bluuebunny/crossref_metadata_2025_split huggingface dataset:
The probability of joint monophyly of all species in an arbitrary species tree
Authors: Mehta Rohan S. , Steel Mike , Rosenberg Noah A. 
Published: December 2021

AbstractMonophyly is a feature of a set of genetic lineages in which every lineage in the set is more closely related to all other members of the set than it is to any lineage outside the set. Multiple sets of lineages that are separately monophyletic are said to be reciprocally monophyletic, or jointly monophyletic. The prevalence of reciprocal monophyly, or joint monophyly, has been used to evaluate phylogenetic and phylogeographic hypotheses, as well as to delimit species. These applications often make use of a probability of joint monophyly under models of gene lineage evolution. Studies in coalescent theory have computed this joint monophyly probability for small numbers of separate groups in arbitrary species trees, and for arbitrary numbers of separate groups in trivial species trees. Here, generalizing existing results on monophyly probabilities under the multispecies coalescent, we derive the probability of joint monophyly for arbitrary numbers of separate groups in arbitrary species trees. We illustrate how our result collapses to previously examined cases. We also study the effect of tree height, sample size, and number of species on the probability of joint monophyly. The result also enables computation of relatively simple lower and upper bounds on the joint monophyly probability. Our results expand the scope of joint monophyly calculations beyond small numbers of species, subsuming past formulas that have been used in simpler cases.
Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq
Authors: Replogle Joseph M. , Saunders Reuben A. , Pogson Angela N. , Hussmann Jeffrey A. , Lenail Alexander , Guna Alina , Mascibroda Lauren , Wagner Eric J. , Adelman Karen , Lithwick-Yanai Gila , Iremadze Nika , Oberstrass Florian , Lipson Doron , Bonnar Jessica L. , Jost Marco , Norman Thomas M. , Weissman Jonathan S. 
Published: December 2021

AbstractA central goal of genetics is to define the relationships between genotypes and phenotypes. High-content phenotypic screens such as Perturb-seq (pooled CRISPR-based screens with single-cell RNA-sequencing readouts) enable massively parallel functional genomic mapping but, to date, have been used at limited scales. Here, we perform genome-scale Perturb-seq targeting all expressed genes with CRISPR interference (CRISPRi) across >2.5 million human cells and present a framework to power biological discovery with the resulting genotype-phenotype map. We use transcriptional phenotypes to predict the function of poorly-characterized genes, uncovering new regulators of ribosome biogenesis (includingCCDC86,ZNF236, andSPATA5L1), transcription (C7orf26), and mitochondrial respiration (TMEM242). In addition to assigning gene function, single-cell transcriptional phenotypes allow for in-depth dissection of complex cellular phenomena – from RNA processing to differentiation. We leverage this ability to systematically identify the genetic drivers and consequences of aneuploidy and to discover an unanticipated layer of stress-specific regulation of the mitochondrial genome. Our information-rich genotype-phenotype map reveals a multidimensional portrait of gene function and cellular behavior.
Auxin-driven ecophysiological diversification of leaves in domesticated tomato
Authors: Moreira Juliene d. R. , Rosa Bruno L. , Lira Bruno S. , Lima Joni E. , Souza Ludmila N. , Otoni Wagner C. , Figueira Antonio , Freschi Luciano , Sakamoto Tetsu , Peres Lázaro E. P. , Rossi Magdalena , Zsögön Agustin 
Published: December 2021

AbstractHeterobaric leaves have bundle sheath extensions (BSEs) that compartmentalise the parenchyma, whereas homobaric leaves do not. The presence of BSEs affects leaf hydraulics and photosynthetic rate. The tomato (Solanum lycopersicum) obscuravenosa (obv) mutant lacks BSEs. Here we identify the obv gene and the causative mutation, a non-synonymous amino acid change that disrupts a C2H2 zinc finger motif in a putative transcription factor. This mutation exists as a rare polymorphism in the natural range of wild tomatoes, but has increased in frequency in domesticated tomatoes, suggesting that the latter diversified into heterobaric and homobaric leaf types. The obv mutant displays reduced vein density, leaf hydraulic conductance and photosynthetic assimilation rate. We show that these and other effects on plant development, including changes in leaf insertion angle, leaf margin serration, minor vein density and fruit shape, are controlled by OBV via changes in auxin signalling. Loss of function of the transcriptional regulator AUXIN RESPONSE FACTOR (ARF4) also results in defective BSE development, revealing an additional component of a novel genetic module controlling aspects of leaf development important for ecological adaptation and subject to breeding selection.One sentence summarydistribution of tomato heterobaric and homobaric leaves is controlled by a single-nucleotide polymorphism in an auxin-related transcription factor
ICoRD: Iterative correlation-based ROI detection method for the extraction of neural signals in calcium imaging
Authors: Kang Seongtak , Park Jiho , Kim Kyungsoo , Lim Sung-Ho , Kim Samhwan , Choi Joon Ho , Rah Jong-Cheol , Choi Ji-Woong 
Published: December 2021

AbstractIn vivo calcium imaging is a standard neuroimaging technique that allows selective observation of target neuronal activities. In calcium imaging, neuron activation signals provide key information for the investigation of neural circuits. For efficient extraction of the calcium signals of neurons, selective detection of the region of interest (ROI) pixels corresponding to the active subcellular region of the target neuron is essential. However, current ROI detection methods for calcium imaging data exhibit a relatively low signal extraction performance from neurons with a low signal-to-noise power ratio (SNR). This is problematic because a low SNR is unavoidable in many biological experiments. Therefore, we propose an iterative correlation-based ROI detection (ICoRD) method that robustly extracts the calcium signal of the target neuron from a calcium imaging series with severe noise. ICoRD extracts calcium signals closer to the ground-truth calcium signal than the conventional method from simulated calcium imaging data in all low SNR ranges. Additionally, this study confirmed that ICoRD robustly extracts activation signals against noise, even within in vivo environments. ICoRD showed reliable detection from neurons with a low SNR and sparse activation, which were not detected by conventional methods. ICoRD will facilitate our understanding of neural circuit activity by providing significantly improved ROI detection in noisy images.
Nuclei function as wedges to pry open spaces and promote collective, confined cell migrationin vivo
Authors: Penfield Lauren , Montell Denise J. 
Published: December 2021

AbstractCells migrate collectively through confined environments during development and cancer metastasis. The nucleus, a stiff organelle, impedes single cells from squeezing into narrow channels within artificial environments, but how nuclei affect collective cell migration into compact tissuesin vivois unknown. Here, we use border cells in the fly ovary to study nuclear dynamics in collective, confinedin vivomigration. Border cells delaminate from the follicular epithelium and squeeze into tiny spaces between cells called nurse cells. The lead cell nucleus transiently deforms as it extends into the lead cell protrusion, which then widens. The nuclei of follower cells deform less. Depletion of theDrosophilaB-type lamin, Lam, compromises nuclear integrity, hinders expansion of a leading protrusion, and impedes border cell movement. Cortical myosin II accumulates behind the nucleus and moves it into the protrusion in wildtype but not Lam-depleted cells. These data suggest that the nucleus stabilizes lead cell protrusions to help cells wedge open spaces between nurse cells.SummaryDuringDrosophilaborder cell migration, the B-type lamin Lam maintains nuclear envelope integrity, stabilizes the lead cell protrusion, and promotes cluster invasion between nurse cells. The nucleus may function as a wedge to prom collective, confinedin vivomovement.
Amino acid substitutions in human growth hormone affect coiled-coil content and receptor binding
Authors: Rajkovic Andrei , Kanchugal Sandesh , Abdurakhmanov Eldar , Howard Rebecca , Gräslund Astrid , Wärmländer Sebastian , Erwin Joseph , Danielson Helena , Flores Samuel 
Published: December 2021

AbstractThe interaction between human Growth Hormone (hGH) and hGH Receptor (hGHR) has great relevance to human diseases such as acromegaly and cancer. HGH has been extensively engineered by other workers to improve binding and other properties. We used a computational screen to select substitutions at single hGH positions within the hGHR-binding site. We find that, while many successfully slow down dissociation of the hGH-hGHR complex once bound, they also slow down the association of hGH to hGHR. We are particularly interested in E174 which belongs to the hGH zinc-binding triad, and which spans coiled-coil helices and obeys the coiled-coil heptad pattern. Surprisingly, substituting E174 with A leads to substantial increase in an experimental measure of coiled-coil content. E174A is known to increase affinity of hGH against hGHR; here we show that this is simply because the off-rate is slowed down more than the on-rate, in line with what has been found for other affinity-improving mutations. For E174Y (and mutations at other sites) the slowdown in on-rate was greater, leading to decreased affinity. The results point to a link between coiled-coiling, zinc binding, and hGHR-binding affinity in hGH, and also suggest rules for choosing affinity-increasing substitutions.
Genomic characteristics of recently recognized Vibrio cholerae El Tor lineages associated with cholera in Bangladesh, 1991-2017
Authors: Monir Md Mamun , Hossain Talal , Morita Masatomo , Ohnishi Makoto , Johura Fatema-Tuz , Sultana Marzia , Monira Shirajum , Ahmed Tahmeed , Thomson Nicholas , Watanabe Haruo , Huq Anwar , Colwell Rita R. , Seed Kimberley , Alam Munirul 
Published: December 2021

AbstractComparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in depth whole genome study of V. cholerae El Tor clinical strains isolated during endemic cholera in Bangladesh (1991 – 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. cholerae El Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera 2004-2017. Genome wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of the endemic cholera in Bangladesh, with implications for global cholera epidemiology.ImportanceCholera is a global disease with specific reference to the Bay of Bengal Ganges Delta where Vibrio cholerae O1 El Tor, causative agent of the disease showed two circulating lineages, one dominant in Bangladesh and the other in India. Results of in-depth genomic study of V. cholerae associated with endemic cholera during the past 27 years (1991 – 2017) indicate emergence and succession of the two lineages, BD-1 and BD-2, arising from a common ancestral paraphylatic group, BD-0, comprising the early strains and short-term evolution of the bacterium in Bangladesh. Among the two V. cholerae lineages, BD-2 supersedes BD-1 and is predominant in the most recent endemic cholera in Bangladesh. The BD-2 lineage contained significantly more SNPs and indels, and showed richness in gene abundance, including antimicrobial resistance genes, gene cassettes, and PLE to fight against bacteriophage infection, acquired over time. These findings have important epidemic implications at a global scale.
Risk of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19--related hospital admissions in children and young people: birth cohort study
Authors: Hardelid Pia , Favarato Graziella , Wijlaars Linda , Fenton Lynda , McMenamin Jim , Clemens Tom , Dibben Chris , Milojevic Ai , Macfarlane Alison , Taylor Jonathon , Cunningham Steven , Wood Rachael 
Published: December 2021

AbstractBackgroundThere have been no population-based studies of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19-related hospital admissions across the full paediatric age range. We examine the epidemiology of SARS-CoV-2 in children and young people (CYP) aged <23 years.MethodsWe used a birth cohort of all children born in Scotland since 1997, constructed via linkage between vital statistics, hospital records and SARS-CoV-2 surveillance data. We calculated risks of tests and PCR-confirmed infections per 1000 CYP-years between August and December 2020, and COVID-19-related hospital admissions per 100,000 CYP-years between February and December 2020. We used Poisson and Cox proportional hazards regression models to determine risk factors.ResultsAmong the 1226855 CYP in the cohort, there were 378402 tests, 19005 PCR confirmed infections and 346 admissions, corresponding to rates of 770.8/1000 (95% confidence interval 768.4-773.3), 179.4 (176.9-182.0) and 29.4/100,000 (26.3-32.8) CYP-years respectively. Infants had the highest COVID-19-related admission rates. Chronic conditions, particularly multiple types of conditions, was strongly associated with COVID-19-related admissions across all ages. The hazard ratio for >1 chronic condition type was 12.2 (7.9-18.82) compared to children with no chronic conditions. 89% of admitted children had no chronic conditions recorded.ConclusionsInfants, and CYP with chronic conditions are at highest risk of admission with COVID-19, however the majority of admitted CYP have no chronic conditions. These results provide evidence to support risk/benefit analyses for paediatric COVID-19 vaccination programmes. Studies examining whether maternal vaccine during pregnancy prevents COVID-19 admissions in infants are urgently needed.FundingUK Research and Innovation-Medical Research Council
A dynamic model to estimate evolving risk of major bleeding after percutaneous coronary intervention
Authors: Hurley Nathan C , Desai Nihar , Dhruva Sanket S. , Khera Rohan , Schulz Wade , Huang Chenxi , Curtis Jeptha , Masoudi Frederick , Rumsfeld John , Negahban Sahand , Krumholz Harlan M. , Mortazavi Bobak J. 
Published: December 2021

AbstractBackgroundBleeding is a complication of percutaneous coronary intervention (PCI), leading to significant morbidity, mortality, and cost. Existing risk models produce a single estimate of bleeding risk anchored at a single point in time and do not update estimates as clinical information emerges, despite the dynamic nature of risk.ObjectiveWe sought to develop models that update estimates of bleeding risk over time, incorporating evolving clinical information, and to demonstrate updated predictive performance.MethodsUsing data available from the National Cardiovascular Data Registry (NCDR) CathPCI, we trained 6 different tree-based machine learning models to estimate the risk of bleeding at key decision points: 1) choice of access site, 2) prescription of medication prior to PCI, and 3) the choice of closure device.ResultsWe included 2,868,808 PCIs; 2,314,446 (80.7%) prior to 2014 for training and 554,362 (19.3%) remaining for validation. Discrimination improved from an AUROC of 0.812 (95% Confidence Interval: 0.812-0.812) using only presentation variables to 0.845 (0.845-0.845) using all variables. Among 123,712 patients classified as low risk by the initial model, 14,441 were reclassified as moderate risk (1.4% experienced bleeds), while 723 were reclassified as high risk (12.5% experienced bleeds). Among 160,165 patients classified as high risk by the initial model, 40 were reclassified to low risk (0% experienced bleeds), and 43,265 to moderate risk (2.5% experienced bleeds).ConclusionAccounting for the time-varying nature of data and capturing the association between treatment decisions and changes in risk provide up-to-date information that may guide individualized care throughout a hospitalization.Condensed AbstractExisting risk models for bleeding with PCI produce a single estimate anchored at a single point in time. We developed models that update estimates of bleeding risk over time, incorporating evolving clinical information, using data available from the National Cardiovascular Data Registry (NCDR) CathPCI. We trained 6 different machine learning models to estimate the risk of bleeding at key decision points, improving discrimination from an AUROC of 0.812 to 0.845, over time. Accounting for the time-varying nature of data and capturing association between treatments and changes in risk provide up-to-date information that may guide individualized care throughout a hospitalization.
Resource Profile: The Regenstrief Institute COVID-19 Research Data Commons (CoRDaCo)
Authors: Allen Katie S. , Zidan Nader , Dey Vishal , Mendonca Eneida A. , Grannis Shaun , Kasturi Suranga , Khan Babar , Zappone Sarah , Haggstrom David , Ruppert Laura , Schleyer Titus , Ning Xia , Embi Peter , Tachinardi Umberto 
Published: December 2021

AbstractThe primary objective of the COVID-19 Research Data Commons (CoRDaCo) is to provide broad and efficient access to a large corpus of clinical data related to COVID-19 in Indiana, facilitating research and discovery. This curated collection of data elements provides information on a significant portion of COVID-19 positive patients in the State from the beginning of the pandemic, as well as two years of health information prior its onset. CoRDaCo combines data from multiple sources, including clinical data from a large, regional health information exchange, clinical data repositories of two health systems, and state laboratory reporting and vital records, as well as geographic-based social variables. Clinical data cover information such as healthcare encounters, vital measurements, laboratory orders and results, medications, diagnoses, the Charlson Comorbidity Index and Pediatric Early Warning Score, COVID-19 vaccinations, mechanical ventilation, restraint use, intensive care unit and ICU and hospital lengths of stay, and mortality. Interested researchers can visit ridata.org or email askrds@regenstrief.org to discuss access to CoRDaCo.Key FeaturesCoRDaCo includes patient-level data on diagnosis and treatment, healthcare utilization, outcomes, and demographics. The level of detail available for each patient varies depending on the source of the clinical data.CoRDaCo uses geographic identifiers to link patient-specific data to area-level social factors, such as census variables and social deprivation indices.As of 4/30/21, the CoRDaCo cohort consists of over 776,000 cases, including granular data on over 15,000 patients who were admitted to an intensive care unit, and over 1,362,000 COVID-19-negative controls. Data is currently refreshed two times per month.The most prevalent comorbidities in the data set include hypertension, diabetes, chronic pulmonary disease, renal disease, cancer, and congestive heart failure.
Syndromic Surveillance-Based Estimates of Vaccine Efficacy Against COVID-Like Illness from Emerging Omicron and COVID-19 Variants
Authors: Varrelman Tanner J. , Rader Benjamin , Astley Christina M. , Brownstein John S. 
Published: December 2021

AbstractNew infections from the omicron variant of SARS-CoV-2 have been increasing dramatically in South Africa since first identification in November 2021. Despite increasing uptake of COVID-19 vaccine, there are concerns vaccine protection against omicron may be reduced compared to other variants. We sought to characterize a surrogate measure of vaccine efficacy in Gauteng, South Africa by leveraging real-time syndromic surveillance data. The University of Maryland Global COVID Trends and Impact Survey (UMD-CTIS) is an online, cross-sectional survey conducted among users sampled from the Facebook active user base. We derived three COVID-like illness (CLI) definitions (stringent, classic, and broad) using combinations of self-reported symptoms (present or not in the prior 24 hours) that broadly tracked with reported COVID-19 cases during June 18, 2021 - December 14, 2021 (inclusive of the delta wave and up-trend of the omicron wave). We used syndromic-surveillance-based CLI prevalence measures among the vaccinated (PV) and unvaccinated (PU) respondents to estimate V ECLIP = 1 - (PV /PU), a proxy for vaccine efficacy, during the delta (June 18-July 18, N= 9,387 surveys) and omicron (December 4-14, N= 2,389 surveys) wave periods. We assume no waning immunity, CLI prevalence approximates incident infection with each variant, and vaccinated and unvaccinated survey respondents in the two variant wave periods are exchangeable. The vaccine appears to have consistently lower V ECLIP against omicron, compared to delta, regardless of the CLI definition used. Stringent CLI (i.e. anosmia plus fever, cough and/or myalgias) yielded a delta V ECLIP = 0.85 [0.54, 0.95] higher than omicron V ECLIP = 0.62 [0.46, 0.72]. Classic CLI (cough plus anosmia, fever, and/or myalgias) gave lower estimates (delta V ECLIP = 0.76 [0.54, 0.87], omicron V ECLIP = 0.51 [0.42, 0.59]), but omicron was still lower than delta. We acknowledge the potential for measurement, confounding, and selection bias, as well as limitations for generalizability for these self-reported, syndromic surveillance-based V ECLIP measures. Thus V ECLIP as estimates of true, population-level vaccine efficacy should therefore be taken with caution. Nevertheless, these preliminary findings demonstrating declining V ECLIP raise concern for a true decline in vaccine efficacy versus waning immunity as a potential contributor to the omicron variant taking hold in Gauteng and elsewhere.
Antibody Responses to 3rd Dose mRNA Vaccines in Nursing Home and Assisted Living Residents
Authors: Zhang Ali , Breznik Jessica A. , Clare Rumi , Nazy Ishac , Miller Matthew S. , Bowdish Dawn M. E. , Costa Andrew P. 
Published: December 2021

AbstractA comparison of SARS-CoV-2 wild-type and the beta variant virus neutralization capacity between 2 and 3 mRNA vaccine series in nursing home residents, and between nursing home and assisted living residents strongly supports 3rd dose vaccine recommendations, and equivalent polices for nursing homes and assisted living settings. Findings suggest that residents mount a robust humoral response to a 3rd mRNA vaccination, and have greater neuralization capacity compared to a 2 dose series.