bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Recombinant Human-Soluble Thrombomodulin for Severe Acute Pancreatitis in a Rat Experimental Model
Authors: Matsumoto Masataka , Kamei Keiko , Chikugo Takaaki , Matsumoto Ippei , Kawaguchi Kohei , Takeyama Yoshifumi 
Published: April 2020

Objectives
Early death in severe acute pancreatitis (SAP) is caused by pancreatic necrosis and multiple-organ failure due to microcirculation disorder. The aim of this study was to prove that recombinant human-soluble thrombomodulin (rTM) has therapeutic effects on SAP by preventing pancreatic necrosis and organ failure.

Methods
Male Wister rats were used. Cerulein was administered intraperitoneally 4 times every 1 hour, and lipopolysaccharide was administered intraperitoneally 3 hours after. One hour after administration of lipopolysaccharide, rTM was injected intravenously. Rats were observed for 24 hours after starting the experiment, and the survival rate was evaluated. All surviving rats were killed, and the blood sample, liver, and pancreas were excised. Serum amylase, aspartate aminotransferase, alanine aminotransferase, and high mobility group box 1 were measured, and the liver and pancreas were examined histologically. For the evaluation of microcirculation, von Willebrand factor staining was performed.

Results

Serum amylase, aspartate aminotransferase, and alanine aminotransferase were significantly decreased. The survival rate was significantly improved to 100%. Moreover, serum high mobility group box 1 was decreased. Liver injury and pancreatic necrosis became less severe, and microcirculation was preserved histologically.

Conclusions
Early administration of rTM prevents organ failure by maintenance of microcirculation and improves prognoses of SAP.
Augmenting an Inpatient Fall Program With Video Observation
Authors: Davis James E. , Carter-Templeton Heather 
Published: April 2020

Background:
Keeping patients safe is a goal for all health care facilities. Facilities should look at technology as a way to help improve outcomes. Patient falls are a dangerous, costly, and preventable health care–associated event.

Local Problem:
The fall rate on the host facility's orthopedic unit was 2.6 per 1000 patient-days.

Methods:
Patients on an inpatient orthopedic unit who had a fall risk score greater than 13, based on the Johns Hopkins Fall Risk Assessment Tool, were provided with an added intervention, video observation.

Intervention:
Video observation units with 2-way communication were introduced to help prevent patient falls.

Results:
The fall rate per 1000 patient-days after implementing this intervention for 6 weeks was 0 falls per 1000 patient-days.

Conclusions:
There was a 100% decrease in patient falls on the inpatient unit where video observation was implemented.
Based on current trends, almost all African countries are likely to report over 1 000 COVID-19 cases by the end of April 2020, and over 10 000 a few weeks after that
Authors: Pearson Carl A. B. , Van Schalkwyk Cari , Foss Anna M. , O’Reilly Kathleen M. ,   SACEMA Modelling and Analysis Response Team,   CMMID COVID-19 working group, Pulliam Juliet R. C. 
Published: April 2020

AbstractFor African countries currently reporting COVID-19 cases, we estimate when they will report more than 1 000 and 10 000 cases. Assuming current trends, more than 80% are likely to exceed 1 000 cases by the end of April 2020, with most exceeding 10 000 a few weeks later.
Nitric oxide gas inhalation to prevent COVID-2019 in healthcare providers
Authors: Gianni Stefano , Fakhr Bijan Safaee , Araujo Morais Caio Cesar , Fenza Raffaele Di , Larson Grant , Pinciroli Riccardo , Houle Timothy , Mueller Ariel Louise , Bellavia Andrea , Kacmarek Robert , Carroll Ryan , Berra Lorenzo 
Published: April 2020

AbstractIntroductionIn human hosts, SARS-CoV-2 causes a respiratory syndrome (named COVID-19) which can range from a mild involvement of the upper airways to a severe pneumonia with acute respiratory syndrome that requires mechanical ventilation in an intensive care unit (ICU). Hospital-associated transmission is an important route of spreading for the SARS-CoV-2 virus and healthcare providers are at the highest risk. As of February 2020, 1716, Chinese healthcare workers had confirmed SARS-CoV-2 infections and at least 6 died. Unfortunately, there is currently no vaccine or pharmacological prophylaxis to decrease the risk of healthcare providers contracting the infection.Methods and analysisWe will randomize 470 healthcare providers scheduled to work with COVID 19 patients to receive nitric oxide gas administration (NO group, n=235) or no gas administration (control group, n=235). The primary endpoint of this study is the incidence of subjects with COVID-19 disease at 14 days from enrollment. Secondary endpoints are the proportion of healthcare providers who present a positive real time RT-PCR test for SARS-CoV- 2 14 days after enrollment, the proportion of healthcare providers requiring quarantine, and the total number of quarantine days in the two groups.Ethics and disseminationThe trial protocol is under the approval of The Partners Human Research Committee of Massachusetts General Hospital (Boston, USA) and recruitment is expected to start in April 2020. The results of this study will be published in scientific journals and presented at scientific meetings.
Functional Immune Deficiency Syndrome via Intestinal Infection in COVID-19
Authors: Prates Erica T. , Garvin Michael R. , Pavicic Mirko , Jones Piet , Shah Manesh , Alvarez Christiane , Kainer David , Demerdash Omar , Amos B Kirtley , Geiger Armin , Pestian John , Jin Kang , Mitelpunkt Alexis , Bardes Eric , Aronow Bruce , Jacobson Daniel 
Published: April 2020

AbstractUsing a Systems Biology approach, we integrated genomic, transcriptomic, proteomic, and molecular structure information to provide a holistic understanding of the COVID-19 pandemic. The expression data analysis of the Renin Angiotensin System indicates mild nasal, oral or throat infections are likely and that the gastrointestinal tissues are a common primary target of SARS-CoV-2. Extreme symptoms in the lower respiratory system likely result from a secondary-infection possibly by a comorbidity-driven upregulation of ACE2 in the lung. The remarkable differences in expression of other RAS elements, the elimination of macrophages and the activation of cytokines in COVID-19 bronchoalveolar samples suggest that a functional immune deficiency is a critical outcome of COVID-19. We posit that using a non-respiratory system as a major pathway of infection is likely determining the unprecedented global spread of this coronavirus.One Sentence SummaryA Systems Approach Indicates Non-respiratory Pathways of Infection as Key for the COVID-19 Pandemic
High-throughput PRPF31 variant characterisation pipeline consistent with ACMG/AMP clinical variant interpretation guidelines
Authors: Nazlamova Liliya , Cheung Man-Kim , Legebeke Jelmer , Lord Jenny , Pengelly Reuben J. , Tapper William , Wheway Gabrielle 
Published: April 2020

AbstractMutations in PRPF31 are the second most common cause of the degenerative retinal condition autosomal dominant retinitis pigmentosa. Difficulty in characterising missense variants in this gene presents a significant challenge in providing accurate diagnosis for patients to enable targeted testing of other family members, aid family planning, allow pre-implantation diagnosis and inform eligibility for gene therapy trials. With PRPF31 gene therapy in development, there is an urgent need for tools for accurate molecular diagnosis. Here we present a high-throughput high content imaging assay providing quantitative measure of effect of missense variants in PRPF31 which meets the recently published criteria for a baseline standard in vitro test for clinical variant interpretation. This assay utilizes a new and well-characterized PRPF31+/- human retinal cell line generated using CRISPR gene editing, which allows testing of PRPF31 variants which may be causing disease through either haploinsufficiency or dominant negative effects, or a combination of both. The mutant cells have significantly fewer cilia than wild-type cells, allowing rescue of ciliogenesis with benign or mild variants, but do not totally lack cilia, so dominant negative effects can be observed. The results of the assay provide BS3_supporting evidence to the benign classification of two novel uncharacterized PRPF31 variants and suggest that one novel uncharacterized PRPF31 variant may be pathogenic. We hope that this will be a useful tool for clinical characterisation of PRPF31 variants of unknown significance, and can be extended to variant classification in other ciliopathies.
Risk Factors Analysis of Acute Kidney Injury in Adult Patients Receiving Extracorporeal Membrane Oxygenation
Authors: Mou Zhixiang 
Published: April 2020

AbstractBackgroundAcute kidney injury (AKI) has been reported as one of the most common complication in patients receiving extracorporeal membrane oxygenation (ECMO), the risk factors of AKI on ECMO is unknown. This meta-analysis aimed to find out the risk factors of AKI among adult patients receiving ECMO.MethodsA literature search was performed using PubMed,Web of Science, and Embase fulfilled the pre-specified criteria until April 2020 to include studies reported the necessary clinic characteristics, then the gender, cancer, diffuse intravascular coagulation (DIC), massive/severe Bleeding, intra-aortic balloon pump (IABP), post-cardiotomy, diabetes mellitus, liver cirrhosis and ECMO support duration were pooled for further analysis by STATA to get conclusion.ResultsThis research is first time to provide the evidence that patients developed AKI/severe AKI with a longer ECMO support duration (pooled WMD, 4.09 days; 95% CI: 2.45-5.73 days, Z= 4.89, P= 0.000, I2= 73.4%, χ2P= 0.023/pooled WMD, 1.52 days; 95% CI: 0.19-2.85 days, Z= 2.25, P= 0.025, I2= 77.4%, χ2P= 0.001) and the risk of severe AKI requiring RRT was higher (pooled OR, 2.22; 95% CI: 1.24-3.99, Z= 2.68, P= 0.007, I2= 0.0%, χ2P= 0.634) in liver cirrhosis patients by systemic analysis, indicated ECMO support duration and liver cirrhosis may act as risk factors of AKI in adult patients received ECMO.
Data model to predict prevalence of COVID-19 in Pakistan
Authors: Qasim Muhammad , Ahmad Waqas , Zhang Shenghuan , Yasir Muhammad , Azhar Muhammad 
Published: April 2020

AbstractCoronavirus disease 2019 (COVID19) has spread to 181 countries and regions and leaving behind 1,133,788 confirmed cases and 62784 deaths worldwide. Countries with lower health services and facilities like Pakistan are on great risk. Pakistan so far has 3,277 confirmed cases and 50 reported deaths due to COVID19. Various mathematical models had presented to predict the global and regional size of pandemic. However, all those models have certain limitation due to their dependence on different variables and analyses are subject to potential bias. As each country has its own dimension therefore country specific model are required to develop accurate estimate. Here we present a data model to predict the size of COVID19 in Pakistan. In this mathematical data model, we used the time sequence mean weighting (TSMW) to estimate the expected future number of COVID19 cases in Pakistan until 29th April 2020. For future expected numbers of cases for long terms the data collection have to be maintained in real time.
A study of SARS-CoV-2 epidemiology in Italy: from early days to secondary effects after social distancing
Authors: Traini Marco Claudio , Caponi Carla , Ferrari Riccardo , De Socio Giuseppe Vittorio 
Published: April 2020

BackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 101739 confirmed cases, in Italy, as of March 30th, 2020. While the analogous event in China appears to be under control at the moment, the outbreaks in western countries are still at an early stage of development. Italy, at present, is playing a major role in understanding the transmission dynamics of these new infections and evaluating the effectiveness of control measures in a western social context.MethodsWe combined a quarantined model with early-stage development data in Italy (during the period February 20th - March 30th) to predict longer-term progression (up to March 30th, and till June 25th, 2020 in a longterm view) with different control measures. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies leading to faster confirmation of the SARS-CoV-2 infections, we made use of time-dependent contact and diagnosis rates to estimate when the effective daily reproduction ratio can fall below 1. Within the same framework, we analyze the possible secondary infection event after relaxing the isolation measures.Outcomes and interpretationWe study two simplified scenarios compatible with the observation data and the effects of two stringent measures on the evolution of the epidemic. On one side, the contact rate must be kept as low as possible, but it is also clear that, in a modern developed country, it cannot fall under certain minimum levels and for a long time. The complementary parameter tuned is the transition rate of the symptomatic infected individuals to the quarantined class, a parameter δI connected with the time tI = 1/δI needed to perform diagnostic tests. Within the conditions of the outbreak in Italy, this time must fall under 12-8 hours in order to make the reproduction number less than 1 to minimize the case numbers. Moreover, we show how the same parameter plays an even more important role in mitigating the effects of a possible secondary infection event.FundingNo funding has been provided by private or public actors beyond the current clinical practice (National Health Service).
COVID-19: Tracking the Pandemic with A Simple Curve Approximation Tool (SCAT)
Authors: Courtney Jane 
Published: April 2020

AbstractIn the current COVID-19 pandemic, much focus is put on ‘flattening the curve’. This epidemiological ‘curve’ refers to the cases versus time graph, which shows the rise of a disease to its peak before descending. The aim in a pandemic is to flatten this curve by reducing the peak and spreading out the timeline. However, the models used to predict this curve are often not clearly outlined, no model parameters are given, and models are not tested against real data. This lack of detail makes it difficult to recreate the curve. What is much needed is a simple tool for approximating the curve to allow ideas to be tested and comparisons made.This work presents a Simple Curve Approximation Tool (SCAT) which can be used by anyone. This tool allows the user to approximate and draw the curve and allows testing of assumptions, trajectories and the wildly varying figures reported in the media. The mathematics behind SCAT is clearly outlined here but understanding of this is not required. SCAT is provided online as a downloadable MS Excel workbook with some sample cases shown. Throughout this work, the parameters used are specified so that all results can be easily reproduced.Although not intended as a prediction tool, SCAT has achieved less than 0.5 % error in short-term forward prediction. It also shows a very significant improvement on the pandemic exponential approximations found throughout media reporting. As a comparison tool, it highlights obvious differences between COVID-19 and other diseases, such as influenza, and between countries at different stages of the pandemic (China, Italy and the UK are used here for demonstration purposes).SCAT allows for quick approximation of the curve and creates meaningful comparisons and understandable visualisations for COVID-19 and other diseases.
A virus that has gone viral: Amino acid mutation in S protein of Indian isolate of Coronavirus COVID-19 might impact receptor binding and thus infectivity
Authors: Saha Priyanka , Banerjee Arup Kumar , Tripathi Prem Prakash , Srivastava Amit Kumar , Ray Upasana 
Published: April 2020

AbstractSince 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002, MERS-CoV in 2012, and the recent outbreak of SARS-CoV-2 late in 2019 (also named as COVID-19 or novel coronavirus 2019 or nCoV2019. Spike(S) protein, one of the structural proteins of this virus plays key role in receptor (ACE2) binding and thus virus entry. Thus, this protein has attracted scientists for detailed study and therapeutic targeting. As the 2019 novel coronavirus takes its course throughout the world, more and more sequence analyses are been done and genome sequences getting deposited in various databases. From India two clinical isolates have been sequenced and the full genome deposited in GenBank. We have performed sequence analyses of the spike protein of the Indian isolates and compared with that of the Wuhan, China (where the outbreak was first reported). While all the sequences of Wuhan isolates are identical, we found point mutations in the Indian isolates. Out of the two isolates one was found to harbour a mutation in its Receptor binding domain (RBD) at position 407. At this site arginine (a positively charged amino acid) was replaced by isoleucine (a hydrophobic amino acid that is also a C-beta branched amino acid). This mutation has been seen to change the secondary structure of the protein at that region and this can potentially alter receptor ding of the virus. Although this finding needs further validation and more sequencing, the information might be useful in rational drug designing and vaccine engineering.
Vulnerabilities of the SARS-CoV-2 virus to proteotoxicity – opportunity for repurposed chemotherapy of COVID-19 infection
Authors: Al-Motawa Maryam , Abbas Hafsa , Wijten Patrick , de la Fuente Alberto , Xue Mingzhan , Rabbani Naila , Thornalley Paul J. 
Published: April 2020

SUMMARYThe global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments whilst effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 predicted to be in functional domains, we examined which are activated towards modification by MG – residues with predicted or expected low pKaby neighbouring group in interactions. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in relatedcoronaviridae: SARS-COV and MERS. Finally, we identified drugs which increase cellular MG concentration to virucidal levels: antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel. Our findings provide evidence of potential vulnerability of SARS-CoV-2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.
Pat1 increases the range of decay factors and RNA bound by the Lsm1-7 complex
Authors: Lobel Joseph H. , Gross John D. 
Published: April 2020

AbstractPat1 promotes the activation and assembly of multiple proteins during mRNA decay. After deadenylation, the Pat1/Lsm1-7 complex binds to transcripts containing oligo(A) tails, which can be modified by the addition of several terminal uridine residues. Pat1 enhances Lsm1-7 binding to the 3’ end, but it is unknown how this interaction is influenced by nucleotide composition. Here we examine Pat1/Lsm1-7 binding to a series of oligoribonucleotides containing different A/U contents using recombinant purified proteins from fission yeast. We observe a positive correlation between fractional uridine content and Lsm1-7 binding affinity. Addition of Pat1 broadens RNA specificity of Lsm1-7 by enhancing binding to A-rich RNAs and increases cooperativity on all oligonucleotides tested. Consistent with increased cooperativity, Pat1 promotes multimerization of the Lsm1-7 complex, which is potentiated by RNA binding. Furthermore, the inherent ability of Pat1 to multimerize drives liquid-liquid phase separation with multivalent decapping enzyme complexes of Dcp1/Dcp2. Our results uncover how Pat1 regulates RNA binding and higher order assembly by mRNA decay factors.
Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach
Authors: Lokman Syed Mohammad , Rasheduzzaman Md. , Salauddin Asma , Barua Rocktim , Tanzina Afsana Yeasmin , Rumi Meheadi Hasan , Hossain Md. Imran , Siddiki Amam Zonaed , Mannan Adnan , Hasan Md. Mahbub 
Published: April 2020

AbstractThe newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.