bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coinfection with chytrid genotypes drives divergent infection dynamics reflecting broad epidemiological patterns
Authors: Carvalho Tamilie , Medina Daniel , Ribeiro Luisa P. , Rodriguez David , Jenkinson Thomas S. , Becker C. Guilherme , Toledo Luís Felipe , Hite Jessica 
Published: September 2022

ABSTRACTBy altering the abundance, diversity, and distribution of species — and their pathogens — globalization may inadvertently select for more virulent pathogens. In Brazil’s Atlantic Forest, a hotspot of amphibian biodiversity, the pet trade has facilitated the co-occurrence of previously isolated enzootic and panzootic lineages of the pathogenic amphibian-chytrid (‘Bd’) and generated new virulent recombinant genotypes (‘hybrid’). Epidemiological data indicate that amphibian declines are most severe in hybrid zones, suggesting that coinfections are causing more severe infections or selecting for higher virulence. We investigated how coinfections involving these genotypes shaped virulence and transmission. Overall, coinfection favored the more virulent and competitively superior panzootic genotype, despite dampening its virulence and transmission. However, for the least virulent and least competitive genotype, coinfection increased both pathogen virulence and transmission. Thus, by integrating experimental and epidemiological data, our results provide mechanistic insight into how globalization can select for, and propel, the emergence of introduced hypervirulent lineages, such as the globally distributed panzootic lineage of Bd.
Polygenic scoring accuracy varies across the genetic ancestry continuum in all human populations
Authors: Ding Yi , Hou Kangcheng , Xu Ziqi , Pimplaskar Aditya , Petter Ella , Boulier Kristin , Privé Florian , Vilhjálmsson Bjarni J. , Loohuis Loes Olde , Pasaniuc Bogdan 
Published: September 2022

AbstractPolygenic scores (PGS) have limited portability across different groupings of individuals (e.g., by genetic ancestries and/or social determinants of health), preventing their equitable use. PGS portability has typically been assessed using a single aggregate population-level statistic (e.g., R2), ignoring inter-individual variation within the population. Here we evaluate PGS accuracy at individual-level resolution, independent of its annotated genetic ancestries. We show that PGS accuracy varies between individuals across the genetic ancestry continuum in all ancestries, even within traditionally “homogeneous” genetic ancestry clusters. Using a large and diverse Los Angeles biobank (ATLAS, N= 36,778) along with the UK Biobank (UKBB, N= 487,409), we show that PGS accuracy decreases along a continuum of genetic ancestries in all considered populations and the trend is well-captured by a continuous measure of genetic distance (GD) from the PGS training data; Pearson correlation of −0.95 between GD and PGS accuracy averaged across 84 traits. When applying PGS models trained in UKBB “white British” individuals to European-ancestry individuals of ATLAS, individuals in the highest GD decile have 14% lower accuracy relative to the lowest decile; notably the lowest GD decile of Hispanic/Latino American ancestry individuals showed similar PGS performance as the highest GD decile of European ancestry ATLAS individuals. GD is significantly correlated with PGS estimates themselves for 82 out of 84 traits, further emphasizing the importance of incorporating the continuum of genetic ancestry in PGS interpretation. Our results highlight the need for moving away from discrete genetic ancestry clusters towards the continuum of genetic ancestries when considering PGS and their applications.
Chromosome-scale reference genome and RAD-based genetic map of yellow starthistle (Centaurea solstitialis) reveal putative structural variation and QTL associated with invader traits
Authors: Reatini Bryan , Pelosi Jessie A. , Cang F. Alice , Jiang Qiuyu , McKibben Michael T. W. , Barker Michael S. , Rieseberg Loren H. , Dlugosch Katrina M. 
Published: September 2022

AbstractInvasive species offer outstanding opportunities to identify the genomic sources of variation that contribute to rapid adaptation, as well as the genetic mechanisms facilitating invasions. The Eurasian plant yellow starthistle (Centaurea solstitialis) is highly invasive in North and South American grasslands and known to have evolved increased growth and reproduction during invasion. Here we develop new genomic resources forC. solstitialisand map the genetic basis of invasiveness traits. We present a chromosome-scale (1N = 8) reference genome using PacBio CLR and Dovetail Omni-C technologies, and functional gene annotation using RNAseq. We find repeat structure typical of the family Asteraceae, with over 25% of gene content derived from ancestral whole genome duplications (paleologs). Using an F2 mapping population derived from a cross between native and invading parents, with a restriction site-associated DNA (RAD)-based genetic map, we validate the assembly and identify 13 QTL underpinning size traits that have evolved during invasion. We find evidence that large effect QTL may be associated with structural variants between native and invading genotypes, including a variant with an overdominant and pleiotropic effect on key invader traits. We also find evidence of significant paleolog enrichment under two QTL. Our results add to growing evidence of the importance of structural variants in evolution, and to understanding of the rapid evolution of invaders.Significance StatementInvasive species often evolve rapidly in new environments, potentially informing our understanding of the genomic basis of adaptation, but genomic studies of these non-model systems are limited. We provide a chromosome-scale reference genome, annotation, and genetic map for the invasive plant yellow starthistle, and we investigate the genetic basis of invader trait evolution in this system. We find regions of the genome with large effects on traits that differ between native and invading genotypes, and evidence suggesting genome structural variants and past genome duplications could play a role in rapid adaptation of invading populations. These genomic resources and evolutionary insights aid in our understanding of the sources of genomic variation for adaptation, and how their evolution facilitates invasion.
TIVAN-indel: A computational framework for annotating and predicting noncoding regulatory small insertion and deletion
Authors: Agarwal Aman , Chen Li 
Published: September 2022

AbstractMotivationSmall insertion and deletion (sindel) of human genome has an important implication for human disease. One important mechanism for noncoding sindel to have an impact on human diseases and phenotypes is through the regulation of gene expression. Nevertheless, current sequencing technology may lack statistical power and resolution to pinpoint the causal sindel due to lower minor allele frequency or small effect. As an alternative solution, a supervised machine learning method can identify the otherwise missing causal sindels by predicting the regulatory potential of sindels directly. However, computational methods for annotating and predicting the regulatory sindels, especially in the noncoding regions, are underdeveloped.ResultsBy leveraging recognized sindels incis-expression quantitative trait loci (cis-eQTLs) across 44 tissues and cell types in GTEx, and a compilation of both generic functional annotations and tissue/cell typespecific multi-omics features generated by a sequence-based deep learning model, we developed TIVAN-indel, which is an XGBoost-based supervised framework for scoring noncoding sindels based their potential to regulate the nearby gene expression. As a result, we demonstrate that TIVAN-indel achieves the best prediction performance in both cross-validation with-tissue prediction and independent cross-tissue evaluation. As an independent evaluation, we train TIVAN-indel from “Whole Blood” tissue in GTEx data and test the model using 15 immune cell types from an independent study DICE. Lastly, we perform an enrichment analysis for both recognized and predicted sindels in key regulatory regions such as chromatin interactions, open chromatin and histone modification sites, and find biologically meaningful enrichment patterns.Availability and implementationhttps://github.com/lichen-lab/TIVAN-indelContactli.chen1@ufl.edu
King- and queen-specific degradation of uric acid is the key to reproduction in termites
Authors: Konishi Takao , Tasaki Eisuke , Takata Mamoru , Matsuura Kenji 
Published: September 2022

AbstractCaste-based reproductive division of labour in social insects is built on asymmetries in resource allocation within colonies. Kings and queens dominantly consume limited resources for reproduction, while non-reproductive castes such as workers and soldiers help reproductive castes. Studying the regulation of such asymmetries in resource allocation is crucial for understanding the maintenance of sociality in insects, although the molecular background is poorly understood. We focused on uric acid, which is reserved and utilized as a valuable nitrogen source in wood-eating termites. We found that king- and queen-specific degradation of uric acid is the key to reproduction in the subterranean termite Reticulitermes speratus. The urate oxidase gene (RsUAOX), which catalyses the first step of nitrogen recycling from stored uric acid, was highly expressed in mature kings and queens, and upregulated with differentiation into neotenic kings/queens. Suppression of uric acid degradation decreased the number of eggs laid per queen. Uric acid was shown to be provided by workers to reproductive castes. Our results suggest that the capacity to use nitrogen, which is essential for the protein synthesis required for reproduction, contributes to colony cohesion expressed as the reproductive monopoly held by kings and queens.
Assessment of pre-clinical liver models based on their ability to predict the liver-tropism of AAV vectors
Authors: Westhaus Adrian , Cabanes-Creus Marti , Dilworth Kimberley L. , Zhu Erhua , Gómez David Salas , Navarro Renina G. , Amaya Anais K. , Scott Suzanne , Kwiatek Magdalena , McCorkindale Alexandra L. , Hayman Tara E. , Frahm Silke , Perocheau Dany P. , Tran Bang Manh , Vincan Elizabeth , Wong Sharon L. , Waters Shafagh A. , Wilson Laurence O. W. , Baruteau Julien , Diecke Sebastian , González-Aseguinolaza Gloria , Santilli Giorgia , Thrasher Adrian J. , Alexander Ian E. , Lisowski Leszek 
Published: September 2022

AbstractThe liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors (rAAV). Multiple clinical trials have been undertaken for this target in the past 15 years, however we are still to see market approval of the first liver-targeted AAV-based gene therapy. Inefficient expression of the therapeutic transgene, vector-induced liver toxicity and capsid, and/or transgene-mediated immune responses reported at high vector doses are the main challenges to date. One of the contributing factors to the insufficient clinical outcomes, despite highly encouraging preclinical data, is the lack of robust, biologically- and clinically-predictive preclinical models. To this end, this study reports findings of a functional evaluation of six AAV vectors in twelve preclinical models of the human liver, with the aim to uncover which model is the most relevant for the selection of AAV capsid variant for safe and efficient transgene delivery to primary human hepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepatocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses of each system. This should allow the development of novel gene therapies targeting the human liver.
Prediction of heart transplant rejection from routine pathology slides with self-supervised Deep Learning
Authors: Seraphin Tobias Paul , Luedde Mark , Roderburg Christoph , van Treeck Marko , Scheider Pascal , Buelow Roman D. , Boor Peter , Loosen Sven H. , Provaznik Zdenek , Mendelsohn Daniel , Berisha Filip , Magnussen Christina , Westermann Dirk , Luedde Tom , Brochhausen Christoph , Sossalla Samuel , Kather Jakob Nikolas 
Published: September 2022

AbstractBackground and AimsOne of the most important complications of heart transplantation is organ rejection, which is diagnosed on endomyocardial biopsies by pathologists. Computer-based systems could assist in the diagnostic process and potentially improve reproducibility. Here, we evaluated the feasibility of using deep learning in predicting the degree of cellular rejection from pathology slides as defined by the International Society for Heart and Lung Transplantation (ISHLT) grading system.MethodsWe collected 1079 histopathology slides from 325 patients from three transplant centers in Germany. We trained an attention-based deep neural network to predict rejection in the primary cohort and evaluated its performance using cross validation and by deploying it to three cohorts.ResultsFor binary prediction (rejection yes/no) the mean Area Under the Receiver Operating Curve (AUROC) was 0.849 in the cross-validated experiment and 0.734, 0.729 and 0.716 in external validation cohorts. For a prediction of the ISHLT grade (0R, 1R, 2/3R), AUROCs were 0.835, 0.633 and 0.905 in the cross-validated experiment and 0.764, 0.597, 0.913, and 0.631, 0.633, 0.682, and 0.722, 0.601, 0.805 in the validation cohorts, respectively. The predictions of the AI model were interpretable by human experts and highlighted plausible morphological patterns.ConclusionsWe conclude that artificial intelligence can detect patterns of cellular transplant rejection in routine pathology, even when trained on small cohorts.
Smartphone videos of the sit-to-stand test predict osteoarthritis and health outcomes in a nationwide study
Authors: Boswell Melissa , Kidziński Łukasz , Hicks Jennifer , Uhlrich Scott , Falisse Antoine , Delp Scott 
Published: September 2022

AbstractPhysical function decline due to aging or disease can be assessed with quantitative motion analysis, but this currently requires expensive laboratory equipment. We introduce a self-guided quantitative motion analysis of the widely used five-repetition sit-to-stand test using a smartphone. Across 35 US states, 405 participants recorded a video performing the test in their homes. We found novel relationships not detectable in a clinical implementation of this test. Trunk angle during the sit-to-stand transition was greater in individuals with osteoarthritis and differed across ethnicities. In individuals 50 years of age or older, those with greater trunk angular acceleration had a higher mental health score. We also detected known associations between longer time to complete the five repetitions and lower physical health scores, higher BMI, and older age. Our findings demonstrate that at-home movement analysis goes beyond established clinical metrics to provide objective and inexpensive digital outcome metrics for nationwide studies.
Retrospective and prospective studies evaluating the performance of the SARS-Cov-2 “AQ+ COVID-19 Ag Rapid Test” from InTec on symptomatic and non-symptomatic patients
Authors: Prazuck Thierry , Serreau Raphael , Theillay Aurelie , Pallay Sandra , Pires-Roteia Daniela , Prazuck Fanny , Lesne Fabien 
Published: September 2022

AbstractFor the last two years, the SARS-CoV-2 virus spread all around the world and led to the COVID-19 pandemic. The need of methods to control the pandemic and to propose rapid and efficient diagnostic tools has emerged. In this perspective, SARS-CoV-2 rapid antigen detection tests (RADT) have been developed. We performed a retrospective study on 638 collected nasopharyngeal samples used for reference RT-qPCR diagnosis to compare the AQ+ COVID-19 Ag Rapid Test” from InTec (AQ+ InTec test) performance with other commercially available RADT. We analysed the sensitivity and specificity of the different tests and showed a better overall performance of the AQ+ InTec test, which was confirmed on the SARS-Cov-2 Omicron variant. We then conducted a prospective study on 1428 patients, to evaluate the sensitivity and specificity of the AQ+ InTec test on nasal and nasopharyngeal samples in a point of care setting. We showed that sensitivity and specificity reach acceptable criteria regarding the official recommendations of the MDCG 2021-21 in both symptomatic and asymptomatic patients. Overall, the results of these two studies confirm that the AQ+ InTec test is a valuable tool for testing in a pandemic context with a high proportion of asymptomatic patients who are potential carriers for the SARS-CoV-2 virus and is performant on the most current circulating variant Omicron.HighlightsThe sensitivity of the AQ+ COVID-19 Ag Rapid Test from InTec reaches 94.4% on nasal samples and 97.4% on nasopharyngeal samples.The performance of the test remains high on asymptomatic patients with a sensitivity of 89.2% on nasal samples and 97.0% on nasopharyngeal samples.Prospective study in a point of care setting revealed a better sensitivity compared with other commercially available rapid antigen detection tests
Falls Efficacy Scale International (FES-I) as a predictor of gait and balance abnormalities in community dwelling older people
Authors: McColl Lewis , Strassheim Victoria , Linsley Matthew , Green David , Dunkel Charlotte , Trundle Heidi , Gibbon Jake R , Parry Steve W 
Published: September 2022

AbstractBackgroundFear of falling (FoF) is common amongst community-dwelling older adults and is associated with higher falls risk. FoF is common amongst those with gait and balance abnormalities (GABAb), yet the ability of FoF measures to predict GABAb has not been assessed.MethodsData were reviewed from attendees of the North Tyneside Community Falls Prevention Service. The Falls Efficacy Scale International (FES-I) was used to measure falls efficacy, with a score larger than 23.5 indicating a concern for falling. Gait and balance measures were assessed, with cut-offs used to indicate poor and non-poor results for timed up and go (TUG) (>14s), five times sit to stand (FTSS) (>15s) and gait speed (GS) (<1 m/s). Receiver operating characteristic curves were generated for sensitivity and specificity analysis.ResultsFES-I score had good to excellent sensitivity when predicting TUG (87.1%), FTSS (82.9%) and GS results (73.0%) indicative of significant GABAb. Moderate specificity was also observed when predicting GS (62%) and FTSS (62.3%); a low to moderate specificity was observed when predicting TUG (50.0%).ConclusionA FES-I score of 23.5 or more showed high specificity in identifying those with prolonged TUG and FTSS and slower GS, with moderate specificity.
Benefits and barriers to implementing precision preventive care: results of a national physician survey
Authors: Vassy Jason L. , Kerman Benjamin J. , Harris Elizabeth J. , Lemke Amy A. , Clayman Marla L. , Antwi Ashley A. , MacIsaac Katharine , Yi Thomas , Brunette Charles A. 
Published: September 2022

BackgroundClinical implementation of polygenic risk scores (PRS) for precision prevention depends on the utility and barriers primary care physicians (PCPs) perceive to their use.MethodsAn online survey asked PCPs in a national database about the clinical utility of PRS they perceived for categories of medical decision-making and perceived benefits of and barriers to that use. Latent class analysis (LCA) was used to identify subgroups of PCPs based on response patterns.ResultsAmong 367 respondents (email open rate 10.8%; participation rate 96.3%; completion rate 93.1%), mean (SD) age was 54.9 (12.9) years, 137 (37.3%) were female, and mean (SD) time since medical school graduation was 27.2 (13.3) years. Respondents reported greater perceived utility for more clinical action (e.g., earlier or more intensive screening, preventive medications, or lifestyle modification) for patients with high-risk PRS than for delayed or discontinued prevention actions for low-risk patients (p<0.001). Respondents most often chose out-of-pocket costs (48%), lack of clinical guidelines (24%), and patient insurance discrimination concerns (22%) as extreme barriers to PRS implementation. LCA identified 3 subclasses of respondents. Skeptics (n=83, 22.6%) endorsed less agreement with individual clinical utilities, saw patient anxiety and insurance discrimination as significant barriers, and agreed less often that PRS could help patients make better health decisions. Learners (n=134, 36.5%) and enthusiasts (n=150, 40.9%) expressed similar levels of agreement that PRS had utility for preventive actions and that PRS could be useful for patient decision-making. Compared with enthusiasts, however, learners perceived greater barriers to the clinical use of PRS.ConclusionPCPs generally endorsed using PRS to guide medical decision-making about preventive care, with a preference for more clinical action over less. Barriers identified suggest interventions to address the needs and concerns of PCPs along the spectrum of acceptance and uptake.
Associations of conservatism/jumping to conclusions biases with aberrant salience and default mode network
Authors: Miyata Jun , Sasamoto Akihiko , Ezaki Takahiro , Isobe Masanori , Kochiyama Takanori , Masuda Naoki , Mori Yasuo , Sakai Yuki , Sawamoto Nobukatsu , Tei Shisei , Ubukata Shiho , Aso Toshihiko , Murai Toshiya , Takahashi Hidehiko 
Published: September 2022

AbstractBackground and hypothesisWhile the conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, people with schizophrenia and delusion require less evidence, known as the jumping to conclusions (JTC) bias. The midbrain-striatal aberrant salience of schizophrenia is postulated to form delusion; however, the association between conservatism/JTC and aberrant salience and their neural correlates are unclear.Study designThirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large/small numbers of bead draws to decision (DTD) used as an index of conservative/hasty (JTC) decisions, respectively. We performed meta-independent component analysis and thresholded dual regression of resting functional magnetic resonance imaging (MRI) data, and structural covariance network analysis (SCNA) of structural and diffusion MRI data. We investigated interactions between diagnosis and DTD, and main effects of DTD for each imaging modality.Study resultsWe found no significant interactions. We identified main effects of DTD (positive correlation) for: 1) functional connectivity between the striatum and default mode network (DMN), 2) DMN-like structural SCNA network, and 3) the diffusion SCNA network connecting networks of 1) and 2) (all p < 0.05, family-wise error [FWE] correction). The functional connectivity between the striatum and DMN was also negatively correlated with delusion severity in patients (p < 0.05, FWE), indicating that the greater the anti-correlation, the stronger the JTC and delusion.ConclusionsOur results support a novel concept that conservatism/JTC biases are associated with aberrant salience of schizophrenia and the default brain mode.