title: Systems biology approach: Panacea for unravelling host-virus interactions and dynamics of vaccine induced immune response

text: Abstract Systems biology is an interdisciplinary research field in life sciences, which involves a comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. For the past 50years the discipline of virology has overly focused on the pathogen itself. However, we now know that the host response is equally or more important in defining the eventual pathological outcome of infection. Systems biology has in recent years been increasingly recognised for its importance to infectious disease research. Host-virus interactions can be better understood by taking into account the dynamical molecular networks that constitute a biological system. To decipher the pathobiological mechanisms of any disease requires a deep knowledge of how multiple and concurrent signal-transduction pathways operate and are deregulated. Hence the intricacies of signalling pathways can be dissected only by system level approaches.


title: Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease?

text: PURPOSE OF REVIEW: The highly infectious transmissible disease, the novel SARS-CoV-2, causing the coronavirus disease (COVID-19), has a median incubation time of 5 to 15 days. The symptoms vary from person to person and many are “hidden carriers.” Few people experience immediate reaction and even death within 48 h of infection. However, many show mild to chronic symptoms and recover. Nevertheless, the death rate due to COVID-19 transmission is high especially among patients with non-communicable diseases. The purpose of this review is to provide evidence to consider vitamins as epigenetic modifiers to enhance immunity and reduce inflammatory response in COVID-19 patients with non-communicable diseases. RECENT FINDINGS: Clinical evidence has suggested the risk of getting infected is high among individuals with non-communicable diseases such as cardiovascular disease, type-2 diabetes, cancer, acute respiratory distress syndrome, and renal disease, as well as the elderly with high mortality rate among the cohort. The impact is due to an already compromised immune system of patients. Every patient has a different response to COVID-19, which shows that the ability to combat the deadly virus varies individually. Thus, treatment can be personalized and adjusted to help protect and combat COVID-19 infections, especially in individuals with non-communicable diseases. SUMMARY: Based on current published scientific and medical evidence, the suggestions made in this article for combination of vitamin therapy as epigenetic modifiers to control the unregulated inflammatory and cytokine marker expressions, further needs to be clinically proven. Future research and clinical trials can apply the suggestions given in this article to support metabolic activities in patients and enhance the immune response.


title: Discovery of a divergent HPIV4 from respiratory secretions using second and third generation metagenomic sequencing

text: Molecular detection of viruses has been aided by high-throughput sequencing, permitting the genomic characterization of emerging strains. In this study, we comprehensively screened 500 respiratory secretions from children with upper and/or lower respiratory tract infections for viral pathogens. The viruses detected are described, including a divergent human parainfluenza virus type 4 from GS FLX pyrosequencing of 92 specimens. Complete full-genome characterization of the virus followed, using Single Molecule, Real-Time (SMRT) sequencing. Subsequent “primer walking” combined with Sanger sequencing validated the RS platform's utility in viral sequencing from complex clinical samples. Comparative genomics reveals the divergent strain clusters with the only completely sequenced HPIV4a subtype. However, it also exhibits various structural features present in one of the HPIV4b reference strains, opening questions regarding their lifecycle and evolutionary relationships among these viruses. Clinical data from patients infected with the strain, as well as viral prevalence estimates using real-time PCR, is also described.


title: Chapter 53 Eye

text: Abstract The Eye chapter of the 3rd edition of Haschek and Rousseaux’s Handbook of Toxicologic Pathology brings a comprehensive description of pathological processes affecting the ocular tissues in the most commonly used laboratory animals and their correlations with human diseases of interest in toxicology. Also presented are detailed descriptions of the structure and function of the different ocular tissues, the most advanced techniques applied in the toxicological evaluation of the eye, useful animal models of human disease, and known mechanisms of ocular toxicity. The introductory sections of the chapter also feature such essential topics as ocular embryology, an overview of clinical ophthalmic evaluation, and eye-specific techniques of tissue processing.


title: Persistent viral RNA positivity during recovery period of a patient with SARS‐CoV‐2 infection

text: As an emerging infectious disease, the clinical course and virological course of SARS‐CoV‐2 infection remain to be further investigated. In this case report, we described a case of SARS‐CoV‐2 infection with clinical course more than two months. This patient had recovered from the pneumonia after treatment. The viral RNA of throat swabs became negative and the viral specific antibodies were produced during recovery period. However, the viral RNA reappeared and additionally persisted in throat swabs for more than 40 days. In addition, the viral RNA was detected in multiple types of specimens with extremely high titers in the saliva. In conclusion, these findings indicate that SARS‐CoV‐2 can cause a long clinical course. The coexistence of viral RNA and viral specific antibodies may imply an immune evasion of SARAS‐CoV‐2 from host's immune system. This article is protected by copyright. All rights reserved.


Intracranial Hemorrhage in COVID-19 Patients on ECMO: Challenges and Future Directions


Biospecimen Repositories and Integrated Databases as Critical Infrastructure for Pathogen Discovery and Pathobiology Research


title: Papular cutaneous lesions in a cat associated with feline infectious peritonitis

text: A 7‐month‐old‐intact male domestic shorthair cat was presented with fever, anterior uveitis in the right eye and respiratory distress when handled. These signs along with mild changes in serum protein levels and the exclusion of other potential causes were suggestive of feline infectious peritonitis (FIP). As the disease progressed, more clinical signs consistent with FIP, including renal involvement and later pleural effusion, became evident. Non‐pruritic cutaneous lesions, characterized by slightly raised intradermal papules over the dorsal neck and over both lateral thoracic walls, were recognized at the end stage of the disease. The identification of papules in well‐haired skin was difficult, and clipping of the fur facilitated their detection. Definitive diagnosis of FIP was made by histopathology and by immunohistochemical demonstration of coronavirus antigen in macrophages within kidney and skin lesions. The case was classified as a mixed form of FIP. Recognition of associated cutaneous lesions may facilitate a diagnosis of FIP in suspicious cases.


title: One Health stakeholder and institutional analysis in Kenya

text: INTRODUCTION: One Health (OH) can be considered a complex emerging policy to resolve health issues at the animal–human and environmental interface. It is expected to drive system changes in terms of new formal and informal institutional and organisational arrangements. This study, using Rift Valley fever (RVF) as a zoonotic problem requiring an OH approach, sought to understand the institutionalisation process at national and subnational levels in an early adopting country, Kenya. MATERIALS AND METHODS: Social network analysis methodologies were used. Stakeholder roles and relational data were collected at national and subnational levels in 2012. Key informants from stakeholder organisations were interviewed, guided by a checklist. Public sector animal and public health organisations were interviewed first to identify other stakeholders with whom they had financial, information sharing and joint cooperation relationships. Visualisation of the OH social network and relationships were shown in sociograms and mathematical (degree and centrality) characteristics of the network summarised. RESULTS AND DISCUSSION: Thirty-two and 20 stakeholders relevant to OH were identified at national and subnational levels, respectively. Their roles spanned wildlife, livestock, and public health sectors as well as weather prediction. About 50% of national-level stakeholders had made significant progress on OH institutionalisation to an extent that formal coordination structures (zoonoses disease unit and a technical working group) had been created. However, the process had not trickled down to subnational levels although cross-sectoral and sectoral collaborations were identified. The overall binary social network density for the stakeholders showed that 35 and 21% of the possible ties between the RVF and OH stakeholders existed at national and subnational levels, respectively, while public health actors’ collaborations were identified at community/grassroots level. We recommend extending the OH network to include the other 50% stakeholders and fostering of the process at subnational-level building on available cross-sectoral platforms.


title: Pathological consequences of the unfolded protein response and downstream protein disulphide isomerases in pulmonary viral infection and disease

text: Protein folding within the endoplasmic reticulum (ER) exists in a delicate balance; perturbations of this balance can overload the folding capacity of the ER and disruptions of ER homoeostasis is implicated in numerous diseases. The unfolded protein response (UPR), a complex adaptive stress response, attempts to restore normal proteostasis, in part, through the up-regulation of various foldases and chaperone proteins including redox-active protein disulphide isomerases (PDIs). There are currently over 20 members of the PDI family each consisting of varying numbers of thioredoxin-like domains which, generally, assist in oxidative folding and disulphide bond rearrangement of peptides. While there is a large amount of redundancy in client proteins of the various PDIs, the size of the family would indicate more nuanced roles for the individual PDIs. However, the role of individual PDIs in disease pathogenesis remains uncertain. The following review briefly discusses recent findings of ER stress, the UPR and the role of individual PDIs in various respiratory disease states.


title: Single‐cell RNA analysis on ACE2 expression provides insights into SARS‐CoV‐2 potential entry into the bloodstream and heart injury

text: Coronavirus disease‐2019 (COVID‐19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID‐19, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS‐CoV. The pathological investigation of COVID‐19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS‐CoV‐2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell‐type‐specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single‐cell RNA‐seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS‐CoV‐2. Failed human hearts have a higher percentage of ACE2‐expressing cardiomyocytes, and SARS‐CoV‐2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS‐CoV‐2 infection. The SARS‐CoV‐2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS‐CoV‐2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.


title: Recomendaciones sobre el manejo de pacientes adultos con enfermedades reumáticas en el contexto de la infección por SARS-CoV-2 / COVID-19. Asociación Colombiana de Reumatología

text: Resumen Objetivo: generar las recomendaciones para la atención de pacientes con enfermedades reumáticas que reciben terapias inmunomoduladoras e inmunosupresoras (fármacos convencionales, biológicos y moléculas pequeñas) durante la pandemia por COVID-19. Materiales y métodos: las recomendaciones se realizaron utilizando el método Delphi como herramienta de acuerdo. Se conformó un panel de expertos con trayectoria académica y experiencia en investigación en reumatología. Se realizó la búsqueda de la literatura y se generó el cuestionario del ejercicio Delphi conformado por 42 preguntas (Annexo 1). El grado de acuerdo se logró con el 80% de aprobación de los participantes. Resultados: se conformó un grupo de once reumatólogos de siete ciudades del país. La tasa de respuesta fue del 100 % para las tres rondas de consulta. En la primera ronda se logró acuerdo en 35 preguntas, en la segunda ronda 37 y en la tercera ronda se logró el acuerdo de las 42 preguntas. Conclusión: la recomendación para la mayoría de los tratamientos inmunomoduladores utilizados en reumatología es continuar con las terapias en pacientes que no tengan la infección y suspenderlas en aquellos con diagnóstico de SARS-CoV-2 / COVID-19. Abstract Objective: To produce recommendations for patients with rheumatological diseases receiving immunomodulatory and immunosuppressive therapies (conventional drugs, biologicals, and small molecules) during the COVID-19 pandemic. Materials and methods: The recommendations were determined using the Delphi method as an agreement tool. A panel of experts was formed, with academic backgrounds and research experience in rheumatology. A literature search was conducted and 42 questions were generated. The level of agreement was made with 80% of approval by the participants. Results: A group of eleven rheumatologists from 7 cities in the country participated. The response rate was 100% for the three consultation rounds. In the first round, agreement was reached on 35 questions, on 37 in the second round, and on 42 questions in the third round. Conclusion: The recommendation for the majority of the pharmacological treatments used in rheumatology is to continue with immunomodulatory or immunosuppressive therapies in patients who do not have the infection, and to suspend it in patients with a diagnosis of SARS-CoV-2 / COVID-19.


title: COVID-19-Related Information Sources and Psychological Well-being: An Online Survey Study in Taiwan

text: • For the public, receiving information sources from medical staff and the Internet was associated with better and poorer psychological well-being, respectively. • For health care workers, attending formal lessons was significantly associated with better psychological well-being in coping with COVID-19. • People used a variety of sources of information on COVID-19, where Internet and traditional media were the most common used sources.


title: Acute Respiratory Infections in a Recently Arrived Traveler to Your Part of the World*

text: Many acute infectious pulmonary diseases have incubation periods that are long enough for travelers to have symptoms after returning home to a health-care system that is not familiar with “foreign” infections. Respiratory infections have a relatively limited repertoire of clinical manifestations, so that there is often nothing characteristic enough about a specific infection to make the diagnosis obvious. Thus, the pathway to the diagnosis of infections that are not endemic in a region relies heavily on taking a thorough history of both itinerary and of specific exposures. One important caveat is that on occasion, the history of a recent trip creates an element of “tunnel vision” in the evaluating health-care provider. It is tempting to relate a person's problem to that recent trip; however, when evaluating recent returnees, it is always important to remember that the travel may have nothing to do with the patient's presentation. Recent travel may add diagnostic considerations to the list of possibilities, but an astute clinician must not disregard the possibility that the patient's illness has nothing to do with the recent trip.


title: Effects of awareness diffusion and self-initiated awareness behavior on epidemic spreading - An approach based on multiplex networks

text: Abstract In this paper, we study the interplay between the epidemic spreading and the diffusion of awareness in multiplex networks. In the model, an infectious disease can spread in one network representing the paths of epidemic spreading (contact network), leading to the diffusion of awareness in the other network (information network), and then the diffusion of awareness will cause individuals to take social distances, which in turn affects the epidemic spreading. As for the diffusion of awareness, we assume that, on the one hand, individuals can be informed by other aware neighbors in information network, on the other hand, the susceptible individuals can be self-awareness induced by the infected neighbors in the contact networks (local information) or mass media (global information). Through Markov chain approach and numerical computations, we find that the density of infected individuals and the epidemic threshold can be affected by the structures of the two networks and the effective transmission rate of the awareness. However, we prove that though the introduction of the self-awareness can lower the density of infection, which cannot increase the epidemic threshold no matter of the local information or global information. Our finding is remarkably different to many previous results on single-layer network: local information based behavioral response can alter the epidemic threshold. Furthermore, our results indicate that the nodes with more neighbors (hub nodes) in information networks are easier to be informed, as a result, their risk of infection in contact networks can be effectively reduced.


title: Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold

text: Purpose: To present a critical evaluation of the current evidence concerning the therapeutic value of vitamin C for the prophylaxis and treatment of the common cold. Data sources: Cochrane, PubMed, Natural Standard, and the National Center for Complementary and Alternative Medicine databases were searched to identify and acquire primary research reports, literature reviews, and secondary analyses related to the clinical objective. Published clinical trials, literature reviews, meta‐analyses, and systematic reviews were evaluated for evidence‐based practice implications. Conclusions: Vitamin C is frequently used for the treatment and prophylaxis of the common cold; however, no published recommendations were found in a review of the nurse practitioner literature that specifically address the efficacy of vitamin C for the common cold. Our literature review revealed that vitamin C is not effective at preventing the common cold in the general adult population; however, it is effective at preventing colds when consumed regularly by athletes training in subarctic conditions. We also found that regular vitamin C consumption may reduce the duration of cold symptoms in both adults and children, but it does not decrease the severity of cold symptoms. Implications for practice: NPs should counsel their patients that regular vitamin C consumption may decrease the duration of cold symptoms, but does not affect symptom severity or act as a prophylaxis.


title: Brief clinical evaluation of six high-throughput SARS-CoV-2 IgG antibody assays

text: Serological SARS-CoV-2 assays are urgently needed for diagnosis, contact tracing and for epidemiological studies. So far, there is limited data on how recently commercially available, high-throughput immunoassays, using different recombinant SARS-CoV-2 antigens, perform with clinical samples. Focusing on IgG and total antibodies, we demonstrate the performance of four automated immunoassays (Abbott Architect™ i2000 (N protein-based)), Roche cobas™ e 411 analyzer (N protein-based, not differentiating between IgA, IgM or IgG antibodies), LIAISON®XL platform (S1 and S2 protein-based), VIRCLIA® automation system (S1 and N protein-based) in comparison two ELISA assays (Euroimmun SARS-CoV-2 IgG (S1 protein-based) and Virotech SARS-CoV-2 IgG ELISA (N protein-based)) and an in-house developed plaque reduction neutralization test (PRNT). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. When calculating the overall sensitivity, in a time frame of 49 days after first PCR-positivity, the PRNT as gold standard, showed the highest sensitivity with 93.3% followed by the dual-target assay for the VIRCLIA® automation system with 89%. The overall sensitivity in the group of N protein-based assays ranged from 66.7 to 77.8% and in the S protein-based-assays from 71.1 to 75.6%. Five follow-up samples of three individuals were only detected in either an S and/or N protein-based assay, indicating an individual different immune response to SARS-CoV-2 and the influence of the used assay in the detection of IgG antibodies. This should be further analysed. The specificity of the examined assays was ≥ 97%. However, because of the low or unknown prevalence of SARS-CoV-2, the examined assays in this study are currently primarily eligible for epidemiological investigations, as they have limited information in individual testing.


title: Absolute and Relative Quantification of Multiplex DNA Assays Based on an Elemental Labeling Strategy

text: Elements and quantification: A nucleic acid assay has been developed, based on an elemental labeling strategy using magnetic microparticles (MMPs), which provides quantification of multiple DNA targets. Rare‐earth elements, indium, and stable isotopes could be labeled with oligonucleotides serving as DNA probes. Quantitative analysis was then carried out using the designed systems (see picture) and elemental mass spectrometry.[Image: see text]


title: Modelling insights into the COVID-19 pandemic

text: Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was declared a pandemic by the World Health Organization on 11th March, 2020. Response to this pandemic has required extensive collaboration across the scientific community in an attempt to contain the virus and limit further transmission. Mathematical modelling has been at the forefront of these response efforts by: (1) providing initial estimates of the SARS-CoV-2 reproduction rate, R(0) (of approximately 2-3); (2) updating these estimates following intervention implementation (with significantly reduced, often sub-critical, transmission rates); (3) assessing the potential for global spread through predictions of the exportation of COVID-19 before significant case numbers had been reported internationally; and (4) quantifying the severity and burden of COVID-19, indicating that the true infection rates are orders of magnitude greater than estimates based on confirmed case counts alone. In this review, we highlight the critical role played by mathematical modelling to understand COVID-19 thus far, the challenges posed by data availability and uncertainty, and the continuing utility of modelling-based approaches to inform the public health response. †Unless otherwise stated, all bracketed error margins correspond to the 95% credible interval (CrI) for reported estimates.


title: Filovirus Entry

text: A number of advances in recent years have significantly furthered our understanding of filovirus attachment and cellular tropism. For example, several cell-surface molecules have been identified as attachment factors with the potential to facilitate the in vivo targeting of particular cell types such as macrophages and hepatic cells. Furthermore, our knowledge of internalization and subsequent events during filovirus entry has also been widened, adding new variations to the paradigms for viral entry established for HIV and influenza. In particular, host cell factors such as endosomal proteases and the intracellular receptor Niemann-Pick C1 are now known to play a vital role in activating the membrane fusion potential of filovirus glycoproteins.


title: 4.17 Enzymes Involved in Processing Glutathione Conjugates

text: Many potentially toxic electrophiles react with glutathione to form glutathione S-conjugates in reactions catalyzed or enhanced by glutathione S-transferases. The glutathione S-conjugate is sequentially converted to the cysteinylglycine-, cysteine- and N-acetyl-cysteine S-conjugate (mercapturate). The mercapturate is generally more polar and water soluble than the parent electrophile and is readily excreted. Excretion of the mercapturate represents a detoxication mechanism. Some endogenous compounds, such as leukotrienes, prostaglandin (PG) A2, 15-deoxy-Δ12,14-PGJ2, and hydroxynonenal can also be metabolized to mercapturates and excreted. On occasion, however, formation of glutathione S- and cysteine S-conjugates are bioactivation events as the metabolites are mutagenic and/or cytotoxic. When the cysteine S-conjugate contains a strong electron-withdrawing group attached at the sulfur, it may be converted by cysteine S-conjugate β-lyases to pyruvate, ammonium and the original electrophile modified to contain an –SH group. If this modified electrophile is highly reactive then the enzymes of the mercapturate pathway together with the cysteine S-conjugate β-lyases constitute a bioactivation pathway. Some endogenous halogenated environmental contaminants and drugs are bioactivated by this mechanism. Recent studies suggest that coupling of enzymes of the mercapturate pathway to cysteine S-conjugate β-lyases may be more common in nature and more widespread in the metabolism of electrophilic xenobiotics than previously realized.


title: Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study

text: BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57–70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5–17) days, and the duration from onset of symptoms to the study date was 31 (24–36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2–8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4


title: Experimental and numerical investigation of micro-environmental conditions in public transportation buses

text: Abstract This study examines both numerically and experimentally the micro-environmental conditions in public transportation buses. A Computational Fluid Dynamics (CFD) model was developed and experimentally validated. The developed CFD model was used to calculate the spatial distributions of the mean age and mean residual lifetime of air in the bus environment and evaluate the efficiency of the bus ventilation system. Additionally, the passengers’ exposures to a variety of environmental conditions were experimentally monitored in “real world” field campaigns using the Harvard University shuttle bus system. Real time continuous monitoring systems were used to assess indoor environmental quality in the buses. It was found that CO levels were very low, while the levels of particulate matter varied and were influenced by the ambient air penetrated into the bus through the operation of the doors and the ventilation system. The CO2 level was found elevated and greatly affected by occupancy conditions. The elevated CO2 level indicates that the current bus ventilation is insufficient to dilute air pollutants in the bus especially under heavy occupancy conditions. This lack of sufficient ventilation indicates an elevated risk for airborne transmitted diseases in such a popular public transportation system.


title: Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus

text: To determine if a hypersensitive-type lung pathology might occur when mice were given an inactivated MERS-CoV vaccine and challenged with infectious virus as was seen with SARS-CoV vaccines, we prepared and vaccinated mice with an inactivated MERS-CoV vaccine. Neutralizing antibody was induced by vaccine with and without adjuvant and lung virus was reduced in vaccinated mice after challenge. Lung mononuclear infiltrates occurred in all groups after virus challenge but with increased infiltrates that contained eosinophils and increases in the eosinophil promoting IL-5 and IL-13 cytokines only in the vaccine groups. Inactivated MERS-CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS-CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection.


title: Respiratory DNA viruses are undetectable in nasopharyngeal secretions from adenotonsillectomized children

text: Respiratory viruses are frequently detected in association with chronic tonsillar hypertrophy in the absence of symptoms of acute respiratory infection (ARI). The present analysis was done in follow-up to a previous clinical study done by this same group. Nasopharyngeal washes (NPWs) were obtained from 83 of 120 individuals at variable times post adenotonsillectomy, in the absence of ARI symptoms. A look back at virus detection results in NPWs from the same 83 individuals at the time of tonsillectomy revealed that 73.5% (61/83) were positive for one or more viruses. The overall frequency of respiratory virus detection in post-tonsillectomy NPWs was 58.8%. Rhinovirus (RV) was the agent most frequently detected, in 38 of 83 subjects (45.8%), followed by enterovirus in 7 (8.4%), human metapneumovirus in 6 (7.2%), human respiratory syncytial virus in 3 (3.6%) and human coronavirus in 1 (1.2%). Remarkably, there was no detection of adenovirus (HAdV) or human bocavirus (HBoV) in asymptomatic individuals in follow-up of adenotonsillectomy. In keeping with persistence of respiratory DNA viruses in human tonsils, tonsillectomy significantly reduces asymptomatic shedding of HAdV and HBoV in NPWs.


title: The effect of travel restrictions on the spread of the 2019 novel coronavirus (2019-nCoV) outbreak

text: Motivated by the rapid spread of a novel coronavirus (2019-nCoV) in Mainland China, we use a global metapopulation disease transmission model to project the impact of both domestic and international travel limitations on the national and international spread of the epidemic. The model is calibrated on the evidence of internationally imported cases before the implementation of the travel quarantine of Wuhan. By assuming a generation time of 7.5 days, the reproduction number is estimated to be 2.4 [90% CI 2.2–2.6]. The median estimate for number of cases before the travel ban implementation on January 23, 2020 is 58,956 [90% CI 40,759 – 87,471] in Wuhan and 3,491 [90% CI 1,924 – 7,360] in other locations in Mainland China. The model shows that as of January 23, most Chinese cities had already received a considerable number of infected cases, and the travel quarantine delays the overall epidemic progression by only 3 to 5 days. The travel quarantine has a more marked effect at the international scale, where we estimate the number of case importations to be reduced by 80% until the end of February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.


title: Research progress in SELDI-TOF MS and its clinical applications

text: Abstract Proteinchip profiling is a powerful and innovative proteomic technology for the discovery of biomarkers and the development of diagnostic/prognostic assays. On the basis of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), Ciphergen’s proteinchip system offers a single, unified, and high throughput platform for a multitude of proteomic research applications. Proteins are the major functional components of the cell. The study of proteomics helps to better understand the mechanism of a disease. Remarkable findings in disease biomarkers have shed light on the early diagnosis, monitoring, and prognosis of various diseases, especially for cancer. In this paper, the development and technology of SELDI-TOF MS are introduced. The research progress and encouraging research results in malignancies, infectious diseases, neurological diseases, and diabetes mellitus using SELDI-TOF MS are reviewed. This paper concludes by evaluating the pros and cons, and the future perspectives are also expounded.


title: Next-generation sequencing library preparation method for identification of RNA viruses on the Ion Torrent Sequencing Platform

text: Next generation sequencing (NGS) is a powerful tool for the characterization, discovery, and molecular identification of RNA viruses. There were multiple NGS library preparation methods published for strand-specific RNA-seq, but some methods are not suitable for identifying and characterizing RNA viruses. In this study, we report a NGS library preparation method to identify RNA viruses using the Ion Torrent PGM platform. The NGS sequencing adapters were directly inserted into the sequencing library through reverse transcription and polymerase chain reaction, without fragmentation and ligation of nucleic acids. The results show that this method is simple to perform, able to identify multiple species of RNA viruses in clinical samples.


title: Trends in global warming and evolution of matrix protein 2 family from influenza A virus

text: The global warming is an important factor affecting the biological evolution, and the influenza is an important disease that threatens humans with possible epidemics or pandemics. In this study, we attempted to analyze the trends in global warming and evolution of matrix protein 2 family from influenza A virus, because this protein is a target of anti-flu drug, and its mutation would have significant effect on the resistance to anti-flu drugs. The evolution of matrix protein 2 of influenza A virus from 1959 to 2008 was defined using the unpredictable portion of amino-acid pair predictability. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site, and species carrying influenza A virus. The results showed the similar trends in global warming and in evolution of M2 proteins although we could not correlate them at this stage of study. The study suggested the potential impact of global warming on the evolution of proteins from influenza A virus.


title: Implications for COVID-19: a systematic review of nurses’ experiences of working in acute care hospital settings during a respiratory pandemic

text: Abstract Background Pandemics and epidemics are a public health emergencies that can result in substantial deaths and socio-economic disruption. Nurses play a key role in the public health response to such crises, delivering direct patient care and risk of exposure to the infectious disease. The experience of providing nursing care in this context has the potential to have significant short and long term consequences for individuals, society and the nursing profession. Objectives To synthesize and present the best available evidence on the experiences of nurses working in acute hospital settings during a pandemic. Design This review was conducted using the Joanna Briggs Institute methodology for systematic reviews. Data sources A structured search using CINAHL, MEDLINE, EMBASE, PubMed, Google Scholar, Cochrane Library, MedNar, ProQuest and Index to Theses was conducted. Review methods All studies describing nurses’ experiences were included regardless of methodology. Themes and narrative statements were extracted from included papers using the SUMARI data extraction tool from Joanna Briggs Institute. Results Thirteen qualitative studies were included in the review. The experiences of 348 nurses generated a total of 116 findings, which formed seven categories based on similarity of meaning. Three synthesized findings were generated from the categories: (i) Supportive nursing teams providing quality care; (ii) Acknowledging the physical and emotional impact; and (iii) Responsiveness of systematised organizational reaction. Conclusions Nurses are pivotal to the health care response to infectious disease pandemics and epidemics. This systematic review emphasises that nurses’ require Governments, policy makers and nursing groups to actively engage in supporting nurses, both during and following a pandemic or epidemic. Without this, nurses are likely to experience substantial psychological issues that can lead to burnout and loss from the nursing workforce.


title: Effect of COVID‐19 in selecting otolaryngology as a specialty

text: Coronavirus disease 2019 has undoubtedly impacted the health care system while causing lasting and profound implications for medical education. Senior medical students seeking exposure to the field of otolaryngology now find themselves in the challenging position of obtaining the experiences to make an informed decision on a future specialty. Virtual electives using comprehensive online material, discussion, and videos as well as the advent of telemedicine may be potential solutions to increase exposure to otolaryngology. While incorporating opportunities for authentic patient interactions is still a challenge, it is crucial that the academic otolaryngology community prioritize seeking solutions for interested medical students.


title: Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)

text: Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.


title: Toll-like receptor 3 in viral pathogenesis: friend or foe?

text: Viral infections frequently induce acute and chronic inflammatory diseases, yet the contribution of the innate immune response to a detrimental host response remains poorly understood. In virus-infected cells, double-stranded RNA (dsRNA) is generated as an intermediate during viral replication. Cell necrosis (and the release of endogenous dsRNA) is a common event during both sterile and infectious inflammatory processes. The discovery of Toll-like receptor 3 (TLR3) as an interferon-inducing dsRNA sensor led to the assumption that TLR3 was the master sentinel against viral infections. This simplistic view has been challenged by the discovery of at least three members of the DExd/H-box helicase cytosolic sensors of dsRNA that share with TLR3 the Toll–interleukin-1 receptor (TIR) -adapter molecule TIR domain-containing adaptor protein interferon-β (TRIF) for downstream type I interferon signalling. Data are conflicting on the role of TLR3 in protective immunity against viruses in the mouse model. Varying susceptibility to infection and disease outcomes have been reported in TLR3-immunodeficient mice. Surprisingly, the susceptibility to develop herpes simplex virus-1 encephalitis in humans with inborn defects of the TLR3 pathway varies, and TLR3-deficient humans do not show increased susceptibility to other viral infections. Therefore, a current challenge is to understand the protective versus pathogenic contribution of TLR3 in viral infections. We review recent advances in the identification of TLR3-signalling pathways, endogenous and virus-induced negative regulators of the TLR3 cascade, and discuss the protective versus pathogenic role of TLR3 in viral pathogenesis.


title: Coronavirus Disease 2019 Myocarditis: Insights into Pathophysiology and Management

text: The world is dealing with a global pandemic of severe acute respiratory coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19), which is the illness caused by SARS-CoV-2, is overwhelming healthcare systems around the world. Although the main clinical manifestations of COVID-19 are respiratory symptoms, several reports have noted myocarditis, cardiomyopathy, arrhythmias and cardiac arrests as COVID-19 complications. Here, the authors highlight the current understanding of the pathophysiology of myocarditis related to COVID-19 and its management.


title: Risky Bodies in the Plasma Bioeconomy: A Feminist Analysis

text: In 2003 the UK National Blood Service introduced a policy of ‘male donor preference’ which involved women’s plasma being discarded following blood collection. The policy was based on the view that data relating to the incidence of Transfusion-Related Acute Lung Injury (TRALI) was linked to transfusion with women’s plasma. While appearing to treat female donors as equal to male donors, exclusion criteria operate after donation at the stage of processing blood, thus perpetuating myths of universality even though only certain ‘extractions’ from women are retained for use in transfusion. Many women in the UK receive a plasma-derived product called Anti-D immunoglobulin which is manufactured from pooled male plasma. This article examines ways in which gender has significance for understanding blood relations, and how the blood economy is gendered. In our study of relations between blood donors and recipients, we explore how gendered bodies are produced through the discursive and material practices within blood services. We examine both how donation policies and the manufacturing and use of blood products produces gendered blood relations.


title: Correlates of symptoms of anxiety and depression and mental wellbeing associated with COVID-19: a cross-sectional study of UK-based respondents

text: Background: The aim was to assess the impact of COVID-19 self-isolation/social distancing on mental health, and potential correlates, among a sample of the UK population. Methods: A cross-sectional study. Mental health was measured using the Beck Anxiety and Depression Inventory. Mental wellbeing was measured using The Short Warwick-Edinburgh Mental Well-being Scale. Data collected on predictors included sex, age, marital status, employment, annual income, region, current smoking, current alcohol consumption, physical multimorbidity, any physical symptoms experienced during self-isolation/social distancing, and the number of days of self-isolation/social distancing. The association between potential predictors and poor mental health was studied using a multivariable logistic regression. Results: 932 participants were included. Factors associated with poor mental health were sex (reference: male; female: OR=1.89, 95%CI=1.34-2.68), age (18-24 years: reference;45-54 years: OR=0.27, 95%CI=0.14-0.53; 55-64 years: OR=0.24, 95%CI=0.12-0.47; 65-74years: OR=0.10, 95% CI=0.05-0.22; and ≥75years: OR=0.08,95% CI=0.03-0.24),annual income (<£15,000: reference; £25,000-<£40,000: OR=0.54, 95% CI=0.31-0.93; £40,000-<£60,000: OR=0.39, 95% CI=0.22-0.69; and ≥£60,000: OR=0.38, 95% CI=0.21-0.67), current smoking (yes: OR=2.59, 95%CI=1.62-4.20), and physical multimorbidity (OR=2.35, 95%CI=1.61-3.46). Conclusions: In this sample of UK adults self-isolating/social distancing females, younger age groups, those with a lower annual income, current smokers and those with physical multimorbidity were associated with higher levels of poor mental health.


title: Tuberculosis and novel Wuhan coronavirus infection: Pathological interrelationship

text: • Letter discussing on important new emerging disease.


title: Unintentional Injury Fatalities in the Context of Rising U.S. Suicide Rates: A Five-Year Review of the Web-Based Injury Statistics Query and Reporting System

text: This archival study focuses specifically on suicide fatalities in relation to unintentional and undetermined injury fatalities in an effort to determine whether or not these rates are rising consistently. This question may serve to inform whether or not suicides are being accurately reported and documented. Data from all 50 states from the years 2012-2016 were obtained from the Web-based Injury Statistics Query and Reporting System (WISQARS) developed by the Centers for Disease Control and Prevention. A total of 213,726 suicide fatalities, 702,176 unintentional injury fatalities, and 24,533 undetermined injury fatalities comprised the dataset. Injury fatality rates depicted annual increases in both suicide and unintentional injury fatalities but variability in undetermined injury fatalities. Bivariate analyses discovered a statistically significant association between annual suicide fatality rates and unintentional (nonsuicidal) injury fatality rates. It would be suspected, ceteris paribus, that calculated rate changes over these years would follow suit. However, this was not observed. Given the trends and increasing stigma surrounding suicide, it is worth considering the degree to which suicides may be underreported or -documented and the epidemiological and translational ramifications of these trends as they pertain to future suicide research.


title: A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

text: ABSTRACT: Stephania tetrandra S. Moore (S. tetrandra) is distributed widely in tropical and subtropical regions of Asia and Africa. The root of this plant is known in Chinese as “Fen Fang Ji”. It is commonly used in traditional Chinese medicine to treat arthralgia caused by rheumatism, wet beriberi, dysuria, eczema and inflamed sores. Although promising reports have been published on the various chemical constituents and activities of S. tetrandra, no review comprehensively summarizes its traditional uses, phytochemistry, pharmacology and toxicology. Therefore, the review aims to provide a critical and comprehensive evaluation of the traditional use, phytochemistry, pharmacological properties, pharmacokinetics and toxicology of S. tetrandra in China, and meaningful guidelines for future investigations. GRAPHIC ABSTRACT: [Image: see text]


title: Influenza Vaccination Is Not Associated With Detection of Noninfluenza Respiratory Viruses in Seasonal Studies of Influenza Vaccine Effectiveness

text: Background. The test-negative control study design is the basis for observational studies of influenza vaccine effectiveness (VE). Recent studies have suggested that influenza vaccination increases the risk of noninfluenza respiratory virus infection. Such an effect could create bias in VE studies using influenza-negative controls. We investigated the association between influenza infection, vaccination, and detection of other respiratory viruses among children <5 years old and adults ≥50 years old with acute respiratory illness who participated in seasonal studies of influenza vaccine effectiveness. Methods. Nasal/nasopharyngeal samples collected from 2004–2005 through 2009–2010 were tested for 19 respiratory virus targets using a multiplex reverse-transcription polymerase chain reaction (RT-PCR) platform. Vaccination status was determined using a validated registry. Adjusted odds ratios for influenza and vaccination status were calculated using three different control groups: influenza-negative, other respiratory virus positive, and pan-negative. Results. Influenza was detected in 12% of 2010 children and 20% of 1738 adults. Noninfluenza respiratory viruses were detected in 70% of children and 38% of adults without influenza. The proportion vaccinated did not vary between virus-positive controls and pan-negative controls in children (P = .62) or adults (P = .33). Influenza infection was associated with reduced odds of vaccination, but adjusted odds ratios differed by no more than 0.02 when the analysis used influenza-negative or virus-positive controls. Conclusions. Influenza vaccination was not associated with detection of noninfluenza respiratory viruses. Use of influenza-negative controls did not generate a biased estimate of vaccine effectiveness due to an effect of vaccination on other respiratory virus infections.


title: A multivalent HIV-1 fusion inhibitor based on small helical foldamers

text: The peptide sequence AcNH–TEG–Glu-Aib-Trp-AibAib-Trp-AibAib-Ile-Asp–OH (1), designed to display the WWI epitope found near the C-terminus of gp41, an envelope glycoprotein decorating the surface of the HIV-1 virus, has been synthesized and proved to have a relevant content of helical conformation because of the presence of five α-aminoisobutyric acid (Aib) units. Three copies of it have been connected to a tripodal platform based on 2,4,6-triethylbenzene-1,3,5-trimethylamine. The tripodal template 2 is even more structured than 1 thus suggesting a significant interaction between the three sequences connected to the platform. Preliminary inhibition assays of HIV-mediated cell fusion indicated that while the single peptide 1 is inactive within the concentration range of our assay, when it is conjugated to the tripodal platform, it is moderately active. These promising results suggest that our approach constitute a valid alternative to those reported so far.


title: Highly pathogenic avian influenza A virus H5N1 non-structural protein 1 is associated with apoptotic activation of the intrinsic mitochondrial pathway

text: Outbreaks of avian influenza A (H5N1) virus infection have significant health and economic consequences. Non-structural protein 1 (NS1) is an essential virulence factor of the highly pathogenic H5N1 avian influenza virus and of the apoptosis associated with the pathogenesis of H5N1. Previous studies have revealed that the NS1 protein is able to induce apoptosis via an extrinsic pathway. However, it remains unclear whether the intrinsic pathway is also associated with this apoptosis. The present study used a clone of the NS1 gene from avian influenza A/Jiangsu/1/2007 and observed the localization of the NS1 protein and cytochrome c release from mitochondria and the change of mitochondrial membrane potential (MMP) in lung cancer cells. Cytotoxicity was detected using an MTT assay and the number of apoptotic cells was counted using a flow cytometer. Following the isolation of mitochondria, western blotting was performed to compare cytochrome c release from the mitochondria in cells before and after apoptosis. The change of MMP was detected using JC-1 staining. Furthermore, the results reveal that the majority of the NS1 protein was localized in the cell nucleus, and that it may induce apoptosis of human lung epithelial cells. The apoptosis occurred with marked cytochrome c release from mitochondria and a change of the MMP. This indicated that the NS1 protein may be associated with apoptosis induced by an intrinsic mitochondrial pathway.


title: Improving Virus Taxonomy by Recontextualizing Sequence-Based Classification with Biologically Relevant Data: the Case of the Alphacoronavirus 1 Species

text: The difficulties related to virus taxonomy have been amplified by recent advances in next-generation sequencing and metagenomics, prompting the field to revisit the question of what constitutes a useful viral classification. Here, taking a challenging classification found in coronaviruses, we argue that consideration of biological properties in addition to sequence-based demarcations is critical for generating useful taxonomy that recapitulates complex evolutionary histories. Within the Alphacoronavirus genus, the Alphacoronavirus 1 species encompasses several biologically distinct viruses. We carried out functionally based phylogenetic analysis, centered on the spike gene, which encodes the main surface antigen and primary driver of tropism and pathogenesis. Within the Alphacoronavirus 1 species, we identify clade A (encompassing serotype I feline coronavirus [FCoV] and canine coronavirus [CCoV]) and clade B (grouping serotype II FCoV and CCoV and transmissible gastroenteritis virus [TGEV]-like viruses). We propose this clade designation, along with the newly proposed Alphacoronavirus 2 species, as an improved way to classify the Alphacoronavirus genus. IMPORTANCE Our work focuses on improving the classification of the Alphacoronavirus genus. The Alphacoronavirus 1 species groups viruses of veterinary importance that infect distinct mammalian hosts and includes canine and feline coronaviruses and transmissible gastroenteritis virus. It is the prototype species of the Alphacoronavirus genus; however, it encompasses biologically distinct viruses. To better characterize this prototypical species, we performed phylogenetic analyses based on the sequences of the spike protein, one of the main determinants of tropism and pathogenesis, and reveal the existence of two subgroups or clades that fit with previously established serotype demarcations. We propose a new clade designation to better classify Alphacoronavirus 1 members.


Lessons learned from SARS to COVID-19 in the Taiwanese population


title: Using remote interventions in promoting the health of frail older persons following the COVID-19 lockdown: challenges and solutions

text: In light of the Covid-19 pandemic, many older people across the world are being asked to self-isolate to protect their health. This has led to a rapid reconfiguration of health promotion services, which are diverse in focus, and may include exercise, dietary interventions or psychosocial interventions, towards remote delivery, for example by phone or using computers. Whilst currently they are unable to be safely delivered any other way, there are concerns that these remote interventions may replace face-to-face interventions beyond the end of social restrictions. We advocate caution with taking this forward, particularly for frailer older people.


title: COVID‐19 pandemic: perspectives on an unfolding crisis

text: A time of crisis


title: Artificial Intelligence-Empowered Mobilization of Assessments in COVID-19-like Pandemics: A Case Study for Early Flattening of the Curve

text: The global outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic has uncovered the fragility of healthcare and public health preparedness and planning against epidemics/pandemics. In addition to the medical practice for treatment and immunization, it is vital to have a thorough understanding of community spread phenomena as related research reports 17.9–30.8% confirmed cases to remain asymptomatic. Therefore, an effective assessment strategy is vital to maximize tested population in a short amount of time. This article proposes an Artificial Intelligence (AI)-driven mobilization strategy for mobile assessment agents for epidemics/pandemics. To this end, a self-organizing feature map (SOFM) is trained by using data acquired from past mobile crowdsensing (MCS) campaigns to model mobility patterns of individuals in multiple districts of a city so to maximize the assessed population with minimum agents in the shortest possible time. Through simulation results for a real street map on a mobile crowdsensing simulator and considering the worst case analysis, it is shown that on the 15th day following the first confirmed case in the city under the risk of community spread, AI-enabled mobilization of assessment centers can reduce the unassessed population size down to one fourth of the unassessed population under the case when assessment agents are randomly deployed over the entire city.


title: Acute Disseminated Encephalomyelitis: Clinical and Pathogenesis Features

text: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated disorder of the central nervous system (CNS). Disease typically starts with an abrupt onset of neurologic symptoms and signs within days to weeks after a viral infection or immunization. Neuropathological examination of the CNS in ADEM reveals involvement of white matter, with infiltration of monocytoid cells and perivenous demyelination.


title: Crude incidence in two-phase designs in the presence of competing risks

text: BACKGROUND: In many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome. METHODS: We develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard. RESULTS: The proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care. CONCLUSIONS: A valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived.


title: Three unique Sendai virus antigenic peptides screened from nucleocapsid protein by overlapping peptide array

text: Abstract Sendai virus (SeV) is strictly monitored in laboratory rodents. Currently, complete virions have been used as antigens in SeV serological tests. However, the complexity of SeV virion antigen limits the accuracy of the diagnostic method. In the current study, complete SeV virion antigen was separated on SDS-PAGE and analyzed, with nucleocapsid protein (NP) showing predominant antigenicity. A peptide array containing overlapping 14-mer peptides covering the entire NP was developed. The array used SeV positive serum and resulted in four antigenic linear peptides being identified, which were located in the carboxyl-terminus of NP. The four peptides were coated on ELISA plates and tested with SeV positive and SeV negative sera, and the antigenicity of three peptides, NP413–428, NP473–490 and NP507–524, was confirmed. Mixture of the three peptides showed comparable sensitivity and better specificity in clinical rat sera ELISA tests compared with complete SeV virion antigen. In conclusion, the three peptides, NP413–428, NP473–490 and NP507–524, would be good candidates as linear antigens for SeV detection.


An early assessment of the impact of COVID-19 on air transport: Just another crisis or the end of aviation as we know it?


title: High-resolution epidemic simulation using within-host infection and contact data

text: BACKGROUND: Recent epidemics have entailed global discussions on revamping epidemic control and prevention approaches. A general consensus is that all sources of data should be embraced to improve epidemic preparedness. As a disease transmission is inherently governed by individual-level responses, pathogen dynamics within infected hosts posit high potentials to inform population-level phenomena. We propose a multiscale approach showing that individual dynamics were able to reproduce population-level observations. METHODS: Using experimental data, we formulated mathematical models of pathogen infection dynamics from which we simulated mechanistically its transmission parameters. The models were then embedded in our implementation of an age-specific contact network that allows to express individual differences relevant to the transmission processes. This approach is illustrated with an example of Ebola virus (EBOV). RESULTS: The results showed that a within-host infection model can reproduce EBOV’s transmission parameters obtained from population data. At the same time, population age-structure, contact distribution and patterns can be expressed using network generating algorithm. This framework opens a vast opportunity to investigate individual roles of factors involved in the epidemic processes. Estimating EBOV’s reproduction number revealed a heterogeneous pattern among age-groups, prompting cautions on estimates unadjusted for contact pattern. Assessments of mass vaccination strategies showed that vaccination conducted in a time window from five months before to one week after the start of an epidemic appeared to strongly reduce epidemic size. Noticeably, compared to a non-intervention scenario, a low critical vaccination coverage of 33% cannot ensure epidemic extinction but could reduce the number of cases by ten to hundred times as well as lessen the case-fatality rate. CONCLUSIONS: Experimental data on the within-host infection have been able to capture upfront key transmission parameters of a pathogen; the applications of this approach will give us more time to prepare for potential epidemics. The population of interest in epidemic assessments could be modelled with an age-specific contact network without exhaustive amount of data. Further assessments and adaptations for different pathogens and scenarios to explore multilevel aspects in infectious diseases epidemics are underway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-018-5709-x) contains supplementary material, which is available to authorized users.


title: gp41: HIV's shy protein

text: The first X-ray crystal structures of gp41, the protein that mediates fusion of HIV-1 to target cells, were solved in the mid-1990s. The structures provide a foundation for understanding viral entry and the mechanism of action of compounds that block fusion. The first fusion inhibitor has recently entered the clinic, and the hope is that more potent and broadly active compounds, based on molecular design, will follow.


title: Systematic review and meta-analysis for the use of ultrasound versus radiology in diagnosing of pneumonia

text: BACKGROUND: Physicians are increasingly using point of care lung ultrasound (LUS) for diagnosing pneumonia, especially in critical situations as it represents relatively easy and immediately available tool. They also used it in many associated pathological conditions such as consolidation, pleural effusion, and interstitial syndrome with some reports of more accuracy than chest X-ray. This systematic review and meta-analysis are aimed to estimate the pooled diagnostic accuracy of ultrasound for the diagnosis of pneumonia versus the standard chest radiological imaging. METHODS AND MAIN RESULTS: A systematic literature search was conducted for all published studies comparing the diagnostic accuracy of LUS against a reference Chest radiological exam (C X-ray or Chest computed Tomography CT scan), combined with clinical criteria for pneumonia in all age groups. Eligible studies were required to have a Chest X-ray and/or CT scan at the time of clinical evaluation. The authors extracted qualitative and quantitative information from eligible studies, and calculated pooled sensitivity and specificity and pooled positive/negative likelihood ratios (LR). Twenty studies containing 2513 subjects were included in this meta-analysis. The pooled estimates for lung ultrasound in the diagnosis of pneumonia were, respectively, as follows: Overall pooled sensitivity and specificity for diagnosis of pneumonia by lung ultrasound were 0.85 (0.84–0.87) and 0.93 (0.92–0.95), respectively. Overall pooled positive and negative LRs were 11.05 (3.76–32.50) and 0.08 (0.04–0.15), pooled diagnostic Odds ratio was 173.64 (38.79–777.35), and area under the pooled ROC (AUC for SROC) was 0.978. CONCLUSION: Point of care lung ultrasound is an accurate tool for the diagnosis of pneumonia. Considering being easy, readily availability, low cost, and free from radiological hazards, it can be considered as important diagnostic strategy in this condition.


title: Comparison of atopic and nonatopic children with chronic cough: Bronchoalveolar lavage cell profile

text: Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1–11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39 × 10(4), range: 20–123; nonatopic: median 22 × 10(4), range: 17–132) compared to nonatopic controls (median 11 × 10(4), range 9–30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5–88.5%; nonatopic: median 6%, range 1.0–55.0%) compared to controls (median 1.55%, range 0.5–7.0%; atopics vs. controls, P < 0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice. Pediatr Pulmonol. 2007;42:857–863. © 2007 Wiley‐Liss, Inc.


title: Emergence of Community-Acquired Adenovirus Type 55 as a Cause of Community-Onset Pneumonia

text: Background Since 2008, severe cases of emerging human adenovirus (HAdV) type 55 (HAdV-55) were reported sporadically in China. But no comparative studies had been conducted to discern the differences in epidemiologic and clinical abnormalities between HAdV-55 and other types (HAdV-7, HAdV-3, HAdV-14, HAdV-50, and HAdV-C). Methods A multicenter surveillance study for adult and adolescent community-acquired pneumonia (CAP) was conducted prospectively in Beijing and Yan Tai between November 2010 and April 2012. A standardized data form was used to record clinical information. The viral DNA extracted from the clinical samples or adenovirus viral isolates was sequenced. Results Among 969 cases, 48 (5%) were identified as adenovirus pneumonia. Six branches were clustered: HAdV-55 in 21, HAdV-7 in 11, HAdV-3 in nine, HAdV-14 in four, HAdV-50 in two, and HAdV-C in one. Most HAdV-55 cases were identified during February and March. All the hypervariable regions of the hexon genes of the 21 HAdV-55 strains were completely identical. Patients who had HAdV-55 were about 10 years older (P = .027) and had higher pneumonia severity index scores (P = .030) compared with those with other types (HAdV-7, HAdV-3, HAdV-14, HAdV-50, and HAdV-C). Systemic BP was also higher among patients in the HAdV-55 group (P = .006). Unilateral or bilateral consolidations were the most common radiologic findings in both patients with HAdV-55 and those with other types (57.9% vs 36%). More than one-half of the patients were admitted to hospital; oxygen therapy was given to 29.2% of the 48 patients, and two needed mechanical ventilation. Conclusions HAdV-55 has established itself as a major pneumonia pathogen in the Chinese population, and further surveillance and monitoring of this agent as a cause of CAP is warranted.


title: Pulmonary Therapy 2020 Update and Podcast: Meet the Journal’s Editors-in-Chief

text: The Editors-in-Chief of Pulmonary Therapy have prepared podcasts summarizing their current research, recent highlights from the field, and future predictions. Audio-only versions and the transcripts can be downloaded here: https://doi.org/10.6084/m9.figshare.11938863. Following this is a written summary of the journal’s recent developments and the transcripts from the podcasts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41030-020-00114-9) contains supplementary material, which is available to authorized users.


title: The effect of dietary intake of the acidic protein fraction of bovine colostrum on influenza A (H1N1) virus infection

text: Acidic protein levels in the milk decrease markedly as lactation progresses, suggesting that it is an important part of the colostrum. However, little attention has been paid to their biological function. In this study, we isolated the acidic protein fraction of bovine colostrum (AFC, isoelectric point <5) by anion-exchange chromatography, and investigated the effect of its dietary intake on influenza A (H1N1) virus infection. 100% of mice infected with 1 LD(50) of the virus survived when administered AFC for 14 days prior to infection, compared with 33% survival when administered phosphate buffered saline (PBS). Moreover, consumption of AFC reduced the weight loss associated with infection. We propose that dietary intake of AFC has a prophylactic effect on influenza A virus infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12275-013-2683-y and is accessible for authorized users.


title: Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China Dong Y, Mo X, Hu Y, et al. Pediatrics. 2020; doi: 10.1542/peds.2020-0702.

text: Novel coronavirus (SARS-CoV-2, which causes COVID-19) is a pandemic with many countries employing massive public health responses. Little is known about the severity of illness in the pediatric population. This study sought to identify demographic information and severity of disease in pediatric patients with COVID-19. This was a retrospective study conducted on patients less than 18 years who were suspected or confirmed to have COVID-19 and were reported to the Chinese Centers for Disease Control (China CDC). Children were considered high risk and suspected if they had positive exposure to an endemic area or a confirmed case of COVID-19. High suspicion also included those with fever, respiratory symptoms, digestive symptoms, or fatigue, normal or low white blood cell count and increased C-reactive protein, or abnormal chest radiography, or those at lower risk for whom influenza or other respiratory illnesses were ruled out. Confirmed cases were defined as having a nasopharyngeal swab or blood sample positive via PCR or a genetic sampling of respiratory secretions or blood consistent with SARS-CoV-2. Once identified, patients were categorized by severity of disease using clinical features as well as laboratory and radiographic findings. Severity categories included asymptomatic (no symptoms but positive test), mild (mild respiratory symptoms and normal lung exam), moderate (pneumonia, fever, and cough but without hypoxemia or respiratory distress), severe (above symptoms as well as oxygen saturation less than 92% and respiratory distress), or critical disease (acute respiratory failure, acute respiratory distress syndrome, shock, or other life-threatening organ dysfunction). There were 2143 patients included who were suspected (65.9%) or confirmed (34.1%) to have COVID-19. Median age was 7 years (IQR 2-13) and the majority (56.6%) were male. The median time from onset of symptoms to presentation was 2 days (range 0-42). Nearly all were categorized as asymptomatic (4.4%), mild (50.9%), or moderate (38.8%) severity, leaving only 5.9% as severe or critical. Looking at breakdown by age, infants made up the highest proportion of severe or critical disease (32%) with preschool ages (1-5 years) next with 28.8%. Half (7) of the 13 critical patients were under 1 year old. No significant differences were seen between male or female patients. There was one death in the sample: a 14-year old boy. Limitations included lack of clinical characteristics, as only data from the Chinese CDC was used rather than electronic medical records from individual patients. Additionally the majority of cases were suspected, not confirmed, and some of the children remained hospitalized at the end of the study therefore severity of disease may not be accurate. The authors concluded that COVID-19 caused infection in all ages without obvious gender differences, however younger children appeared to have higher severity of disease. Comment: This is the largest cohort of pediatric COVID-19 patients to date. This study is based on the China CDC dataset and is limited to the variables that are reported to the CDC. We cannot assume children in the United States will be affected similarly. Overall, this dataset suggests that critical disease is rare in children with COVID-19. Emergency physicians should use caution with infants and young children, however, as they appear to be at highest risk of severe disease and may need closer observation in the emergency department or inpatient admission.


title: Analysis of Ebola virus polymerase domains to find strain-specific differences and to gain insight on their pathogenicity

text: Ebola virus, a member of the family Filoviridae has caused immense morbidity and mortality in recent times, especially in West Africa. The infection characterized by chills, fever, diarrhea, and myalgia can progress to hemorrhage and death. Hence, it is a high priority area to better understand its biology in order to expedite vaccine development pipelines. In this regard, this study analyzes the domains in RNA polymerase of fifteen publicly-available Ebola isolates belonging to three strains (Zaire, Sudan and Reston). The protein FASTA sequences of the isolates belonging Zaire, Sudan and Reston strains were extracted from UniProt database and submitted to the interactive web tool SMART for the polymerase domain profiles. Subsequent in silico investigation furnished interesting results that sure can contribute to the understanding of Ebola pathogenesis. The key findings and patterns have been presented, and based on them hypotheses have been formulated for further empirical validation.


title: Expression of 9-O- and 7,9-O-Acetyl Modified Sialic Acid in Cells and Their Effects on Influenza Viruses

text: Sialic acids (Sia) are widely displayed on the surfaces of cells and tissues. Sia come in a variety of chemically modified forms, including those with acetyl modifications at the C-7, C-8, and C-9 positions. Here, we analyzed the distribution and amounts of these acetyl modifications in different human and canine cells. Since Sia or their variant forms are receptors for influenza A, B, C, and D viruses, we examined the effects of these modifications on virus infections. We confirmed that 9-O-acetyl and 7,9-O-acetyl modified Sia are widely but variably expressed across cell lines from both humans and canines. Although they were expressed on the cell surfaces of canine MDCK cell lines, they were located primarily within the Golgi compartment of human HEK-293 and A549 cells. The O-acetyl modified Sia were expressed at low levels of 1 to 2% of total Sia in these cell lines. We knocked out and overexpressed the sialate O-acetyltransferase gene (CasD1) and knocked out the sialate O-acetylesterase gene (SIAE) using CRISPR/Cas9 editing. Knocking out CasD1 removed 7,9-O- and 9-O-acetyl Sia expression, confirming previous reports. However, overexpression of CasD1 and knockout of SIAE gave only modest increases in 9-O-acetyl levels in cells and no change in 7,9-O-acetyl levels, indicating that there are complex regulations of these modifications. These modifications were essential for influenza C and D infection but had no obvious effect on influenza A and B infection.


title: T cells can mediate viral clearance from ependyma but not from brain parenchyma in a major histocompatibility class I- and perforin-independent manner

text: Viral infection of the central nervous system can lead to disability and death. Yet the majority of viral infections with central nervous system involvement resolve with only mild clinical manifestations, if any. This is generally attributed to efficient elimination of the infection from the brain coverings, i.e. the meninges, ependyma and chorioplexus, which are the primary targets of haematogeneous viral spread. How the immune system is able to purge these structures from viral infection with only minimal detrimental effects is still poorly understood. In the present work we studied how an attenuated lymphocytic choriomeningitis virus can be cleared from the central nervous system in the absence of overt disease. We show that elimination of the virus from brain ependyma, but not from brain parenchyma, could be achieved by a T cell-dependent mechanism operating independently of major histocompatibility class I antigens and perforin. Considering that cytotoxic T lymphocyte-mediated cytotoxicity is a leading cause of viral immunopathology and tissue damage, our findings may explain why the most common viral intruders of the central nervous system rarely represent a serious threat to our health.


title: A blended cognitive behavioral intervention for patients with adjustment disorder with anxiety: A randomized controlled trial

text: Adjustment disorder with anxiety (ADA) is a common psychiatric pathology worldwide, but it is often undertreated. Cognitive behavioral therapy (CBT) is the first-line treatment, but very few studies have been carried out for the treatment of ADA. Internet-delivered CBT (iCBT) appears to be an effective treatment option, with the potential to reach a larger proportion of individuals suffering from ADA. Guidance is a beneficial feature of iCBT, provided in most studies by email or telephone (traditional guided iCBT). Blended CBT, which combines an online intervention and therapeutic guidance provided in person (face-to-face), could be a way to benefit from both the advantages of face-to-face CBT regarding human interactional quality and the advantages of internet-based CBT in terms of improved access to treatment. In this randomized controlled trial, the effectiveness of two forms of administration of Seren@ctif, a 5-week CBT program for patients with ADA according the DSM-5, was examined: one delivered through face-to-face sessions (face-to-face CBT) and the other delivered online and guided with face-to-face contact with a nurse (blended CBT); these formats were compared with a wait-list control group (WLC). A total of 120 patients were included and randomized to one of these three conditions. Measures were administered before treatment, after treatment and 6 months after inclusion in the study. Both treatment conditions displayed significant decreases in anxiety, depression, worry and perceived stress at posttreatment when compared to the WLC group. The decrease in symptoms was mostly maintained 6 months after inclusion for the two experimental groups. Blended CBT showed significantly greater reductions in anxiety and depression than did face-to-face CBT on some secondary outcome measures. We conclude that both face-to-face CBT and blended CBT are effective treatments for patients with ADA, and we suggest that blended CBT may be slightly more effective than classical face-to-face CBT. Trial Registration: Clinicaltrials.gov NCT02621775;https://clinicaltrials.gov/ct2/show/NCT02621775(Archived by WebCite at http://www.webcitation.org/6tQrkPs1u).


title: Prevision of multidisciplinary head and neck cancer survivorship care during the 2019 novel coronavirus pandemic

text: The 2019 Coronavirus Pandemic challenges the delivery of care for patients with head and neck cancer. An important aspect of this care has been the evolution of enhanced survivorship services, which include surveillance for recurring cancer and prevention of second primaries. The application of evidence‐based approaches to the identification and management of treatment and tumor‐related toxicities has embraced the use of validated patient‐reported outcomes instruments, health promotion, and care coordination. In this manuscript, we describe how our multidisciplinary team of survivorship providers has accommodated to the need to provide patients with social distancing while acknowledging the importance of continued care during treatment and through the spectrum of survivorship.


title: WU and KI Polyomavirus Prevalence in Invasive Respiratory Samples From Transplant Recipients in Cantabria, Spain

text: Abstract Background WU and KI polyomaviruses were discovered in 2007 in samples of respiratory secretions of children with acute respiratory symptoms. Seroepidemiologic studies have shown that these viruses are widely distributed throughout the world, but their incidence in Spain has not been determined. In transplant patients, early detection and treatment of viral infections may influence prognosis and survival, because they are associated with increased morbidity and mortality, including graft failure. Methods We aimed to determine the prevalence and clinical characteristics of WU and KI polyomaviruses among patients undergoing hematologic or solid organ transplant in the Hospital Marqués de Valdecilla (Santander, Spain). An in-house polymerase chain reaction with the use of specific primers was carried out in invasive lower respiratory samples from hospitalized patients with suspected respiratory infection and/or graft dysfunction and compared with asymptomatic transplant patients. Results Overall, we obtained 5.5% KI-positive samples and 1.4% WU-positive samples, with a higher prevalence of WU and KI polyomaviruses in the symptomatic population compared with the control group. Although the data suggest that their detection in respiratory samples is sporadic and often associated with other microorganisms, we should pay special attention to their association with cases of graft failure. Studies are needed with a larger number of samples to explore the potential clinical impact of these emerging polyomaviruses in transplant recipients.


title: No-wait two-stage flowshop problem with multi-task flexibility of the first machine

text: For the creation of intelligent management systems in hospitals, efficient resource arrangement is essential. Motivated by a real-world scenario in hospitals, we introduce the no-wait two-stage flowshop scheduling problem with the first-stage machine having multi-task flexibility. In this problem, each job has two operations which are processed in order on a two-stage flowshop without preemption and time delay between or on machines. The multi-task flexibility allows the first-stage machine to process the second-stage operations. The goal is to minimize the maximum completion time of all jobs. To the best of our knowledge, this is a pioneering work on this problem. We discover several novel structural properties, based on which we present a linear-time combinatorial algorithm with an approximation ratio [Formula: see text]. This problem and its variants can find many other meaningful applications in modern manufacturing systems, such as the robot cell scheduling with computer numerical control machines or printed circuit boards. The idea behind our algorithm may inspire more practical algorithms.


From the IASLC Tobacco Control Committee


title: Autophagy: The multi‐purpose bridge in viral infections and host cells

text: Autophagy signaling pathway is involved in cellular homeostasis, developmental processes, cellular stress responses, and immune pathways. The aim of this review is to summarize the relationship between autophagy and viruses. It is not possible to be fully comprehensive, or to provide a complete “overview of all viruses”. In this review, we will focus on the interaction of autophagy and viruses and survey how human viruses exploit multiple steps in the autophagy pathway to help viral propagation and escape immune response. We discuss the role that macroautophagy plays in cells infected with hepatitis C virus, hepatitis B virus, rotavirus gastroenteritis, immune cells infected with human immunodeficiency virus, and viral respiratory tract infections both influenza virus and coronavirus.


title: Process integration for emerging challenges: optimal allocation of antivirals under resource constraints

text: ABSTRACT: The global scientific community has intensified efforts to develop, test, and commercialize pharmaceutical products to deal with the COVID-19 pandemic. Trials for both antivirals and vaccines are in progress; candidates include existing repurposed drugs that were originally developed for other ailments. Once these are shown to be effective, their production will need to be ramped up rapidly to keep pace with the growing demand as the pandemic progresses. It is highly likely that the drugs will be in short supply in the interim, which leaves policymakers and medical personnel with the difficult task of determining how to allocate them. Under such conditions, mathematical models can provide valuable decision support. In particular, useful models can be derived from process integration techniques that deal with tight resource constraints. In this paper, a linear programming model is developed to determine the optimal allocation of COVID-19 drugs that minimizes patient fatalities, taking into account additional hospital capacity constraints. Two hypothetical case studies are solved to illustrate the computational capability of the model, which can generate an allocation plan with outcomes that are superior to simple ad hoc allocation. GRAPHIC ABSTRACT: [Image: see text]


title: Risk Attitudes Affect Livestock Biosecurity Decisions With Ramifications for Disease Control in a Simulated Production System

text: Hog producers' operational decisions can be informed by an awareness of risks associated with emergent and endemic diseases. Outbreaks of porcine epidemic diarrhea virus (PEDv) have been re-occurring every year since the first onset in 2013 with substantial losses across the hog production supply chain. Interestingly, a decreasing trend in PEDv incidence is visible. We assert that changes in human behaviors may underlie this trend. Disease prevention using biosecurity practices is used to minimize risk of infection but its efficacy is conditional on human behavior and risk attitude. Standard epidemiological models bring important insights into disease dynamics but have limited predictive ability. Since research shows that human behavior plays a driving role in the disease spread process, the explicit inclusion of human behavior into models adds an important dimension to understanding disease spread. Here we analyze PEDv incidence emerging from an agent-based model (ABM) that uses both epidemiological dynamics and algorithms that incorporate heterogeneous human decisions. We investigate the effects of shifting fractions of hog producers between risk tolerant and risk averse positions. These shifts affect the dynamics describing willingness to increase biosecurity as a response to disease threats and, indirectly, change infection probabilities and the resultant intensity and impact of the disease outbreak. Our ABM generates empirically verifiable patterns of PEDv transmission. Scenario results show that relatively small shifts (10% of the producer agents) toward a risk averse position can lead to a significant decrease in total incidence. For significantly steeper decreases in disease incidence, the model's hog producer population needed at least 37.5% of risk averse. Our study provides insight into the link between risk attitude, decisions related to biosecurity, and consequent spread of disease within a livestock production system. We suggest that it is possible to create positive, lasting changes in animal health by nudging the population of livestock producers toward more risk averse behaviors. We make a case for integrating social and epidemiological aspects in disease spread models to test intervention strategies intended to improve biosecurity and animal health at the system scale.


title: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

text: Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis.


title: Asthma phenotypes

text: The many roads leading to the syndrome of asthma have proven to be intricately interconnected. The chronic inflammation of asthma is characterized by airway hyperreactivity and variable reversibility. Past classification systems relied on assessment of daily impairment and the distinction between intrinsic (nonallergic) and extrinsic (allergic). With more precise asthma phenotypes, association studies likely will have greater significance. In addition, patients at higher risk for severe disease can be more effectively managed, and treatments can be directed to responders. In this review, we look at eight identified phenotypes: atopic and nonatopic status, pre-asthma wheezing, inflammatory mediator predominance, aspirin-sensitive, exercise-induced, severe, and flare-prone asthma. Although significant overlap exists among the distinctions, any future phenotype classification system will need to incorporate these eight clinical asthmatic populations.


title: Protection of swine by live and inactivated vaccines prepared from a leader proteinase-deficient serotype A12 foot-and-mouth disease virus

text: Abstract Previously, we demonstrated that a genetically engineered variant of foot-and-mouth disease virus (FMDV) serotype A12 lacking the leader proteinase-coding region (A12-LLV2) was attenuated and induced an immune response that partially protected cattle from FMD. In this study, A12-LLV2 was tested in swine as a live or chemically inactivated vaccine. Animals vaccinated with chemically inactivated A12-LLV2 or wild-type (WT) virus in oil adjuvant developed high levels of neutralizing antibodies and were protected from FMD upon challenge. Animals vaccinated with live A12-LLV2 did not exhibit signs of FMD, did not spread virus to other animals, developed a neutralizing antibody response and antibodies to nonstructural protein 3D, and were partially protected from FMD. Animals given a similar dose of chemically inactivated A12-LLV2 in the absence of adjuvant developed a poor immune response and were not protected from FMD, indicating that limited replication was responsible for the improved immune response found in animals vaccinated with live A12-LLV2. The results demonstrate the potential of A12-LLV2 as a live-attenuated vaccine as well as a safe source of antigen for chemically inactivated vaccines.


title: Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS

text: All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CL(pro) from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CL(pro) is less efficient at processing a peptide substrate due to MERS-CoV 3CL(pro) being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CL(pro) enzymes are tightly associated dimers. Analytical ultracentrifugation studies support that MERS-CoV 3CL(pro) is a weakly associated dimer (K(d) ∼52 μm) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CL(pro) were synthesized and utilized in analytical ultracentrifugation experiments and demonstrate that MERS-CoV 3CL(pro) undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at a low compound concentration as a result of induced dimerization. Primary sequence comparisons and x-ray structural analyses of two MERS-CoV 3CLpro and inhibitor complexes, determined to 1.6 Å, reveal remarkable structural similarity of the dimer interface with 3CL(pro) from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long range interactions by the nonconserved amino acids distant from the dimer interface may control MERS-CoV 3CL(pro) dimerization. Activation of MERS-CoV 3CL(pro) through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CL(pro) inhibitors as antiviral agents.


title: COVID‐19 Related Oral Manifestations, Early Disease Features?

text: The outbreak of novel communicable diseases urges epidemiologic and clinical researchers to establish highly sensitive case definitions to track all true positive cases; therefore, there is emerging evidence on the oral lesions that may be indicative of the coronavirus disease (COVID-19).


title: Risks of an epidemic in a two-layered railway-local area traveling network

text: In view of the huge investments into the construction of high speed rails systems in USA, Japan, and China, we present a two-layer traveling network model to study the risks that the railway network poses in case of an epidemic outbreak. The model consists of two layers with one layer representing the railway network and the other representing the local-area transportation subnetworks. To reveal the underlying mechanism, we also study a simplified model that focuses on how a major railway affects an epidemic. We assume that the individuals, when they travel, take on the shortest path to the destination and become non-travelers upon arrival. When an infection process co-evolves with the traveling dynamics, the railway serves to gather a crowd, transmit the disease, and spread infected agents to local area subnetworks. The railway leads to a faster initial increase in infected agents and a higher steady state infection, and thus poses risks; and frequent traveling leads to a more severe infection. These features revealed in simulations are in agreement with analytic results of a simplified version of the model.