe and orderly work of the department.


Health scare


title: Emerging Cancer Vaccines: The Promise of Genetic Vectors

text: Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.


title: Has the COVID-19 Pandemic Affected MPs’ Representational Activities?

text: The COVID-19 pandemic has necessarily affected the operation of Canada's Parliament and, thus, the activities of Members of Parliament (MPs) (Malloy, 2020; Rayment and VandenBeukel, 2020). Here, we explore how the pandemic has affected the representational activities of individual MPs.


title: A model of supply‐chain decisions for resource sharing with an application to ventilator allocation to combat COVID‐19

text: We present a stochastic optimization model for allocating and sharing a critical resource in the case of a pandemic. The demand for different entities peaks at different times, and an initial inventory for a central agency are to be allocated. The entities (states) may share the critical resource with a different state under a risk‐averse condition. The model is applied to study the allocation of ventilator inventory in the COVID‐19 pandemic by FEMA to different U.S. states. Findings suggest that if less than 60% of the ventilator inventory is available for non‐COVID‐19 patients, FEMA's stockpile of 20 000 ventilators (as of March 23, 2020) would be nearly adequate to meet the projected needs in slightly above average demand scenarios. However, when more than 75% of the available ventilator inventory must be reserved for non‐COVID‐19 patients, various degrees of shortfall are expected. In a severe case, where the demand is concentrated in the top‐most quartile of the forecast confidence interval and states are not willing to share their stockpile of ventilators, the total shortfall over the planning horizon (until May 31, 2020) is about 232 000 ventilator days, with a peak shortfall of 17 200 ventilators on April 19, 2020. Results are also reported for a worst‐case where the demand is at the upper limit of the 95% confidence interval. An important finding of this study is that a central agency (FEMA) can act as a coordinator for sharing critical resources that are in short supply over time to add efficiency in the system. Moreover, through properly managing risk‐aversion of different entities (states) additional efficiency can be gained. An additional implication is that ramping up production early in the planning cycle allows to reduce shortfall significantly. An optimal timing of this production ramp‐up consideration can be based on a cost‐benefit analysis.


title: Severe weather warnings predict fracture epidemics

text: Abstract Winter epidemics of fractures have been described that greatly exceed normal seasonal variations and overwhelm resources. We investigated the relationship between severe weather warnings, the frequency of fractures, and fracture related workload. There was a significant increase in fractures with cold and inclement weather, mostly low-energy fractures treated with day-case surgery or in fracture clinics. The number of patients treated as inpatients for fractures did not increase. Hip fractures were not associated with weather. Severe weather warnings for icy roads were predictive of fracture epidemics (p <0.01) with an associated 40% (95% confidence limits 20–52%) increase in fractures. Meteorological Office issued severe weather warnings can provide a trigger to plan for an increased workload of low-energy fractures, with opportunities for anticipatory public health measures.


The pandemic present


title: Engendering enthusiasm for sustainable disaster critical care response: why this is of consequence to critical care professionals?

text: Disaster medical response has historically focused on the pre-hospital and initial treatment needs of casualties. In particular, the critical care component of many disaster response plans is incomplete. Equally important, routinely available critical care resources are almost always insufficient to respond to disasters that generate anything beyond a 'modest' casualty stream. Large-scale monetary funding to effectively remedy these shortfalls is unavailable. Education, training, and improved planning are our most effective initial steps. We suggest several areas for further development, including dual usage of resources that may specifically augment critical care disaster medical capabilities over time.


title: Mitigation Strategies for Pandemic Influenza A: Balancing Conflicting Policy Objectives

text: Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R(0) and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic.


title: An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila

text: Circular RNAs (circRNAs) are abundant and accumulate with age in neurons of diverse species. However, only few circRNAs have been functionally characterized, and their role during aging has not been addressed. Here, we use transcriptome profiling during aging and find that accumulation of circRNAs is slowed down in long-lived insulin mutant flies. Next, we characterize the in vivo function of a circRNA generated by the sulfateless gene (circSfl), which is consistently upregulated, particularly in the brain and muscle, of diverse long-lived insulin mutants. Strikingly, lifespan extension of insulin mutants is dependent on circSfl, and overexpression of circSfl alone is sufficient to extend the lifespan. Moreover, circSfl is translated into a protein that shares the N terminus and potentially some functions with the full-length Sfl protein encoded by the host gene. Our study demonstrates that insulin signaling affects global circRNA accumulation and reveals an important role of circSfl during aging in vivo.


title: Influenza A virus in Taiwan, 1980–2006: Phylogenetic and antigenic characteristics of the hemagglutinin gene

text: Limited amount of information is available in Taiwan on the genetic or antigenic characteristics of influenza A virus prior to the establishment of a Taiwan surveillance network in 2000. Isolates of H1N1 and H3N2 viruses in Taiwan between 1980 and 2006 were studied, and part of the hemagglutinin gene was analyzed due to its importance in terms of viral infection and antibody neutralization. Results from a phylogenetic analysis indicate continuous evolutionary topology in H3N2 isolates, and two distinct H1N1 lineages. Many genetic relationships between vaccine strains and epidemic isolates appearing in Taiwan before other global locations were also observed and recorded in addition to a gradual increase in the number of N‐linked glycosylation sites on partial HA1 proteins since 1980. The results from pairwise comparisons of HA1 nucleotide and deduced amino acid sequences indicate shared identities within groups organized according to their bootstrap and P‐values of approximately 95.5–100% and 95.7–100% in H1N1 and 94.5–100% and 93.2–100% in H3N2 viruses, respectively. Comparisons of amino acid substitutions in the five antigenic regions reveal highly non‐synonymous changes occurring in the Sb region of H1N1 and in the B region of H3N2. The results of an antigenic analysis using a hemagglutinin inhibition (HI) test indicate the presence of some epidemic strains 1–2 years earlier in Taiwan than in other parts of the world, as well as higher vaccine mismatch rates. This information supports the need for continuous surveillance of emerging influenza viruses in Taiwan, which will be useful for making global vaccine decisions. J. Med. Virol. 81:1457–1470, 2009. © 2009 Wiley‐Liss, Inc.


title: Antibody dynamics in BRSV-infected Danish dairy herds as determined by isotype-specific immunoglobulins

text: Abstract Using specific ELISAs, antibody levels of four different isotypes to bovine respiratory syncytial virus (BRSV) were determined in calves, following experimental BRSV infection. Most calves experienced an increase in the specific IgM and IgG1 titres about 6–10 days after infection with BRSV. The IgM titre was transient showing positive titres for only 5–10 days, while specific IgG1 was present for a longer time. IgA was detected concomitantly with IgM but at a lower level. Production of IgG2 anti-BRSV antibodies was detected from 3 weeks after infection. In two closed herds, repeated blood samplings were performed on young stock to analyse maternal immunity. The passively transferred antibodies were mainly of the IgG1 isotype and the half-life of IgG1 to BRSV was estimated to be 26.6 days. One of the herds had an outbreak of enzootic pneumonia, diagnosed to be caused by BRSV. Furthermore, another herd with acute BRSV was followed by weekly blood samples in six calves; in both herds IgM and IgG1 was detected shortly after the appearance of clinical signs. Serum samples from 50 Danish dairy herds (453 samples) were tested for immunoglobulins of the isotypes IgG1, IgG2 and IgM. The presence of antibodies to BRSV was widespread and more than 54% of the samples had BRSV antibodies of both the IgG1 and IgG2 isotypes indicating a high herd prevalence to BRSV. Test samples from two herds out of 50 were free from all isotypes to BRSV.


title: First Isolation of Rotavirus Associated with Neonatal Diarrhoea in Guanacos (Lama guanicoe) in the Argentinean Patagonia Region

text: Group A rotavirus (RV) and coronavirus (CV) are common viral pathogens associated with neonatal diarrhoea in numerous animal species. The purpose of this work was to investigate the presence of these viral agents in two farm populations of captured guanacos (Lama guanicoe) in the Argentinean Patagonia region, that developed severe diarrhoea outbreaks. Stool and serum samples were analysed for RV and bovine CV antigen and antibody by enzyme‐linked immunosorbent assay. Rotavirus was detected in faeces from two new‐born guanacos with acute diarrhoea, one in each farm. After electrophoretic analysis, each isolated strain, showed a distinctive long dsRNA electropherotype characteristic of group A rotaviruses (4:2:3:2). In addition, 95% (38 of 40) of the sampled animals were positive for RV antibodies, suggesting a high prevalence of RV infection in the populations tested. No evidence of CV circulation by antigen or antibody analysis was observed. To our knowledge, this is the first report of the detection and isolation of RV associated with neonatal diarrhoea in Lama guanicoe.


title: Middle East respiratory syndrome: current status and future prospects for vaccine development

text: The outbreaks of Middle East respiratory syndrome (MERS) previously in Middle East and recently in South Korea have raised serious concerns world-wide, reinforcing the importance of developing effective and safe vaccines against MERS-coronavirus (MERS-CoV). A number of vaccine candidates have been developed on the basis of viral vectors, recombinant proteins, DNAs, nanoparticles, and recombinant MERS-CoV, and some of them have shown efficacy in laboratory animals. However, the paucity of financial support has made it difficult to transfer effective candidates from the preclinical stage to clinical trials. Here, we summarize currently available MERS vaccine candidates and illustrate strategies for future development, with the aim of provoking government agencies and Big Pharma to invest more funds for developing efficacious and safe MERS vaccines.


title: Ocular Manifestations of Systemic Disease in Cats

text: Systemic feline diseases (parasitic, bacterial, fungal, viral, neoplastic, metabolic, vascular, and immune-mediated) are often associated with ocular symptoms. An ocular examination is an important diagnostic tool and should be part of any physical examination. Conversely, cats afflicted with systemic disease require periodic ocular examinations for prognostic information and to prevent vision threatening complications. Typical feline systemic diseases encountered by the practicing clinician are presented with their commonly associated ocular signs.


title: ¿Existe transmisión materno-fetal del SARS_CoV-2 durante la gestación?

text: Resumen Antecedentes y objetivo: El pasado 7 de enero de 2020 se identificó un nuevo coronavirus, el SARS-CoV-2, responsable de una nueva enfermedad en el humano: la COVID-19. Dada su reciente aparición, nuestro conocimiento actual sobre la posible influencia que esta enfermedad puede ejercer en el embarazo es muy limitado. Una de las incógnitas que hay que despejar es si existe transmisión vertical de la infección durante la gestación. Pacientes y métodos: Mediante técnicas de reacción en cadena de la polimerasa en tiempo real para ácidos nucleicos del SARS-CoV-2 se investigó la posible presencia de dicho germen en el flujo vaginal y el líquido amniótico de cuatro pacientes embarazadas de raza caucásica afectadas por cuadros agudos leves de COVID-19 durante el segundo trimestre de la gestación. Resultados: No existen evidencias de laboratorio que sugieran un posible paso del SARS-CoV-2 desde la madre infectada al líquido amniótico. Conclusiones. Es preciso ampliar la investigación de casos de COVID-19 diagnosticados durante la gestación para poder aclarar la influencia real que el SARS-CoV-2 ejerce sobre las embarazadas y su descendencia, así como aquellos factores que modulan la enfermedad. Abstract Background and objective: On January 7th, 2020, a new coronavirus, SARS-CoV-2, was identified, as responsible for a new human disease: COVID-19. Given its recent appearance, our current knowledge about the possible influence that this disease can exert on pregnancy is very limited. One of the unknowns to be solved is whether there is a vertical transmission of the infection during pregnancy. Patients and methods: Using the Real-time Polymerase Chain Reaction techniques for SARS-CoV-2 nucleic acids, the possible presence of this germ in vaginal discharge and amniotic fluid was investigated in four pregnant Caucasian patients affected by mild acute symptoms of COVID-19 during the second trimester of pregnancy. Results. There is no laboratory evidence to suggest a possible passage of SARS-CoV-2 from the infected mother to the amniotic fluid. Conclusions: It is necessary to expand the investigation of COVID-19 cases diagnosed during pregnancy to clarify the real influence that SARS-CoV-2 has on pregnant women and their offspring, as well as those factors that modulate the disease.


title: Comparison of the Aerosol Stability of 2 Strains of Zaire ebolavirus From the 1976 and 2013 Outbreaks

text: The largest outbreak of Ebola virus disease began in Guéckédou, Guinea, West Africa, in December 2013 and rapidly spread to major population centers in 3 West African countries. Early reports in some scientific and public media speculated that the virus had evolved to more effectively transmit between humans. One route of transmission postulated was aerosol transmission, although there was little epidemiological evidence to support this claim. This study investigates the viability of 2 Zaire ebolavirus strains within aerosols at 22°C and 80% relative humidity over time. The results presented here indicate that there is no difference in virus stability between the 2 strains and that viable virus can be recovered from an aerosol 180 minutes after it is generated.


title: Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients

text: Over 1 000 000 cases of coronavirus disease 2019 (COVID‐19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID‐19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus–related hepatocellular carcinoma and was confirmed to have COVID‐19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low‐dose methylprednisolone‐based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living‐related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID‐19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID‐19. These effectively treated cases can provide a basis for immunosuppressant management of COVID‐19‐positive SOT recipients.


title: In silico study of airway/lung mechanics in normal human breathing

text: The airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy. The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall. Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance. The model could be used in the study of the interaction between respiratory and cardiovascular systems in pathophysiological conditions.


Twitter and the pursuit of global health-care during COVID-19 Pandemic


title: Management guidelines for pregnant healthcare workers exposed to infectious dermatoses

text: Abstract Exanthematous diseases are frequently of infectious origin, posing risks, especially for pregnant healthcare workers (HCWs) who treat them. The shift from cell-mediated (Th1 cytokine profile) to humoral (Th2 cytokine profile) immunity during pregnancy can influence the mother’s susceptibility to infection and lead to complications for both mother and fetus. The potential for vertical transmission must be considered when evaluating the risks for pregnant HCWs treating infected patients, as fetal infection can often have devastating consequences. Given the high proportion of women of childbearing age among HCWs, the pregnancy-related risks of infectious exposure are an important topic in both patient care and occupational health. Contagious patients with cutaneous manifestations often present to dermatology or pediatric clinics, where female providers are particularly prevalent, as a growing number of these physicians are female. Unfortunately, the risks of infection for pregnant HCWs are not well defined. To our knowledge, there is limited guidance on safe practices for pregnant HCWs who encounter infectious dermatologic diseases. In this article, we review several infectious exanthems, their transmissibility to pregnant women, the likelihood of vertical transmission, and the potential consequences of infection for the mother and the fetus. Additionally, we discuss recommendations with respect to avoidance, contact and respiratory precautions, and the need for treatment following exposure.


Section Virology


title: An opportunity to incentivize innovation to increase vaccine safety in the United States by improving vaccine delivery using vaccine patches

text: Abstract Vaccines represent cost-effective and safe interventions that provide substantial health and economic benefits to individuals and populations. The US vaccine enterprise that supports all aspects of immunization continues to encourage innovation. Despite some limited historical recommendations to create a fund to support investments in vaccine safety, and recent legislation that supports innovation for new vaccines (the 21st Century Cures Act, Public Law 114-255), to date the US lacks financial incentives to fund innovation in vaccine delivery technologies. Building on separate reviews of the US Vaccine Injury Compensation Program (VICP) and the state of development of vaccine patches as an innovative vaccine delivery platform, we suggest an opportunity to allocate some VICP Trust Fund resources to prevent future VICP claims by creating a new incentives fund to support translational studies for improving vaccine delivery technologies. We identify shoulder injury related to vaccine administration (SIRVA) as a test case.


title: Test performance evaluation of SARS-CoV-2 serological assays

text: BACKGROUND: Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. METHOD: We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. RESULTS: Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8–100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3–100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7–94.8%. No consistent cross-reactivity was observed. CONCLUSION: Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.


title: How Can We Quarantine Without a Home? Responses of Activism and Urban Social Movements in Times of COVID‐19 Pandemic Crisis in Lisbon

text: In Lisbon, during the COVID‐19 pandemic period, new spaces for contestation and the action of urban social movements intensified, capitalising on the visibility for the right to housing, as a basic human right and an unconditional public health imperative, to fulfil the duties of lockdown and social isolation, imposed by the State of Exception. Its narrative and strategies reinforces the counter‐hegemonic movement that denounces the logics of commodification and financialisation in the housing sector, placing hope in a post‐capitalist transition in the post‐COVID horizon. We conclude that the actors in this urban struggle have limited power over the changes they initiate, or make an effort to inflict, if they are not involved in a concerted and politically integrated action, not least because the achievements they obtain are temporary and exceptional, like the state of emergency imposed by COVID‐19.


title: Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding

text: Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.


title: Grazing Management Effects on Sediment, Phosphorus, and Pathogen Loading of Streams in Cool‐Season Grass Pastures

text: Erosion and runoff from pastures may lead to degradation of surface water. A 2‐yr grazing study was conducted to quantify the effects of grazing management on sediment, phosphorus (P), and pathogen loading of streams in cool‐season grass pastures. Six adjoining 12.1‐ha pastures bisected by a stream in central Iowa were divided into three treatments: continuous stocking with unrestricted stream access (CSU), continuous stocking with restricted stream access (CSR), and rotational stocking (RS). Rainfall simulations on stream banks resulted in greater (P < 0.10) proportions of applied precipitation and amounts of sediment and P transported in runoff from bare sites than from vegetated sites across grazing treatments. Similar differences were observed comparing vegetated sites in CSU and RS pastures with vegetated sites in CSR pastures. Bovine enterovirus was shed by an average of 24.3% of cows during the study period and was collected in the runoff of 8.3 and 16.7% of runoff simulations on bare sites in CSU pastures in June and October of 2008, respectively, and from 8.3% of runoff simulations on vegetated sites in CSU pastures in April 2009. Fecal pathogens (bovine coronavirus [BCV], bovine rotavirus group A, and Escherichia coli O157:H7) shed or detected in runoff were almost nonexistent; only BCV was detected in feces of one cow in August of 2008. Erosion of cut‐banks was the greatest contributor of sediment and P loading to the stream; contributions from surface runoff and grazing animals were considerably less and were minimized by grazing management practices that reduced congregation of cattle by pasture streams.


title: Is dengue a threat to the blood supply?

text: Dengue is the most common arthropod-borne infection worldwide, affecting at least 50 million people every year and endemic in more than 100 countries. The dengue virus is a single-stranded RNA virus with four major serotypes. Infection with one serotype confers homotypic immunity but not heterologous immunity, and secondary infection with another serotype may lead to more severe disease. The major route of transmission occurs through the Aedes aegypti mosquito vector, but dengue has also been transmitted through blood transfusion and organ transplantation. Infection results in a spectrum of clinical illness ranging from asymptomatic infection, undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF) to dengue shock syndrome (DSS). Dengue is spreading rapidly to new areas and with increasing frequency of major outbreaks. A trend has also been observed towards increasing age among infected patients. This will impact blood supply availability as more blood donors are deferred because of dengue infection or exposure to infection. The risk of transmission through transfusion of blood from asymptomatic viraemic donors will also increase. Although screening tests for dengue and effective pathogen reduction processes are now available for the blood supply, the value of implementing these costly measures needs to be carefully considered. Demand for platelets and fresh frozen plasma will rise with increasing number of DHF/DSS. Evidence-based guidelines for the clinical use of these blood components in the management of patients with DHF/DSS have not been well established, and inappropriate use will contribute to the challenges faced by blood services.


title: Mammalian orthoreovirus Infection is Enhanced in Cells Pre-Treated with Sodium Arsenite

text: Following reovirus infection, cells activate stress responses that repress canonical translation as a mechanism to limit progeny virion production. Work by others suggests that these stress responses, which are part of the integrated stress response (ISR), may benefit rather than repress reovirus replication. Here, we report that compared to untreated cells, treating cells with sodium arsenite (SA) to activate the ISR prior to infection enhanced viral protein expression, percent infectivity, and viral titer. SA-mediated enhancement was not strain-specific, but was cell-type specific. While SA pre-treatment of cells offered the greatest enhancement, treatment within the first 4 h of infection increased the percent of cells infected. SA activates the heme-regulated eIF2α (HRI) kinase, which phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α) to induce stress granule (SG) formation. Heat shock (HS), another activator of HRI, also induced eIF2α phosphorylation and SGs in cells. However, HS had no effect on percent infectivity or viral yield but did enhance viral protein expression. These data suggest that SA pre-treatment perturbs the cell in a way that is beneficial for reovirus and that this enhancement is independent of SG induction. Understanding how to manipulate the cellular stress responses during infection to enhance replication could help to maximize the oncolytic potential of reovirus.


title: 1.13 The Role of Small- or Medium-Sized Enterprises in Drug Discovery

text: The past 10 years has seen the rise of large numbers of small- and medium-size enterprises (SMEs) engaging in some or many of the aspects of drug research. Few of these companies have been able to take candidate drugs to market due to development costs not being met by funding opportunities, but those companies that have been able to challenge traditional big pharma in the marketplace. Most SMEs have instead supplied traditional pharma with pipeline candidate drugs, either by licensing them or by the large companies actually acquiring the whole of the SME which owns the intellectual property. Many other companies engage in providing traditional big pharma or other SMEs with technologies and services. Hundreds of such companies have arisen, many clustered around centres of academic excellence on the coasts of the USA, or in certain regions in Europe and Asia – such clustering of scientific prowess has changed the location of where even big pharma tends to perform its research. By 2006, a large proportion (but generally less than 50%) of new drugs could be track to an origin in an SME, trends indicate that the proportion will rise even though the common prediction that large pharma will abandon internal research in favour of in-licensing from SMEs remains far from reality.


Increased Viral Titers and Subtle Changes in Plaque Morphology Upon Passage of SARS-CoV in Cells from Different Species


title: Governance, technology and citizen behavior in pandemic: Lessons from COVID-19 in East Asia

text: Abstract Corona Virus (CODID-19) was first reported in Wuhan in December 2019, then spread in different parts of China, and gradually became a global pandemic in March 2020. While the death toll is still increasing, the epicenter of casualty has shifted from Asia to Europe, and that of the affected people has shifted to USA. This paper analyzes the responses in East Asian countries, in China, Japan and South Korea, and provides some commonalities and lessons. While countries have different governance mechanism, it was found that a few governance decisions in respective countries made a difference, along with strong community solidarity and community behavior. Extensive use of emerging technologies is made along with medical/health care treatment to make the response more effective and reduce the risk of the spread of the disease. Although the pandemic was a global one, its responses were local, depending on the local governance, socio-economic and cultural context.


title: Viral Appropriation: Laying Claim to Host Nuclear Transport Machinery

text: Protein nuclear transport is an integral process to many cellular pathways and often plays a critical role during viral infection. To overcome the barrier presented by the nuclear membrane and gain access to the nucleus, virally encoded proteins have evolved ways to appropriate components of the nuclear transport machinery. By binding karyopherins, or the nuclear pore complex, viral proteins influence their own transport as well as the transport of key cellular regulatory proteins. This review covers how viral proteins can interact with different components of the nuclear import machinery and how this influences viral replicative cycles. We also highlight the effects that viral perturbation of nuclear transport has on the infected host and how we can exploit viruses as tools to study novel mechanisms of protein nuclear import. Finally, we discuss the possibility that drugs targeting these transport pathways could be repurposed for treating viral infections.


docid: xymbqulg

title: Caring for Critically Ill Adults in PICUs Is Not “Child’s Play”*


Historical, New, and Reemerging Links between Human and Animal Health


title: A Dual Protease Approach for Expression and Affinity Purification of Recombinant Proteins

text: We describe a new method for affinity purification of recombinant proteins using a dual protease protocol. Escherichia coli maltose binding protein (MBP) is employed as an N-terminal tag to increase the yield and solubility of its fusion partners. The MBP moiety is then removed by rhinovirus 3C protease, prior to purification, to yield an N-terminally His(6)-tagged protein. Proteins that are only temporarily rendered soluble by fusing them to MBP are readily identified at this stage because they will precipitate after the MBP tag is removed by 3C protease. The remaining soluble His(6)-tagged protein, if any, is subsequently purified by immobilized metal affinity chromatography (IMAC). Finally, the N-terminal His(6) tag is removed by His(6)-tagged tobacco etch virus (TEV) protease to yield the native recombinant protein, and the His(6)-tagged contaminants are removed by adsorption during a second round of IMAC, leaving only the untagged recombinant protein in the column effluent. The generic strategy described here saves time and effort by removing insoluble aggregates at an early stage in the process while also reducing the tendency of MBP to “stick” to its fusion partners during affinity purification.


title: Effect of Cryptosporidium parvum infection on the absorptive capacity and paracellular permeability of the small intestine in neonatal calves

text: Abstract Cryptosporidium parvum is recognized as one of the most important pathogens causing enteritis and severe diarrhoea in calves up to 1 month of age. Although the infection may be responsible for some mortality, its impact is mainly associated with the impairment of intestinal functions and lower performance of animals. The aim of this study was to determine the effect of cryptosporidiosis on the intestinal functions in neonatal experimentally infected Holstein calves. Absorption tests with d-xylose and retinyl-palmitate, and the lactulose/mannitol test of intestinal permeability were simultaneously performed in 1-week intervals from challenge to full recovery. In infected animals, reduced intestinal absorptive capacity for both d-xylose and retinyl-palmitate was observed on day 7 post-infection (p.i.). At the same time, a more than 100% elevation of intestinal permeability was observed in the infected calves. All intestinal functions, except absorption of retinyl-palmitate, were significantly affected and changes were detected up to day 14 p.i. In contrast, results of all tests obtained on day 21 p.i. suggest full recovery of the infected intestine. Significantly, growth of the calves which had recovered from cryptosporidiosis was still affected between days 14 and 21 p.i.


title: Coronavirus Pandemic: Applying a Whole-of-Society Model for the Whole-of-the World

text: During a pandemic, a national government is often considered solely responsible for dealing with the outbreak with local-based policies. A whole-of-society approach to a pandemic is evidence-based and used successfully in countries with a history of pandemic infections. This collaborative approach assumes that no single entity has the capacity to successfully manage the dynamic, complex problems that arise in a pandemic environment. Application of the whole-of-society model globally would provide a more harmonious and concerted response with mutual and synergistic benefits to all affected nations. Central entities within the model include; Civil society, business and government. These are addressed at the community, local government and sub-national level. Nine essential services are also identified including Health, defence, Law & order, Finance, Transport, Telecommunication, Energy, Food and Water. A continuing cycle of readiness, response and recovery of services encapsulates this model. Pandemics affect the whole of the world, a global whole-ofsociety approach is therefore needed to tackle them.


title: Interaction of L-SIGN with Hepatitis C Virus Envelope Protein E2 Up-Regulates Raf–MEK–ERK Pathway

text: Liver/lymph node-specific intercellular adhesion molecule-3-grabbing integrin (L-SIGN) facilitates hepatitis C virus (HCV) infection through interaction with HCV envelope protein E2. Signaling events triggered by the E2 via L-SIGN are poorly understood. Here, kinase cascades of Raf–MEK–ERK pathway were defined upon the E2 treatment in NIH3T3 cells with stable expression of L-SIGN. The E2 bound to the cells through interaction with L-SIGN and such binding subsequently resulted in phosphorylation and activation of Raf, MEK, and ERK. Blockage of L-SIGN with antibody against L-SIGN reduced the E2-induced phosphorylation of Raf, MEK, and ERK. In the cells infected with cell culture-derived HCV, phosphorylation of these kinases was enhanced by the E2. Up-regulation of Raf–MEK–ERK pathway by HCV E2 via L-SIGN provides new insights into signaling cascade of L-SIGN, and might be a potential target for control and prevention of HCV infection.


title: Vaccine platforms for the prevention of Lassa fever

text: Abstract Lassa fever is an acute viral haemorrhagic illness caused by Lassa virus (LASV), which is endemic throughout much of West Africa. The virus primarily circulates in the Mastomys natalensis reservoir and is transmitted to humans through contact with infectious rodents or their secretions; human-to-human transmission is documented as well. With the exception of Dengue fever, LASV has the highest human impact of any haemorrhagic fever virus. On-going outbreaks in Nigeria have resulted in unprecedented mortality. Consequently, the World Health Organization (WHO) has listed LASV as a high priority pathogen for the development of treatments and prophylactics. Currently, there are no licensed vaccines to protect against LASV infection. Although numerous candidates have demonstrated efficacy in animal models, to date, only a single candidate has advanced to clinical trials. Lassa fever vaccine development efforts have been hindered by the high cost of biocontainment requirements, the absence of established correlates of protection, and uncertainty regarding the extent to which animal models are predictive of vaccine efficacy in humans. This review briefly discusses the epidemiology and biology of LASV infection and highlights recent progress in vaccine development.


title: The ER stress sensor IRE1 and MAP kinase ERK modulate autophagy induction in cells infected with coronavirus infectious bronchitis virus

text: Abstract Coronavirus infection induces the generation of autophagosomes, and certain host proteins regulating cellular autophagy are hijacked by some coronaviruses to facilitate the formation of double membrane vesicles. However, mechanisms underlying coronavirus-induced autophagy remain largely unknown. In this study, we demonstrate that autophagosome formation and apparent autophagic flux are induced in cells infected with infectious bronchitis virus (IBV) – a gammacoronavirus. Notably, IBV-induced autophagy was dependent on autophagy related 5 (ATG5) but not beclin1 (BECN1), although both are essential proteins in the canonical autophagy pathway. Moreover, the ER stress sensor inositol requiring enzyme 1 (IRE1), but not its substrate X-box protein 1 (XBP1), was also essential for the induction of autophagy during IBV infection. Finally, the anti-apoptotic extracellular signal-regulated kinase 1/2 (ERK1/2) also contributed to IBV-induced autophagy. Our findings add new knowledge to the regulatory mechanisms governing coronavirus-induced autophagy, highlighting an extensive cross-talk among cellular signaling pathways during coronavirus infection.


title: Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone

text: Abstract Aims: The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS). Methods: Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 μg/kg). 24 h later, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 h. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for hematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically. Results: Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P <0.05). Compared to baseline, a significant decrease in ratio of tissue-type plasminogen activator/plasminogen activator inhibitor 1, activated partial thromboplatin time and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ON rabbits (P <0.05). Dynamic MRI showed a significant decrease in the perfusion index ‘maximum enhancement’ in the ON rabbits (P <0.05), and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON, and no rabbits died throughout the experiment period. Conclusion: Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.


title: Primary care physicians’ response to pandemic influenza in Hong Kong: a mixed quantitative and qualitative study

text: Summary Objectives The current study was conducted to use a developed framework to appraise the public primary care response to pandemic 2009 influenza A H1N1 virus in Hong Kong in 2009. Methods A cross-sectional survey was conducted of 300 doctors working in public primary care clinics. In addition, a qualitative study was conducted in two selected general outpatient clinics (GOPCs) with 10 doctors between September and December 2009. Results We found that there was an increase in clinical service demand for public primary care doctors and that there was lower compliance with hand washing as compared to the wearing of masks among GOPC doctors during the study period. Conclusions Since hand hygiene and influenza vaccination are effective methods to prevent the spread of influenza infection, future studies should explore the reasons for non-compliance with these preventive behaviors among doctors. More education and training in dealing with influenza A H1N1 infection may be needed.


title: Anatid herpesvirus 1 CH virulent strain induces syncytium and apoptosis in duck embryo fibroblast cultures

text: Abstract Anatid herpesvirus 1 (AHV-1) CH virulent strain was first isolated from an infected duck and it was found that this virus strain could induce cytopathic effect (CPE) in duck embryo fibroblast (DEF). Following AHV-1 infection, DEF showed morphological changes such as cell rounding, improved refractivity and detachment from the culture surface. However, its pathological characteristics were not adequately known. Related studies were performed and the results showed that syncytium formation could be observed as the other type of CPE in AHV-1 infection. Hematoxylin-eosin staining and 4’, 6-diamidino-2-phenylindole (DAPI) staining of infected DEF were each used to visualize the shape and distribution of chromatin within nuclei and nuclear fragmentation was observed. Chromatin condensation and margination, as well as formation of apoptotic bodies were observed by transmission electron microscopy (TEM). DNA ladder formation was detected in AHV-1 infected cells and apoptosis of the infected DEF was also detected by flow cytometry analysis of Annexin V-FITC/PI staining method. Therefore, it was suggested that AHV-1 virulent strain can induce syncytium and apoptosis in DEF. Syncytium formation and apoptosis observed in this study may contribute to the elucidation of AHV-1 pathogenesis.


title: Computational Design of High-Affinity Epitope Scaffolds by Backbone Grafting of a Linear Epitope

text: Abstract Computational grafting of functional motifs onto scaffold proteins is a promising way to engineer novel proteins with pre-specified functionalities. Typically, protein grafting involves the transplantation of protein side chains from a functional motif onto structurally homologous regions of scaffold proteins. Using this approach, we previously transplanted the human immunodeficiency virus 2F5 and 4E10 epitopes onto heterologous proteins to design novel “epitope-scaffold” antigens. However, side-chain grafting is limited by the availability of scaffolds with compatible backbone for a given epitope structure and offers no route to modify backbone structure to improve mimicry or binding affinity. To address this, we report here a new and more aggressive computational method—backbone grafting of linear motifs—that transplants the backbone and side chains of linear functional motifs onto scaffold proteins. To test this method, we first used side-chain grafting to design new 2F5 epitope scaffolds with improved biophysical characteristics. We then independently transplanted the 2F5 epitope onto three of the same parent scaffolds using the newly developed backbone grafting procedure. Crystal structures of side-chain and backbone grafting designs showed close agreement with both the computational models and the desired epitope structure. In two cases, backbone grafting scaffolds bound antibody 2F5 with 30- and 9-fold higher affinity than corresponding side-chain grafting designs. These results demonstrate that flexible backbone methods for epitope grafting can significantly improve binding affinities over those achieved by fixed backbone methods alone. Backbone grafting of linear motifs is a general method to transplant functional motifs when backbone remodeling of the target scaffold is necessary.


title: Oncology Treatment in the Era of COVID‐19: We Cannot Afford to Hit the Pause Button

text: The COVID‐19 pandemic has far‐reaching ramifications for patients undergoing cancer treatment. Oncologists and institutions have adjusted treatment practices and, in many cases, significantly curtailed clinical trial conduct. Whether these adjustments mitigate the risk of COVID‐19 complications without jeopardizing treatment of the cancer is unknown. Given the expected duration of the pandemic, it is imperative that treatment of the patient's cancer remain the priority and that advances in drug development continue through appropriately designed clinical trials.


title: Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer

text: Breast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor‐associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine‐resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen‐sensitive (MCF7‐S) or ‐resistant (MCF7‐R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC‐chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor‐positive breast cancer. We found that macrophages cultured in the CM of MCF7‐S and MCF7‐R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P < .001), and patients with high CCL2 expression presented shorter progression‐free survival than those with low CCL2 expression (P < .05). We conclude that CCL2 secreted by TAM activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the TME, suggesting that CCL2 and TAM may be novel therapeutic targets for patients with endocrine‐resistant breast cancer.


title: Antimicrobial and immunomodulatory activity induced by loperamide in mycobacterial infections

text: • Loperamide modulates macrophages immune responses towards mycobacteria. • Loperamide is an immunoregulator of inflammation during mycobacterial infection. • Loperamide induces immunomodulatory responses and bactericidal mechanisms. • The activation of opioid receptors by loperamide is involved in its immunomodulatory activity.


title: Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection

text: Abstract Autophagy is an important cellular process by which ATG5 initiates the formation of double membrane vesicles (DMVs). Upon infection, DMVs have been shown to harbor the replicase complex of positive-strand RNA viruses such as MHV, poliovirus, and equine arteritis virus. Recently, it has been shown that autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection. Here, we identified ATG5 as an interacting protein for the HCV NS5B. ATG5/NS5B interaction was confirmed by co-IP and metabolic labeling studies. Furthermore, ATG5 protein colocalizes with NS4B, a constituent of the membranous web. Importantly, immunofluorescence staining demonstrated a strong colocalization of ATG5 and NS5B within perinuclear regions of infected cells at 2days postinfection. However, colocalization was completely lacking at 5DPI, suggesting that HCV utilizes ATG5 as a proviral factor during the onset of viral infection. Finally, inhibition of autophagy through ATG5 silencing blocks HCV replication.


title: Early stage COVID-19 disease dynamics in Germany: models and parameter identification

text: Since the end of 2019 an outbreak of a new strain of coronavirus, called SARS-CoV-2, is reported from China and later other parts of the world. Since January 21, World Health Organization (WHO) reports daily data on confirmed cases and deaths from both China and other countries (www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports). The Johns Hopkins University (github.com/CSSEGISandData/COVID-19/blob/master/csse_COVID_19_data/csse_COVID_19_time_series/time_series_COVID19_confirmed_global.csv) collects those data from various sources worldwide on a daily basis. For Germany, the Robert-Koch-Institute (RKI) also issues daily reports on the current number of infections and infection related fatal cases (www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Situationsberichte/Gesamt.html). However, due to delays in the data collection, the data from RKI always lags behind those reported by Johns Hopkins. In this work we present an extended SEIRD-model to describe the disease dynamics in Germany. The parameter values are identified by matching the model output to the officially reported cases. An additional parameter to capture the influence of unidentified cases is also included in the model.


title: Clinical cystoisosporosis associated to porcine cytomegalovirus (PCMV, Suid herpesvirus 2) infection in fattening pigs

text: Abstract Cystoisospora (syn. Isospora) suis is the causative agent of neonatal porcine coccidiosis and one of the main causes of diarrhoea in suckling piglets worldwide. Infection with porcine cytomegalovirus (PCMV, Suid herpesvirus 2) causes inclusion body rhinitis in pigs. In a Swiss pig herd (n =2 boars, 7 sows, 2 gilts, 18 finishing pigs, 30 fattening pigs, 54 suckling piglets), an outbreak of PCMV infection with high morbidity in all age categories, characterized by fever, anorexia, reduced general condition, respiratory signs and increased piglet mortality, was diagnosed by histopathology and molecular methods. Five fattening pigs (age~17weeks) additionally showed diarrhoea, not typical for PCMV infections, and one fattener had to be euthanized due to poor condition. Histopathologically, severe fibrinopurulent jejunoileitis with extensive atrophy and fusion of intestinal villi, loss of goblet cells and crypt abscesses associated to C. suis infection were present. In the liver, herpesvirus intranuclear inclusion bodies were observed and PCMV was confirmed by PCR/sequencing. No further infectious causes of diarrhoea (i.e. Rotavirus A; TGEV; PEDV; PCV-2; enterotoxigenic Escherichia coli or Lawsonia intracellularis) were detected in the euthanized fattener. Coproscopically, C. suis oocysts were identified in the faeces from further fatteners with diarrhoea. While C. suis usually produces disease only in suckling piglets, its association with severe intestinal lesions and diarrhoea in ~17-week-old fatteners was surprising. It is supposed that the underlying PCMV infection might have contributed to the presentation of clinical cystoisosporosis in fattening pigs. The interaction mechanisms between these two pathogens are unknown.


title: Seasonal and interannual risks of dengue introduction from South-East Asia into China, 2005-2015

text: Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005–15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.