bluuebunny/crossref_metadata_2025_split huggingface dataset:
State-level variation of initial COVID-19 dynamics in the United States: The role of local government interventions
Authors: White Easton R. , Hébert-Dufresne Laurent 
Published: April 2020

AbstractDuring an epidemic, metrics such asR0, doubling time, and case fatality rates are important in understanding and predicting the course of an epidemic. However, if collected over country or regional scales, these metrics hide important smaller-scale, local dynamics. We examine how commonly used epidemiological metrics differ for each individual state within the United States during the initial COVID-19 outbreak. We found that the case number, and trajectory of cases, differs considerably between states. We show that early non-pharmaceutical, government actions, were the most important determinant of epidemic dynamics. In particular, restricting restaurant operations was correlated with increased doubling times. Although individual states are clearly not independent, they can serve as small, natural experiments in how different demographic patterns and government responses can impact the course of an epidemic.Daily updates to figures in this manuscript are available at:https://github.com/eastonwhite/COVID19_US_States
Predicting hospital demand during the COVID-19 outbreak in Bogotá, Colombia
Authors: Rivera-Rodriguez Claudia , Urdinola Piedad 
Published: April 2020

ABSTRACTColombia, like many developing nations, does not have a strong health system able to respond to a pandemic of the magnitude of Covid-19. There is an increasing need to create a model that allows particular clinics and hospitals to estimate the number of patients that require Intensive Care Units-ICU care (critical), and the number of patients that require hospital care (severe), but not ICU care, in order to manage their limited resources.This paper presents a prediction of the total number of ICU and regular beds that will be needed during the pandemic COVID-19 for Bogotá-Colombia. We use a SEIR model that includes three different compartments of infection: those who can stay at home, those in regular hospital beds and those in need of ICU treatment. The model allows for a time varying transmission rate which we use to incorporate the measures introduced by the government over the period of one semester. The model predicts that by mid October 2020, the city will need 4 524 prevalent ICUs needed and 16 738 regular hospital beds needed. By the third week of July 2020, the number of patients that need ICUs will overpass the capacity set at 1 200 beds for ICU hospital beds in the city. The model predicts that the death toll by the same date will reach 1 752 people and the number of cases will be 30 216 inhabitants by then. We provide a Shiny app available in https://claudia-rivera-rodriguez.shinyapps.io/shinyappcovidclinic/. The original values in the app reproduce the results of this paper, but the parameters and starting values can be changed according to the users needs. COVID-19 has posed too many challenges to health systems around the globe, this model is an useful tool for cities, hospitals and clinics in Colombia that need to prepare for the excess demand of services that a pandemic like this one generates. Unfortunately, the model predicts that by the third week of July the projected capacity of the system in Bogotá will not be enough. We expect the lockdown rules strength in the future days, so the death toll is not as bad as predicted by this model.
Failing our Most Vulnerable: COVID-19 and Long-Term Care Facilities in Ontario
Authors: Fisman David N. , Bogoch Isaac , Lapointe-Shaw Lauren , McCready Janine , Tuite Ashleigh R. ,   the COVID-19 Ontario Modelling Group
Published: April 2020

AbstractBackgroundThe COVID-19 epidemic has taken a fearsome toll on individuals residing in long-term care facilities (LTC). As of April 10, 2020 half of Canada’s COVID-19 deaths had occurred in LTC. We sought to better understand trends and risk factors for COVID-19 death in LTC in Ontario.MethodsWe analyzed a COVID-19 outbreak database created by the Ontario Ministry of Health, for the period March 29-April 7, 2020. Mortality incidence rate ratios for LTC were calculated with community living Ontarians aged > 69 used as the comparator group. Count-based regression methods were used to model temporal trends and identify associations between infection risk in staff and residents, and subsequent LTC resident death.ResultsConfirmed or suspected cases of COVID-19 were identified in 272/627 LTC by April 7, 2020. The incidence rate ratio for COVID-19 death was 13.1 (9.9-17.3) relative to community living adults over 69. Incidence rate ratio increased over time and was 87.28 (90% CrI 9.98 to 557.08) by April 7, 2020. Lagged infection in staff was a strong predictor of death in residents (e.g., adjusted IRR for death per infected staff member 1.17, 95% CI 1.11 to 1.26 at a 6-day lag).InterpretationMortality risk in elders in Ontario is currently concentrated in LTC, and this risk has increased sharply over a short period of time. Early identification of risk requires a focus on testing and provision of personal protective equipment to staff, and restructuring the LTC workforce to prevent movement of COVID-19 between LTC.FundingThe research was supported by a grant to DNF from the Canadian Institutes for Health Research (2019 COVID-19 rapid researching funding OV4-170360).
Applying the SEIR Model in Forecasting The COVID-19 Trend in Malaysia: A Preliminary Study
Authors: Mahmud Aidalina , Lim Poh Ying 
Published: April 2020

AbstractOn March 18, 2020 the Malaysian government implemented a 14-day Movement Control Order (MCO) as part of the mitigation plan in controlling the COVID-19 epidemic in the country. The MCO aims to limit the contact rates among the population and hence prevent the surge of infected individuals. However, the trend of the epidemic before and after the MCO was not apparent. By applying the Susceptible, Exposed, Infectious and Removed (SEIR) mathematical model, we aimed to forecast the trend of COVID-19 epidemic in Malaysia using data from March 17 to 27, 2020. Based on several predetermined assumptions, the results of the analyses showed that after the implementation of the 14-day MCO from March 18 to 31, 2020, it is forecasted that the epidemic in Malaysia will peak approximately in the end of April 2020 and will subside by about the first week of July 2020. The MCO will “flatten the epidemic curve” but will prolong the duration of the epidemic. Decision to extend the duration of the MCO should depend on the consideration of socioeconomic factors as well.Author summaryDr. Aidalina Mahmud is a Public Health Specialist and a medical lecturer in the Department of Community Health, Universiti Putra Malaysia. Dr. Lim Poh Ying is a Biostatistician and is a senior lecturer in the Department of Community Health, Universiti Putra Malaysia.
Nosocomial Infections Among Patients with COVID-19, SARS and MERS: A Rapid Review and Meta-Analysis
Authors: Zhou Qi , Gao Yelei , Wang Xingmei , Liu Rui , Du Peipei , Wang Xiaoqing , Zhang Xianzhuo , Lu Shuya , Wang Zijun , Shi Qianling , Li Weiguo , Ma Yanfang , Luo Xufei , Fukuoka Toshio , Ahn Hyeong Sik , Lee Myeong Soo , Liu Enmei , Chen Yaolong , Luo Zhengxiu , Yang Kehu 
Published: April 2020

AbstractBackgroundCOVID-19, a disease caused by SARS-CoV-2 coronavirus, has now spread to most countries and regions of the world. As patients potentially infected by SARS-CoV-2 need to visit hospitals, the incidence of nosocomial infection can be expected to be high. Therefore, a comprehensive and objective understanding of nosocomial infection is needed to guide the prevention and control of the epidemic.MethodsWe searched major international and Chinese databases Medicine, Web of science, Embase, Cochrane, CBM(China Biology Medicine disc), CNKI (China National Knowledge Infrastructure) and Wanfang database)) for case series or case reports on nosocomial infections of COVID-19, SARS(Severe Acute Respiratory Syndromes) and MERS(Middle East Respiratory Syndrome) from their inception to March 31st, 2020. We conducted a meta-analysis of the proportion of nosocomial infection patients in the diagnosed patients, occupational distribution of nosocomial infection medical staff and other indicators.ResultsWe included 40 studies. Among the confirmed patients, the proportions of nosocomial infections were 44.0%, 36.0% and 56.0% for COVID-19, SARS and MERS, respectively. Of the confirmed patients, the medical staff and other hospital-acquired infections accounted for 33.0% and 2.0% of COVID-19 cases, 37.0% and 24.0% of SARS cases, and 19.0% and 36.0% of MERS cases, respectively. Nurses and doctors were the most affected among the infected medical staff. The mean numbers of secondary cases caused by one index patient were 29.3 and 6.3 for SARS and MERS, respectively.ConclusionsThe proportion of nosocomial infection in patients with COVID-19 was 44%. Patients attending hospitals should take personal protection. Medical staff should be awareness of the disease to protect themselves and the patients.
Population anxiety and positive behaviour change during the COVID-19 epidemic: Cross-sectional surveys in Singapore, China and Italy
Authors: Lim Jane M , Tun Zaw Myo , Kumar Vishakha , Quaye Sharon Esi Duoduwa , Offeddu Vittoria , Cook Alex R , Lwin May Oo , Jiang Shaohai , Tam Clarence C 
Published: April 2020

AbstractBackgroundOn 31 December 2019, an epidemic of pneumonia of unknown aetiology was first reported in the city of Wuhan, Hubei Province, People’s Republic of China. A rapidly progressing epidemic of COVID-19 ensued within China, with multiple exportations to other countries. We aimed to measure perceptions and responses towards COVID-19 in three countries to understand how population-level anxiety can be mitigated in the early phases of a pandemic.MethodsBetween February and March 2020, we conducted online surveys in Singapore, China and Italy with a total of 4,505 respondents to measure respondents’ knowledge, perceptions, anxiety and behaviours towards the COVID-19 epidemic, and identified factors associated with lower anxiety and more positive behavioural responses.FindingsRespondents reported high awareness of COVID-19 and its accompanying symptoms, comparable information seeking habits and similarly high levels of information sufficiency, adherence to and acceptance of public health control measures. Higher self-efficacy was associated with lower anxiety levels in all three countries, while willingness to comply with restrictive measures and greater information sufficiency were associated with more positive behavioural changes to reduce spread of infection.InterpretationPopulation-level anxiety and behavioural responses to an outbreak can be influenced by information provided. This should be used to inform future outbreak preparedness plans, taking into account the importance of increasing population-level self-efficacy and information sufficiency to reduce anxiety and promote positive behavioural changes.FundingThis was supported by the Saw Swee Hock School of Public Health, the Department of Communications and New Media, National University of Singapore, and the National Medical Research Council, Singapore
Basic estimation-prediction techniques for Covid-19, and a prediction for Stockholm
Authors: Britton Tom 
Published: April 2020

AbstractPredicting future infections for covid-19 is essential in planning healthcare system as well as deciding on relaxed or strengthened preventive measures. Here a quick and simple estimation-prediction method for an urban area is presented, a method which only uses the observed initial doubling time andR0, and prediction is performed without or with preventive measures put in place. The method is applied to the urban area of Stockholm, and predictions indicate that the peak of infections happened in mid-April and infections start settling towards end of May.
Three-dimensional regulation ofHOXAcluster genes by acis-element in hematopoietic stem cell and leukemia
Authors: David Wang Xue Qing , Gore Haley , Himadewi Pamela , Feng Fan , Yang Lu , Zhou Wanding , Liu Yushuai , Wang Xinyu , Chen Chun-wei , Su Jianzhong , Liu Jie , Pfeifer Gerd , Zhang Xiaotian 
Published: April 2020

AbstractProper gene regulation is crucial for cellular differentiation, and dysregulation of key genes can lead to diseased states such as cancer. The HOX transcription factors play such a role during hematopoiesis, and aberrant expression of certainHOXAgenes is found in certain acute myeloid leukemias (AMLs). While studies have shown that these genes are targeted by a variety of mutant proteins including mutant NPM1, MLL fusions, and NUP98 fusions, little is known about how long-range 3D chromatin interactions regulate theHOXAgenes in normal hematopoiesis and leukemia. Here, we report the interaction between theHOXAcluster with a ∼1.3 Mb upstream DNA methylation Canyon termed “Geneless Canyon” (GLC) in human CD34+/CD38-hematopoietic stem cells (HSCs) and AML cell lines. We show that CRISPR-Cas9 mediated deletion of the wholeGLCregion reduces the expression of the distalHOXAgenes and compromises HSC and leukemia cells self-renewal. This long-range chromatin interaction brings theHOXAcluster in contact with the nuclear pore complex (NPC) at the nuclear periphery, which promotesHOXAgene expression and maintains HSC and leukemia cell self-renewal. These findings reveal how long-range 3D chromatin organization regulates key transcription factor genes in both normal and diseased hematopoietic cells.
Connexin26 mediates CO2-dependent regulation of breathing via glial cells of the medulla oblongata
Authors: Van de Wiel Joseph , Meigh Louise , Bhandare Amol , Cook Jonathan , Nijjar Sarbjit , Huckstepp Robert , Dale Nicholas 
Published: April 2020

AbstractBreathing is highly sensitive to the PCO2of arterial blood. Although CO2is detected via the proxy of pH, CO2acting directly via Cx26 may also contribute to the regulation of breathing. Here we exploit our knowledge of the structural motif of CO2-binding to Cx26 to devise a dominant negative subunit (Cx26DN) that removes the CO2-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26DNin glial cells of a circumscribed region of the medulla - the caudal parapyramidal area – reduced the adaptive change in tidal volume and minute ventilation by approximately 30% at 6% inspired CO2. As central chemosensors mediate about 70% of the total response to hypercapnia, CO2-sensing via Cx26 in the caudal parapyramidal area contributed about 45% of the centrally-mediated ventilatory response to CO2. Our data unequivocally links the direct sensing of CO2to the chemosensory control of breathing and demonstrates that CO2-binding to Cx26 is a key transduction step in this fundamental process.
A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals
Authors: Riva Laura , Yuan Shuofeng , Yin Xin , Martin-Sancho Laura , Matsunaga Naoko , Burgstaller-Muehlbacher Sebastian , Pache Lars , De Jesus Paul P. , Hull Mitchell V. , Chang Max , Chan Jasper Fuk-Woo , Cao Jianli , Poon Vincent Kwok-Man , Herbert Kristina , Nguyen Tu-Trinh , Pu Yuan , Nguyen Courtney , Rubanov Andrey , Martinez-Sobrido Luis , Liu Wen-Chun , Miorin Lisa , White Kris M. , Johnson Jeffrey R. , Benner Christopher , Sun Ren , Schultz Peter G. , Su Andrew , Garcia-Sastre Adolfo , Chatterjee Arnab K. , Yuen Kwok-Yung , Chanda Sumit K. 
Published: April 2020

AbstractThe emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. As the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug registration of an antiviral is >10 years, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.
Transgenerational inheritance of abnormal spermatogenesis withIgf2/H19epigenetic alteration in CD1 mouse induced byin uteroarsenic exposure
Authors: Yin Guoying , Xia Liting , Hou Yaxing , Li Yaoyan , Cao Deqing , Liu Yanan , Chen Jingshan , Liu Juan , Zhang Liwen , Yang Qiaoyun , Zhang Qiang , Tang Naijun 
Published: April 2020

AbstractDevelopmental exposure to environmental toxicants can induce transgenerational reproductive disease phenotypes through epigenetic mechanisms. However, little is known about the transgenerational effects of arsenic exposure. We hypothesize that prenatal arsenic exposure may result in impaired spermatogenesis in subsequent generations of male mice. To test our hypothesis, we treated pregnant CD-1 (F0) mice with drinking water containing sodium arsenite (85 ppm) from days 8 to 18 of gestation. Male offspring were bred with untreated female mice until the F3 generation was produced. Our results revealed that transient exposure of the F0 gestating female to arsenic can result in decreased sperm quality and histological abnormalities in testes of male offspring in the F1 and F3 generations. The overall methylation status ofIgf2DMR2 andH19DMR was significantly lower in the arsenic-exposed group than that of the control group in both F1 and F3 generations. The relative mRNA expression levels ofIgf2andH19in arsenic-exposed males were significantly higher than in the control males in both F1 and F3 generations. This study indicates that ancestral exposure to arsenic may result in transgenerational inheritance of an impaired spermatogenesis phenotyping involving both epigenetic alterations and the abnormal expression ofIgf2andH19.
Immunosuppressive effect of theFusariumsecondary metabolite butenolide in human colon epithelial cells
Authors: Woelflingseder Lydia , Adam Gerhard , Marko Doris 
Published: April 2020

ABSTRACTButenolide (BUT, 4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone) is a secondary metabolite produced by severalFusariumspecies and is co-produced with the major trichothecene mycotoxin deoxynivalenol (DON) on cereal grains throughout the world. BUT has low acute toxicity and only very limited occurrence and exposure data are available. The intestinal epithelium represents the first physiological barrier against food contaminants. We aimed to elucidate the intestinal inflammatory response of the human, non-cancer epithelial HCEC-1CT cells to BUT and to characterize potential combinatory interactions with co-occurring trichothecenes, such as DON and NX-3. Using a reporter gene approach, BUT (≥5μM, 20 h) was found to decrease lipopolysaccharide (LPS; 10 ng/mL) induced nuclear factor kappa B (NF-κB) activation in a dose-dependent manner, and in combinatory treatments represses trichothecene-induced enhancement of this important inflammatory pathway. Analyzing transcription and secretion levels of NF-κB-dependent, pro-inflammatory cytokines, revealed a significant down-regulation of IL-1β, IL-6 and TNF-α in IL-1β-stimulated (25 ng/mL) HCEC-1CT cells after BUT exposure (10μM). Trichothecene-induced expression of pro-in-flammatory cytokines by the presence of 1μM DON or NX-3 was substantially suppressed in the presence of 10μM BUT. The emerging mycotoxin BUT has the ability to suppress NF-κB-induced intestinal inflammatory response mechanisms and to modulate substantially the immune responsiveness of HCEC-1CT cells after trichothecene treatment. Our results suggest that BUT, present in naturally occurring mixtures ofFusariumfungal metabolites, should be increasingly monitored, and the mechanism of inhibition of NF-κB that might affect the pathogenesis or progression of intestinal inflammatory disorders, should be further investigated.
Defining the transcriptional responses ofAspergillus nidulansto cation/alkaline pH stress and the role of the transcription factor SltA
Authors: Picazo Irene , Etxebeste Oier , Requena Elena , Garzia Aitor , Espeso Eduardo A. 
Published: April 2020

AbstractFungi have developed the ability to overcome extreme growth conditions and thrive in hostile environments. The model fungusAspergillus nidulanstolerates, for example, ambient alkalinity up to pH 10 or molar concentrations of multiple cations. The ability to grow under alkaline pH or saline stress depends on the effective function of, at least, three regulatory pathways mediated by high hierarchy zinc-finger transcription factors: PacC, which mediates the ambient pH regulatory pathway, the calcineurin-dependent CrzA and the cation-homeostasis responsive factor SltA. Using RNA sequencing, we determined the effect of external pH alkalinisation or sodium stress on gene expression. Data show that each condition triggers transcriptional responses with a low degree of overlap. By sequencing the transcriptomes of the null mutant, the role of SltA in the abovementioned homeostasis mechanisms was also studied. Results show that the transcriptional role of SltA is wider than initially expected and implies, for example, the positive control of the PacC-dependent ambient pH regulatory pathway. Overall, our data strongly suggest that the stress-response pathways in fungi include some common but mostly exclusive constituents, and that there is a hierarchy of authority among the main regulators of stress response, with SltA controllingpacCexpression at least inA. nidulans.
Isolation of Chemically Cyclized Peptide Binders Using Yeast Surface Display
Authors: Bacon Kaitlyn , Blain Abigail , Burroughs Matthew , McArthur Nikki , Rao Balaji M. , Menegatti Stefano 
Published: April 2020

AbstractCyclic peptides with engineered protein-binding activity have gained increasing attention for use in therapeutic and biotechnology applications. We describe the efficient isolation and characterization of cyclic peptide binders from genetically encoded combinatorial libraries using yeast surface display. Here, peptide cyclization is achieved by disuccinimidyl glutarate-mediated crosslinking of amine groups within a linear peptide sequence that is expressed as a yeast cell surface fusion. Using this approach, we first screened a library of cyclic heptapeptides by magnetic selection and fluorescence activated cell sorting (FACS), to isolate binders for a model target (lysozyme) with low micromolar binding affinity (KD~ 1.2 - 3.7 µM). The isolated peptides bound lysozyme selectively, and only when cyclized. Importantly, we showed that yeast surface displayed cyclic peptides could be used to efficiently obtain quantitative estimates of binding affinity, without chemical synthesis of the selected peptides. Subsequently, to demonstrate broader applicability of our approach, we isolated cyclic heptapeptides that bind human interleukin-17 (IL-17) using yeast-displayed IL-17 as a target for magnetic selection, followed by FACS using recombinant IL-17. Molecular docking simulations and follow-up experimental analyses identified a candidate cyclic peptide that binds IL-17 in its receptor binding region with moderate affinity (KD~ 300 nM). Taken together, our results show that yeast surface display can be used to efficiently isolate and characterize cyclic peptides generated by chemical modification from combinatorial libraries.