title: Defective Interfering RNAs: Foes of Viruses and Friends of Virologists

text: Defective interfering (DI) RNAs are subviral RNAs produced during multiplication of RNA viruses by the error-prone viral replicase. DI-RNAs are parasitic RNAs that are derived from and associated with the parent virus, taking advantage of viral-coded protein factors for their multiplication. Recent advances in the field of DI RNA biology has led to a greater understanding about generation and evolution of DI-RNAs as well as the mechanism of symptom attenuation. Moreover, DI-RNAs are versatile tools in the hands of virologists and are used as less complex surrogate templates to understand the biology of their helper viruses. The ease of their genetic manipulation has resulted in rapid discoveries on cis-acting RNA replication elements required for replication and recombination. DI-RNAs have been further exploited to discover host factors that modulate Tomato bushy stunt virus replication, as well as viral RNA recombination. This review discusses the current models on generation and evolution of DI-RNAs, the roles of viral and host factors in DI-RNA replication, and the mechanisms of disease attenuation.


title: Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus)

text: BACKGROUND: The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained.


title: Proteomic Profiling of the TRAF3 Interactome Network Reveals a New Role for the ER-to-Golgi Transport Compartments in Innate Immunity

text: Tumor Necrosis Factor receptor-associated factor-3 (TRAF3) is a central mediator important for inducing type I interferon (IFN) production in response to intracellular double-stranded RNA (dsRNA). Here, we report the identification of Sec16A and p115, two proteins of the ER-to-Golgi vesicular transport system, as novel components of the TRAF3 interactome network. Notably, in non-infected cells, TRAF3 was found associated with markers of the ER-Exit-Sites (ERES), ER-to-Golgi intermediate compartment (ERGIC) and the cis-Golgi apparatus. Upon dsRNA and dsDNA sensing however, the Golgi apparatus fragmented into cytoplasmic punctated structures containing TRAF3 allowing its colocalization and interaction with Mitochondrial AntiViral Signaling (MAVS), the essential mitochondria-bound RIG-I-like Helicase (RLH) adaptor. In contrast, retention of TRAF3 at the ER-to-Golgi vesicular transport system blunted the ability of TRAF3 to interact with MAVS upon viral infection and consequently decreased type I IFN response. Moreover, depletion of Sec16A and p115 led to a drastic disorganization of the Golgi paralleled by the relocalization of TRAF3, which under these conditions was unable to associate with MAVS. Consequently, upon dsRNA and dsDNA sensing, ablation of Sec16A and p115 was found to inhibit IRF3 activation and anti-viral gene expression. Reciprocally, mild overexpression of Sec16A or p115 in Hec1B cells increased the activation of IFNβ, ISG56 and NF-κB -dependent promoters following viral infection and ectopic expression of MAVS and Tank-binding kinase-1 (TBK1). In line with these results, TRAF3 was found enriched in immunocomplexes composed of p115, Sec16A and TBK1 upon infection. Hence, we propose a model where dsDNA and dsRNA sensing induces the formation of membrane-bound compartments originating from the Golgi, which mediate the dynamic association of TRAF3 with MAVS leading to an optimal induction of innate immune responses.


title: Transmissibility of COVID-19 in 11 major cities in China and its association with temperature and humidity in Beijing, Shanghai, Guangzhou, and Chengdu

text: BACKGROUND: The new coronavirus disease COVID-19 began in December 2019 and has spread rapidly by human-to-human transmission. This study evaluated the transmissibility of the infectious disease and analyzed its association with temperature and humidity to study the propagation pattern of COVID-19. METHODS: In this study, we revised the reported data in Wuhan based on several assumptions to estimate the actual number of confirmed cases considering that perhaps not all cases could be detected and reported in the complex situation there. Then we used the equation derived from the Susceptible-Exposed-Infectious-Recovered (SEIR) model to calculate R(0) from January 24, 2020 to February 13, 2020 in 11 major cities in China for comparison. With the calculation results, we conducted correlation analysis and regression analysis between R(0) and temperature and humidity for four major cities in China to see the association between the transmissibility of COVID-19 and the weather variables. RESULTS: It was estimated that the cumulative number of confirmed cases had exceeded 45 000 by February 13, 2020 in Wuhan. The average R(0) in Wuhan was 2.7, significantly higher than those in other cities ranging from 1.8 to 2.4. The inflection points in the cities outside Hubei Province were between January 30, 2020 and February 3, 2020, while there had not been an obvious downward trend of R(0) in Wuhan. R(0) negatively correlated with both temperature and humidity, which was significant at the 0.01 level. CONCLUSIONS: The transmissibility of COVID-19 was strong and importance should be attached to the intervention of its transmission especially in Wuhan. According to the correlation between R(0) and weather, the spread of disease will be suppressed as the weather warms.


title: Working hard or hardly working? Regulatory bottlenecks in developing a COVID-19 vaccine

text: Abstract Vaccine solutions rarely reach the public until after an outbreak abates; an Ebola vaccine was approved 5-years after peak outbreak and SARS, MERS, and Zika vaccines are still in clinical development. Despite massive leaps forward in rapid science, other regulatory bottlenecks are hamstringing the global effort for pandemic vaccines.


title: Relative space-based GIS data model to analyze the group dynamics of moving objects

text: Abstract The relative motion of moving objects is an essential research topic in geographical information science (GIScience), which supports the innovation of geodatabases, spatial indexing, and geospatial services. This analysis is very popular in the domains of urban governance, transportation engineering, logistics and geospatial information services for individuals or industrials. Importantly, data models of moving objects are one of the most crucial approaches to support the analysis for dynamic relative motion between moving objects, even in the age of big data and cloud computing. Traditional geographic information systems (GIS) usually organize moving objects as point objects in absolute coordinated space. The derivation of relative motions among moving objects is not efficient because of the additional geo-computation of transformation between absolute space and relative space. Therefore, current GISs require an innovative approach to directly store, analyze and interpret the relative relationships of moving objects to support their efficient analysis. This paper proposes a relative space-based GIS data model of moving objects (RSMO) to construct, operate and analyze moving objects’ relationships and introduces two algorithms (relationship querying and relative relationship dynamic pattern matching) to derive and analyze the dynamic relationships of moving objects. Three scenarios (epidemic spreading, tracker finding, and motion-trend derivation of nearby crowds) are implemented to demonstrate the feasibility of the proposed model. The experimental results indicates the execution times of the proposed model are approximately 5–50% those of the absolute GIS method for the same function of these three scenarios. It’s better computational performance of the proposed model when analyzing the relative relationships of moving objects than the absolute methods in a famous commercial GIS software based on this experimental results. The proposed approach fills the gap of traditional GIS and shows promise for relative space-based geo-computation, analysis and service.


RAAS blockers in hypertension posing a higher risk towards the COVID‐19


title: Coronavirus disease 2019: Utilizing an ethical framework for rationing absolutely scarce health‐care resources in transplant allocation decisions

text: The novel Coronavirus disease 2019 (COVID‐19) is impacting transplant programs around the world, and, as the center of the pandemic shifts to the United States, we have to prepare to make decisions about which patients to transplant during times of constrained resources. In this paper, we discuss how to transition from the traditional justice vs utility consideration in organ allocation to a more nuanced allocation scheme based on ethical values that drive decisions in times of absolute scarcity. We recognize that many decisions are made based on the practical limitations that transplant programs face, especially at the extremes. As programs make the transition from a standard approach to a resource‐constrained approach to transplantation, we utilize a framework for ethical decisions in settings of absolutely scarce resources to help guide programs in deciding which patients to transplant, which donors to accept, how to minimize risk, and how to ensure the best utilization of transplant team members.


title: Functional Involvement of Interferon-Inducible Transmembrane Proteins in Antiviral Immunity

text: Interferons (IFNs) play crucial roles in host defense against viral infections by inducing the expression of numerous IFN-stimulated genes (ISGs) that can activate host antiviral immunity. Interferon-inducible transmembrane proteins (IFITMs), a family of small transmembrane proteins, are critical ISG products. Compelling evidence has implicated that IFITMs can establish an innate immune state to eliminate pathogens efficiently. IFITM proteins can impede broad-spectrum viral infection through various mechanisms. It is generally believed that IFITMs can block the viral entry by suppressing viral membrane fusion. However, some findings indicated that IFITMs might also inhibit viral gene expression and viral protein synthesis and thereby impair viral replication. IFITMs may incorporate into virions during viral assembly and thus reduce the infectivity of nascent virions. The precise inhibitory mechanism of IFITMs on viral infection and replication still requires further exploration. In this review, we highlight the recent findings regarding critical roles of IFITMs in host-virus interaction. We also discuss the molecular mechanisms underlying their functions in antiviral responses.


title: The European Respiratory Society course on acute respiratory pandemics: how to plan for and manage them

text: Learn about the @ERStalk course on acute respiratory pandemics http://ow.ly/XGe430i7743


title: Potential role of ovomucin and its peptides in modulation of intestinal health: A review

text: Intestinal dysfunction, which may cause a series of metabolic diseases, has become a worldwide health problem. In the past few years, studies have shown that consumption of poultry eggs has the potential to prevent a variety of metabolic diseases, and increasing attention has been directed to the bioactive proteins and their peptides in poultry eggs. This review mainly focused on the biological activities of an important egg-derived protein named ovomucin. Ovomucin and its derivatives have good anti-inflammatory, antioxidant, immunity-regulating and other biological functions. These activities may affect the physical, biological and immune barriers associated with intestinal health. This paper reviewed the structure and the structure-activity relationship of ovomucin，the potential role of ovomucin and its derivatives in modulation of intestinal health are also summarized. Finally, the potential applications of ovomucin and its peptides as functional food components to prevent and assist in the pretreatment of intestinal health problems are prospected.


title: Interdisciplinary Perspectives on Health Literacy Research Around the World: More Important Than Ever in a Time of COVID-19

text: As we write our editorial for a health literacy special issue in the midst of the international COVID-19 crisis, we take this opportunity to highlight the importance of individual, community, and population health literacy. We are not only in a “pandemic” but also an “infodemic”. Health literacy is more important than ever in the face of these global health threats, which have impacted outcomes across the levels of the socio-ecological model (SEM), including individual health behaviors, family relationships, organizational behavior, state policy-making, national mortality statistics, and the international economy in the span of weeks. Our special issue sought to pull together interdisciplinary threads guided by two principles. The first was defining health literacy as essential skills and situational resources needed for people to find, understand, evaluate, communicate, and use information and services in a variety of forms across various settings throughout their life course to promote health and wellbeing. The second was the idea that enhancing health literacy in populations and systems is critical to achieving health equity. In this time of public health need across traditional borders, the inter-sectoral and international perspectives of special issue articles are more urgent than ever. A greater understanding, appreciation, and application of health literacy can support policy action on multiple levels to address major public health challenges. Health literacy should be built deliberately as a population-level resource and community asset. We have summarized the set of articles in this special issue across the levels of the SEM, hoping their thoughtful considerations and interesting findings will help to support global health and wellness and inspire future research, policy, and practice in this global public health emergency and beyond.


title: Establishment and optimization of a liquid bead array for the simultaneous detection of ten insect-borne pathogens

text: BACKGROUND: Insect-borne diseases could induce severe symptoms in human and clinical signs in animals, such as febrility, erythra, arthralgia and hemorrhagic fever, and cause significant economic losses and pose public health threat all over the world. The significant advantages of Luminex xMAP technology are high-throughput, high parallel and automation. This study aimed to establish a liquid bead array based on Luminex xMAP technology that was able to simultaneously detect multiple insect-borne pathogens. METHODS: Specific probes and primers to detect the nucleic acid of 10 insect-borne pathogens were designed. Probes were coupled with fluorescent carboxylated microspheres. The parameters of the system were optimized, including ratio of forward/reverse primers (1:2), hybridization temperature (50 °C) and duration (30 min) and quantity of PCR product (2 μl). The sensitivity and specificity of the system were also evaluated. Moreover mixed nucleic acid of 10 insect-borne pathogens, including Bluetongue virus, Epizootic hemorrhagic disease virus of deer, Coxiella burnetii, African swine fever virus, West Nile fever virus, Borrelia burgdorferi, vesicular stomatitis virus, Rift Valley fever virus, Ebola virus and Schmalenberg’s disease virus, and 3000 clinical samples were tested for practicability. RESULTS: The optimized detection system showed high sensitivity, specificity and reproducibility. Each probe showed specific fluorescence signal intensity without any cross-hybridization for the other insect-borne pathogens tested, which included dengue virus, tick-borne encephalitis virus, Japanese encephalitis virus, Xinjiang hemorrhagic fever virus, spotted fever group rickettsiae, ehrlichiae and chikungunya virus. The limit of detection was 10 copies of target gene. Insect-borne pathogens were successfully detected among the 3000 clinical samples, and the results were consistent with those obtained using gold-standard assays or commercial nucleic acid detection kits. CONCLUSIONS: This optimized liquid array detection system was high-throughput and highly specific and sensitive in screening of the insect-borne pathogens. It was promising in detection of these pathogens for molecular epidemiological studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2996-0) contains supplementary material, which is available to authorized users.


Nurses responding to the world health organization (WHO) priority for emergency care systems for universal health coverage


Supporting people with severe mental health conditions during the COVID-19 pandemic: considerations for low- and middle-income countries using telehealth case management


title: Prerequisites for Effective Implementation of Telemedicine: Focusing on Current Situations in Korea

text: OBJECTIVES: The practice of telemedicine requires social interventions and systems for efficient implementation. Further, it requires sufficient discussions among related parties because the purpose of telemedicine is diagnosis and treatment, and the participation of medical specialists is essential. Based on the characteristics of the healthcare structure of Korea, which has a low proportion of public healthcare and most patients are taken care of by a few large tertiary care hospitals, the fundamental issues need to be discussed. METHODS: A comparison was conducted with overseas cases to discuss the prerequisites for the effective implementation of telemedicine in South Korea under the current situation. We also examined the structural characteristics of the Korean medical community. RESULTS: The current paper recommends that an in-depth analysis and studies are conducted on the following aspects: a search for telemedicine services focused on public healthcare, a search of services for illnesses that impose high levels of burden on households, and the development and implementation of a telemedicine system for follow-up management at primary and secondary care hospitals after the patient undergoes surgery or treatment at tertiary care hospitals. CONCLUSIONS: As the technology develops, the focus should also be on factors such as safety, usefulness, availability, and how the functions will be realized in order to enable user communication. A clear system should be established to regulate and manage the lack of sufficient discussions. In addition, seeking projects and systems that reflect the characteristics of each country will facilitate the efficient implementation of telemedicine.


title: Becoming bovine: Mechanics and metamorphosis in Hokkaido's animal-human-machine

text: Abstract The fieldwork for my doctoral degree was carried out over nineteen months, a year of which was spent working on an industrial dairy farm in Hokkaido, Japan's northernmost Island. As in much of the industrialised world, dairy farming in Japan is rapidly changing. Many farmers are forced by neo-liberal agricultural policies to shift from small family operated farms to high-tech, high-speed, and high overhead industrial operations. This paper focuses on the history of dairy farming in the Tokachi region; more specifically one farm and the shift over a generation to a rotary parlour milking system. It addresses the linkages this mode of production has cultivated amongst humans, dairy cows and industrialized space. The parlour system at Great Hopes Farm allows five workers (aided by three more stall staff) to milk over 1000 cows, fifty at a time, three times a day. The impetus behind moving to parlour technology is that it increases productivity through mechanically enhanced observation and control. However this recent mechanical separation of human and cow during the milking process has led to affectively shared interspecies and inter-human alienation. The technology of the parlour system sets daily rhythms for bovine and human alike, and separates both from a process formerly dependent upon, specialized knowledge, affective empathy, and embodied knowledge. Human and bovine experience the systemic violence of the machine and what remains is a complex bio-politics of interspecies affect and the separation of “bare” and “political” life.


title: The 798 Art District: Multi-scalar drivers of land use succession and industrial restructuring in Beijing

text: Since the post-1980 economic reforms, Chinese cities, in particular large cites, have experienced far reaching industrial restructuring and spatial transformation. A decentralization of manufacturing industries from urban centres was accompanied by the rise of service and creative industry districts on previous industrial sites. This article explores the interconnections of global forces, state–market relationships, land use policies, art markets, the Chinese system of governance, and other trans-local factors in transforming Beijing from an industrial city to a service and creative industries-oriented global metropolis, by examining the rise and transformation of Beijing 798 Art District. The case study finds that decommissioned industrial sites had characteristics that made them attractive when central and local governments started to promote creative industries, but, with development of urban art districts, the impact of avant-garde artists on the direction of development was reduced, and developers, high profile galleries and multinational corporations had an increasing influence. The results of our study indicate that the literature on intra-metropolitan location and change, and the evolution of industrial districts should pay more attention to the reuse of the decommissioned industrial land and sites for industrial restructuring, and particularly to the role of multi-scalar factors in reshaping the geography of cities.


Comment on “ACE inhibitors and COVID‐19: We don't know yet”


The pathogenesis of thromboembolic disease in covid-19 patients: Could be a catastrophic antiphospholipid syndrome?


title: Aktueller Überblick zum MERS-Virus

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered for the first time in Saudi Arabia in 2012. On a global scale 1200 infections have been registered with approximately 50 % resulting in a fatal outcome. It is currently not fully clear how MERS-CoV is transmitted and insufficient research has so far been carried out. Taking the sudden increase of cases in South Korea into consideration, this article discusses which preventive measures should be recommended for international travelers in order to prevent infections. A literature search of the most recent publications indicated that appropriate standard hygiene measures are sufficient and no travel restrictions are therefore necessary.


title: A joint analysis of influenza-associated hospitalizations and mortality in Hong Kong, 1998–2013

text: Influenza viruses may cause severe human infections leading to hospitalization or death. Linear regression models were fitted to population-based data on hospitalizations and deaths. Surveillance data on influenza virus activity permitted inference on influenza-associated hospitalizations and deaths. The ratios of these estimates were used as a potential indicator of severity. Influenza was associated with 431 (95% CrI: 358–503) respiratory deaths and 12,700 (95% CrI: 11,700–13,700) respiratory hospitalizations per year. Majority of the excess deaths occurred in persons ≥65 y of age. The ratios of deaths to hospitalizations in adults ≥65 y were significantly higher for influenza A(H1N1) and A(H1N1)pdm09 compared to A(H3N2) and B. Substantial disease burden associated with influenza viruses were estimated in Hong Kong particularly among children and elderly in 1998–2013. Infections with influenza A(H1N1) was suggested to be more serious than A(H3N2) in older adults.


title: Antiviral Strategies

text: Viruses are obligatory intracellular parasites, whose replication depends on pathways and functions of the host cell. Consequently, it is difficult to define virus-specific functions as suitable targets for anti-infective therapy. However, significant progress has been made in the past 50 years towards the development of effective and specific antivirals. In particular, human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, which cause chronic infections affecting millions of individuals world-wide, are a major focus of antiviral research. Initially, antivirals were mainly directed against virus-specific enzymes; more recently, drugs inhibiting the steps of virus entry or release have been developed. Rational approaches towards drug development, based on information about structure and function of viral proteins and molecular mechanisms of virus-host interactions, have become increasingly successful. Novel strategies currently explored in basic research or preclinical studies include approaches targeting host factors important for virus replication, the exploitation of the innate immune response system as well as the use of gene silencing strategies aimed at interfering with viral gene expression. Today, a number of effective virostatics targeting various viral replication steps are approved for treatment of important viral diseases. However, the use of these drugs is limited by the rapid development of antiviral resistance, which represents a central problem of current antiviral therapy.


title: Diagnostic issues and capabilities in 48 isolation facilities in 16 European countries: data from EuroNHID surveys

text: BACKGROUND: Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. The sampling, handling and transport of specimens from patients with HIDs present specific bio-safety concerns. FINDINGS: The European Network for HID project aimed to record, in a cross-sectional study, the infection control capabilities of referral centers for HIDs across Europe and assesses the level of achievement to previously published guidelines. In this paper, we report the current diagnostic capabilities and bio-safety measures applied to diagnostic procedures in these referral centers. Overall, 48 isolation facilities in 16 European countries were evaluated. Although 81% of these referral centers are located near a biosafety level 3 laboratory, 11% and 31% of them still performed their microbiological and routine diagnostic analyses, respectively, without bio-safety measures. CONCLUSIONS: The discrepancies among the referral centers surveyed between the level of practices and the European Network of Infectious Diseases (EUNID) recommendations have multiple reasons of which the interest of the individuals in charge and the investment they put in preparedness to emerging outbreaks. Despite the fact that the less prepared centers can improve by just updating their practice and policies any support to help them to achieve an acceptable level of biosecurity is welcome.


title: Comparative Analysis of Gene Expression in Virulent and Attenuated Strains of Infectious Bronchitis Virus at Subcodon Resolution

text: Like all coronaviruses, avian infectious bronchitis virus (IBV) possesses a long, single-stranded, positive-sense RNA genome (∼27 kb) and has a complex replication strategy that includes the production of a nested set of subgenomic mRNAs (sgmRNAs). Here, we used whole-transcriptome sequencing (RNASeq) and ribosome profiling (RiboSeq) to delineate gene expression in the IBV M41-CK and Beau-R strains at subcodon resolution. RNASeq facilitated a comparative analysis of viral RNA synthesis and revealed two novel transcription junction sites in the attenuated Beau-R strain, one of which would generate a sgmRNA encoding a ribosomally occupied open reading frame (dORF) located downstream of the nucleocapsid coding region. RiboSeq permitted quantification of the translational efficiency of virus gene expression and identified, for the first time, sites of ribosomal pausing on the genome. Quantification of reads flanking the programmed ribosomal frameshifting (PRF) signal at the genomic RNA ORF1a/ORF1b junction revealed that PRF in IBV is highly efficient (33 to 40%). Triplet phasing of RiboSeq data allowed precise determination of reading frames and revealed the translation of two ORFs (ORF4b and ORF4c on sgmRNA IR), which are widely conserved across IBV isolates. Analysis of differential gene expression in infected primary chick kidney cells indicated that the host cell response to IBV occurs primarily at the level of transcription, with global upregulation of immune-related mRNA transcripts following infection and comparatively modest changes in the translation efficiencies of host genes. Cellular genes and gene networks differentially expressed during virus infection were also identified, giving insights into the host cell response to IBV infection. IMPORTANCE IBV is a major avian pathogen and presents a substantial economic burden to the poultry industry. Improved vaccination strategies are urgently needed to curb the global spread of this virus, and the development of suitable vaccine candidates will be aided by an improved understanding of IBV molecular biology. Our high-resolution data have enabled a precise study of transcription and translation in cells infected with both pathogenic and attenuated forms of IBV and expand our understanding of gammacoronaviral gene expression. We demonstrate that gene expression shows considerable intraspecies variation, with single nucleotide polymorphisms being associated with altered production of sgmRNA transcripts, and our RiboSeq data sets enabled us to uncover novel ribosomally occupied ORFs in both strains. The numerous cellular genes and gene networks found to be differentially expressed during virus infection provide insights into the host cell response to IBV infection.


title: Contemporary HIV/AIDS research: Insights from knowledge management theory

text: Knowledge management as a field is concerned with the management of knowledge, including the management of knowledge in research processes. Knowledge management theory has the potential to support research into problems such as HIV, antibiotic resistance and others, particularly in terms of aspects of scientific research related to the contribution of social science. To date, however, these challenges remain with us, and theoretical contributions that can complement natural science efforts to eradicate these problems are needed. This paper seeks to offer a theoretical contribution grounded in Kuhn’s paradigm theory of innovation, and in the argument by Lakatos that scientific research can be fundamentally non-innovative, which suggests that social science aspects of knowledge creation may hold the key to more effective biomedical innovation. Given the consequences of ongoing and emerging global crises, and the failure of knowledge systems of scientific research to solve such problems outright, this paper provides a review of theory and literature arguing for a new paradigm in scientific research, based on the development of global systems to maximise research collaborations. A global systems approach effectively includes social science theory development as an important complement to the natural sciences research process. Arguably, information technology and social media technology have developed to the point at which solutions to knowledge aggregation challenges can enable solutions to knowledge problems on a scale hitherto unimaginable. Expert and non-expert crowdsourced inputs can enable problem-solving through exponentially increasing problem-solving inputs, using the ‘crowd,’ thereby increasing collaborations dramatically. It is argued that these developments herald a new era of participatory research, or a democratisation of research, which offers new hope for solving global social problems. This paper seeks to contribute to this end, and to the recognition of the important role of social theory in the scientific research process.


title: Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection

text: Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality.


title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin influences bovine herpesvirus 1 replication through upregulation of SIRT3 and cytoskeletal reorganization

text: Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which accelerates BoHV-1-induced apoptosis and increases virus replication. Herein, to elucidate the mechanism through TCDD modifies BoHV-1 infection, we analyzed the modulation of a members of Sirtuin proteins family in MDBK cells. We found that mitochondrial SIRT3 was upregulated during infection. This change was accompanied by cytoskeletal rearrangements and cell extensions. All these trends were drastically modified by TCDD. We hypothesize that, taken together, these results might further clarify the processes responsible for the action of TCDD on the BoHV-1 replication, resulting in enhanced virus production.


title: Waiting and Care in Pandemic Times Collection

text: This editorial introduces a collection of research articles and reflections on what it means to wait during the time of the COVID-19 pandemic. Written from conditions of lockdown, this collection gathers together the initial thoughts of a group of interdisciplinary scholars in the humanities and social sciences who have been working on questions of waiting and care through a project called Waiting Times.


title: Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Spike Protein Proteolytic Processing

text: The coronavirus spike envelope glycoprotein is an essential viral component that mediates virus entry events. Biochemical assessment of the spike protein is critical for understanding structure–function relationships and the roles of the protein in the viral life cycle. Coronavirus spike proteins are typically proteolytically processed and activated by host cell enzymes such as trypsin-like proteases, cathepsins, or proprotein-convertases. Analysis of coronavirus spike proteins by western blot allows the visualization and assessment of proteolytic processing by endogenous or exogenous proteases. Here, we present a method based on western blot analysis to investigate spike protein proteolytic cleavage by transient transfection of HEK-293 T cells allowing expression of the spike protein of the highly pathogenic Middle East respiratory syndrome coronavirus in the presence or absence of a cellular trypsin-like transmembrane serine protease, matriptase. Such analysis enables the characterization of cleavage patterns produced by a host protease on a coronavirus spike glycoprotein.


Hypoxia Inducible Factor-1 Protects Against COVID-19: A Hypothesis


title: Cytokine Patterns and Endotypes in Acute and Chronic Rhinosinusitis

text: Since rhinosinusitis is an inflammatory disease, cytokines as key regulators of inflammation play a central role in its pathophysiology. In acute rhinosinusitis, several proinflammatory cytokines of different types have been identified. Initial information about the involvement of the inflammasome in rhinosinusitis has been gained, but this area remains open for more detailed research. Although it has been accepted now that chronic rhinosinusitis (CRS) needs to be differentiated into CRS with and without nasal polyps, it has become clear that this distinction is insufficient to clearly define subgroups with uniform pathophysiology and cytokine patterns. While Th1-cytokines are mostly found in CRSsNP and Th2 cytokines in CRSwNP, there is a substantial overlap, and several other cytokines have also been detected. Attempts to identify CRS endotypes based on cytokines are ongoing but not yet generally accepted. Despite the central role of cytokines in rhinosinusitis, no specific cytokine-targeted therapies are currently available, and only very few studies have specifically addressed the effects of such biologicals in rhinosinusitis.


title: Dynamic graphs, community detection, and Riemannian geometry

text: A community is a subset of a wider network where the members of that subset are more strongly connected to each other than they are to the rest of the network. In this paper, we consider the problem of identifying and tracking communities in graphs that change over time – dynamic community detection – and present a framework based on Riemannian geometry to aid in this task. Our framework currently supports several important operations such as interpolating between and averaging over graph snapshots. We compare these Riemannian methods with entry-wise linear interpolation and find that the Riemannian methods are generally better suited to dynamic community detection. Next steps with the Riemannian framework include producing a Riemannian least-squares regression method for working with noisy data and developing support methods, such as spectral sparsification, to improve the scalability of our current methods. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41109-018-0059-2) contains supplementary material, which is available to authorized users.


title: Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation

text: Summary Background Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe lower respiratory tract infection in people. Previous studies suggested dromedary camels were a reservoir for this virus. We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. Methods We took nose swabs, rectal swabs, and blood samples from all camels on the Qatari farm. We tested swabs with RT-PCR, with amplification targeting the E gene (upE), nucleocapsid (N) gene, and open reading frame (ORF) 1a. PCR positive samples were tested by different MERS-CoV specific PCRs and obtained sequences were used for phylogentic analysis together with sequences from the linked human cases and other human cases. We tested serum samples from the camels for IgG immunofluorescence assay, protein microarray, and virus neutralisation assay. Findings We obtained samples from 14 camels on Oct 17, 2013. We detected MERS-CoV in nose swabs from three camels by three independent RT-PCRs and sequencing. The nucleotide sequence of an ORF1a fragment (940 nucleotides) and a 4·2 kb concatenated fragment were very similar to the MERS-CoV from two human cases on the same farm and a MERS-CoV isolate from Hafr-Al-Batin. Eight additional camel nose swabs were positive on one or more RT-PCRs, but could not be confirmed by sequencing. All camels had MERS-CoV spike-binding antibodies that correlated well with the presence of neutralising antibodies to MERS-CoV. Interpretation Our study provides virological confirmation of MERS-CoV in camels and suggests a recent outbreak affecting both human beings and camels. We cannot conclude whether the people on the farm were infected by the camels or vice versa, or if a third source was responsible. Funding European Union projects EMPERIE (contract number 223498), ANTIGONE (contract number 278976), and the VIRGO consortium.


Betriebswirtschaftliche Entscheidungen in besonderen Zeiten


Autopsy of patients with COVID-19: A balance of fear and curiosity


title: Collectivism and activism in housing management in Hong Kong

text: Management of apartment buildings is never straightforward because of the need for collective homeowner action. Mancur Olson suggests that a rational individual will not participate in collective action which provides no positive net benefit for him or her. Based on this premise, it would seem that rationality drives homeowners to free-ride on others’ efforts and that, as a result, no collective action will take place. However, some homeowners do actively participate in housing management, and it is worthwhile to examine why some participate and others do not. Building on the wide-ranging applications of the collective interest model (CIM) in explaining political participation and environmental activism, this paper expands its relevance to the arena of housing management. The explanatory analysis which is based on the findings of a structured questionnaire survey in Hong Kong corroborates the central propositions of the CIM and provides a theoretical account of housing management activism. In brief, housing management activism is a function of beliefs about personal and group efficacy, the value of the collective good, and the selective benefits and costs of participation. These findings have far-reaching implications for the formulation of government policies promoting homeowners’ active involvement in housing management in Hong Kong and other megacities.


title: Power dynamics in peer-to-peer accommodation: Insights from Airbnb hosts

text: This study explores power dynamics in peer-to-peer (P2P) accommodation by examining how they manifest in the host-guest relationship. In so doing, it advances understanding on the role of hosts in the P2P practice and contributes insights on the factors conditioning the reciprocity of the P2P exchange. Drawing from power theories, the study uncovers how the interdependencies among hosts, guests and platforms influence power constellations emanating from P2P accommodation growth and reflexively redefine host practice. Specifically, the study illustrates how hosts are attempting to resist power imbalances characterising the exchange and how the dynamic environment of P2P accommodation leads to distinct representations of host types. The study makes explicit a conceptual framework that captures the power shifts noticeable in P2P accommodation that may be of theoretical and practical value to academics and policymakers alike.


title: Epidemiological evaluation of cat health at a first-response animal shelter in Fukushima, following the Great East Japan Earthquakes of 2011

text: The Great East Japan Earthquakes of March 11, 2011 caused immense harm to the community and subsequent nuclear accident in Fukushima Prefecture extended the damage. Local residents were forced to evacuated without pets and the left behind animals were rescued from the restricted zone one month later. Unplanned animal rescue and unregulated sheltering caused secondary damage to animals such as disease epidemics at impounded animal shelter. The purpose of this study was to retrospectively evaluate the incidence of upper respiratory infection (URI) and diarrhea in cats at the first response animal shelter in Fukushima, and investigate factors affecting the duration of disease and determinants of treatments performed. Eighty percent and 59% of impounded cats developed URI, 71% and 54% of cats developed diarrhea, and 91% and 83% of cats had at least one disease in 2011 and 2012, respectively. Uses of multiple drug administration (more than five drugs) was associated with prolonged URI and diarrhea. Multiple antibiotics, antihistamines, interferon, and steroids were associated with relapse of and prolonged URI. Developing a standardized treatment protocol for commonly observed diseases at Japanese animal shelters to prevent and control diseases, to promote animal welfare, and protect public health in the face of future disasters is overdue.


title: Chinese health biotech and the billion-patient market

text: Chinese government support and 'sea turtles' are spurring the sector, but investors lack exits. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nbt0108-37) contains supplementary material, which is available to authorized users.


title: Cooperative financial institutions: A review of the literature

text: Abstract Financial cooperatives play an important role in the financial systems of many countries. They act as a safe haven for deposits and are major sources of credit for households and small- and medium-sized firms. A not-for-profit orientation (in many cases) and a focus on maximising benefits to members have ensured the enduring popularity and sustainability of financial cooperatives. This is particularly evident since the global financial crisis when financial cooperatives continued to extend credit to members as many profit-orientated commercial banks restricted credit to households and firms. The overarching theme of the first part of this review is the structural and behavioural characteristics of financial cooperatives. In this part we consider, the origin and diffusion of financial cooperatives, network arrangements, the business model, relationship banking, balancing the interest of members, tax treatment and regulatory framework. The second part has performance and contribution to the real economy as the overarching theme. In this part we consider, efficiency and sustainability, mergers, acquisitions and failures, the benefits (and challenges) of FinTech and the contribution of financial cooperatives to the real economy including during times of crisis. The paper concludes with a summary of what we now know (and do not know) about financial cooperatives and provides suggestions as to where future research may usefully concentrate.


title: Monitoring of perceptions, anticipated behavioral, and psychological responses related to H5N1 influenza

text: BACKGROUND: The aim of this study was to monitor changes in behavioral and emotional responses to human H5N1 in the community over a 28-month period (from November 2005 to February 2008). METHODS: A total of 3,527 Hong Kong Chinese adults were interviewed by telephone within the framework of six identical cross-sectional surveys carried out during the 28-month study period. Given a hypothetical scenario that two to three new human-to-human H5N1 cases had been reported in Hong Kong, the trends of the respondents in various H5N1-related risk perceptions, anticipated personal psychological responses, and anticipated personal preventive behaviors were investigated. RESULTS: Over time, a decreased proportion of the respondents (1) felt susceptible to contracting H5N1, (2) expected a large outbreak would eventually occur, (3) believed that the impacts of H5N1 were worse than those of severe acute respiratory syndrome (SARS), and (4) anticipated adopting more types of preventive measures and experiencing mental distress in the case of a small-scale outbreak in Hong Kong (AOR from 0.27 to 0.43, p < 0.001), but the public remained vigilant on public health behaviors, such as hand-washing. The prevalence of misconceptions on the mode of transmission declined, but remained high; perceptions on the fatality of H5N1 remained largely underestimated. The SARS experience and unconfirmed beliefs about the transmission modes were associated with variables on anticipated preventive behaviors and emotional distress. CONCLUSION: Starting in 2005 through to 2008, respondents perceived a decreasing level of susceptibility, severity, and anticipated stress towards a hypothetical human-to-human H5N1 outbreak, possibly due to the low efficiency of transmission. The public’s general preparedness was still relatively good and rational, even though individual preventive behaviors were less common. However, misconceptions were prevalent among the respondents. Based on these results, public education is warranted to rectify these misconceptions.


title: Two novel bocaparvovirus species identified in wild Himalayan marmots

text: Bocaparvovirus (BOV) is a genetically diverse group of DNA viruses and a possible cause of respiratory, enteric, and neurological diseases in humans and animals. Here, two highly divergent BOVs (tentatively named as Himalayan marmot BOV, HMBOV1 and HMBOV2) were identified in the livers and feces of wild Himalayan marmots in China, by viral metagenomic analysis. Five of 300 liver samples from Himalayan marmots were positive for HMBOV1 and five of 99 fecal samples from these animals for HMBOV2. Their nearly complete genome sequences are 4,672 and 4,887 nucleotides long, respectively, with a standard genomic organization and containing protein-coding motifs typical for BOVs. Based on their NS1, NP1, and VP1, HMBOV1 and HMBOV2 are most closely related to porcine BOV SX/1-2 (approximately 77.0%/50.0%, 50.0%/53.0%, and 79.0%/54.0% amino acid identity, respectively). Phylogenetic analysis of these three proteins showed that HMBOV1 and HMBOV2 formed two distinctly independent branches in BOVs. According to these results, HMBOV1 and HMBOV2 are two different novel species in the Bocaparvovirus genus. Their identification expands our knowledge of the genetic diversity and evolution of BOVs. Further studies are needed to investigate their potential pathogenicity and their impact on Himalayan marmots and humans.


title: The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods

text: BACKGROUND: Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation. METHODS: Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed Salmonella enterica, were cultured in the absence or presence of cadmium (Cd) acetate or mercuric (Hg) chloride. In vivo experiments were set up where BALB/c mice were exposed to sub-lethal doses of Cd or Hg salts for 3 or 5 weeks. Cytotoxicity was assessed by MTT-reduction assay. Modulation of cytokine profiles was evaluated by enzyme-linked immunosorbent assay (ELISA), cytometric bead-based array (CBA) and real-time polymerase chain reaction (RT-PCR); the relevance of these methods of cytokine quantification was explored. RESULTS: Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios in vivo correlated significantly with up- or down-regulation of IL-12 levels in both cases of investigated metals. CONCLUSION: It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.


title: Medical genetics education in the midst of the COVID‐19 pandemic: Shared resources

text: In the midst of the COVID‐19 pandemic, it is appropriate that our focus is on patient care and preparation. However, the genetics community is well poised to fill in the educational gap created by medical students transitioning to limiting patient contact, creation of telemedicine patient care, and online learning modules. Our history of agility in learning and teaching is now only inhibited by the time constraints of current clinical demands on the genetics community. This publication is designed to offer ideas and resources for quickly transitioning our education to meet the current demands in the time of a pandemic. Not only will this allow us to continue our strong history of education, it will enhance our strong commitment to using modern educational techniques and tools to address the genetics workforce issues that have defined the recent past. We have the opportunity to aggressively educate for trainees that now have the capacity to learn, and to lead the way in showing how the genetics community rallies together no matter the challenge.


title: Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial

text: ABSTRACT: Iota-carrageenan (I-C) is active against respiratory viruses in vitro and was effective as nasal spray in three previous clinical trials. The current trial served to further investigate I-C in patients with early common cold symptoms. METHODS: This randomized, placebo-controlled, double-blind phase IV trial was conducted in 200 adult patients with self-diagnosed colds of <48 h’ duration that were confirmed by baseline cold symptom scores. Patients were to self-administer 0.12 % I-C or placebo spray (NaCl 0.5 %) four times daily for four to ten days and record symptom information for ten days. Common respiratory viruses were quantified by RT-PCR during pretreatment and on Day 3 or 4. The primary endpoint was the mean total symptom score (TSS) of eight cold symptoms on Days 2–4 (TSS(2–4)). RESULTS: Patients in both treatment groups had similar baseline TSSs (mean TSS: 6.75 for I-C and 6.79 for placebo). Viruses were detected in baseline samples from 53 of 98 I-C patients (54.1 %) and 54 of 97 placebo patients (55.7 %). Mean ± SE for TSS(2–4) was 5.78 ± 0.25 for I-C patients and 6.39 ± 0.25 for placebo (p = 0.0895). Exploratory analyses after unblinding (TSS(2–4) excluding a patient with aberrantly high symptom scores [TSS(2–4, ex 1pt)]; mean of TSS over Days 1–4 [TSS(1–4)]; change in TSS(1–4) relative to baseline [TSS(1–4, rel)]) demonstrated treatment differences in favor of I-C (p = 0.0364, p = 0.0495 and p = 0.0421, respectively). For patients with quantifiable rhinovirus/enterovirus at baseline, there was a trend towards greater reduction of virus load at Day 3 or 4 (p = 0.0958; I-C: 90.2 % reduction in viral load; placebo: 72.0 %). Treatments were well tolerated with no differences in adverse event rates. CONCLUSIONS: The primary endpoint did not demonstrate a statistically significant difference between I-C and placebo but showed a trend towards I-C benefit. Exploratory analyses indicated significant reduction of cold symptoms in the I-C group relative to placebo during the first four days when symptoms were most severe, and also substantiated I-C’s activity against rhinovirus/enterovirus. TRIAL REGISTRATION: NCT01944631 (clinicaltrials.gov)


title: Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses

text: Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the “stealth phase”, defined as the time between infection and the earliest detectable inflammatory response. We propose that the “stealth phase” phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication.


title: Labouring geography: Negotiating scales, strategies and future directions

text: Abstract In our editorial introduction to this themed issue on labour geography, we outline some important on-going debates in the relatively young field of labour geography and suggest future directions for research. First, there is the key question of labour as an active agent in the production of economic landscapes. The agency of labour will likely remain a defining feature of labour geography, but perhaps it is not as important to construct theoretical analytical boundaries as it is to define labour geography as a political project. Second, debates continue surrounding the production of scale and the multiscalarity of organized labour. Third, labour geographers have yet to engage in any sustained fashion with unpacking the complex identities of workers and the way in which those identities simultaneously are shaped by and shape the economic and cultural landscape. Fourth, there is some debate on the costs and benefits of a ‘normative’ labour geography which emphasizes what workers and their organizations ‘could’ or even ‘should’ do. Lastly, we challenge the assumption that labour geographers have not yet asserted themselves as activists in their own right. We conclude the editorial by introducing the articles included in the issue. While these articles may not address every gap in the literature, they do contribute in significant ways to move the labour geography project forward.


title: An overview of calf diarrhea - infectious etiology, diagnosis, and intervention

text: Calf diarrhea is a commonly reported disease in young animals, and still a major cause of productivity and economic loss to cattle producers worldwide. In the report of the 2007 National Animal Health Monitoring System for U.S. dairy, half of the deaths among unweaned calves was attributed to diarrhea. Multiple pathogens are known or postulated to cause or contribute to calf diarrhea development. Other factors including both the environment and management practices influence disease severity or outcomes. The multifactorial nature of calf diarrhea makes this disease hard to control effectively in modern cow-calf operations. The purpose of this review is to provide a better understanding of a) the ecology and pathogenesis of well-known and potential bovine enteric pathogens implicated in calf diarrhea, b) describe diagnostic tests used to detect various enteric pathogens along with their pros and cons, and c) propose improved intervention strategies for treating calf diarrhea.


title: Considerations for Oral and Maxillofacial Surgeons in COVID-19 era: Can we sustain the solutions to keep our patients and healthcare personnel safe?

text: There are several uncertainties as to how we will conduct these clinical, didactic, business and social activities as this COVID-19 global pandemic abates and social distancing guidelines are relaxed. We anticipate changes in the way we interact with our patients and other providers, the way we design patient workflow, the way we conduct our teaching sessions and, how we perform procedures in different clinical settings. The objective of this paper is to review some of the changes to consider in clinical and academic oral and maxillofacial surgery workflow to make this transition smoother, efficient, and less risky for our patients and health care personnel. New infection control policies should be strictly enforced and monitored in all clinical and non-clinical settings, with an overall goal to decrease the risk of exposure and transmission. Screening for Covid-19 symptoms, testing when indicated, and, establishing epidemiologic linkage, will be crucial to contain and prevent new COVID-19 cases until there is a vaccine or an alternate solution. Additionally, we will have to take into consideration the shortage of essential supplies such as drugs, personal protective equipment (PPE), the design and ventilation of workspaces and waiting areas, increase in overhead costs and possible absence of staff, if quarantine is necessary. This shift in our workflow and patient care paths is likely to continue in the short-term at least through 2021 or next 12-24 months. We have to prioritize surgery balancing patient preferences and healthcare personnel risks. We have an opportunity now to make changes and embrace telemedicine and other collaborative virtual platforms for teaching and clinical care. It is crucial that we maintain Covid-19 awareness, proper surveillance in our microenvironments, good clinical judgment and, ethical values to continue to deliver high quality economical and accessible patient care.


title: Canine Coronavirus Infection in Turkish Dog Population

text: Canine coronavirus (CCoV) is one of the most important viral agents affecting the gastrointestinal system of dogs. In this study virological and serological investigations were performed to demonstrate the existence and prevalence of CCoV infection in a Turkish dog population. A total of 269 animals were subjected to the study. Of 179 dogs tested for CCoV antibodies, 112 (62.5%) were found to be positive by serum neutralization test, while 133 (74.3%) were positive by ELISA. The highest prevalence (94.2%) was detected in kennel dogs. Detection of CCoV genome in faeces was performed in samples from 90 diarrhoeic puppies by reverse transcription‐polymerase chain reaction. Fourteen (15.5%) faeces were positive for CCoV RNA, five of which were characterized as CCoV type I. The widespread CCoV infection in the Turkish dog population may be attributed as an important cause of viral diarrhoea in dogs.


title: Protective Behavior and West Nile Virus Risk

text: We conducted a cross-sectional, household survey in Oakville, Ontario, where an outbreak of West Nile virus (WNV) in 2002 led to an unprecedented number of cases of meningitis and encephalitis. Practicing >2 personal protective behavior traits reduced the risk for WNV infection by half.


title: The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs

text: There are limited reports of the impact of the coronavirus disease 2019 pandemic focused on U.S. and Canadian PICUs. This hypothesis-generating report aims to identify the United States and Canadian trends of coronavirus disease 2019 in PICUs. DESIGN AND SETTING: To better understand how the coronavirus disease 2019 pandemic was affecting U.S. and Canadian PICUs, an open voluntary daily data collection process of Canadian and U.S. PICUs was initiated by Virtual Pediatric Systems, LLC (Los Angeles, CA; http://www.myvps.org) in mid-March 2020. Information was made available online to all PICUs wishing to participate. A secondary data collection was performed to follow-up on patients discharged from those PICUs reporting coronavirus disease 2019 positive patients. MEASUREMENTS AND MAIN RESULTS: To date, over 180 PICUs have responded detailing 530 PICU admissions requiring over 3,467 days of PICU care with 30 deaths. The preponderance of cases was in the eastern regions. Twenty-four percent of the patients admitted to the PICUs were over 18 years old. Fourteen percent of admissions were under 2 years old. Nearly 60% of children had comorbidities at admission with the average length of stay increasing by age and by severity of comorbidity. Advanced respiratory support was necessary during 67% of the current days of care, with 69% being conventional mechanical ventilation. CONCLUSIONS: PICUs have been significantly impacted by the pandemic. They have provided care not only for children but also adults. Patients with coronavirus disease 2019 have a high frequency of comorbidities, require longer stays, more ventilatory support than usual PICU admissions. These data suggest several avenues for further exploration.


title: Clinical Characteristics and Morbidity Associated With Coronavirus Disease 2019 in a Series of Patients in Metropolitan Detroit

text: IMPORTANCE: In late December 2019, an outbreak caused by a novel severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China. Data on the clinical characteristics and outcomes of infected patients in urban communities in the US are limited. OBJECTIVES: To describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and to perform a comparative analysis of hospitalized and ambulatory patient populations. DESIGN, SETTING, AND PARTICIPANTS: This study is a case series of 463 consecutive patients with COVID-19 evaluated at Henry Ford Health System in metropolitan Detroit, Michigan, from March 9 to March 27, 2020. Data analysis was performed from March to April 2020. EXPOSURE: Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. MAIN OUTCOMES AND MEASURES: Demographic data, underlying comorbidities, clinical presentation, complications, treatment, and outcomes were collected. RESULTS: Of 463 patients with COVID-19 (mean [SD] age, 57.5 [16.8] years), 259 (55.9%) were female, and 334 (72.1%) were African American. Most patients (435 [94.0%]) had at least 1 comorbidity, including hypertension (295 patients [63.7%]), chronic kidney disease (182 patients [39.3%]), and diabetes (178 patients [38.4%]). Common symptoms at presentation were cough (347 patients [74.9%]), fever (315 patients [68.0%]), and dyspnea (282 patients [60.9%]). Three hundred fifty-five patients (76.7%) were hospitalized; 141 (39.7%) required intensive care unit management and 114 (80.8%) of those patients required invasive mechanical ventilation. Male sex (odds ratio [OR], 2.0; 95% CI, 1.3-3.2; P = .001), severe obesity (OR, 2.0; 95% CI, 1.4-3.6; P = .02), and chronic kidney disease (OR, 2.0; 95% CI, 1.3-3.3; P = .006) were independently associated with intensive care unit admission. Patients admitted to the intensive care unit had longer length of stay and higher incidence of respiratory failure and acute respiratory distress syndrome requiring invasive mechanical ventilation, acute kidney injury requiring dialysis, shock, and mortality (57 patients [40.4%] vs 15 patients [7.0%]) compared with patients in the general practice unit. Twenty-nine (11.2%) of those discharged from the hospital were readmitted and, overall, 20.0% died within 30 days. Male sex (OR, 1.8; 95% CI, 1.1-3.1; P = .03) and age older than 60 years (OR, 5.3; 95% CI, 2.9-9.7; P < .001) were significantly associated with mortality, whereas African American race was not (OR, 0.98; 95% CI, 0.54-1.8; P = .86). CONCLUSIONS AND RELEVANCE: In this review of urban metropolitan patients with COVID-19, most were African American with a high prevalence of comorbid conditions and high rates of hospitalization, intensive care unit admission, complications, and mortality due to COVID-19.


title: Design and Validation with Influenza A Virus of an Aerosol Transmission Chamber for Ferrets

text: Background: The importance of aerosols in the spread of viruses like influenza is still a subject of debate. Indeed, most viruses can also be transmitted through direct contact and droplets. Therefore, the importance of the airborne route in a clinical context is difficult to determine. The aim of this study was to design a chamber system to study the airborne transmission of viruses between ferrets. Methods: A system composed of three chambers connected in series, each one housing one ferret and preventing direct contact, was designed. The chambers were designed to house the ferrets for several days and to study the transmission of viruses from an infected (index) ferret to two naïve ferrets via aerosols and droplets or aerosols only. A particle separator was designed that can be used to modulate the size of the particles traveling between the chambers. The chamber system was validated using standard dust as well as with ferrets infected with influenza A virus. Conclusions: The 50% efficiency cut-off of the separator could be modulated between a 5-µm and an 8-µm aerodynamic diameter. In the described setup, influenza A virus was transmitted through the aerosol route in two out of three experiments, and through aerosols and droplets in all three experiments.


Community Universal Face Mask Use during the COVID 19 pandemic—from households to travelers and public spaces


title: Prostaglandin D2 signaling in dendritic cells is critical for the development of EAE

text: Priming of autoreactive T cells in lymph nodes by dendritic cells (DCs) is critical for the pathogenesis of experimental autoimmune encephalitis (EAE). DC activation reflects a balance of pro- and anti-inflammatory signals. One anti-inflammatory factor is prostaglandin D2 signaling through its cognate receptor, D-prostanoid receptor 1 (PTGDR), on myeloid cells. Loss of PTGDR signaling might be expected to enhance DC activation and EAE but here we show that PTGDR(−/)(−) mice developed only mild signs of MOG(35-55) peptide immunization-induced EAE. Compared to wild type mice, PTGDR(−/)(−) mice exhibited less demyelination, decreased leukocyte infiltration and diminished microglia activation. These effects resulted from increased pro-inflammatory responses in the lymph nodes, most notably in IL-1β production, with the unexpected consequence of increased activation-induced apoptosis of MOG(35-55) peptide-specific T cells. Conditional deletion of PTGDR on DCs, and not other myeloid cells ameliorated EAE. Together, these results demonstrate the indispensable role that PGD(2)/PTGDR signaling on DCs has in development of pathogenic T cells in autoimmune demyelination.


title: Improved Algorithmic Complexity for the 3SEQ Recombination Detection Algorithm

text: Identifying recombinant sequences in an era of large genomic databases is challenging as it requires an efficient algorithm to identify candidate recombinants and parents, as well as appropriate statistical methods to correct for the large number of comparisons performed. In 2007, a computation was introduced for an exact nonparametric mosaicism statistic that gave high-precision P values for putative recombinants. This exact computation meant that multiple-comparisons corrected P values also had high precision, which is crucial when performing millions or billions of tests in large databases. Here, we introduce an improvement to the algorithmic complexity of this computation from O(mn(3)) to O(mn(2)), where m and n are the numbers of recombination-informative sites in the candidate recombinant. This new computation allows for recombination analysis to be performed in alignments with thousands of polymorphic sites. Benchmark runs are presented on viral genome sequence alignments, new features are introduced, and applications outside recombination analysis are discussed.


title: “COVID-19 and cervical artery dissection- A causative association?”

text: COVID-19 is a pandemic disease which predominantly affects the respiratory system, however it also causes multi-organ dysfunction in a subset of patients. There is a growing evidence that it increases the propensity of strokes in younger patients. Besides producing a prothrombotic state, arterial dissection could be one of its many manifestations, increasing the risks of stroke. Herein, we report the first case of spontaneous bilateral vertebral artery dissection in a patient with COVID-19. 39-year female presented with spontaneous bilateral vertebral artery dissections without any instigating traumatic events and no history of connective tissue disorders. Whether this patient's vertebral artery dissections were triggered by exaggerated inflammatory response or arteriopathy secondary to COVID-19 remains speculative. Nonetheless, arterial dissection could be one of it's complications. It is important for the physicians to be aware of different clinical manifestations of COVID-19 as we manage these patients with no historical experience, to provide adequate care.


title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody

text: SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths1,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.


title: Chapter 2 Transport Networks and Impacts on Transport Nodes

text: Abstract Transport networks are comprised of gateway and hub cities where goods are transshipped between transport modes along established trade corridors. The economics of gateways and hubs depends on the competitiveness of their trade corridors. Trade corridor routes are determined by geophysical features, political borders, proximity to markets, and investment in transportation infrastructure. The advantages of location can be altered by changes in transportation and communications technologies that favor some locations at the expense of others. Over time, hierarchies of hub and gateway cities have formed based on their trade of goods and increasingly on the services they provide. This chapter sets out a framework to analyze the evolution of transport networks and nodes where transshipments occur.


title: Influence of mechanical ventilation system on indoor carbon dioxide and particulate matter concentration

text: Abstract Common ventilation strategies may fail to maintain indoor air quality when atmosphere is heavily polluted by particulate matter. This paper evaluates the performances of common constant air volume (CAV) system and variable air volume (VAV) system when carbon dioxide and particles are significantly present in outdoor environment. Major system parameters including filter efficiency, occupancy number, ventilation air rate, and outdoor particle concentration are thoroughly examined. Firstly, a full-scale chamber experiment is performed to investigate the dynamics of CO2 and airborne particles under steady and non-steady scenarios. The result is further validated with a previously-developed state-space model. Secondly, an exhaustive case study is conducted using an established mathematical model. In order to reduce CO2 concentration, both CAV and CO2-based demand-controlled VAV may cause an undesirable increase in particle concentration when outdoor air is heavily polluted by particles. This dilemma requires further studies on the optimization of ventilation schemes.


title: Cyclodextrins: Emerging Medicines of the New Millennium

text: Cyclodextrins, since their discovery in the late 19th century, were mainly regarded as excipients. Nevertheless, developments in cyclodextrin research have shown that some of these hosts can capture and include biomolecules, highlighting fatty acids and cholesterol, which implies that they are not inert and that their action may be used in specific medicinal purposes. The present review, centered on literature reports from the year 2000 until the present day, presents a comprehensive description of the known biological activities of cyclodextrins and their implications for medicinal applications. The paper is divided into two main sections, one devoted to the properties and applications of cyclodextrins as active pharmaceutical ingredients in a variety of pathologies, from infectious ailments to cardiovascular dysfunctions and metabolic diseases. The second section is dedicated to the use of cyclodextrins in a range of biomedical technologies.


title: Fire lines as fault lines: increased trade barriers during the COVID-19 pandemic further shatter the global food system

text: In this opinion piece, we highlight that trade barriers established during COVID-19 as “fire lines” to prevent cross-border transmission of the pandemic could become “fault lines” that demolish the global food system. We review restrictions on both international agricultural exports and imports, especially unilateral border controls such as import refusals and alerts, in previous epidemics and arising with two novel features amid COVID-19. Institutional causes to pervasive trade barriers in epidemics that are embedded in the WHO-WTO coordination scheme have been discussed. In the meantime, discussions on potential economic outcomes and policy recommendations have been provided.


title: The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock

text: Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.


Editorial: Volume 61: Intellectual Property information in the time of corona virus


title: Potential Role of Zinc Supplementation in Prophylaxis and Treatment of COVID-19

text: Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the largest current health challenge for the society. At the moment, the therapeutic strategies to deal with this disease are only supportive. It is well known that zinc (Zn) possesses a variety of direct and indirect antiviral properties, which are realized through different mechanisms. Administration of Zn supplement has a potential to enhance antiviral immunity, both innate and humoral, and to restore depleted immune cell function or to improve normal immune cell function, in particular in immunocompromised or elderly patients. Zn may also act in a synergistic manner when co-administered with the standard antiviral therapy, as was demonstrated in patients with hepatitis C, HIV, and SARS-CoV-1. Effectiveness of Zn against a number of viral species is mainly realized through the physical processes, such as virus attachment, infection, and uncoating. Zn may also protect or stabilize the cell membrane which could contribute to blocking of the virus entry into the cell. On the other hand, it was demonstrated that Zn may inhibit viral replication by alteration of the proteolytic processing of replicase polyproteins and RNA-dependent RNA polymerase (RdRp) in rhinoviruses, HCV, and influenza virus, and diminish the RNA-synthesizing activity of nidoviruses, for which SARS-CoV-2 belongs. Therefore, it may be hypothesized that Zn supplementation may be of potential benefit for prophylaxis and treatment of COVID-19.


title: Risk of Water and Food-Borne Communicable Diseases in Travelers Entering Korea

text: OBJECTIVES: It was supposed to analyze status and affecting factors in water and food-borne communicable disease by screening entrants with diarrhea symptom at the point of entry in Korea METHODS: Symptomatic travelers with water and food-borne communicable diseases who entered Korea were diagnosed by a health declaration and detection of causative agents in water and food using laboratory tests. Among those entered in 2017, the affecting factors in the incidence of communicable diseases among those who had diarrhea at the entry into Korea, were analyzed, with frequency and chi-square test. RESULTS: The number of travel entrants with gastrointestinal communicable diseases increased by 40.19% from 2013 to 2017. The percentage of causative agents of water and food-borne communicable diseases was the highest at 69.2% from July to September. The rate of detection of causative agents of communicable disease pathogens in travelers from Southeast Asia entering Korea was 70.2%, which was higher than people arriving from East Asia and Central Asia (57.5%; p < 0.001). CONCLUSION: The positive ratio of causative agents of water and food-borne communicable diseases was high among travelers that had entered Korea from July to September, with a high number among entrants from Southeast Asia. Based on the positive detection of causative agents, the entry period and countries visited were statistically significant affecting factors (p < 0.001).


title: Validity of aqueocentesis as a component of anterior uveitis investigation in dogs and cats

text: OBJECTIVE: To describe aqueocentesis cytopathology results from dogs and cats presenting for uveitis investigation and to determine whether this is a useful and safe procedure. ANIMAL STUDIED: Dogs and cats presenting for investigation of anterior uveitis (April 2008–December 2013). PROCEDURES: Aqueous was collected via limbal entry under sedation/general anesthesia, for cytopathology and occasionally bacterial culture or polymerase chain reaction (PCR) testing. Further workup included blood testing (hematology, biochemistry, and serology), diagnostic imaging, nonocular cytopathology, and available histopathology. RESULTS: Fifty‐six dogs and 39 cats were included in the study. An aqueous cytopathologic diagnosis of lymphoma (or discrete cell neoplasia) was made in six dogs and seven cats, and a diagnosis of large cell carcinoma made in one dog. This diagnosis of lymphoma was confirmed by ocular histopathology in two dogs and one cat; nonocular cytopathology corroborated lymphoma in another three dogs and five cats. Lymphoma was not evident on aqueous cytopathology but confirmed on nonocular histopathology in two dogs and by cytopathology in one cat. Additionally, aqueous cytopathology in three cats suggested, but was not considered diagnostic of, lymphoma; one of these cats had a confirmatory diagnosis of lymphoma on subsequent clinical investigation. Aqueous humor cytopathology alone was not diagnostic in non‐neoplastic anterior uveitis cases, but supplemented the clinical picture with other systemic diagnostic tests. No clinically important complications were reported in association with aqueocentesis. CONCLUSIONS: Aqueocentesis is performed readily with minimal risk. The results were primarily useful in aiding a diagnosis of lymphoma in both dogs and cats.


title: An innovative personalized displacement ventilation system for airliner cabins

text: Abstract In airliner cabins, mixing ventilation systems with gaspers are not efficient in controlling contaminant transport. To improve the cabin environment, this investigation proposed an innovative ventilation system that would reduce contaminant transport and maintain thermal comfort. We manufactured and installed the proposed ventilation system in an occupied seven-row, single-aisle aircraft cabin mockup. Air velocity, air temperature, and contaminant distribution in the cabin mockup were obtained by experimental measurements. The investigation used the experimental data to validate the results of CFD simulation. The validated CFD program was then used to study the impact of the locations and number of exhausts on contaminant removal and thermal comfort in a one-row section of a fully occupied Boeing-737 cabin. Although the diffusers in the proposed system were close to the passengers' legs, the air velocity magnitude was acceptable in the lower part of the cabin and the leg area. The proposed system provided an acceptable thermal environment in the cabin, although passengers could feel cold when placing their legs directly in front of the diffusers. The four-exhaust configuration of the new ventilation system was the best, and it decreased the average exposure in the cabin by 57% and 53%, respectively, when compared with the mixing and displacement ventilation systems.


title: The economic impact of the Coronavirus 2019 (Covid-2019): Implications for the mining industry

text: Abstract The Coronavirus 2019 (Covid-19) global pandemic has not only caused infections and deaths, but it has also wreaked havoc with the global economy on a scale not seen since at least the Great Depression. Covid-19 has the potential to destroy individual livelihoods, businesses, industries and entire economies. The mining sector is not immune to these impacts, and the crisis has the potential to have severe consequences in the short, medium and long-term for the industry. Understanding these impacts, and analysing their significance for the industry, and the role it plays in wider economic development is a crucial task for academic research.


Fully automated diagnosis of MERS-CoV infection in respiratory specimen on the IdyllaTM MDx Platform


Outbreak Response and Incident Management: SHEA Guidance and Resources for Healthcare Epidemiologists in United States Acute-Care Hospitals


title: The porcine translational research database: a manually curated, genomics and proteomics-based research resource

text: BACKGROUND: The use of swine in biomedical research has increased dramatically in the last decade. Diverse genomic- and proteomic databases have been developed to facilitate research using human and rodent models. Current porcine gene databases, however, lack the robust annotation to study pig models that are relevant to human studies and for comparative evaluation with rodent models. Furthermore, they contain a significant number of errors due to their primary reliance on machine-based annotation. To address these deficiencies, a comprehensive literature-based survey was conducted to identify certain selected genes that have demonstrated function in humans, mice or pigs. RESULTS: The process identified 13,054 candidate human, bovine, mouse or rat genes/proteins used to select potential porcine homologs by searching multiple online sources of porcine gene information. The data in the Porcine Translational Research Database ((http://www.ars.usda.gov/Services/docs.htm?docid=6065) is supported by >5800 references, and contains 65 data fields for each entry, including >9700 full length (5′ and 3′) unambiguous pig sequences, >2400 real time PCR assays and reactivity information on >1700 antibodies. It also contains gene and/or protein expression data for >2200 genes and identifies and corrects 8187 errors (gene duplications artifacts, mis-assemblies, mis-annotations, and incorrect species assignments) for 5337 porcine genes. CONCLUSIONS: This database is the largest manually curated database for any single veterinary species and is unique among porcine gene databases in regard to linking gene expression to gene function, identifying related gene pathways, and connecting data with other porcine gene databases. This database provides the first comprehensive description of three major Super-families or functionally related groups of proteins (Cluster of Differentiation (CD) Marker genes, Solute Carrier Superfamily, ATP binding Cassette Superfamily), and a comparative description of porcine microRNAs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-4009-7) contains supplementary material, which is available to authorized users.


title: New paths for sustainable solutions to tackle global and emerging infectious threats

text: Abstract With the dramatic background of a newly emerged virus (SARS-CoV-2) spreading around the world, Coronavirus and other infectious health threats for the human and animal populations were illustrated and debated in excellent presentations at the IABS meeting 26–28 of February 2020. Historical evidence of pandemics and lessons learned from recent epidemics or epizootics caused by many pathogens (e.g., Ebola, Zika, and African Swine Fever viruses) illustrated the overarching need for close international cooperation. New and old technologies in vaccine development and their use were presented, resulting in a call for greater interaction between the human and the veterinary fields in order to leverage the expertise and knowledge in both human and animal medicine. The One Health concept was also emphasized for eliminating the 59,000 fatal human rabies cases annually attributed to unvaccinated dogs. For preventable, infectious diseases commonly spreading in the poorer regions of the world, a new regulatory approach and governance structure was called for to give access to affordable vaccines. Vaccines were touted as one of the most successful health invention ever introduced; on a similar level to health improvements due to clean water.


INDEX TO VOLUME I,


title: A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes

text: Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.


UK food system resilience tested by COVID-19


title: A pneumonia outbreak associated with a new coronavirus of probable bat origin

text: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats(1–4). Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans(5–7). Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.


title: An introduction to economic studies, health emergencies, and COVID‐19

text: The COVID‐19 pandemic has created widespread harm and disruption. Countries have implemented unprecedented measures to protect the lives and livelihoods of their inhabitants. The scope and composition of these responses are shaped, in part, by research and analysis about the estimated economic impacts of the COVID‐19 Pandemic and proposed responses to it. This analysis outlines basic features and principles involved in economic studies, specifically economic impact studies and economic evaluations, which have formed a significant part of the ever‐increasing evidence base about COVID‐19. This analysis introduces economic studies in this context, highlighting what they can do, their limitations, and key steps involved in conducting them. It highlights examples of economic analysis focused on COVID‐19 and on health emergencies and disasters more broadly. Knowing how economic studies are conducted, and their limitations, will help introduce how their findings can be a useful, usable, and used part of efforts to tackle this global health crisis.


title: Spiritual care – ‘A deeper immunity’ – A response to Covid-19 pandemic

text: Coronavirus disease 2019 (COVID-19) has presented unprecedented health challenges across all strata in society throughout the world. The COVID experience has caused us to reflect on quality of life, health and well-being and, just as important, end of life. During this time, spiritual care forms a vital component of holistic health management, especially in terms of coping, coming to terms with illness, suffering and ultimately death. The relationship with the transcendent or sacred has a strong influence on a people’s beliefs, attitudes, emotions and behaviour. Populations, communities, families and individuals have always found solace through their religious or philosophical beliefs during times of personal adversity and widespread anxiety or disaster. Although spiritual care has always been a part of the domain of religious beliefs, a more contemporary perspective is that spiritual care forms part of the human psyche and thus forms part of human care, health and well-being for families, patients and healthcare workers. Spiritual care deals with the provision of compassion and empathy during periods of heightened stress, distress and anxiety within care. This article provides insights into the necessity of providing spiritual care as a means of coping and well-being for families, patients and healthcare workers during the COVID-19 pandemic.


title: Polymerase Chain Reaction Is More Sensitive than Viral Culture and Antigen Testing for the Detection of Respiratory Viruses in Adults with Hematological Cancer and Pneumonia

text: We retrospectively analyzed the value of polymerase chain reaction (PCR) for the detection of respiratory viral infections in 43 patients with hematological cancer whose bronchoalveolar lavage (BAL) samples had been stored. In addition, 17 nose-throat (NT) swabs and 29 blood samples had been obtained. PCR was performed to detect parainfluenza viruses 1–3, respiratory syncytial virus, rhinovirus, influenza viruses A and B, enteroviruses, and coronaviruses. Viral cultures or antigen testing of BAL samples revealed 9 respiratory viruses in 8 patients. By use of PCR, 8 more respiratory viruses were detected in another 7 patients, increasing the rate of identification from 19% to 35% (P < .0005). Available NT swabs yielded the same results with PCR as did BAL samples. We conclude that PCR is more sensitive than viral culture or antigen or serologic testing for detection of respiratory viruses in patients with hematological malignancies, and that it offers the possibility for early, more rapid diagnosis.