bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating rates of SARS-CoV-2 lineage spread from graph theory analysis and data mining of genetic sequence data streams
Authors: Goldberg Emma E. , Kupperman Michael D. , Ke Ruian 
Published: February 2025

AbstractThe modern enormous scale of viral genomic data, as exemplified by SARS-CoV-2, presents unique opportunities for epidemic inference and real-time monitoring. Existing methods, however, cannot efficiently process the extremely large stream of sequence data and simultaneously identify small subsets of sequences that may represent rapid population growth of newly emerged lineages. To address this gap, we developed a new approach that combines techniques in traditional graph theory and modern data mining. We represent small subsets of sequences as graph Laplacians and identify from them features of rapid population growth. From early sequence data collected in the US and the UK between 2021 and mid-2022, we identified two features—genetic diversity and matrix connectivity—that allow us to reliably estimate growth rates of newly emerged lineages. To test our model, we used data collected from mid-2022 and end-2024 and accurately predicted the growth rates of lineages that appeared during this period. Furthermore, for data collected in 2023 when the sequencing efforts were relatively high (thousands of sequences per day) in the US and the UK, our model correctly identified the most rapidly expanding lineages when they were still at low frequencies (between 1-6%). Overall, our work provides a scalable and adaptable tool to estimate the growth rate of newly emerged SARS-CoV-2 lineages. More broadly, the interpretable logic of our method suggests potential for rapid outbreak identification for other rapidly evolving pathogens.Significance StatementThe COVID-19 pandemic has underscored the importance of rapidly identifying emerging SARS-CoV-2 lineages that may cause large outbreaks. Methods are needed that can handle a large amount of incoming genomic data and at the same time identify small groups of cases that may represent rapid growth of newly emerged lineages. To address this need, we developed an approach utilizing graph theory and data mining techniques, which we show reliably estimates the growth rates of newly emerged SARS-CoV-2 lineages. Our approach can promptly identify rapidly growing lineages, often weeks or months before they became dominant. This demonstrates its potential as a scalable tool for transmission dynamics inference, real-time outbreak monitoring, and pandemic preparedness.
Variation and Standardization in Prior Authorization Requirements
Authors: Zaari Jabri Aya , Asher Jacob , Sandling Jacqueline , Schulman Kevin , Scheinker David 
Published: February 2025

AbstractImportancePrior authorization rules are neither regulated nor standardized and contribute to wasted spending, delays in care, and physician burnout.ObjectiveTo examine and compare the prior authorization rules of large private US insurers.DesignThis study converted prior authorization rules into a single framework; quantified variations, inconsistencies, and contradictions within and across insurers; and developed a single algorithm to reproduce and compare the prior authorization rules of all insurers.SettingPrior authorization rules from the providers manuals of Humana, United Healthcare, Anthem California, and Aetna.ParticipantsThe prior authorization rules for in-network providers and internally managed contracts were included while the rules for out-of-network providers, for determining provider network status, and for services managed by external vendors were excluded.ResultsThe provider manuals cover 19,637 services and medications. Of these, Humana requires prior authorization for 3,048, United Healthcare for 2,682, Anthem California for 2,188, and Aetna for 842. To determine if PA is required, Anthem California provides a medical criteria document for each service and medication. The other insurers use six criteria for varying sets and categories of services and medications. There are 18 potential requirements to obtain prior authorization from Anthem California and a total of five across the other insurers. The manuals contain duplicated, ambiguous, and contradictory guidelines.ConclusionsIn an analysis of the provider manuals of four large US insurers, prior authorization rules differed significantly across services within each provider manual and across provider manuals. The rules were reproduced with a simple framework of 6 criteria to determine if prior authorization is required and 23 requirements to obtain prior authorization, providing an empirical example of a single standardized contract reproducing the rules of several contracts from different large health insurers. The methods presented to standardize and simplify contracts may help inform efforts to rationalize and improve the prior authorization process as well as broader efforts to reduce administrative costs and waste through standardization.Key PointsQuestionDo prior authorization rules, purportedly derived from evidence-based coverage policies, differ across large private US insurers?FindingPrior authorization rules differed significantly across services and across insurers with contradictions and inconsistencies. The rules were reproduced with a framework of 6 criteria to determine if prior authorization is required and 23 requirements to obtain prior authorization.MeaningThe methods presented to reproduce the prior authorization rules of four large insurers in a single framework may help inform efforts to standardize the prior authorization process. The present approach may inform broader efforts to reduce administrative costs and waste through contract standardization.
High-risk HPV Prevalence and Distribution in Cervical Cancer Screening: Extended Genotyping in Correlation with Cytology and p16/Ki67 Dual Stain Results
Authors: Trzeszcz Martyna , Mazurec Karolina , Mazurec Maciej , Jach Robert , Halon Agnieszka 
Published: February 2025

AbstractThe prevalence of high-risk human papillomavirus (HR-HPV) in cytology combined with p16/Ki67 status using limited and two types of extended HPV genotyping has not yet been described. A total of 32,724 screening tests results between 2015-2024 were included. The overall HR-HPV-positivity rate was 15.0%. The HR-HPV prevalence in limited genotyping group was 13.9%, in extended genotyping 1 (17.8%), in extended genotyping 2 (17.2%), with statistically significant difference in the proportions of positive/negative cases (p<0.0001). No statistically significant difference was noted between extended genotyping groups (p=0.706). Extended genotyping 1: the highest p16/Ki67-positivity was observed for HR-HPV 33/58 (100.0%) and 31 (58.8%), the lowest for HR-HPV 45 (18.2%), 18 (25.0%) and 59/56/66 (28.9%). Extended genotyping 2: the highest p16/Ki67-positivity was for HR-HPV 16 (66.7%) and 31/33/52/58 (58.8%). A combined approach, implementing new technologies, could help healthcare providers in more informed decisions about patient care, supporting the prevention of cervical precancer and cancer.Statement of SignificanceThe transition to HPV-based cervical cancer screening is progressively advancing. By investigating of HR-HPV prevalence and distribution in limited or extended genotyping, cytology and p16/Ki67 dual-stain, our study aimed to support evidence-based decision-making processes and help guide of medical interventions of public health policies targeted to incorporation of new technologies.
Global, regional, and national burden of chronic kidney disease-related heart failure from 1990 to 2021: an analysis of data from the Global Burden of Disease Study 2021
Authors: Ji Jinzhong , Chu Feifan , Guan Qing , Chen Lumin , Ma Yuning , Chen Zujie , Ji Qiwei , Sun Mingxin , Ren Gaozhan , Huang Tingyang , Song Haihan , Lin Weiqiang , Lin Xiuquan , Zhou Hao 
Published: February 2025

AbstractBackgroundThe global burden of chronic kidney diseases related heart failure (CKD-related HF) has yet to be reported. The study aims to analyze the global burden of CKD-related HF.MethodsUtilizing the data from the Global Burden of Disease Study 2021, we delineated the prevalence and years lived with disability (YLDs) of CKD-related HF at global, regional, and national levels, alongside its age and sex distributions, as well as temporal trends. Furthermore, we conducted transnational inequality analysis and frontier analysis. Additionally, we analyzed the burden of CKD-related HF with diverse etiological factors.ResultsOver the past three decades, the global burden of CKD-related HF has escalated, reaching 1,936,886 cases in 2021, with an age-standardized prevalence of 24.21 per 100,000 and an age-standardized YLDs rate of 3.07 per 100,000. This burden is projected to continue rising over the next decade. The burden of CKD-related HF is notably concentrated among the elderly and children. Notably, there is health inequity in its distribution, disproportionately affecting low sociodemographic index (SDI) groups, although alleviation opportunities exist across all SDI levels. Globally, the primary contributors to CKD-related HF are type 2 Diabetes Mellitus (T2DM) and hypertension, apart from CKD of other and unspecified causes.ConclusionsThe global burden of CKD-related HF has witnessed increase and is projected to persist over the next decade. Certain populations, including children, the elderly, and regions with low SDI levels, experienced a heavier burden. Effective management of primary diseases contributes to mitigating the burden of CKD-related HF.
Sex and gender differences in OCD: A scoping review
Authors: Van Zandt Meghan , Olfson Emily , Stahnke Brittany , Taylor Samantha , Bloch Michael H. , Pittenger Christopher , Pushkarskaya Helen 
Published: February 2025

AbstractThis scoping review explores sex and gender differences in obsessive-compulsive disorder (OCD) as reported in the literature between 2009 and 2021. A comprehensive PubMed search was conducted without restrictions, using terms related to sex, gender, and OCD. 5,973 articles were screened by two reviewers, with 909 assessed at the full-text level. Of these, 541 were included: 37 meta-analyses, 8 systematic reviews, 25 narrative reviews, and 471 original reports. Original reports were categorized by focus — symptomology and burden (66), comorbidities (121), epidemiology (134), human genetics (68), altered neurocognitive and neurobiological functioning (36), treatment (42), and animal models (29) — and assessed for quality using CASP checklists. There was abundant research on sex and gender effects in OCD, but limited synthesis. Identified methodological concerns included inconsistent assessments of sex and gender, variability in OCD symptom measurement, failure to account for menstrual cycle effects, and a lack of genome-wide and full-brain imaging studies. Biases in results may arise from not accounting for gender differences in insight, help-seeking behaviors, and comorbidity. We identify critical knowledge gaps and develop hypotheses for future research, incorporating recommendations for precision medicine approaches. Investigating sex and gender differences in OCD can advance equitable mental health care by addressing the specific needs of diverse populations. Appreciating these effects offers a pathway to better understanding the complexity of OCD, fostering targeted interventions and a more nuanced approach to treatment and prevention.
Senolytics restore hematopoietic stem cell function in sickle cell disease
Authors: Barve Aditya , Cornwell Adam , Sriram Pramika , Kopyov Alex , Dabas Preeti , Kooienga Emilia , Kelley Zakiya , Johnson James , Myers Jacquelyn A. , Obeng Esther A. , Kang Guolian , Olufadi Yunus , Cain Terri , Talbot Lindsay , Spence David , Cortes Mauricio , Miller Sam , Loeffler Dirk , Sharma Akshay , McKinney-Freeman Shannon 
Published: February 2025

AbstractSickle Cell Disease (SCD) is a blood disorder affecting millions worldwide. Emerging evidence reveals that SCD pathophysiology increases risk of myeloid malignancies and hematopoietic stem cell (HSC) dysfunction, possibly due to pathological stress on bone marrow. To investigate this further, we interrogated mice and individuals with SCD and observed extended cell cycle times, oxidative stress, DNA damage, senescence, and dysregulation of molecular programs associated with these processes in bone marrow hematopoietic stem and progenitor cells (HSPCs). Human SCD HSPCs displayed poor hematopoietic potentialex vivo. SCD mice displayed a dramatic loss of transplantable bone marrow HSPCs, which was reversed upon treatment of SCD mice with the senolytic agent, ABT-263 (navitoclax). Thus, senolytics restore bone marrow function during SCD in mice and represent a novel strategy to improve bone marrow health in individuals with SCD and improve the safety of potentially curative gene therapies that utilize autologous HSPCs from individuals with SCD.
Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis
Authors: Chuang Chi-Ning , Hung Ya-Ling , Kim Hong-Xiang , Yao Jhong-Syuan , Liu Hou-Cheng , Chen Sheng-Yuan , Jovanska Lavernchy , Hsueh Yi-Ping , Chen Ruey-Shyang , Wang Ting-Fang 
Published: February 2025

SUMMARYMismatch repair (MMR) is believed to prevent homologous recombination (HR) between homologous chromosomes, causing infertility in hybrids between closely related species. We report that HR and MMR are yin-yang partners in the response to genetic polymorphisms and that several budding yeast HR genes (i.e.,RAD51,RAD54,ZMM) exhibit anti-MMR activities. This yin-yang relationship biases MMR in wild-type interspecies (Saccharomyces cerevisiae/Saccharomyces paradoxus) hybrid zygotes and intraspeciesS. cerevisiaehybrid zygotes with anti-MMR mutations, resulting in excessive (rather than insufficient) interhomolog HR, including negative crossover interference, allelic conversion or even disruption. The anti-MMR function ofS. cerevisiaeRad54 prevails over its accessory role in promoting Rad51-mediated strand exchange during hybrid meiosis. Srs2 (the yeast ortholog ofEsherichia coliUvrD helicase) facilitates the MMR system by dissembling Rad51-ssDNA presynaptic filaments. Sgs1 (the yeast ortholog ofE. coliRecQ helicase) acts after MMR-dependent recognition of heteroduplex mismatches to promote crossover clustering and allelic switching.In briefExcessive interhomolog recombination leads to hybrid infertilityHighlightsHomologous recombination (HR) antagonizes mismatch repair (MMR) in hybrid meiosis.Anti-MMR mutations of HR genes (RAD51,RAD54,orZMM) cause hybrid sterility.Hybrid sterility is due to excessive (rather than insufficient) interhomolog HR.Hybrid sterility-inducing anti-MMR mutations can be rescued by repressing MMR genes.
In vivoImaging and Tracking of VRE-microbiota Interactions via Anaerobic Fluorescent Reporters in Extremely Drug-resistant Bacteria
Authors: Treat Benjamin R. , Hobeika Joseph , Duggar Marygrace , Fields Trinity , Guy Cliff , Black Mollie , Kohler Christina M. , Margolis Elisa B. 
Published: February 2025

AbstractVancomycin-resistantEnterococcus faecium(VREfm) has emerged as a major nosocomial pathogen, but studying its host and microbiome interactions remains challenging due to limited genetic tools. Current obstacles include extensive intrinsic and acquired resistance that precludes use of conventional selection markers, poor plasmid maintenance, and oxygen-dependent reporters unsuitable for gut environments. Here we present an integrated toolkit that enables robust genetic manipulation andin vivotracking of VREfm. We developed a universal puromycin selection system effective across diverse clinical isolates and an enhancedpheS**counterselection marker for stable genomic integration. We identified two neutral genomic loci that support reporter genes insertion without fitness cost. Using this system, we demonstrate long-term tracking of VREfm colonization, strain competition and host-microbiome interactions in mouse models via chromosomally-integrated anaerobic fluorescent proteins (eUnaG2 and smURFP). This toolkit advances the study of VREfm pathogenesis by enabling stable genetic manipulation of even the most resistant clinical isolates and direct visualization of host-microbe interactions in ecologically and immunologically relevantin vivoenvironments.
Multi-Omics Analysis of Wound Microbiome andStaphylococcus aureusin Pressure Ulcer
Authors: Guo Changyuan , Jiang Guilai , Li Yuanyuan , Zhao Jun , Li Jilin , Li Shengkai , Zhou Zhemin , Xie Erfan , Li Heng 
Published: February 2025

AbstractThis study employs a multi-omics approach to investigate the wound microbiome andStaphylococcus aureusin pressure ulcers. Metagenomic sequencing and associated technologies were utilized to examine bacterial populations, identify dominant species, and study biofilm formation inS. aureusthrough metabolomic and proteomic characteristics. The results revealed a significant reduction in microbial diversity in pressure ulcer samples compared to controls, withStaphylococcus, Corynebacterium, andKlebsiellabeing the most prevalent genera. Functional prediction analysis indicated differences in pathogenic invasiveness and biofilm formation factors among the groups. The presence of antimicrobial resistance genes was higher in the pressure ulcer group, particularly inStaphylococcusspp. strains. Whole-genome sequencing of 29S. aureusisolates identified various clonal complexes andspatypes, with the majority possessing genes conferring resistance to β-lactam antimicrobials and virulence factors. Histopathological examination and fluorescent in situ hybridization confirmed the presence ofS. aureusin biofilm structures. In vitro biofilm formation tests and metabolomic and proteomic analyses provided insights into the interactions betweenS. aureusstrains and their biofilm formation, revealing enriched pathways related to metabolic processes and membrane composition. This research offers a scientific foundation for understanding the colonization patterns ofS. aureusbiofilms in pressure ulcer wounds.
ERK plays a conserved dominant role in pancreas cancer cell EMT heterogeneity driven by diverse growth factors and chemotherapies
Authors: Barbeau Michelle C. , Brown Brooke A. , Adair Sara J. , Bauer Todd W. , Lazzara Matthew J. 
Published: February 2025

ABSTRACTEpithelial-mesenchymal transition (EMT) occurs heterogeneously among malignant carcinoma cells to promote chemoresistance. Identifying the signaling pathways involved will nominate drug combinations to promote chemoresponse, but cell population-level studies are inherently fraught, and single-cell transcriptomics are limited to indirect ontology-based inferences. To understand EMT heterogeneity at a signaling protein level, we combined iterative indirect immunofluorescence imaging of pancreas cancer cells and tumors and mutual information (MI) modeling. Focusing first on MAP kinase pathways, MI predicted that cell-to-cell variation in ERK activity surprisingly dominated control of EMT heterogeneity in response to diverse growth factors and chemotherapeutics, but that JNK compensated when MEK was inhibited. Population-level models could not capture these experimentally validated MI predictions. The dominant role of ERK was predicted by MI even when analyzing seven potential EMT-regulating signaling nodes. More generally, this work provides an approach for studying highly multivariate signaling/phenotype relationships based on protein measurements in any setting.
RadiSeq: a single- and bulk-cell whole-genome DNA sequencing simulator for radiation-damaged cell models
Authors: Mathew Felix , Galarneau Luc , Kildea John 
Published: February 2025

AbstractObjectiveTo build and validate a simulation framework to perform single-cell and bulk-cell whole genome sequencing simulation of radiation-exposed Monte Carlo cell models to assist radiation genomics studies.ApproachSequencing the genomes of radiation-damaged cells can provide useful insight into radiation action for radiobiology research. However, carrying out post-irradiation sequencing experiments can often be challenging, expensive, and time-consuming. Although computational simulations have the potential to provide solutions to these experimental challenges, and aid in designing optimal experiments, the absence of tools currently limits such application. Monte Carlo toolkits exist to simulate radiation exposures of cell models but there are no tools to simulate single- and bulk-cell sequencing of cell models containing radiation-damaged DNA. Therefore, we aimed to develop a Monte Carlo simulation framework to address this gap by designing a tool capable of simulating sequencing processes for radiation-damaged cells.Main ResultsWe developed RadiSeq – a multi-threaded whole-genome DNA sequencing simulator written in C++. RadiSeq can be used to simulate Illumina sequencing of radiation-damaged cell models produced by Monte Carlo simulations. RadiSeq has been validated through comparative analysis, where simulated data were matched against experimentally obtained data, demonstrating reasonable agreement between the two. Additionally, it comes with numerous features designed to closely resemble actual whole-genome sequencing. RadiSeq is also highly customizable with a single input parameter file.SignificanceRadiSeq enables the research community to perform complex simulations of radiation-exposed DNA sequencing, supporting the optimization, planning, and validation of costly and time-intensive radiation biology experiments. This framework provides a powerful tool for advancing radiation genomics research.
The extensive diversity of nairoviruses reveals the complexity and high risk of tick-borne diseases in northeastern China
Authors: Liu Ziyan , Wei Zhiwei , Liu Yu , Wang Zedong 
Published: February 2025

AbstractThe increasing burden of tick-borne virus infections is becoming a global public health concern. In the current study, we identified nine tick-borne nairoviral species in northeastern China through metagenomic sequencing, which are phylogenetic classified into four groups: I) Wetland virus (WELV), II;) Songling virus (SGLV), Ji’an nairovirus (JANV), Yanbian nairo tick virus 1 (YBNTV-1), Shanxi tick virus 2 (SXTV-2), III;) Yezo virus (YEZV), and IV;) Beiji nairovirus (BJNV), Yichun nairovirus (YCNV), and Hunchun nairovirus (HCNV). These nairoviruses are influenced by both the species of ticks and their geographical distribution. Apart from the previously isolated pathogenic WELV, SGLV, YEZV, and BJNV, we successfully isolated JANV and YBNTV-1, which can replicate in Vero and HEK-293T cells. Two routes of nairovirus spread into northeastern China were evaluated. Group I and II viruses, vectored byHaemaphysalissp. ticks, likely originated in Central or East China and spread via migratory birds along the Chinese coastline. Group III; and IV viruses, vectored byIxodes persulcatusticks, are believed to have originated in Europe and spread via rodents across the Eurasian continent. Our study reveals the extensive diversity and wide distribution of tick-borne nairoviruses in northeastern China, highlights the potential pathogenic risk of the newly discovered nairoviruses, and clarifies their origins and potential migration routes. The results will be of crucial significance for the tick-borne diseases control and prevention in China.