bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODELING COVID19 IN INDIA (Mar 3-May 7, 2020): HOW FLAT IS FLAT, AND OTHER HARD FACTS
Authors: Dey Smarajit 
Published: May 2020

ABSTRACTA time-series model was developed for Number of Total Infected Cases in India, using data from Mar 3 to May 7, 2020. Two models developed in the early phases were discarded when they lost statistical validity, The third, current, model is a 3rd-degree polynomial that has remained stable over the last 30 days (since Apr 8), with R2 > 0.998 consistently. This model is used to forecast Total Covid cases, after cautionary discussion of triggers that would invalidate the model. The purpose of all forecasts in the study is to provide a comparator to evaluate policy initiatives to control the pandemic - the forecasts are not objectives by themselves. Actual observations less than forecasts mean successful policy interventions. Figures of Doubling Time, Fatality Rate and Recovery Rate used by authorities are questioned. Elongation of doubling rates is inherent in the model, and worthy of mention only when the time actually exceeds what the model predicts. The popular Fatality Rate and Recovery Rate metrics are shown to be illogical. The study defines two terms Ongoing Fatality Rate (OFR), and Ongoing Recovery Rate (ORR) and determines these currently to be ~9% and ~76% respectively in India. Over time, OFR will decline to the eventual Case Fatality Rate (CFR), while ORR will eventually climb to (1-CFR). There is no statistical basis to assume eventual Indian CFR, and China’s 5.5% CFR is used as a proxy. Using these metrics, the current model forecasts by May-end, >150000 Total Infected, ~5000 Deaths and >85000 Active Cases. There is no pull-back evident in the current model in the foreseeable future, and cases continue to rise at progressively slower rates. Subject to usual caveats, the model is used to forecast till Sep 15. The study argues that Indian hospital infrastructure is reasonably ready to handle Active Cases as predicted for Sept 15 – in that sense, the curve is “flat enough”. However, the curve is NOT flat enough with respect to fatalities - nearly 100000 by Sept 15. Setting an arbitrary limit that Total Deaths must be within 50,000 by Sept 15, the study retrofits a model that shows what the desired growth of Covid19 cases should be. It is seen that overall doubling time of 38 days is required in period June 1 to Sep 15, if deaths are to remain below 50000.
COVID-19 pandemic: every day feels like a weekday to most
Authors: Liu Tony , Meyerhoff Jonah , Mohr David C. , Ungar Lyle H. , Kording Konrad P. 
Published: May 2020

AbstractThe COVID-19 outbreak has clear clinical1 and economic2 impacts, but also affects behaviors e.g. through social distancing3, and may increase stress and anxiety. However, while case numbers are tracked daily4, we know little about the psychological effects of the outbreak on individuals in the moment. Here we examine the psychological and behavioral shifts over the initial stages of the outbreak in the United States in an observational longitudinal study. Through GPS phone data we find that homestay is increasing, while being at work dropped precipitously. Using regular real-time experiential surveys, we observe an overall increase in stress and mood levels which is similar in size to the weekend vs. weekday differences. As there is a significant difference between weekday and weekend mood and stress levels, this is an important decrease in wellbeing. For some, especially those affected by job loss, the mental health impact is severe.
Behavioural change towards reduced intensity physical activity is disproportionately prevalent among adults with serious health issues or self-perception of high risk during the UK COVID-19 lockdown
Authors: Rogers Nina Trivedy , Waterlow Naomi , Brindle Hannah , Enria Luisa , Eggo Rosalind M , Lees Shelley , Roberts Chrissy h 
Published: May 2020

AbstractImportanceThere are growing concerns that the UK COVID-19 lockdown has reduced opportunities to maintain health through physical activity, placing individuals at higher risk of chronic disease and leaving them more vulnerable to severe sequelae of COVID-19.ObjectiveTo examine whether the UK’s lockdown measures have had disproportionate impacts on intensity of physical activity in groups who are, or who perceive themselves to be, at heightened risk from COVID-19.Designs, Setting, ParticipantsUK-wide survey of adults aged over 20, data collected between 2020-04-06 and 2020-04-22.ExposuresSelf-reported doctor-diagnosed obesity, hypertension, type I/II diabetes, lung disease, cancer, stroke, heart disease. Self-reported disabilities and depression. Sex, gender, educational qualifications, household income, caring for school-age children. Narrative data on coping strategies.Main Outcomes and MeasuresChange in physical activity intensity after implementation of UK COVID-19 lockdown (self-reported).ResultsMost (60%) participants achieved the same level of intensity of physical activity during the lockdown as before the epidemic. Doing less intensive physical activity during the lockdown was associated with obesity (OR 1.21, 95% CI 1.02-1.41), hypertension (OR 1.52, 1.33-1.71), lung disease (OR 1.31,1.13-1.49), depression (OR 2.02, 1.82-2.22) and disability (OR 2.34, 1.99-2.69). Participants who reduced their physical activity intensity also had higher odds of being female, living alone or having no garden, and more commonly expressed sentiments about personal or household risks in narratives on coping.Conclusions and relevanceGroups who reduced physical activity intensity included disproportionate numbers of people with either heightened objective clinical risks or greater tendency to express subjective perceptions of risk. Policy on exercise for health during lockdowns should include strategies to facilitate health promoting levels of physical activity in vulnerable groups, including those with both objective and subjective risks.
Small RNA signatures of the anterior cruciate ligament from patients with knee joint osteoarthritis
Authors: Kharaz Yalda A. , Fang Yongxiang , Welting Tim , Peffers Mandy , Comerford Eithne J. 
Published: May 2020

ABSTRACTThe anterior cruciate ligaments are susceptible to degeneration, resulting in pain, reduced mobility and development of the degenerative joint disease osteoarthritis. There is currently a paucity of knowledge on how anterior cruciate ligament degeneration and disease can lead to osteoarthritis. Small non-coding RNAs (sncRNAs), such as microRNAs, and small nucleolar RNA, are important regulators of gene expression. We aimed to identify sncRNA profiles of human anterior cruciate ligaments to provide novel insights into their roles in osteoarthritis.RNA was extracted from the anterior cruciate ligaments of non-osteoarthritic knee joints (control) and end-stage osteoarthritis knee joints, used for small RNA sequencing and significantly differentially expressed sncRNAs defined. Bioinformatic analysis was undertaken on the differentially expressed miRNAs and their putative target mRNAs to investigate pathways and biological processes affected.Our analysis identified 184 sncRNA that were differentially expressed between control ACLs derived from osteoarthritic joints with a false discovery adjusted p value<0.05; 68 small nucleolar RNAs, 26 small nuclear RNAs and 90 microRNAs. We identified both novel and previously identified (miR-206, –101, –365 and –29b and –29c) osteoarthritis-related microRNAs and other sncRNAs (including SNORD74, SNORD114, SNORD72) differentially expressed in ligaments derived from osteoarthritic joints. Significant cellular functions deduced by the differentially small nuclear RNAs and 90 microRNAs. We identified expressed miRNAs included differentiation of muscle (P<0.001), inflammation (P<1.42E-10), proliferation of chondrocytes (P<0.03), fibrosis (P<0.001) and cell viability (P<0.03). Putative mRNAs were associated with the canonical pathways ‘Hepatic Fibrosis Signalling’ (P<3.7E-32), and ‘Osteoarthritis’ (P<2.2E-23). Biological processes included apoptosis (P<1.7E-85), fibrosis (P<1.2E-79), inflammation (P<3.4E-88), necrosis (P<7.2E-88) and angiogenesis (P<5.7E-101).SncRNAs are important regulators of anterior cruciate disease during osteoarthritis and may be used as therapeutic targets to prevent and manage anterior cruciate ligament disease and the resultant osteoarthritis.
Weight change and the incidence of cardiovascular diseases in adults with normal weight, overweight and obesity without chronic diseases; emulating trials using electronic health records
Authors: Katsoulis M. , Stavola BD , Ordaz KD , Gomes M. , Lai A , Lagiou P , Wannamethee G , Tsilidis K , Lumbers RT , Denaxas S , Banerjee A , Parisinos CA , Batterham R , Langenberg C , Hemingway H 
Published: May 2020

ABSTRACTBackgroundCross sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.MethodsWe estimated the effect of 2-year weight change interventions on 7-year risk of CVD, by emulating hypothetical target trials using electronic health records. We identified 138.567 individuals in England between 1998 and 2016, aged 45-69 years old, free of chronic diseases at baseline. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying variables. Each individual was classified into a weight loss, maintenance, or gain group.FindingsIn the normal weight, both weight loss and gain were associated with increased risk for CVD [HR vs weight maintenance=1.53 (1.18-1.98) and 1.43 (1.19-1.71 respectively)]. Among overweight individuals, both weight loss and gain groups, compared to weight maintenance, had a moderately higher risk of CVD [HR=1.20 (0.99–1.44) and 1.17 (0.99–1.38), respectively]. In the obese, weight loss had a lower risk lower risk of CHD [HR =0.66 (0.49–0.89)] and a moderately lower risk of CVD [HR =0.90 (0.72–1.13)]. When we assumed that a chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals and estimates for weight loss were stronger among individuals with obesity.InterpretationAmong individuals with obesity, the weight loss group had a lower risk of CHD and moderately lower risk of CVD. Weight gain increased the risk of CVD across BMI groups.
Is the Current N95 Respirator Filtration Efficiency Test Sufficient for Evaluating Protection Against Submicrometer Particles Containing SARS-CoV-2?
Authors: Cai Changjie , Floyd Evan L. , Aithinne Kathleen A. , Oni Toluwanimi 
Published: May 2020

AbstractThe National Institute of Occupational Safety and Health procedure No. TEB-APR-STP-0059 recommend of measuring the respirator filtration efficiency using sodium chloride aerosol with count median diameter of 75 nm ± 20 nm and geometric standard deviation ≤1.86. This study showed that this method would overestimate the respirators’ ability to protect against submicrometer particles. In this study, we converted both mobility diameter and equivalent volume diameter to aerodynamic diameter for comparison. The results showed that one unqualified KN95 respirator (with the filtration efficiency of 72%±3% for ≥300 nm sodium chloride aerosol) still passed the test with a measured overall filtration efficiency of 98%±3%, due to its larger most penetrating particle size compared to the typical N95 respirator. In addition, after three cycle H2O2 plasma vaporous sterilizations, the most penetrating particle size for the N95 grade respirators also shifted to 250 nm – 500 nm, in which size the particles carried the peak concentration of the SARS-CoV-2 in hospitals. This size shift caused the significant difference between the size specific (250 nm – 500 nm) filtration efficiency and overall filtration efficiency using the same NaCl test aerosol. For example, after three cycle H2O2 plasma vaporous sterilizations, the size specific filtration efficiency of the N95 was 55%±2%, however, the measured overall filtration efficiency was still 86%±5%. The size Specific filtration efficiency of the KN95 was 69%±2%, but, the measured overall filtration efficiency was still 90%±3%. In order to protect health care personnel adequately, we recommend increasing the test aerosol size, and measuring the size specific filtration efficiency to evaluate the N95 alternatives (e.g. KN95), and the reuse of N95 level respirators. In addition, multi-cycle sterilization with ultraviolet germicidal irradiation appears to have fewer negative effects than H2O2.
Progression of COVID-19 in Indian States - Forecasting Endpoints Using SIR and Logistic Growth Models
Authors: Malhotra Bhoomika , Kashyap Vishesh 
Published: May 2020

AbstractCOVID-19 has led to the most widespread public health crisis in recent history. The first case of the disease was detected in India on 31 January 2019, and confirmed cases stand at 74,281 as of 13 May 2020. Mathematical modeling can be utilized to forecast the final numbers as well as the endpoint of the disease in India and its states, as well as assess the impact of social distancing measures. In the present work, the Susceptible-Infected-Recovered (SIR) model and the Logistic Growth model have been implemented to predict the endpoint of COVID-19 in India as well as three states accounting for over 55% of the total cases – Maharashtra, Gujarat and Delhi. The results using the SIR model indicate that the disease will reach an endpoint in India on 12 September, while Maharashtra, Gujarat and Delhi will reach endpoints on 20 August, 30 July and 9 September respectively. Using the Logistic Regression model, the endpoint for India is predicted on 23 July, while that for Maharashtra, Gujarat and Delhi is 5 July, 23 June and 10 August respectively. It is also observed that the case numbers predicted by the SIR model are greater than those for the Logistic Growth model in each case. The results suggest that the lockdown enacted by the Government of India has had only a moderate impact on the spread of COVID-19, and emphasize the need for firm implementation of social distancing guidelines.
Modulation of endothelial organelle size as an antithrombotic strategy
Authors: Ferraro Francesco , Costa Joana R. , Ketteler Robin , Kriston-Vizi Janos , Cutler Daniel F. 
Published: May 2020

AbstractIt is long-established that Von Willebrand Factor (VWF) is central to haemostasis and thrombosis. Endothelial VWF is stored in cell-specific secretory granules, Weibel-Palade bodies (WPBs), uniquely rod-like exocytic organelles generated in a wide range of lengths (0.5 to 5.0 µm). It has been shown that WPB size responds to physiological cues and pharmacological treatment and that, under flow, VWF secretion from shortened WPBs produces a dramatic reduction of platelet and plasma VWF adhesion to an endothelial surface. WPB-shortening therefore represents a novel target for antithrombotic therapy acting via modulation of VWF adhesive activity. To this aim, we screened a library of licenced drugs and identified several that prompt WPB size reduction. These compounds therefore constitute a novel set of potentially antithrombotic compounds.SummaryThe size of the endothelial secretory granules that store Von Willebrand Factor correlates with its activity, central to haemostasis and thrombosis. Here, human-licenced drugs that reduce the size of these secretory granules are identified, providing a set of novel potential anti-thrombotic compounds.
Nrf2 Activator PB125®as a Potential Therapeutic Agent Against COVID-19
Authors: McCord Joe M. , Hybertson Brooks M. , Cota-Gomez Adela , Gao Bifeng 
Published: May 2020

AbstractNrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2 activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-Cov-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells we report the marked downregulation by PB125 of 36 genes encoding cytokines. These include IL1-beta, IL6, TNF-α, the cell adhesion molecules ICAM1, VCAM1, and E-selectin, and a group of IFN-γ-induced genes. Many of these cytokines have been specifically identified in the “cytokine storm” observed in fatal cases of COVID-19, suggesting that Nrf2 activation may significantly decrease the intensity of the storm.
Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel
Authors: Cao Yipeng , Yang Rui , Wang Wei , Lee Imshik , Zhang Ruiping , Zhang Wenwen , Sun Jiana , Xu Bo , Meng Xiangfei 
Published: May 2020

AbstractCoronavirus disease 2019 (COVID-19) is caused by a novel coronavirus (SARS-CoV-2) and represents the causative agent of a potentially fatal disease that is of public health emergency of international concern. Coronaviruses, including SARS-CoV-2, encode an envelope (E) protein, which is a small, hydrophobic membrane protein; the E protein of SARS-CoV-2 has high homology with that of severe acute respiratory syndrome coronavirus. (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Our results suggest that the pentameric E protein promotes the penetration of monovalent ions through the channel. Analysis of the potential mean force (PMF), pore radius and diffusion coefficient reveals that Leu10 and Phe19 are the hydrophobic gates of the channel. In addition, the pore demonstrated a clear wetting/dewetting transition with monovalent cation selectivity under transmembrane voltage, which indicates that it is a hydrophobic voltage-dependent channel. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel.
Analysis of High Molecular Weight RNA-induced silencing complex (HMW-RISC) in CD8+T cells identifies miR-7 as a modulator of T cell activation
Authors: Toivakka Matilda , Gordon Katrina , Kumar Sujai , Zamoyska Rose , Buck Amy 
Published: May 2020

ABSTRACTIncreasing evidence suggests mammalian Argonaute (Ago) proteins partition into distinct complexes within cells, but there is still little functional understanding of the miRNAs differentially associated with these complexes. In naive T cells, Ago2 is found almost exclusively in low molecular weight (LMW) complexes which are associated with miRNAs but not their target mRNAs. Upon T cell activation a proportion of these Ago2 complexes move into a newly formed HMW RISC which is characterized by the presence of the GW182 protein that mediates translational repression. To identify the miRNAs expected to be potent in suppressing targets, we followed HMW RISC formation upon activation of CD8+T cells. We show that while most miRNAs distribute between HMW and LMW RISC in activated T cells, several miRNAs were dominant in one complex over the other. Among these, miR-7 is enriched in HMW RISC and inhibition of miR-7 upon T cell activation leads to increased production of IL-2 and expression of IL-2-regulated proteins including the α-subunit of the IL-2 receptor, CD25; transferrin receptor, CD71; and amino acid transporter, CD98, which are direct miR-7 targets. Our data support a model where recruitment of miR-7 to HMW RISC restrains IL-2 signalling and the metabolic processes regulated by IL-2 and thus modulates T cell activation.
Potent programmable antiviral against dengue virus in primary human cells by Cas13b RNP with short spacer and delivery by virus-like particle
Authors: Singsuksawat Ekapot , Onnome Suppachoke , Posiri Pratsaneeyaporn , Suphatrakul Amporn , Srisuk Nittaya , Nantachokchawapan Rapirat , Praneechit Hansa , Sae-kow Chutimon , Chidpratum Pala , Hongeng Suradej , Avirutnan Panisadee , Duangjinda Thaneeya , Siridechadilok Bunpote 
Published: May 2020

SummaryWith sequencing as a standard frontline protocol to identify emerging viruses such zika virus and SARS-CoV2, direct utilization of sequence data to program antivirals against the viruses could accelerate drug development to treat their infections. CRISPR-Cas effectors are promising candidates that could be programmed to inactivate viral genetic material based on sequence data but several challenges such as delivery and design of effective crRNA need to be addressed to realize practical use. Here, we showed that virus-like particle (VLP) could deliver PspCas13b-crRNA ribonucleoprotein (RNP) in nanomolar range to efficiently suppress dengue virus infection in primary human target cells. Shortening spacer length could significantly enhance RNA-targeting efficiency of PspCas13b in mammalian cells compared to the natural length of 30 nucleotides without compromising multiplex targeting by a crRNA array. Our results demonstrate the potentials of applying PspCas13b RNP to suppress RNA virus infection, with implications in targeting host RNA as well.
PSGL-1 inhibits HIV-1 infection by restricting actin dynamics and sequestering HIV envelope proteins
Authors: Liu Ying , Song Yutong , Zhang Siyu , Diao Min , Huang Shanjin , Li Sai , Tan Xu 
Published: May 2020

AbstractPSGL-1 has recently been identified as an HIV restriction factor that inhibits HIV DNA synthesis and more potently, virion infectivity. But the underlying mechanisms of these inhibitions are unknown. Here we show that PSGL-1 directly binds to cellular actin filaments (F-actin) and restricts actin dynamics, which leads to inhibition of HIV DNA synthesis. PSGL-1 is incorporated into nascent virions and restricts actin dynamics in the virions, which partially accounts for the inhibition of virion infectivity. More potently, PSGL-1 inhibits incorporation of Env proteins into nascent virions, leading to loss of envelope spikes on the virions as shown by Cryo-electron microscopy and super-resolution imaging. This loss is associated with a profound defect in viral entry. Mechanistically, PSGL-1 binds gp41 and sequesters gp41 at the plasma membrane, explaining the inhibition of Env incorporation in nascent virions. PSGL-1’s dual anti-HIV mechanisms represent novel strategies of human cells to defend against HIV infection.