bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antarctic biosecurity policy effectively manages the rates of alien introductions
Authors: Leihy Rachel I. , McGeoch Melodie A. , Clarke David A. , Peake Lou , Buba Yehezkel , Belmaker Jonathan , Chown Steven L. 
Published: October 2024

AbstractReducing the rates and impacts of biological invasions is a major policy goal of international biodiversity agreements. Yet the extent to which this goal is being achieved and the agreements hence successful in this respect remains unclear. Here we use a comprehensive record of alien species introduction in the terrestrial Antarctic, including its surrounding Southern Ocean Islands, spanning 115 years (1900–2015), to quantify the impact of biosecurity policy on alien species introduction rates in the region, where invasive alien species are a primary environmental conservation threat and management priority. We show that although many parts of the Antarctic have been colonised by non-indigenous taxa, recent rates of introduction appear to be slowing or static in most parts, compared with increases in the past. Our results vindicate the regional Antarctic focus on biosecurity measures, but also demonstrate the need for stricter enforcement due to rapid socio-environmental changes.Three key pointsBiological invasions present a large and growing threat to Antarctic ecosystems under climate change and expanding human activityOver the 20thcentury, there was no trend in alien species introduction rate in five Antarctic regions and a significantly increasing trend in the remaining five regionsDespite this variation, in most regions, the number of introductions remains low, indicating that Antarctic biosecurity has been effective at slowing the rate of introduction
Same-day discharge versus overnight stay after pulmonary vein isolation: an assessment on clinical outcomes and healthcare utilization
Authors: Slingerland SR (Stacey) , Van den Broek JLPM (Maarten) , Schulz DN (Daniela) , van Steenbergen GJ (Gijs) , Dekker LRC (Lukas) , Ouss AJ (Alexandre) , van Veghel D (Dennis) 
Published: October 2024

AbstractBackgroundAtrial fibrillation is increasingly prevalent and constitutes a severe economic and clinical burden. Pulmonary vein isolation (PVI) is an effective treatment. Evidence on the safety of same-day discharge (SDD) after PVI, instead of overnight stay (ONS), is limited.Methods & resultsThis retrospective study uses data from PVI’s performed between June 2018 and December 2020 in the Netherlands. Baseline characteristics, clinical outcome data and health care utilization, extracted from two national databases, were compared between the implementation of an SDD protocol in a single centre and a national benchmark where majority is an ONS strategy. Descriptive and bivariate analyses were performed. We included data from 11,812 PVI’s; 1,360 in the SDD group and 10,452 for the ONS benchmark. The SDD protocol group performed 57.7% of PVI’s in SDD, the benchmark 5.3% (p<.001). The SDD protocol group performed more cryoballoon PVI (90.8% vs. 39.2%, p<.001). There were no differences in bleeding (p=.830), thromboembolic (p=.893) or vascular complications (p=.720), or cardiac tamponade (p=.634). Peri-procedural hospital stay was significantly shorter in the SDD protocol group (0.50 day vs. 1.52 days, p<.001), without a reallocation of healthcare to outpatient clinic (p=.230), emergency department (p=.132) or higher rate of readmission (p=.092).ConclusionThe SDD protocol group with 57.7% SDD has similar complication rates and lower health care utilization, compared to the national ONS benchmark with 5.3% SDD, indicating that SDD is a safe and effective alternative for ONS in patients undergoing PVI. The 5.3% ONS in the benchmark suggests a potential reduction of nationwide healthcare utilization.
Integer programming framework for pangenome-based genome inference
Authors: Chandra Ghanshyam , Hossen Md Helal , Scholz Stephan , Dilthey Alexander T , Gibney Daniel , Jain Chirag 
Published: October 2024

AbstractAffordable genotyping methods are essential in genomics. Commonly used genotyping methods primarily support single nucleotide variants and short indels but neglect structural variants. Additionally, accuracy of read alignments to a reference genome is unreliable in highly polymorphic and repetitive regions, further impacting genotyping performance. Recent works highlight the advantage of haplotype-resolved pangenome graphs in addressing these challenges. Building on these developments, we propose a rigorous alignment-free genotyping framework. Our formulation seeks a path through the pangenome graph that maximizes the matches between the path and substrings of sequencing reads (e.g.,k-mers) while minimizing recombination events (haplotype switches) along the path. We prove that this problem is NP-Hard and develop efficient integer-programming solutions. We benchmarked the algorithm using downsampled short-read datasets from homozygous human cell lines with coverage ranging from 0.1× to 10×. Our algorithm accurately estimates complete major histocompatibility complex (MHC) haplotype sequences with small edit distances from the ground-truth sequences, providing a significant advantage over existing methods on low-coverage inputs. Although our algorithm is designed for haploid samples, we discuss future extensions to diploid samples.Implementationhttps://github.com/at-cg/PHI
VizCNV: An integrated platform for concurrent phased BAF and CNV analysis with trio genome sequencing data
Authors: Du Haowei , Lun Ming Yin , Gagarina Lidiia , Mehaffey Michele G , Hwang James Paul , Jhangiani Shalini N. , Bhamidipati Sravya V. , Muzny Donna M. , Poli M Cecilia , Ochoa Sebastian , Chinn Ivan K. , Linstrand Anna , Posey Jennifer E. , Gibbs Richard A , Lupski James R. , Carvalho Claudia M. B. 
Published: October 2024

AbstractBackgroundCopy number variation (CNV) is a class of genomic Structural Variation (SV) that underlie genomic disorders and can have profound implications for health. Short-read genome sequencing (sr-GS) enables CNV calling for genomic intervals of variable size and across multiple phenotypes. However, unresolved challenges include an overwhelming number of false-positive calls due to systematic biases from non-uniform read coverage and collapsed calls resulting from the abundance of paralogous segments and repetitive elements in the human genome.MethodsTo address these interpretative challenges, we developed VizCNV. The VizCNV computational tool for inspecting CNV calls uses various data signal sources from sr-GS data, including read depth, phased B-allele frequency, as well as benchmarking signals from other SV calling methods. The interactive features and view modes are adept for analyzing both chromosomal abnormalities [e.g., aneuploidy, segmental aneusomy, and chromosome translocations], gene exonic CNV and non-coding gene regulatory regions. In addition, VizCNV includes a built-in filter schema for trio genomes, prioritizing the detection of impactful germline CNVs, such asde novoCNVs. Upon computational optimization by fine-tuning parameters to maximize sensitivity and specificity, VizCNV demonstrated approximately 83.8% recall and 77.2% precision on the 1000 Genome Project data with an average coverage read depth of 30x.ResultsWe applied VizCNV to 39 families with primary immunodeficiency disease without a molecular diagnosis. With implemented build-in filter, we identified twode novoCNVs and 90 inherited CNVs >10 kb per trio. Genotype-phenotype analyses revealed that a compound heterozygous combination of a paternal 12.8 kb deletion of exon 5 and a maternal missense variant allele ofDOCK8are likely the molecular cause of one proband.ConclusionsVizCNV provides a robust platform for genome-wide relevant CNV discovery and visualization of such CNV using sr-GS data.
Aluminium induces suberin biosynthesis in barley roots via ABA
Authors: Meng Hongjun , Zhang Qihui , Kreszies Tino , Acosta Ivan F. , Schreiber Lukas 
Published: October 2024

AbstractAluminum (Al) toxicity is a major factor limiting plant growth in acidic soils. The beneficial element silicon (Si) can mitigate some effects of Al. However, the impact of Al on suberized apoplastic barriers in roots are largely unknown while the effects of Si on suberin remains controversial.This study employed physiological, histochemical, and analytical methods, along with Laser Capture Microdissection (LCM) RNA-sequencing, to explore the effects of Al and Si on suberin development in barley (Hordeum vulgareL.), a species sensitive to Al stress.Exposure of barley seedlings to Al resulted in increased suberin deposition, which could be restored with the addition of Si, particularly in the root endodermis. Gene expression analyses using LCM RNA-seq across different root tissues demonstrated that Al-induced suberin biosynthesis is mainly regulated by the abscisic acid (ABA) pathway. In addition, the application of fluridone, an inhibitor of ABA synthesis and a suberin mutant, further supported the pivotal role of ABA in the Al response and the role of suberin in influencing Al uptake.Our findings underscore the complex interplay between Al stress and suberin biosynthesis in barley, providing insights into potential strategies for enhancing crop resilience to Al toxicity.
Selective breeding for determinacy and photoperiod sensitivity in common bean (Phaseolus vulgarisL.)
Authors: Denning-James Kate E , Chater Caspar , Cortés Andrés J , Blair Matthew W , Peláez Diana , Hall Anthony , De Vega Jose J 
Published: October 2024

AbstractCommon bean (Phaseolus vulgarisL.) is a legume pulse crop that provides significant dietary and ecosystem benefits globally. We investigated two key traits, determinacy and photoperiod sensitivity, that are integral to its management and crop production, and that were early selected during the domestication of both Mesoamerican and Andean gene pools. Still, significant variation exists among common bean landraces for these traits. Since landraces form the basis for trait introgression in pre-breeding, understanding these traits’ genetic underpinnings and relation with population structure is vital for guiding breeding and genetic studies.We explored genetic admixture, principal component, and phylogenetic analyses to define subpopulations and gene pools, and genome-wide association mapping (GWAS) to identify marker-trait associations in a diversity panel of common bean landraces. We observed a clear correlation between these traits, gene pool and subpopulation structure. We found extensive admixture between the Andean and Mesoamerican gene pools in some regions. We identified 13 QTLs for determinacy and 10 QTLs for photoperiod sensitivity, and underlying causative genes. Most QTLs appear to be firstly described. Our study identified known and novel causative genes and a high proportion of pleiotropic effects for these traits in common bean, and likely translatable to other legume species.HighlightWe identified and explored QTLs for the domestication-related determinacy and photoperiod sensitivity traits, which are traits critically associated with population structure and management and crop production.
Endogenous EWSR1-FLI1 degron alleles enable control of fusion oncoprotein expression in tumor cell lines and xenografts
Authors: McGinnis James H. , Enriquez Alberto Bremauntz , Vandiver Florentina , Bai Xin , Kim Jiwoong , Kilgore Jessica , Saha Purbita , O’Hara Ryan , Xie Yang , Banaszynski Laura A. , Williams Noelle , McFadden David G. 
Published: October 2024

ABSTRACTPediatric malignancies frequently harbor chromosomal translocations that induce expression of fusion oncoproteins. The EWSR1-FLI1 fusion oncoprotein acts as a neomorphic transcription factor and is the dominant genetic driver of Ewing’s sarcoma. Interrogation of the mechanisms by which EWSR1-FLI1 drives tumorigenesis has been limited by a lack of model systems to precisely and selectively control its expression in patient-derived cell lines and xenografts. Here, we report the generation of a panel of patient-derived EWS cell lines in which inducible protein degrons were engineered into the endogenous EWSR1-FLI1 locus. These alleles enabled rapid and efficient depletion of EWSR1-FLI1. Complete suppression of EWSR1-FLI1 induced a reversible cell cycle arrest at the G1-S checkpoint, and we identified a core set of transcripts downstream of EWSR1-FLI1 across multiple cell lines and degron systems. Additionally, depletion of EWSR1-FLI1 potently suppressed tumor growth in xenograft models validating efforts to directly target EWSR1-FLI1 in Ewing’s sarcoma.
Multidimensional Epigenetic Clocks Demonstrate Accelerated Aging Across Physiological Systems in Schizophrenia: A Meta-Analysis
Authors: Harvanek Zachary M. , Sehgal Raghav , Borrus Daniel , Kasamoto Jessica , Priyanka Ahana , Corley Michael J. , Vinkers Christiaan H. , Boks Marco P. , Smith Ryan , Dwaraka Varun B. , Lasky-Su Jessica , Higgins-Chen Albert T. 
Published: October 2024

AbstractImportance: Schizophrenia is associated with increased age-related morbidity, mortality, and frailty, which are not entirely explained by behavioral factors. Prior studies using epigenetic clocks have suggested that schizophrenia is associated with accelerated aging, however these studies have primarily used unidimensional clocks that summarize aging as a single “biological age” score.Objective: This meta-analysis uses multidimensional epigenetic clocks that split aging into multiple scores to analyze biological aging in schizophrenia. These novel clocks may provide more granular insights into the mechanistic relationships between schizophrenia, epigenetic aging, and premature morbidity and mortality.Study selection: Selected studies included patients with schizophrenia-spectrum disorders and non- psychiatric controls with available DNA methylation data. Seven cross-sectional datasets were available for this study, with a total sample size of 1,891 patients with schizophrenia and 1,881 controls.Data extraction and synthesis: Studies were selected by consensus Meta-analyses were performed using fixed-effect models.Main outcomes and measures: We analyzed multidimensional epigenetic clocks, including causality- enriched CausAge clocks, physiological system-specific SystemsAge clocks, RetroelementAge, DNAmEMRAge, and multi omics-informed OMICmAge. Meta-analyses examined clock associations with schizophrenia disease status and clozapine use, after accounting for age and sex.Results: Overall SystemsAge, CausAge, DNAmEMRAge, and OMICmAge scores demonstrated increased epigenetic aging in patients with schizophrenia after strict multiple-comparison testing. Ten of the eleven SystemsAge sub-clocks corresponding to different physiological systems demonstrated increased aging, with strongest effects for Heart and Lung followed by Metabolic and Brain systems. The causality- enriched clocks indicated increases in both damaging and adaptive aging, though these effects were weaker compared to SystemsAge scores. OMICmAge indicated changes in multiple clinical biomarkers, including hematologic and hepatic markers that support system-specific aging, as well as novel proteins and metabolites not previously linked to schizophrenia. Most clocks demonstrated age acceleration at the first psychotic episode. Notably, clozapine use was associated with increased Heart and Inflammation aging, which may partially be driven by smoking. Most results survived strict Bonferroni multiple testing correction.Conclusions and relevance: These are the first analyses of novel multidimensional clocks in patients with schizophrenia and provide a nuanced view of aging that identifies multiple organ systems at high risk for disease in schizophrenia-related disorders.
Barriers and Facilitators to Heart Failure Guideline-Directed Medical Therapy in an Integrated Health System and Federally-Qualified Health Centers: A Thematic Qualitative Analysis
Authors: Philbin Sarah E. , Gleason Lacey P. , Persell Stephen D. , Walter Eve , Petito Lucia C. , Tibrewala Anjan , Yancy Clyde W. , Beidas Rinad S. , Wilcox Jane E. , Mutharasan R. Kannan , Lloyd-Jones Donald , O’Brien Matthew J , Kho Abel N. , McHugh Megan C. , Smith Justin D. , Ahmad Faraz S. 
Published: October 2024

AbstractBackgroundClinical guidelines recommend medications from four drug classes, collectively referred to as quadruple therapy, to improve outcomes for patients with heart failure with reduced ejection fraction (HFrEF). Wide gaps in uptake of these therapies persist across a range of settings. In this qualitative study, we identified determinants (i.e., barriers and facilitators of quadruple therapy intensification, defined as prescribing a new class or increasing the dose of a currently prescribed medication.MethodsWe conducted interviews with physicians, nurse practitioners, physician assistants, and pharmacists working in primary care or cardiology settings in an integrated health system or Federally Qualified Health Centers (FQHCs). We report results with a conceptual model integrating two frameworks: 1) the Theory of Planned Behavior (TPB), which explains how personal attitudes, perception of others’ attitudes, and perceived behavioral control influence intentions and behaviors; and 2) The Consolidated Framework for Implementation Research (CFIR) 2.0 to understand how multi-level factors influence attitudes toward and intention to use quadruple therapy.ResultsThirty-one clinicians, including thirteen eighteen (58%) primary care and (42%) cardiology clinicians, participated in the interviews. Eight (26%) participants were from FQHCs. A common facilitator in both settings was the belief in the importance of quadruple therapy. Common barriers included challenges presented by patient frailty, clinical inertia, and time constraints. In FQHCs, primary care comfort and ownership enhanced the intensification of quadruple therapy while limited access to and communication with cardiology specialists presented a barrier. Results are presented using a combined TPB-CFIR framework to help illustrate the potential impact of contextual factors on individual-level behaviors.ConclusionsDeterminants of quadruple therapy intensification vary by clinician specialty and care setting. Future research should explore implementation strategies that address these determinants by specialty and setting to promote health equity.
A Novel Early Onset Spinocerebellar Ataxia 13 BAC Mouse Model with Cerebellar Hypoplasia, Tremor, and Ataxic Gait
Authors: Yin Junxiang , Nick Jerelyn A. , Khare Swati , Kloefkorn Heidi E. , Gao Ming , Wu Michael , White Jennifer , Resnick James L. , Allen Kyle D. , Nick Harry S. , Waters Michael F. 
Published: October 2024

AbstractSpinocerebellar ataxia 13 (SCA13) is an autosomal dominant neurological disorder caused by mutations inKCNC3. Our previous studies revealed thatKCNC3mutation R423H results in an early-onset form of SCA13. Previous biological models of SCA13 include zebrafish and Drosophila but no mammalian systems. More recently, mouse models withKCNC3mutations presented behavioral abnormalities but without obvious pathological changes in the cerebellum, a hallmark of patients with SCA13. Here, we present a novel transgenic mouse model by bacterial artificial chromosome (BAC) recombineering to express the full-length mouse Kcnc3 expressing the R424H mutation. This BAC-R424H mice exhibited behavioral and pathological changes mimicking the clinical phenotype of the disease. The BAC-R424H mice (homologous to R423H in human) developed early onset clinical symptoms with aberrant gait, tremor, and cerebellar hypoplasia/atrophy. Histopathological analysis of the cerebellum in BAC-R424H mice showed progressive Purkinje cell loss and thinning of the molecular cell layer. Additionally, Purkinje cells of BAC-R424H mice showed significantly lower spontaneous firing frequency with a corresponding increase in inter-spike interval compared to that of wild-type mice. Our SCA13 transgenic mice recapitulate both neuropathological and behavioral changes manifested in human SCA13 R423H patients and provide an advantageous approach to understanding the role of voltage-gated potassium channel in cerebellar morphogenesis and function. This mammalianin vivomodel will lead to further understanding of the R423H allelic form of SCA13 from the molecular to the behavioral level and serve as a platform for testing potential therapeutic compounds.
Craving Connections: Exploring the Relationship Between Pregnancy Cravings, Maternal Health, and Child Preferences in Indian Families
Authors: Kruthi M Nithya , Duraimani Shanthi Lakshmi , Fathima Sarah , Ghori Junaid Ahmed Khan , Saikia Katherine , KM Annervaz , AR Balamurali , Ranganathan Rahul , Thummala Sabitha 
Published: October 2024

AbstractAlthough Pregnancy cravings are a common phenomenon, their implications on maternal health, family dietary habits, and child food preferences remain underexplored, particularly in the Indian context. This study aimed to investigate the prevalence and nature of pregnancy cravings among Indian women and their potential impact on maternal health outcomes and family dietary patterns. A cross-sectional survey was conducted with 119 women who had experienced pregnancy, collecting data on craving patterns, maternal health indicators, and perceived influences on family diet. Results revealed that most women craved sugary snacks, predominantly in the second trimester. Notably, 61.9% of participants’ cravings did not align with their spouse’s food preferences, suggesting potential shifts in family dietary habits. The study also found associations between cravings, mood swings, and morning sickness, highlighting the complex interplay of physiological and psychological factors during pregnancy. These findings underscore the need for culturally sensitive, personalised prenatal care that address both the nutritional and emotional aspects of pregnancy cravings, influencing long-term family health outcomes.
LIMPACAT : Multi-Omics Attention Transformer for Immune Prediction in Liver Cancer Using Whole-Slide Imaging
Authors: Chiu Yen-Jung 
Published: October 2024

AbstractThis study introduces LIMPACAT (Liver Immune Microenvironment Prediction and Classification Attention Transformer), a framework that leverages whole-slide images (WSIs) to predict immune cell levels associated with prognosis in liver cancer. Since direct immune cell composition data is unavailable in the TCGA-LIHC dataset, we inferred immune cell levels using liver-specific single-cell RNA sequencing (scRNA-seq) data to simulate bulk RNA-seq profiles, allowing estimation of immune compositions within the tumor microenvironment. To ensure consistency, we tested three normalization methods—log normalization, canonical correlation analysis (CCA), and SCTransform—for scRNA-seq data integration and preprocessing, which facilitated reliable predictions of immune cell distributions in bulk RNA-seq.By applying this scRNA-seq-informed cell composition deconvolution model to real bulk RNA-seq data from liver cancer samples, we confirmed alignment in immune cell composition estimates between bulk RNA-seq and scRNA-seq. Using a multiple instance learning (MIL) framework with an attention transformer, LIMPACAT achieved approximately 80% accuracy in classifying immune cell levels relevant to patient prognosis. These findings highlight the feasibility of integrating WSIs and multi-omics data to enhance immune profiling and prognostic predictions in liver cancer research.