bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of medical resource capacities and intensities of public mitigation measures on outcomes of COVID-19 outbreaks
Authors: Wang Xia , Li Qian , Sun Xiaodan , He Sha , Xia Fan , Song Pengfei , Shao Yiming , Wu Jianhong , Cheke Robert A. , Tang Sanyi , Xiao Yanni 
Published: April 2020

AbstractThe COVID-19 pandemic is complex and is developing in different ways according to the country involved. To identify the key parameters or processes that have the greatest effects on the pandemic and reveal the different progressions of epidemics in different countries, we quantified enhanced control measures and the dynamics of the production and provision of medical resources. We then nested these within a COVID-19 epidemic transmission model, which is parameterized by multi-source data. We obtained rate functions related to the intensity of mitigation measures, the effective reproduction numbers and the timings and durations of runs on medical resources, given differing control measures implemented in various countries. Increased detection rates may induce runs on medical resources and prolong their durations, depending on resource availability. Nevertheless, improving the detection rate can effectively and rapidly reduce the mortality rate, even after runs on medical resources. Combinations of multiple prevention and control strategies and timely improvement of abilities to supplement medical resources are key to effective control of the COVID-19 epidemic. A 50% reduction in comprehensive control measures would have led to the cumulative numbers of confirmed cases and deaths exceeding 590000 and 60000, respectively, by 27 March 2020 in mainland China. The proposed model can assist health authorities to predict when they will be most in need of hospital beds and equipment such as ventilators, personal protection equipment, drugs and staff.One sentence summaryMultiple data sources and cross validation of a COVID-19 epidemic model, coupled with a medical resource logistic model, reveal that the key factors that affect epidemic progressions and their outbreak patterns in different countries are the type of emergency medical response to avoid runs on medical resources, especially improved detection rates, the ability to promote public health measures, and the synergistic effects of combinations of multiple prevention and control strategies.
Is iron deficiency a major cause of anaemia in Sri Lankan children aged 5-10 years?
Authors: Jayatissa Renuka , Fernando DN , Ranbanda JM , De Silva KH 
Published: April 2020

ABSTRACTBackgroundTo assess the iron status among children aged 5–10 yearsMethodsA cross sectional study in Gampaha district. A sample of 704 children aged 5-10 years resident in a sample of households selected using a two-stage sampling method. A pre tested interviewer administered questionnaire was used to collect information on socio demographic characteristics, housing and sanitation facilities and other relevant variables from the households. Anthropometry was performed on all children aged 5–10 years using standard procedures. Venous blood samples were taken to assess the haemoglobin (Hb) level, levels of Serum Ferritin and C-Reactive Protein.ResultsOverall prevalence rate of anaemia, iron deficiency and iron deficiency anaemia in children aged 5-10 years in Gampaha district was 22.7%, 22.1% and 13.5% respectively. The prevalence of iron deficiency among the urban children was significantly higher than that among rural children. The source of water to the households in the households with piped water had a higher prevalence of iron deficiency which was different from the others. The prevalence of iron deficiency among stunted and wasted children was higher though not at a significant level. A substantial proportion of children who were not anaemic were iron deficient.ConclusionsIron deficiency is an important health problem in this population. Only half of iron deficient children were anaemic and anaemia cannot be solely explained by iron deficiency.
Utah-Stanford Ventilator (Vent4US): Developing a rapidly scalable ventilator for COVID-19 patients with ARDS
Authors: Li Hongquan , Li Ethan , Krishnamurthy Deepak , Kolbay Patrick , Chacin Beca , Hoehne Soeren , Cybulski Jim , Brewer Lara , Petelenz Tomasz , Orr Joseph , Sakata Derek , Clardy Thomas , Kuck Kai , Prakash Manu 
Published: April 2020

AbstractWe describe a minimum, rapidly scalable ventilator designed for COVID-19 patients with ARDS. Our design philosophy is not only to try to address potential ventilator shortages, but also to account for uncertainties in the supply chains of parts commonly used in traditional ventilators. To do so we employ a modular design approach and broadly explore taking advantage of parts from non-traditional supply chains. In our current prototype, we demonstrate volume control with assist control on a test lung and present a linear actuator-driven pinch valve-based implementation for both pressure control and volume control with decelerating inspiratory flow. We estimate the component cost of the system to be around $500. We publish our draft design documents and current implementation which is open and accessible in the hope that broadening the community globally will accelerate arriving at a solution and that peer review will improve the final design.
Diagnostics and prognostic potential of current biomarkers in heart failure with preserved ejection fraction: a systematic review and meta-analysis
Authors: Chen Hao , Chhor Michael , Rayner Benjamin , McGrath Kristine , McClements Lana 
Published: April 2020

ABSTRACTAimsCirculating biomarkers are commonly used in diagnosis and prognosis of heart failure with preserved ejection fraction (HFpEF) in clinical practice. However, the diagnostic and prognostic potential of current biomarkers in HFpEF remain unclear.Methods and resultsWe conducted a search of the PubMed, Web of Science, MEDLINE and SCOPUS (1900 to January 2020) databases of all diagnostic (n=1,104) and prognostic (n=53,497) biomarkers investigated in people with HFpEF. B-type natriuretic peptide (BNP) displayed satisfactory sensitivity (0.81, 95% CI: 0.76 to 0.85; I2=0) and specificity (0.86, 95% CI: 0.82 to 0.89; I2=16.9%) for the diagnosis of HFpEF. Natriuretic peptides (NPs), including N-terminal pro BNP (NT-proBNP) and BNP, were associated with over two-fold increased risk of mortality (NT-proBNP: HR=2.27, 95% CI: 1.69 to 3.06, I2=87.6%; BNP: HR=3.01, 95% CI: 1.27 to 7.21, I2=97.2%), hospitalisation (NT-proBNP: HR=3.54, 95% CI: 2.83 to 4.43, I2=83.4%), and a composite event of both (NT-proBNP: HR=2.55, 95% CI: 2.13 to 3.05, I2=78.1%; BNP: HR=2.28, 95% CI: 1.42 to 3.69, I2=75.8%) in people with HFpEF. Interestingly, Galectin-3 (Gal-3) (sensitivity: 0.70, 95% CI: 0.63 to 0.75, I2=86.7%; specificity: 0.78, 95% CI: 0.69 to 0.85, I2=68.6%) and soluble suppression of tumorigenicity 2 (sST2) (sensitivity: 0.58, 95% CI: 0.52 to 0.64, I2=88.1%; specificity: 0.59, 95% CI: 0.49 to 0.68, I2=69.5%) showed limited diagnostic potential of HFpEF.ConclusionAmongst currently available biomarkers, BNP remains the most reliable diagnostic marker of HFpEF. Although there was high heterogeneity between the studies included, BNP or NT-proBNP could also have promising prognostic potential in HFpEF.
A Chronological and Geographical Analysis of Personal Reports of COVID-19 on Twitter
Authors: Klein Ari Z. , Magge Arjun , O’Connor Karen , Cai Haitao , Weissenbacher Davy , Gonzalez-Hernandez Graciela 
Published: April 2020

ABSTRACTThe rapidly evolving outbreak of COVID-19 presents challenges for actively monitoring its spread. In this study, we assessed a social media mining approach for automatically analyzing the chronological and geographical distribution of users in the United States reporting personal information related to COVID-19 on Twitter. The results suggest that our natural language processing and machine learning framework could help provide an early indication of the spread of COVID-19.
GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background
Authors: Sinnott-Armstrong Nasa , Naqvi Sahin , Rivas Manuel , Pritchard Jonathan K 
Published: April 2020

SummaryGenome-wide association studies (GWAS) have been used to study the genetic basis of a wide variety of complex diseases and other traits. We describe UK Biobank GWAS results for three molecular traits—urate, IGF-1, and testosterone—with better-understood biology than most other complex traits. We find that many of the most significant hits are readily and surprisingly interpretable. We observe huge enrichment of associations near genes involved in the relevant biosynthesis, transport, or signaling pathways. We show how GWAS data illuminate the biology of each trait, including differences in testosterone regulation between females and males. At the same time, even these molecular traits are highly polygenic, with many thousands of variants spread across the genome contributing to trait variance. In summary, for these three molecular traits we identify strong enrichment of signal in putative core gene sets, even while most of the SNP-based heritability is driven by a massively polygenic background.
ILC1-derived TGFβ1 drives intestinal remodelling
Authors: Jowett Geraldine M. , Norman Michael D. A. , Yu Tracy T. L. , Arévalo Patricia Rosell , Hoogland Dominique , Lust Suzette , Read Emily , Hamrud Eva , Walters Nick J. , Niazi Umar , Chung Matthew Wai Heng , Marciano Daniele , Omer Omer Serhan , Zabinski Tomasz , Danovi Davide , Lord Graham M. , Hilborn Jöns , Evans Nicholas D. , Dreiss Cécile A. , Bozec Laurent , Oommen Oommen P. , Lorenz Christian D. , da Silva Ricardo M.P. , Neves Joana F. , Gentleman Eileen 
Published: April 2020

AbstractOrganoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we developed gut organoid co-cultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate for the first time that murine and human ILC1 secrete TGFβ1, driving expansion of CD44v6+epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
Role of c-Met/β1 integrin complex in the metastatic cascade
Authors: Lau Darryl , Wadhwa Harsh , Sudhir Sweta , Jain Saket , Chandra Ankush , Nguyen Alan , Spatz Jordan , Shah Sumedh S. , Cheng Justin , Safaee Michael , Yagnik Garima , Jahangiri Arman , Aghi Manish K. 
Published: April 2020

ABSTRACTMetastases cause 90% of human cancer deaths. The metastatic cascade involves local invasion, intravasation, extravasation, metastatic site colonization, and proliferation. While individual mediators of these processes have been investigated, interactions between these mediators remain less well defined. We previously identified a structural complex between receptor tyrosine kinase c-Met and β1 integrin in metastases. Using novel cell culture andin vivoassays, we found that c-Met/β1 complex induction promotes breast cancer intravasation and adhesion to the vessel wall, but does not increase extravasation. These effects may be driven by the ability of the c-Met/β1 complex to increase mesenchymal and stem cell characteristics. Multiplex transcriptomic analysis revealed upregulated Wnt and hedgehog pathways after c-Met/β1 complex induction. A β1 integrin point mutation that prevented binding to c-Met reduced intravasation. OS2966, a therapeutic antibody disrupting c-Met/β1 binding, decreased invasion and mesenchymal gene expression and morphology of breast cancer cells. Bone-seeking breast cancer cells exhibited higher c-Met/β1 complex levels than parental controls and preferentially adhere to tissue-specific matrix. Patient bone metastases demonstrated higher c-Met/β1 levels than brain metastases. Thus, the c-Met/β1 complex drives breast cancer cell intravasation and preferential affinity for bone tissue-specific matrix. Pharmacological targeting of the complex may prevent metastases, particularly osseous metastases.
Synonymous mutations and the molecular evolution of SARS-Cov-2 origins
Authors: Wang Hongru , Pipes Lenore , Nielsen Rasmus 
Published: April 2020

AbstractHuman severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in thedN/dSratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively.
Dynamical asymmetry exposes 2019-nCoV prefusion spike
Authors: Roy Susmita 
Published: April 2020

AbstractThe novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets.One Sentence SummaryInter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective.
Erythropoietin regulates transcription and YY1 dynamics in a pre-established chromatin architecture
Authors: Perreault Andrea A. , Brown Jonathan D. , Venters Bryan J. 
Published: April 2020

AbstractThe three dimensional architecture of the genome plays an essential role in establishing and maintaining cell identity. By contrast, the magnitude and temporal kinetics of changes in chromatin structure that arise during cell differentiation remain poorly understood. Here, we leverage a murine model of erythropoiesis to study the relationship between chromatin conformation, the epigenome, and transcription in erythroid cells. We discover that acute transcriptional responses induced by erythropoietin (EPO), the hormone necessary for erythroid differentiation, occur within an invariant chromatin topology. Within this pre-established landscape, Yin Yang 1 (YY1) occupancy dynamically redistributes to sites in proximity to EPO-regulated genes. Using HiChIP, we identify chromatin contacts mediated by H3K27ac and YY1 that are enriched for enhancer-promoter interactions of EPO-responsive genes. Taken together, these data are consistent with an emerging model that rapid, signal-dependent transcription occurs in the context of a pre-established chromatin architecture.
Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens
Authors: Liu Jun , Babka April M. , Kearney Brian J. , Radoshitzky Sheli R. , Kuhn Jens H. , Zeng Xiankun 
Published: April 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of human coronavirus disease 2019 (COVID-19), emerged in Wuhan, China in December 2019. The virus rapidly spread globally, resulting in a public-health crisis including more than one million cases and tens of thousands of deaths. Here, we describe the identification and evaluation of commercially available reagents and assays for the molecular detection of SARS-CoV-2 in infected formalin fixed paraffin embedded (FFPE) cell pellets. We identified a suitable rabbit polyclonal anti-SARS-CoV spike protein antibody and a mouse monoclonal anti-SARS-CoV nucleocapsid protein (NP) antibody for cross detection of the respective SARS-CoV-2 proteins by immunohistochemistry (IHC) and immunofluorescence assay (IFA). Next, we established RNAscopein situhybridization (ISH) to detect SARS-CoV-2 RNA. Furthermore, we established a multiplex fluorescence ISH (mFISH) to detect positive-sense SARS-CoV-2 RNA and negative-sense SARS-CoV-2 RNA (a replicative intermediate indicating viral replication). Finally, we developed a dual staining assay using IHC and ISH to detect SARS-CoV-2 antigen and RNA in the same FFPE section. These reagents and assays will accelerate COVID-19 pathogenesis studies in humans and in COVID-19 animal models.
Rab14/MACF2/CAMSAP3 Complex Regulates Endosomal Targeting to the Abscission Site During Cytokinesis
Authors: Gibieža Paulius , Peterman Eric , Hoffman Huxley K. , Van Engeleburg Schuyler , Arvydas Skeberdis Vytenis , Prekeris Rytis 
Published: April 2020

ABSTRACTAbscission is complex cellular process that is required for mitotic division. It is well-established that coordinated and localized changes in actin and microtubule dynamics are vital for cytokinetic ring formation, as well as establishment of the abscission site. Actin cytoskeleton reorganization during abscission would not be possible without the interplay between Rab11- and Rab35-containing endosomes and their effector proteins, whose roles in regulating endocytic pathways at the cleavage furrow have now been studied extensively. Here, we identified Rab14 as novel regulator of abscission. We demonstrate that depletion of Rab14 causes either cytokinesis failure or significantly prolongs division time. We show that Rab14 regulates the efficiency of recruiting Rab11-endosomes to the central spindle microtubules and that Rab14 knockout leads to inhibition of actin clearance at the abscission site. Finally, we demonstrate that Rab14 binds to microtubule minus-end interacting MACF2/CAMSAP3 complex and that this binding is required for targeting of early endosomes to the central spindle. Collectively, our data identified Rab14/MACF2/CAMSAP3 as a protein complex that regulates Rab11-endosome targeting and the establishment of the abscission site.
Two-Step Mixed Model Approach to Analyzing Differential Alternative RNA Splicing
Authors: Luo Li , Kang Huining , Li Xichen , Ness Scott A. , Stidley Christine A. 
Published: April 2020

AbstractChanges in gene expression can correlate with poor disease outcomes in two ways: through changes in relative transcript levels or through alternative RNA splicing leading to changes in relative abundance of individual transcript isoforms. The objective of this research is to develop new statistical methods in detecting and analyzing both differentially expressed and spliced isoforms, which appropriately account for the dependence between isoforms and multiple testing corrections for the multi-dimensional structure of at both the gene- and isoform-level. We developed a linear mixed effects model-based approach for analyzing the complex alternative RNA splicing regulation patterns detected by whole-transcriptome RNA-sequencing technologies. This approach thoroughly characterizes and differentiates three types of genes related to alternative RNA splicing events with distinct differential expression/splicing patterns. We applied the concept of appropriately controlling for the gene-level overall false discovery rate (OFDR) in this multi-dimensional alternative RNA splicing analysis utilizing a two-step hierarchical hypothesis testing framework. In the initial screening test we identify genes that have differentially expressed or spliced isoforms; in the subsequent confirmatory testing stage we examine only the isoforms for genes that have passed the screening tests. Comparisons with other methods through application to a whole transcriptome RNA-Seq study of adenoid cystic carcinoma and extensive simulation studies have demonstrated the advantages and improved performances of our method. Our proposed method appropriately controls the gene-level OFDR, maintains statistical power, and is flexible to incorporate advanced experimental designs.
Climatic drivers ofVerticillium dahliaeoccurrence in Mediterranean olive-growing areas of southern Spain
Authors: Requena-Mullor Juan Miguel , García-Garrido Jose Manuel , García Pedro Antonio , Rodríguez Estefanía 
Published: April 2020

AbstractVerticillium wilt, caused by the soil-borne fungusVerticillium dahliae,is one of the most harmful diseases in Mediterranean olive-growing areas. Although, the effects of both soil temperature and moisture onV. dahliaeare well known, there is scant knowledge about what climatic drivers affect the occurrence of the pathogen on a landscape scale. Here, we investigate what climatic drivers determineV. dahliaeoccurrence in olive-growing areas in southern Spain. In order to bridge this gap in knowledge, a landscape-scale field survey was carried out to collect data on the occurrence ofV. dahliaein 779 olive groves in Granada province. Forty models based on competing combinations of climatic variables were fitted and evaluated using information-theoretic methods. A model that included a multiplicative combination of seasonal and extreme climatic variables was found to be the most viable one. Isothermality and the seasonal distribution of precipitation were the most important variables influencing the occurrence of the pathogen. The isothermal effect was in turn modulated by the seasonality of rainfall, and this became less negative as seasonality increases. Thus,V. dahliaeoccurs more frequently in olive-growing areas where the day-night temperature oscillation is lower than the summer-winter one. We also found that irrigation reduced the influence of isothermality on occurrence. Our results demonstrate that long-term “sophisticated” climatic factors rather than “primary” variables, such as annual trends, can better explain the spatial patterns ofV. dahliaeoccurrence in Mediterranean, southern Spain. One important implication of our study is that appropriate irrigation management, when temperature oscillation approaches optimal conditions forV. dahliaeto thrive, may reduce the appearance of symptoms in olive trees.