bluuebunny/crossref_metadata_2025_split huggingface dataset:
Field-deployable, rapid diagnostic testing of saliva samples for SARS-CoV-2
Authors: Wei Shan , Kohl Esther , Djandji Alexandre , Morgan Stephanie , Whittier Susan , Mansukhani Mahesh , Yeh Raymond , Alejaldre Juan Carlos , Fleck Elaine , Mary D’Alton , Suh Yousin , Williams Zev 
Published: June 2020

AbstractRapid, scalable, point-of-need, COVID-19 diagnostic testing is necessary to safely re-open economies and prevent future outbreaks. We developed an assay that detects single copies of SARS-CoV-2 virus directly from saliva and swab samples in 30 min using a simple, one-step protocol that utilizes only a heat block and microcentrifuge tube prefilled with a mixture containing the necessary reagents and has a sensitivity and specificity of 97% and 100%, respectively.
Quantification of SARS-CoV-2 viral copy number in saliva mouthwash samples using digital droplet PCR
Authors: Oberding Lisa , Hu Jia , Berenger Byron , Mohon Abu Naser , Pillai Dylan R. 
Published: June 2020

AbstractSaliva samples were collected through a simple mouth wash procedure and viral load quantified using a technology called digital droplet PCR. Data suggest ddPCR allows for precise quantification of viral load in clinical samples infected with SARS-CoV-2.
Mental health service activity during COVID-19 lockdown: South London and Maudsley data on working age community and home treatment team services and mortality from February to mid-May 2020
Authors: Stewart Robert , Martin Evangelia , Broadbent Matthew 
Published: June 2020

AbstractThe lockdown and social distancing policy response to the COVID-19 pandemic in the UK has a potentially important impact on provision of mental healthcare; however, there has been relatively little quantification of this. Taking advantage of the Clinical Record Interactive Search (CRIS) data resource with 24-hourly updates of electronic mental health records data, this paper describes daily caseloads and contact numbers (face-to-face and virtual) for home treatment teams (HTTs) and working age adult community mental health teams (CMHTs) from 1st February to 15th May 2020 at the South London and Maudsley NHS Trust (SLaM), a large mental health service provider for 1.2m residents in south London. In addition daily deaths are described for all current and previous SLaM service users over this period and the same dates in 2019. In summary, comparing periods before and after 16th March 2020 the CMHT sector showed relatively stable caseloads and total contact numbers, but a substantial shift from face-to-face to virtual contacts, while HTTs showed the same changeover but reductions in caseloads and total contacts (although potentially an activity rise again during May). Number of deaths for the two months between 16th March and 15th May were 2.4-fold higher in 2020 than 2019, with 958 excess deaths.
Underlying causes of death with changing mortality among adults in the United States, 2013-2017
Authors: Hu Xin , Lin Yong , Zhang Lanjing 
Published: June 2020

AbstractOverall mortality among U.S. adults was stable in the past years, while racial disparity was found in 10 leading causes of death or age-specific mortality in U.S. Blacks or African Americans. However, the trends in sex- and race-adjusted age-standardized cause-specific mortality are poorly understood. This study was aimed at identifying the UCD with sex- and race-adjusted, age-standardized mortality that was changing in recent years. We extracted the data of underlying causes of death (UCD) from the Multiple Cause of Death database of the Centers for Disease Control and Prevention (CDC). Multivariable log-linear regression models were used to estimate trends in sex- and race-adjusted, age-standardized mortality during 2013-2017. A total of 31,029,133 deaths were identified. Among the list of 113 UCD compiled by the CDC, there were 29 UCD with upward trend, 33 UCD with downward trend and 56 UCD with no significant trend. The 2 UCD with largest annual percent change were both nutrition related (annual percent change= 17.73, 95% CI [15.13-20.33] for malnutrition and annual percent change= 17.49, 95% CI [14.94-20.04] for Nutritional deficiencies), followed by Accidental poisoning and exposure to noxious substances. This study thus reported the UCD with changing mortality in recent years, which was sex- and race-adjusted and age-standardized. More efforts and resources should be focused on understanding, prevention and control of the mortality linked to these UCD. Continuous monitoring of mortality trends is recommended.
Binding of Calcium and Magnesium to Cardiac Troponin C
Authors: Rayani K , Seffernick JT , Li YA , Davis JP , Spuches AM , Petegem F Van , Solaro RJ , Lindert S , Tibbits GF 
Published: June 2020

AbstractCardiac troponin C (cTnC) is the Ca2+-sensing component of the thin filament. It contains structural sites (III/IV) which bind both Ca2+and Mg2+, and a regulatory site (II) that has been thought to bind only Ca2+. The latter binding initiates a series of conformational changes that culminate in force production.We have quantified the interaction between site II and Ca2+/Mg2+through Isothermal Titration Calorimetry and Thermodynamic Integration simulations. Direct and competitive binding titrations using wild type and a double mutant that significantly reduces binding to site II demonstrated that physiologically relevant concentrations of both Ca2+/Mg2+interact with the same locus. Cytosolic free Mg2+(~1 mM) could occupy a significant population of available site II, as this concentration of Mg2+decreased the affinity for Ca2+1.4-fold.Interaction of Mg2+with site II of cTnC likely has important functional consequences for the heart at baseline and in diseased states which decrease or increase availability of Mg2+such as secondary hyperparathyroidism or ischemia, respectively.
An enzyme-based immunodetection assay to quantify SARS-CoV-2 infection
Authors: Conzelmann Carina , Gilg Andrea , Groß Rüdiger , Schütz Desirée , Preising Nico , Ständker Ludger , Jahrsdörfer Bernd , Schrezenmeier Hubert , Sparrer Konstantin M. J. , Stamminger Thomas , Stenger Steffen , Münch Jan , Müller Janis A. 
Published: June 2020

AbstractSARS-CoV-2 is a novel pandemic coronavirus that caused a global health and economic crisis. The development of efficient drugs and vaccines against COVID-19 requires detailed knowledge about SARS-CoV-2 biology. Several techniques to detect SARS-CoV-2 infection have been established, mainly based on counting infected cells by staining plaques or foci, or by quantifying the viral genome by PCR. These methods are laborious, time-consuming and expensive and therefore not suitable for a high sample throughput or rapid diagnostics. We here report a novel enzyme-based immunodetection assay that directly quantifies the amount ofde novosynthesized viral spike protein within fixed and permeabilized cells. This in-cell ELISA enables a rapid and quantitative detection of SARS-CoV-2 infection in microtiter format, regardless of the virus isolate or target cell culture. It follows the established method of performing ELISA assays and does not require expensive instrumentation. Utilization of the in-cell ELISA allows to e.g. determine TCID50of virus stocks, antiviral efficiencies (IC50values) of drugs or neutralizing activity of sera. Thus, the in-cell spike ELISA represents a promising alternative to study SARS-CoV-2 infection and inhibition and may facilitate future research.HighlightsDetermination of SARS-CoV-2 infection by enzymatically quantifying the expression of viral spike protein in bulk cell culturesTargeting a highly conserved region in the S2 subunit of the S protein allows broad detection of several SARS-CoV-2 isolates in different cell linesScreening of antivirals in microtiter format and determining the antiviral activity as inhibitory concentrations 50 (IC50)
Suppressors of mRNA decapping defects isolated by experimental evolution ameliorate transcriptome disruption without restoring mRNA decay
Authors: Kim Minseon , van Hoof Ambro 
Published: June 2020

ABSTRACTFaithful degradation of mRNAs is a critical step in gene expression, and eukaryotes share a major conserved mRNA decay pathway. In this major pathway, the two rate determining steps in mRNA degradation are the initial gradual removal of the poly(A) tail, followed by removal of the cap structure. Removal of the cap structure is carried out by the decapping enzyme, containing the Dcp2 catalytic subunit. While the mechanism and regulation of mRNA decay is well-understood, the consequences of defects in mRNA degradation are less clear. Dcp2 has been reported as either essential or nonessential. Here we clarify that Dcp2 is essential for continuous growth and use experimental evolution to identify suppressors of this essentiality. We show that null mutations in at least three different are each sufficient to restore viability to adcp2Δ, of whichkap123Δ andtl(gag)gΔ appear the most specific. Unlike previously reported suppressors of decapping defects, these suppressor do not restore decapping or mRNA decay to normal rates, but instead allow survival while only modestly affecting transcriptome homeostasis. These effects are not limited to mRNAs, but extend to ncRNAs including snoRNAs and XUTs. These results provide important new insight into the importance of decapping and resolves previously conflicting publications about the essentiality ofDCP2.
Definition of a Small Core Transcriptional Circuit Regulated by AML1-ETO
Authors: Stengel Kristy R. , Ellis Jacob , Spielman Clare , Bomber Monica , Hiebert Scott W. 
Published: June 2020

AbstractTranscription factors regulate gene networks controlling normal hematopoiesis and are frequently deregulated in acute myeloid leukemia (AML). Critical to our understanding of the mechanism of cellular transformation by oncogenic transcription factors is the ability to define their direct gene targets. While this seems to be a straight forward task, gene network cascades can change within minutes to hours, making it difficult to distinguish direct from secondary or compensatory transcriptional changes by traditional methodologies. We describe an approach utilizing CRISPR-based genome editing to insert a degron tag into the endogenous AML1-ETO locus of Kasumi-1 cells, as well as overexpression of a degradable AML1-ETO protein in CD34+human cord blood cells, which is a an AML1-ETO-dependent pre-leukemia model. Upon addition of a small molecule proteolysis targeting chimera (PROTAC), the AML1-ETO protein was rapidly degraded in both systems. Furthermore, by combining rapid degradation with nascent transcript analysis (PRO-seq), RNA-seq and Cut&Run, we have defined the core AML1-ETO regulatory network, which consists of fewer than 100 direct gene targets. The ability of AML1-ETO to regulate this relatively small gene pool is critical for maintaining cells in a self-renewing state, and AML1-ETO degradation set off a cascade of transcriptional events resulting in myeloid differentiation.
A high fat containing chicken egg-only diet suppresses fatty liver induced by a lipid-rich methionine and choline deficient diet
Authors: Isobe Ken-ichi , Nishio Naomi , Kuzuya Ami , Kato Kana , Hatanaka Aki , Suzuki Rena , Kawai Miki , Kanjya Aoi , Suitou Chiaki , Nakano Yui , Nagasaki Manae 
Published: June 2020

AbstractNonalcoholic fatty liver disease (NAFLD) is a simple hepatic steatosis, which may proceed to nonalcoholic steatohepatitis (NASH) in the presence of steatosis and inflammation with hepatocyte injury. Obesity induced by a high-fat diet or high monosaccharide diet is considered a risk factor for NAFLD. A popular mouse model of NAFLD is a high-fat diet consisting of 60% energy from fat. A modified methionine and choline deficient (MCD) diet containing 60% energy from fat (CDAHFD) is a quick induction model for NAFLD. Chicken eggs also contain 60% energy from fat with very low carbohydrate. Here we compared liver pathologies in mice fed either a CDAHFD or egg-only diet. We found that a CDAHFD induced NAFLD within only two weeks.Ballooning of hepatocytes with an of immune cell appearance in the liver and high serum ALT and AST indicated that the mice fed CDAHFD developed NAFLD, which could proceed to NASH. However, mice fed an egg-only diet did not develop NAFLD even after 7 weeks. These mice showed normal liver histology with normal ALT and AST. The mice fed an egg-only diet showed high blood ketone bodies and normal blood glucose. Furthermore we found that the mice fed a combination CDAHFD /egg diet or mice fed an egg-only diet after two weeks of CDAHFD diet showed almost normal ALT and AST with reduced levels of fat bodies in the liver. These results indicate that an egg-only diet strongly inhibits high fat and carbohydrates induced NAFLD.
Genome-wide identification of long non-coding RNAs in the gravid ectoparasiteVarroa destructor
Authors: Lin Zheguang , Liu Yibing , Chen Xiaomei , Han Cong , Wang Wei , Ke Yalu , Su Xiaoling , Chen Heng , Xu Hao , Chen Guohong , Ji Ting 
Published: June 2020

AbstractLong non-coding RNAs (lncRNAs) emerge as critical regulators with various biological functions in living organisms. However, to date, no systematic characterization of lncRNAs has been investigated in the ectoparasitic miteVarroa destructor, the most severe biotic threat to honey bees worldwide. Here, we performed an initial genome-wide identification of lncRNAs inV. destructorvia high-throughput sequencing technology and reported, for the first time, the transcriptomic landscape of lncRNAs in the devastating parasite. By means of a lncRNA identification pipeline, 6,645 novel lncRNA transcripts, encoded by 3,897 gene loci, were identified, including 2,066 sense lncRNAs, 2,772 lincRNAs, and 1,807 lncNATs. Compared with protein-coding mRNAs,V. destructorlncRNAs are shorter in terms of full length, as well as of the ORF length, contain less exons, and express at lower level. GO term and KEGG pathway enrichment analyses of the lncRNA target genes demonstrated that these predicted lncRNAs are likely to play key roles in cellular processes, genetic information processing and environmental responses. To our knowledge, this is the first catalog of lncRNA profile in the parasitiformes species, providing a valuable resource for genetic and genomic studies. Understanding the characteristics and features of lncRNAs inV. destructorwould promote sustainable pest control.
Biosystematic Studies on the Status ofSolanum chilense(Dunal) Reiche
Authors: Raduski Andrew R. , Igić Boris 
Published: June 2020

AbstractMembers ofSolanumsect.Lycopersicumare commonly used as a source of exotic germplasm for improvement of the cultivated tomato, and are increasingly employed in basic research. Although it experienced significant early and ongoing work, the taxonomic status of many wild species in this section has undergone a number of significant revisions, and remains uncertain.Here, we examine the taxonomic status of obligately outcrossing Chilean wild tomato (Solanum chilense) using reduced-representation sequencing (RAD-seq), a range of phylogenetic and population genetic analyses, crossing data, and morphological data.Overall, each of our analyses provides some weight of evidence that the Pacific coastal populations and Andean inland populations of the currently describedS. chilenserepresent separately evolving populations.Despite its vast economic importance,Solanumsect.Lycopersiconstill exhibits considerable taxonomic instability. A pattern of under-recognition of outcrossing species may be common across flowering plants. We discuss the possible causes and implications of this observation, with a focus on macroevolutionary inference.
Air Quality and COVID-19 Prevalence/Fatality
Authors: Takagi Hisato , Kuno Toshiki , Yokoyama Yujiro , Ueyama Hiroki , Hari Yosuke , Ando Tomo 
Published: June 2020

AbstractTo investigate the association of real-time/observed ozone/PM2.5 levels with COVID-19 prevalence/fatality, meta-regression of data from the Northeast megalopolis was conducted. Daily Air Quality Index (AQI) values based on available ozone/PM2.5 data in these counties/cities (3/15/2020–5/31/2020) were extracted from US Environmental Protection Agency and World Air Quality Project. In each county/city, total confirmed COVID-19 cases/deaths (5/31/2020) were available from Johns Hopkins Coronavirus Resource Center, and total population was extracted from US Census Bureau. Random-effects meta-regression was performed using OpenMetaAnalyst. A meta-regression graph depicted COVID-19 prevalence and fatality (plotted as logarithm-transformed prevalence/fatality on the y-axis) as a function of mean ozone/PM2.5 AQI (plotted on the x-axis). Coefficients were not statistically significant for ozone (P = 0.212/0.814 for prevalence/fatality) and PM2.5 (P = 0.986/0.499). Although multivariable analysis had been planned, it was not performed because of non-significant covariates of interest in the univariable model. In conclusion, ozone/PM2.5 may be unassociated with COVID-19 prevalence/fatality.
Explore the Possible Impact of BCG Vaccination Policy on the Morbidity, Mortality, and Recovery Rates due to COVID-19 Infection
Authors: Chang Chuan-Hsin , Chang Yue-Cune 
Published: June 2020

ABSTRACTBACKGROUNDThe Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection.METHODSData of COVID-19 confirmed cases, deaths, recoveries, and population were obtained fromhttps://www.worldometers.info/coronavirus/(Accessed on 12 June, 2020). To have meaningful comparisons among countries’ mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates.RESULTSAmong those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively.CONCLUSIONSThat data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials.
NECo: A node embedding algorithm for multiplex heterogeneous networks
Authors: Dursun Cagatay , Smith Jennifer R. , Hayman G. Thomas , Kwitek Anne E. , Bozdag Serdar 
Published: June 2020

AbstractComplex diseases such as hypertension, cancer, and diabetes cause nearly 70% of the deaths in the U.S. and involve multiple genes and their interactions with environmental factors. Therefore, identification of genetic factors to understand and decrease the morbidity and mortality from complex diseases is an important and challenging task. With the generation of an unprecedented amount of multi-omics datasets, network-based methods have become popular to represent the multilayered complex molecular interactions. Particularly node embeddings, the low-dimensional representations of nodes in a network are utilized for gene function prediction. Integrated network analysis of multi-omics data alleviates the issues related to missing data and lack of context-specific datasets. Most of the node embedding methods, however, are unable to integrate multiple types of datasets from genes and phenotypes. To address this limitation, we developed a node embedding algorithm called Node Embeddings of Complex networks (NECo) that can utilize multilayered heterogeneous networks of genes and phenotypes. We evaluated the performance of NECo using genotypic and phenotypic datasets from rat (Rattus norvegicus) disease models to classify hypertension disease-related genes. Our method significantly outperformed the state-of-the-art node embedding methods, with AUC of 94.97% compared 85.98% in the second-best performer, and predicted genes not previously implicated in hypertension.Availability and implementationThe source code is available on GitHub athttps://github.com/bozdaglab/NECo.
Mobile element warfare via CRISPR and anti-CRISPR inPseudomonas aeruginosa
Authors: Leon Lina M. , Park Allyson E. , Borges Adair L. , Zhang Jenny Y. , Bondy-Denomy Joseph 
Published: June 2020

SUMMARYBacteria deploy multiple defense mechanisms to prevent the invasion of mobile genetic elements (MGEs). CRISPR-Cas systems use RNA-guided nucleases to target MGEs, which in turn produce anti-CRISPR (Acr) proteins that inactivate Cas protein effectors. The minimal component Type I-C CRISPR-Cas subtype is highly prevalent in bacteria, and yet a lack of a tractablein vivomodel system has slowed its study, the identification of cognate Acr proteins, and thus our understanding of its true role in nature. Here, we describe MGE-MGE conflict between a mobilePseudomonas aeruginosaType I-C CRISPR-Cas system always encoded on pKLC102-like conjugative elements, which are large mobile islands, and seven new Type I-C anti-CRISPRs (AcrIF2*, AcrIC3-IC8) encoded by phages, other mobile islands, and transposons. TheP. aeruginosaType I-C system possesses a total of 300 non-redundant spacers (from 980 spacers total) across the 42 genomes analyzed, predominantly targetingP. aeruginosaphages. Of the seven new Type I-C anti-CRISPRs, all but one are highly acidic, and four have surprisingly broad inhibition activity, blocking multiple distantly relatedP. aeruginosaType I CRISPR system subtypes (e.g. I-C and I-F, or I-C and I-E), including AcrIF2 (now, AcrIF2*), a previously described DNA mimic. Anti-type I-C activity of AcrIF2* was far more sensitive to mutagenesis of acidic residues in AcrIF2* than anti-type I-F activity, suggesting distinct binding mechanisms for this highly negatively charged protein. Five of the seven Acr proteins block DNA-binding, while the other two act downstream of DNA-binding, likely by preventing Cas3 recruitment or activity. For one such Cas3 inhibitor (AcrIC3), we identify a novel anti-CRISPR evasion strategy: acas3-cas8gene fusion, which also occurs in nature. Collectively, the Type I-C CRISPR spacer diversity and corresponding anti-CRISPR response, all occurring onPseudomonasMGEs, demonstrates an active co-evolutionary battle between parasitic elements.
Impact of bead-beating intensity on microbiome recovery in mouse and human stool:Optimization of DNA extraction
Authors: Zhang Bo , Brock Matthew , Arana Carlos , Dende Chaitanya , Hooper Lora , Raj Prithvi 
Published: June 2020

AbstractDNA extraction methods play an important role in the acquisition of accurate and reproducible 16S sequencing data in microbiome studies. In this study, we assessed the impact of bead-beating intensity during DNA extraction on microbiome recovery in mouse and human stool. We observed a higher DNA yield, better DNA integrity, higherShannon’s entropyandSimpson’s indexin samples beaten for 4 and 9 minutes as compared to unbeaten samples. 16S sequencing data showed that bead beating has a statistically-significant (p<0.05) impact on the recovery of many clinically relevant microbes that live in the mouse and human gut, includingBifidobacterium, SutterellaandVeillonella.It was observed that 4 minutes of bead beating promotes recovery of about 70% of OTUs in mouse and human stool, while the remaining 30% requires longer bead beating. In conclusion, our study indicates adjustments in bead beating treatment based on the composition of the specimen and the targeted bacteria.