bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical analysis of national & municipal corporation level database of COVID-19 cases In India
Authors: Bajaj Naman S. , Pardeshi Sujit S. , Patange Abhishek D. , Kotecha Disha , Mate K. K. 
Published: July 2020

AbstractSince its origin in December 2019, Novel Coronavirus or COVID-19 has caused massive panic in the word by infecting millions of people with a varying fatality rate. The main objective of Governments worldwide is to control the extent of the outbreak until a vaccine or cure has been devised. Machine learning has been an efficient mechanism to train, map, analyze, and predict datasets. This paper aims to utilize regression, a supervised machine learning algorithm to assess time-series datasets of COVID-19 pandemic by performing comparative analysis on datasets of India and two Municipal Corporations of Maharashtra, namely, Mira-Bhayander and Akola. Current study is an attempt towards drawing attention to the dynamics and nature of the pandemic in a controlled locality such as Municipal Corporation; which differs from the exponential nature observed nationally. However, for limited area like the one considered the nature of curve is observed to be cubic for total cases and multi-peak Gaussian for active cases. In conclusion, Government should empower district/ corporations/local authorities to adopt their own methodology and decision-making policy to contain the pandemic at regional-level like the case study discussed herein.
Transparency Assessment of COVID-19 Models
Authors: Jalali Mohammad S. , DiGennaro Catherine , Sridhar Devi 
Published: July 2020

AbstractAs the COVID-19 pandemic has caused major societal unrest, modelers have worked to project future trends of COVID-19 and predict upcoming challenges and impacts of policy action. These models, alone or in aggregate, are influential for decision-makers at every level. Therefore, the method and documentation of COVID-19 models must be highly transparent to ensure that projections and consequential policies put forth have sound epistemological grounds. We evaluated 29 COVID-19 models receiving high attention levels within the scientific community and/or informing government responses. We evaluated these models against 27 transparency criteria. We found high levels of transparency in model documentation aspects such as reporting uncertainty analysis; however, about half of the models do not share code and a quarter do not report equations. These discrepancies underscore the need for transparency and reproducibility to be at the forefront of researchers’ priorities, especially during a global health crisis when stakes are critically high.SummaryEvaluation of 29 impactful COVID-19 models reveals inconsistent adherence to best transparency practices; higher transparency is needed to inform policy.
Do low TB prevalence and lack of BCG Vaccinations Contribute to Emergence of Multisystem Inflammatory Syndrome in Children?
Authors: Raham Tareef Fadhil 
Published: July 2020

AbstractBackgroundEmergence of new multisystem inflammatory syndrome in children (MIS-C) is thought to be associated with COVID-19 pandemic. Covid-19 morbidity and mortality variances among countries have been suggested by previous works to be influenced by BCG and previous latent TB infection (which is reflected by TB prevalence) possibly through inducing heterogeneous immunity against SARS-CoV-2.AimTo examine influence of BCG status and TB prevalence on variances among countries which report new multisystem inflammatory syndrome in children (MIS-C).MethodsWe choose all countries which report MIS-C till 23/6/2020, number of cases for each 10 million inhabitants was examined among 3 categories of countries classified according to BCG program status. TB prevalence, MIS-C no. / 10 million (M) population and Covid-19 deaths/M are taken as markers. Receiver operation characteristic - (ROC) curve, with some relative indicators such as (sensitivity and specificity rates), estimation area of trade - off between sensitivity and specificity, and cutoff points are used with different studied markers for discriminating different three pairs of countries (which have different BCG practices).ResultsBCG vaccinations and high TB prevalence are found to be associated with decrease MIS-C no. and COVID-19 deathsConclusionsFindings might explain variances in MIS-C incidence and in COVID-19 mortality among countries worldwide. Further studies to confirm this relation and to confirm possible similar relations in Kawasaki disease(KD) in previous epidemics is recommended.What is Known-Although the etiology for KD remains unknown, available evidence supports the hypothesis that the pathogenesis is closely associated with dysregulation of immune responses to an infectious agent.-BCG and / or Latent TB have heterogeneous beneficial effects.What is NewOur study shows that TB prevalence and implementing BCG vaccination have negative statistical association with MIS-C cases and COVID-19 mortality.
Cryo-electron Microscopy and Exploratory Antisense Targeting of the 28-kDa Frameshift Stimulation Element from the SARS-CoV-2 RNA Genome
Authors: Zhang Kaiming , Zheludev Ivan N. , Hagey Rachel J. , Wu Marie Teng-Pei , Haslecker Raphael , Hou Yixuan J. , Kretsch Rachael , Pintilie Grigore D. , Rangan Ramya , Kladwang Wipapat , Li Shanshan , Pham Edward A. , Bernardin-Souibgui Claire , Baric Ralph S. , Sheahan Timothy P. , D′Souza Victoria , Glenn Jeffrey S. , Chiu Wah , Das Rhiju 
Published: July 2020

AbstractDrug discovery campaigns against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are beginning to target the viral RNA genome1, 2. The frameshift stimulation element (FSE) of the SARS-CoV-2 genome is required for balanced expression of essential viral proteins and is highly conserved, making it a potential candidate for antiviral targeting by small molecules and oligonucleotides3–6. To aid global efforts focusing on SARS-CoV-2 frameshifting, we report exploratory results from frameshifting and cellular replication experiments with locked nucleic acid (LNA) antisense oligonucleotides (ASOs), which support the FSE as a therapeutic target but highlight difficulties in achieving strong inactivation. To understand current limitations, we applied cryogenic electron microscopy (cryo-EM) and the Ribosolve7 pipeline to determine a three-dimensional structure of the SARS-CoV-2 FSE, validated through an RNA nanostructure tagging method. This is the smallest macromolecule (88 nt; 28 kDa) resolved by single-particle cryo-EM at subnanometer resolution to date. The tertiary structure model, defined to an estimated accuracy of 5.9 Å, presents a topologically complex fold in which the 5′ end threads through a ring formed inside a three-stem pseudoknot. Our results suggest an updated model for SARS-CoV-2 frameshifting as well as binding sites that may be targeted by next generation ASOs and small molecules.
Calibration and Evaluation of a Force Measurement Glove for Field-Based Monitoring of Manual Wheelchair Users
Authors: Anderson Anthony , Hooke Alexander W. , Jayaraman Chandrasekaran , Burns Adam , Fortune Emma , Sosnoff Jacob J. , Morrow Melissa M. 
Published: July 2020

AbstractManual wheelchair users exhibit pain related to repetitive and demanding shoulder activities of daily living. Wearable sensing systems like force measurement gloves can provide insights about upper extremity loading in the community and home environments. We calibrated and evaluated the accuracy of a novel force measurement glove with a body-worn data logger. The device was calibrated with loads of 0-800 N applied to the palmar surface of the glove. Calibration conditions were tested that varied the stiffness of the material in the glove, the temperature, and the curvature of the force applicator. Calibration equations from each condition were evaluated by comparing the glove’s force prediction with the output of an instrumented wheelchair rim during propulsion and weight relief exercises. The force measurement glove detected 72.7% of 355 propulsion peaks and had a strong linear correlation with the instrumented rim force measurements (r=0.80). The most accurate calibration equation was constructed using data from all conditions, with an RMS force measurement error of 64.7 N and 31.7 N for weight relief exercise and propulsion, respectively. The force measurement glove design described here may serve as a useful tool for detection of loading events and relative magnitude changes.
Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2
Authors: Onabajo Olusegun O. , Banday A. Rouf , Yan Wusheng , Obajemu Adeola , Stanifer Megan L. , Santer Deanna M. , Florez-Vargas Oscar , Piontkivska Helen , Vargas Joselin , Kee Carmon , Tyrrell D. Lorne J. , Mendoza Juan L. , Boulant Steeve , Prokunina-Olsson Ludmila 
Published: July 2020

ABSTRACTSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells.ACE2has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability inACE2expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform ofACE2, which we designate asdeltaACE2 (dACE2). We demonstrate thatdACE2, but notACE2, is an ISG.In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge onACE2expression and suggest that the ISG-type induction ofdACE2in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection.
The short- and long-range RNA-RNA Interactome of SARS-CoV-2
Authors: Ziv Omer , Price Jonathan , Shalamova Lyudmila , Kamenova Tsveta , Goodfellow Ian , Weber Friedemann , Miska Eric A. 
Published: July 2020

SUMMARYTheCoronaviridaeis a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped thein vivoRNA-RNA interactome of the full-length SARS-CoV-2 genome and subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome and subgenomes adopt alternative topologies inside cells, and engage in different interactions with host RNAs. Notably, we discovered a long-range RNA-RNA interaction - the FSE-arch - that encircles the programmed ribosomal frameshifting element. The FSE-arch is conserved in the related MERS-CoV and is under purifying selection. Our findings illuminate RNA structure based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses, and will aid future efforts to develop antiviral strategies.
Association of gut microbiota with cerebral cortex and cerebrovascular abnormality in human mild traumatic brain injury
Authors: Bai Lijun , Li Tianhui , Zhang Ming , Wang Shan , Gan Shuoqiu , Jia Xiaoyan , Yang Xuefei , Sun Yinxiang , Xiong Feng , Yin Bo , Ren Yi , Bai Guanghui , Yan Zhihan , Mu Xin , Zhu Feng 
Published: July 2020

AbstractKey roles of the gut–brain axis in brain injury development have been suggested in various mouse models; however, little is known about its functional significance in human mild traumatic brain injury (TBI). Here, we decipher this axis by profiling the gut microbiota in 98 acute mild TBI patients and 62 matched controls, and subgroup of them also measured circulating mediators and applied neuroimaging. Mild TBI patients had increased α-diversity and different overall microbial compositions compared with controls. 25-microbial genus classifiers distinguish patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.889, while adding serum mediators and neuroimaging features further improved performance even in a small sample size (AUC = 0.969). Numerous correlations existed between gut bacteria, aberrant cortical thickness and cerebrovascular injury. Co-occurrence network analysis revealed two unique gut–brain axes in patients: 1) altered intestinalLachnospiraceae_NK4A136_groupandEubacterium_ruminantium_group-increased serum GDNF-subcallosal hypertrophy and cerebrovascular injury; 2) decreased intestinalEubacterium_xylanophilum_group–upregulated IL-6–thinned anterior insula. Our findings provide a new integrated mechanistic understanding and diagnostic model of mild TBI.
Spliceosome-Associated MicroRNAs Identified in Breast Cancer Cells Act on Nuclear Targets and Are Potential Indicators for Tumorigenicity
Authors: Mahlab-Aviv Shelly , Zohar Keren , Cohen Yael , Peretz Ayelet R. , Eliyahu Tsiona , Linial Michal , Sperling Ruth 
Published: July 2020

AbstractMicroRNAs (miRNAs) act as negative regulators of gene expression in the cytoplasm. Previous studies identified miRNAs associated with the spliceosome. Here we study three breast-derived cell-lines with increased tumorigenicity (from MCF-10A to MCF-7 and MDA-MB-231) and compared their miRNA sequences at the spliceosome fraction (SF). We report that the SF-miRNAs expression, identity, and pre-miRNA segmental composition vary across these cell-lines. The expression of the majority of the abundant SF-miRNAs (e.g. miR-100, miR-30a, and let-7 members) shows an opposite trend in view of the literature and breast cancer large cohorts. The results suggest that SF-miRNAs act in the nucleus on alternative targets than in the cytoplasm. One such miRNA is miR-7704 whose genomic position overlaps HAGLR, a cancer-related lncRNA. We found an inverse expression of miR-7704 and HAGLR in the tested cell lines. Moreover, inhibition of miR-7704 caused an increase in HAGLR expression. Furthermore, increasing miR-7704 levels attenuated the MDA-MB-231 cell-division rate. While miR-7704 acts as oncomiR in breast cancer patients, it has a tumor-suppressing function in SF, with HAGLR being its nuclear target. Manipulating miR-7704 levels is a potential lead for altering tumorigenicity. Altogether, we report on the potential of manipulating SF-miRNAs as an unexplored route for breast cancer therapeutics.
ATrypanosoma bruceiORFeome-based Gain-of-Function Library identifies genes that promote survival during melarsoprol treatment
Authors: Carter M , Gomez S , Gritz S , Larson S , Silva-Herzog E , Kim HS , Schulz D , Hovel-Miner GA 
Published: July 2020

ABSTRACTTrypanosoma bruceiis an early branching protozoan parasite that causes human and animal African Trypanosomiasis. Forward genetics approaches are powerful tools for uncovering novel aspects of Trypanosomatid biology, pathogenesis, and therapeutic approaches against trypanosomiasis. Here we have generated aT. bruceicloned ORFeome consisting of over 90% of the targeted 7,245 genes and used it to make an inducible Gain-of-Function parasite library broadly applicable to large-scale forward genetic screens. We conducted a proof of principle genetic screen to identify genes whose expression promotes survival in melarsoprol, a critical drug of last resort. The 57 genes identified as overrepresented in melarsoprol survivor populations included the rate-limiting enzyme for the biosynthesis of an established drug target (trypanothione), validating the tool. In addition, novel genes associated with gene expression, flagellum localization, and mitochondrion localization were identified and a subset of those genes increased melarsoprol resistance upon overexpression in culture. These findings offer new insights into Trypanosomatid basic biology, implications for drugs targets, and direct or indirect drug resistance mechanisms. This study generated aT. bruceiORFeome and Gain-of-Function parasite library, demonstrated the libraries’ usefulness in forward genetic screening, and identified novel aspects of melarsoprol resistance that will be the subject of future investigations. These powerful genetic tools can be used to broadly advance Trypanosomatid research.IMPORTANCETrypanosomatid parasites threaten the health of over 1 billion people worldwide. Because their genomes are highly diverged from well-established eukaryotes, conservation is not always useful in assigning gene functions. However, it is precisely among the Trypanosomatid-specific genes that ideal therapeutic targets might be found. Forward genetics approaches are an effective way to identify novel gene functions. We used an ORFeome approach to clone a large percentage ofTrypanosoma bruceigenes and generate a Gain-of-Function parasite library. This library was used in a genetic screen to identify genes that promote resistance to the clinically significant, yet highly toxic drug, melarsoprol. Hits arising from the screen demonstrated the library’s usefulness in identifying known pathways and uncovered novel aspects of resistance mediated by proteins localized to the flagellum and mitochondrion. The powerful new genetic tools generated herein are expected to promote advances in Trypanosomatid biology and therapeutic development in the years to come.
The COVID-19 outbreak in Sichuan, China: epidemiology and impact of interventions
Authors: Liu Quan-Hui , Bento Ana I. , Yang Kexin , Zhang Hang , Yang Xiaohan , Merler Stefano , Vespignani Alessandro , Lv Jiancheng , Yu Hongjie , Zhang Wei , Zhou Tao , Ajelli Marco 
Published: July 2020

AbstractIn January 2020, a COVID-19 outbreak was detected in Sichuan Province of China. The aim of this work is to characterize the epidemiology of the Sichuan outbreak and estimate the impact of the performed interventions. We analyzed patient records for all laboratory-confirmed cases reported in the province for the period of January 21 to March 16, 2020. To estimate the basic and daily reproduction numbers, we used a Bayesian framework. In addition, we estimate the number of cases averted by the implemented control strategies. The outbreak resulted in 539 confirmed cases, lasted less than two months, and no further local transmission was detected after February 27. The median age of local cases was 8 years older than that of imported cases. Severity of symptoms increased with age. We estimated R0 at 2.4 (95% CI: 1.6–3.7). The epidemic was self-sustained for about 3 weeks before going below the epidemic threshold 3 days after the declaration of a public health emergency by Sichuan authorities. Our findings indicate that, were the control measures be adopted four weeks later, the epidemic could have lasted 49 days longer (95%CI: 31-68 days), causing 9,216 (95%CI: 1,317-25,545) more cases and possibly overwhelming Sichuan healthcare system.
Time series metagenomic sampling of the Thermopyles, Greece, geothermal springs reveals stable microbial communities dominated by novel sulfur-oxidizing chemoautotrophs
Authors: Meziti A. , Nikouli E. , Hatt J.K. , Konstantinidis K. , Kormas K. Ar. 
Published: July 2020

AbstractGeothermal springs are barely affected by environmental conditions aboveground as they are continuously supplied with subsurface water with little variability in chemistry. Therefore, changes in their microbial community composition and function, especially over a long period, are expected to be limited but this assumption has not yet been rigorously tested. Toward closing this knowledge gap, we applied whole metagenome sequencing to 17 water samples collected between 2010 and 2016 (two to four samples per year) from the Thermopyles sulfur geothermal springs in central Greece. As revealed by 16S rRNA gene fragments recovered in the metagenomes,Epsilonproteobacteria-related operational taxonomic units (OTUs) dominated most samples, while grouping of samples based on OTU abundances exhibited no apparent seasonal pattern. Similarities between samples regarding functional gene content were high, especially in comparison to other surface water systems in Greece, with all samples sharing >70% similarity in functional pathways. These community-wide patterns were further confirmed by analysis of metagenome-assembled genomes (MAGs), which showed - in addition- that novel species and genera of the chemoautotrophicCampylobacteralesorder dominated the springs. These MAGs carried different pathways for thiosulfate and/or sulfide oxidation coupled to carbon fixation pathways. Overall, our study showed that even in the long term, functions of microbial communities in a moderately hot terrestrial spring remain stable, driving presumably the corresponding stability in community structure.
Dynamic allocation of carbon storage and nutrient-dependent exudation in a revised genome-scale model ofProchlorococcus
Authors: Ofaim Shany , Sulheim Snorre , Almaas Eivind , Sher Daniel , Segrè Daniel 
Published: July 2020

AbstractMicrobial life in the oceans impacts the entire marine ecosystem, global biogeochemistry and climate. The marine cyanobacteriumProchlorococcus, an abundant component of this ecosystem, releases a significant fraction of the carbon fixed through photosynthesis, but the amount, timing and molecular composition of released carbon are still poorly understood. These depend on several factors, including nutrient availability, light intensity and glycogen storage. Here we combine multiple computational approaches to provide insight into carbon storage and exudation inProchlorococcus. First, with the aid of a new algorithm for recursive filling of metabolic gaps (ReFill), and through substantial manual curation, we extended an existing genome-scale metabolic model ofProchlorococcusMED4. In this revised model (iSO595), we decoupled glycogen biosynthesis/degradation from growth, thus enabling dynamic allocation of carbon storage. In contrast to standard implementations of flux balance modeling, we made use of forced influx of carbon and light into the cell, to recapitulate overflow metabolism due to the decoupling of photosynthesis and carbon fixation from growth during nutrient limitation. By using random sampling in the ensuing flux space, we found that storage of glycogen or exudation of organic acids are favored when the growth is nitrogen limited, while exudation of amino acids becomes more likely when phosphate is the limiting resource. We next used COMETS to simulate day-night cycles and found that the model displays dynamic glycogen allocation and exudation of organic acids. The switch from photosynthesis and glycogen storage to glycogen depletion is associated with a redistribution of fluxes from the Entner-Doudoroff to the Pentose Phosphate pathway. Finally, we show that specific gene knockouts iniSO595 exhibit dynamic anomalies compatible with experimental observations, further demonstrating the value of this model as a tool to probe the metabolic dynamic ofProchlorococcus.