bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segpy: a streamlined, user-friendly pipeline for variant segregation analysis
Authors: Fiorini Michael R. , Amiri Saeid , Dilliott Allison A. , Spiegelman Dan , Rouleau Guy , Farhan Sali M.K. 
Published: December 2024

AbstractUnderstanding the role of genetic variants in disease is essential for diagnostics and the advancement of genomic medicine. While the advent of high-throughput sequencing has been matched by the development of sophisticated genomic analysis tools, these packages often involve complex analytical procedures that can be challenging for researchers with limited computational experience. Additionally, modern genomic datasets require high-performance computing (HPC) systems, which may be difficult to implement for unfamiliar users. To address these challenges, we introduce Segpy, a streamlined, user-friendly pipeline for variant segregation analysis that integrates seamlessly with HPC environments. Segpy supports single-family, multi-family, and population-based datasets, allowing researchers to evaluate how genetic variants co-segregate with disease in pedigree-based analyses and compare allele frequencies between affected and unaffected individuals in case-control analyses. To date, the application of Segpy has facilitated the identification of genetic variants contributing to many human diseases and is now available as a publicly available framework.
Quantitative Susceptibility Mapping Radiomics with Label Noise Compensation for Predicting Deep Brain Stimulation Outcomes in Parkinson’s Disease
Authors: Roberts Alexandra G. , Zhang Jinwei , Tozlu Ceren , Romano Dominick , Akkus Sema , Kim Heejong , Sabuncu Mert R. , Spincemaille Pascal , Li Jianqi , Wang Yi , Wu Xi , Kopell Brian H. 
Published: December 2024

AbstractParkinson’s disease patients with motor complications are often considered for deep brain stimulation (DBS) surgery. DBS candidate selection involves an assessment known as the levodopa challenge test (LCT). The LCT aims to predict DBS outcomes by measuring symptom improvement accompanying changes in levodopa dosage. While used in the patient selection process, inconsistent LCT predictions have been widely documented, verified here with Pearson’s correlationr= 0.12. Estimating symptom improvement to separate DBS responders and non-responders remains an unmet need. Quantitative susceptibility mapping (QSM) is routinely acquired for pre-surgical planning and depicts the iron distribution in substantia nigra and subthalamic nuclei. Iron deposition in these nuclei has correlated with disease progression and motor symptom severity. A novel QSM radiomic approach is presented using a regression model and features extracted from the pre-surgical targeting acquisition. Noise compensation in training labels improves outcome prediction in regression and classification models. The model predicts improvement in the unified Parkinson’s disease rating scale (UPDRS-III) (r= 0.75). Predictive feature maps in deep gray nuclei offer contrast between responders and non-responders. The QSM radiomic approach has potential to improve DBS candidate selection by accurately estimating symptom improvement, eliminating difficult medication manipulation, and avoiding time-consuming evaluations to reduce patient and clinician burden.
Digital health citizenship: Mapping existing tools for digital, health and civic literacy
Authors: Ogundipe Racheal 
Published: December 2024

ABSTRACTDigital Health Citizenship (DHC) integrates digital, health, and civic literacy to empower individuals, particularly young people, to navigate digital health ecosystems effectively. This framework promotes equitable access to health information, informed decision-making, and active participation in personal and public health outcomes while addressing critical issues of digital literacy disparities, privacy, and inclusivity. Young people often lack access to resources that address their unique challenges, such as navigating misinformation, safeguarding privacy, understanding health and civic responsibilities, and effectively engaging in digital and societal spaces. The research aimed to identify existing DHC tools and evaluate them based on the specific needs of young people, to inform the development of more tools tailored specifically to their needs.This research was conducted in two stages: a landscape analysis, followed by an assessment of existing tools and resources for strengths and weaknesses. The research approach integrates a literature review, walkthrough method and comparative analysis to evaluate tools/resources comprehensively and assess their strengths and weaknesses.The study evaluated 38 existing tools and resources addressing digital, health, and civic literacy, using criteria such as equity, trustworthiness, human-centric design, inclusivity, ethics, and capacity building. The analysis revealed significant gaps in current resources. Most tools lack multilingual support and alternative formats, excluding users with disabilities or limited digital access. The fragmented approach to literacy—where tools typically address only one aspect of DHC—reduces their effectiveness in fostering comprehensive digital health citizenship. Additionally, while existing resources successfully convey information, they often fail to develop practical skills across all three literacy domains. The heavy reliance on internet connectivity further limits accessibility for individuals in low-resource settings.Digital health citizenship is more than providing information. It is about equipping young people with the skills and confidence to engage with their health in a meaningful way. This can be done by providing DHC toolkits that meet the needs of young people globally, including cultural, social and digital needs. It is also important for stakeholders in the digital, health and civic space to be more proactive in ensuring that adequate resources are available to young people.Through this targeted approach to developing comprehensive DHC tools/resources, we can better empower young people to become active participants in their health journey while ensuring no one is left behind in the digital health transformation.
Reshaping epigenomic landscapes in facilitating the speciation of bread wheat
Authors: Zhang Zhaoheng , Lin Xuelei , Yue Jingjing , Xu Yongxin , Miao Lingfeng , Tang Wenqiang , Guo Weilong , Xiao Jun 
Published: December 2024

SummaryPolyploidization is a driving force of wheat evolution and speciation, yet its impact on epigenetic regulation and gene expression remains unclear.Here, we constructed a high-resolution epigenetic landscape across leaves, spikes, and roots of hexaploidy wheat and its tetraploid and diploid relatives. Inter-species stable-expression genes exhibited conserved amino acid sequences under strong purifying selection, while dynamic-expression genes were linked to species-specific adaptation. During hexaploidization, dominant D-subgenome homoeolog expression was suppressed via reduced activating epigenetic signals, converging expression with the A and B subgenomes. Proximal chromatin regions near genes were more stable, whereas distal regions, particularly enhancer-like elements mediated by H3K27ac and H3K4me3, exhibit higher dynamism. Sequence variations in these enhancers lead to differential gene regulation, influencing traits such as spike development. For instance, the two haplotypes of dCRE region ofTaDEP-B1resulted in significant differences in its expression and spikelet numbers. We also observed a coevolution of transcription factors and their binding sites, particularly within the expanded ERF family, which regulates spike morphology.This study highlights the interplay between sequence variation and epigenetic modifications in shaping transcriptional regulation during wheat speciation, offering valuable insights for genetic improvement.
ATP synthesis ofEnterococcus hiraeV-ATPase driven by sodium motive force
Authors: Otomo Akihiro , Hui Zhu Lucy Gao , Okuni Yasuko , Yamamoto Mayuko , Iino Ryota 
Published: December 2024

AbstractV-ATPases generally function as ion pumps driven by ATP hydrolysis in the cell, but their capability of ATP synthesis remains largely unexplored. Here we show ATP synthesis of Na+-transportingEnterococcus hiraeV-ATPase (EhVoV1) driven by electrochemical potential gradient of Na+across the membrane (sodium motive force,smf). We reconstituted EhVoV1into liposome and performed a luciferin/luciferase-based assay to analyze ATP synthesis quantitatively. Our result demonstrates that EhVoV1synthesizes ATP with a rate of 4.7 s-1under highsmf(269.3 mV). The Michaelis constants for ADP (21 µM) and inorganic phosphate (2.1 mM) in ATP synthesis reaction were comparable to those for ATP synthases, suggesting similar substrate affinities among rotary ATPases regardless of their physiological functions. Both components ofsmf, Na+concentration gradient across the membrane (ΔpNa) and membrane potential (Δψ), contributed to ATP synthesis, with ΔpNa showing a slightly larger impact. At the equilibrium points wheresmfand Gibbs free energy of ATP synthesis are balanced, EhVoV1showed reversible reactions between ATP synthesis and hydrolysis. The obtained Na+/ATP ratio (3.2 ± 0.4) closely matched the value expected from the structural symmetry ratio between EhVoand EhV1(10/3 = 3.3), indicating tight coupling between ATP synthesis/hydrolysis and Na+transport. These results reveal inherent functional reversibility of EhVoV1. We propose that physiological function of EhVoV1in vivois determined by relatively smallsmfagainst large Gibbs free energy of ATP synthesis, in addition to the absence of inhibitory mechanisms of ATP hydrolysis which are known for ATP synthases.
Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia
Authors: Li Runjia , Gagliano Taliun Sarah A. , Liao Kevin , Flickinger Matthew , Sobell Janet L. , Genovese Giulio , Locke Adam E. , Chiu Rebeca Rothwell , LeFaive Jonathon , Wang Jiongming , Martins Taylor , Chapman Sinéad , Neumann Anna , Handsaker Robert E. , Arnett Donna K. , Barnes Kathleen C. , Boerwinkle Eric , Braff David , Cade Brian E. , Fornage Myriam , Gibbs Richard A. , Hoth Karin F. , Hou Lifang , Kooperberg Charles , Loos Ruth J.F. , Metcalf Ginger A. , Montgomery Courtney G. , Morrison Alanna C. , Qin Zhaohui S. , Redline Susan , Reiner Alexander P. , Rich Stephen S. , Rotter Jerome I. , Taylor Kent D. , Viaud-Martinez Karine A. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   Genomic Psychiatry Cohort investigators, Bigdeli Tim B. , Gabriel Stacey , Zollner Sebastian , Smith Albert V. , Abecasis Goncalo , McCarroll Steve , Pato Michele T. , Pato Carlos N. , Boehnke Michael , Knowles James , Kang Hyun Min , Ophoff Roel A. , Ernst Jason , Scott Laura J. 
Published: December 2024

AbstractIn studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of 17,463 controls. To identify variants and sets of variants associated with BD and/or SZ, we performed single-variant tests, gene-based tests for singleton protein truncating variants, and rare and low-frequency variant annotation-based tests with conservation and universal chromatin states and sliding windows. We found suggestive evidence of BD association with single-variants on chromosome 18 and of lower BD risk associated with rare and low-frequency variants on chromosome 11 in a region with multiple BD GWAS loci, using a sliding window approach. We also found that chromatin and conservation state tests can be used to detect differential calling of variants in controls sequenced at different centers and to assess the effectiveness of sequencing metric covariate adjustments. Our findings reinforce the need for continued whole genome sequencing in additional samples of African American individuals and more comprehensive functional annotation of non-coding variants.
An approach for early diagnosis of atherosclerosis: correlation between blood levels of endothelin and D-dimers with atherogenic index in African black subjects
Authors: Tchame Claudric Roosvelt , Yiagnigni Mfopou Euloge 
Published: December 2024

SUMMARYGlobal mortality due to cardiovascular disease (CVDs) is continuously increasing. In this regard, several authors have investigated the origins of CVD, with atherosclerosis being the most involved pathological process in CVD. In our study, we aimed to measure some parameters (endothelin, D-dimers) that could be involved in the early diagnosis of atherosclerosis and compare them to a classical marker Atherogenic index (AI) to see if there would be a correlation between these parameters and a possible use of them in diagnosis.To do this, patients at risk of atherosclerosis, hypertensive and diabetic, were recruited over a period of 5 months at the Bonne Santé clinic in Yaounde. Out of a population of 84 patients, 10 hypertensive diabetics were selected, 77 hypertensive and 17 diabetics. The data analysis was conducted using the Spearman’s Rho test, after which we did not observe any significant correlation between endothelin and AI, with a correlation coefficient of 0.065 and a P value of 0.556. However, a significant correlation between D-dimers and AI was observed, with a correlation coefficient of 0.231 and a P value of 0.034; and a significant negative correlation between endothelin and D-dimers was observed, with a correlation coefficient of -0.232 and a P value of 0.033.By comparing these data with those from other articles, we concluded that endothelin alone is not a good diagnostic marker for atherosclerosis. However, D-dimers can be used as associated markers for atherosclerosis diagnosis. These results directed us towards the process and different initiatic factors of atherosclerosis.
Early pregnancy health behaviors, hypertensive disorders of pregnancy, and maternal blood pressure after pregnancy
Authors: Kozai Andrea C , Levine Lisa D , Lane Abbi D , Grobman William , Greenland Philip , Hoffman Matthew K , Zee Phyllis C , Mims Lisa , Cameron Natalie A , Saade George , Silver Robert M , Miller Eliza C , Reddy Uma M , Whitaker Kara M 
Published: December 2024

AbstractBackgroundIndividual health behaviors are associated with pregnancy outcomes, but their joint effects are rarely considered. We aimed to examine associations between combinations of first trimester health behaviors and hypertensive disorders of pregnancy (HDP), normotensive adverse pregnancy outcomes (APOs), and blood pressure (BP) 2-7 years after delivery.MethodsParticipants in the nuMoM2b and follow-up Heart Health Study were included. Physical activity, diet, smoking, and sleep duration were scored using the Life’s Essential 8 metric. APOs were categorized as HDP (gestational hypertension, preeclampsia, super-imposed preeclampsia, or eclampsia) or normotensive APOs: preterm birth, gestational diabetes, small-for-gestational-age birth, and/or stillbirth. Latent profiles of health behaviors were constructed with structural equation modelling. Differences in risk of HDP, normotensive APOs, and BP 2-7 years after delivery based on behavioral profiles were assessed with multinomial logistic or linear regression. Mediation analysis examined the proportion of associations between behavioral profiles and BP mediated by APOs.ResultsAmong 8,508 nulliparas, four behavioral profiles were identified: Healthiest Behaviors (37%), Healthy Activity/Sleep with Poor Diet/Smoking (20%), Healthy Sleep Only (32%), and Least Healthy Behaviors (11%). Adjusted risk of HDP and normotensive APOs was 21-41% higher in those with poorer behavioral patterns compared to the Healthiest Behaviors profile. Diastolic BP was 1.04 mmHg higher2-7 years after delivery in the Healthy Sleep Only profile compared to the Healthiest Behaviors profile. Associations between behavioral profiles and BP were not significantly mediated by APOs.ConclusionsCombined health behavior profiles in early pregnancy were associated with APOs and higher diastolic BP 2-7 years after delivery.
Inter-laboratory comparison of HbA1c can effectively improve test consistency of primary medical institutions
Authors: Liping Pan , Jun Yang , Kun Luo , Hao Yun , Shen Wei , Jin Tan , Ming Lin 
Published: December 2024

AbstractBackgroundGlycated hemoglobin (HbA1c) represents a diagnostic index and an important long-term measure for monitoring Diabetes mellitus (DM). In this study, we investigated the quality of HBA1c test in primary medical institutions, and conducted a comparison project of HBA1c test for two years, analyzed and evaluated the test consistency of HBA1c.MethodsA cohort study was conducted by Wuhan Center for Clinical Laboratory, involving 51 primary medical institutions and 29 tier-three hospitals. Fresh frozen blood samples were prepared by a clinical laboratory certificated by the National Glycohemoglobin Standardization Program (NGSP), and distributed to 80 participating institutions every three months. Microsoft Excel 2021 software was employed to analyze the mean, standard deviation and coefficient of variation of the test results.ResultsResults showed that 60.8% HBA1c test results cannot reach the quality requirements of HbA1c measurement (CV<3.5%) in primary medical institutions. After executing the project, the laboratory pass rate of HBA1c test increased from 39.2% to 64.6%, and the maximum coefficient of variation (CV) within the immunological assays of HBA1c test dropped from 18.0% to 11.4%.ConclusionsInter-laboratory comparison of HbA1c can effectively improve test consistency of primary medical institutions. The finding has implications for diabetes management strategies, emphasizing the importance of continuous comparison of HBA1c test in primary medical institutions, providing a practical example to accelerate the mutual recognition of medical test results in a wider range.
Sex Disparities in Cognitive Impairment Research: A Scoping Review in Informatics Literature
Authors: Garg Muskan , Liu Xingyi , Lin Jie , Vassilaki Maria , Petersen Ronald C , St Sauver Jennifer , Kapoor Ekta , Sohn Sunghwan 
Published: December 2024

AbstractRationaleA scoping review was conducted to investigate knowledge gaps in the informatics research literature regarding sex differences in cognitive decline, identifying existing studies and areas where further studies are needed.Materials and MethodsWe searched Ovid and other databases for studies on sex differences and cognitive decline, focusing on publications in peer-reviewed informatics journals and conference proceedings from 2000 to 2023. The selected manuscripts were analyzed and summarized through discussion among three reviewers.ResultsA total of 13 articles were selected and examined for metadata and attributes analysis. Most studies are conducted in United States (n=5) and European Union (n=4), about a half are published after 2020 (n=6), and most studies are published in Springer and Elsevier. Our attributes-based analysis highlights the different aspects of reported studies such as task, method, dataset and its size, and sex-specific inferences.DiscussionSex-specific disparities in cognitive decline remain a critical issue in healthcare, yet most informatics research has primarily concentrated on identifying basic sex differences, such as tracking the progression of cognitive decline in men and women. While these studies are valuable, they fall short of addressing the more complex underlying causes of these sex-specific disparities in progression of cognitive decline.ConclusionThere is a significant gap using informatics in understanding how biological, social, and behavioral factors contribute to sex-specific disparities. This limited focus restricts the development of effective intervention strategies for mitigating sex-specific differences in cognitive health outcomes, underscoring the need for more comprehensive research that goes beyond mere identification to find the root cause of these disparities in healthcare.
Integration of Transplanted Interneurons Over a New Period of Ocular Dominance Plasticity in Adult Visual Cortex
Authors: Rakela Benjamin , Sun Jennifer , Marchetta Philine , Alvarez-Buylla Arturo , Hasenstaub Andrea , Stryker Michael 
Published: December 2024

AbstractCortical interneurons play an important role in mediating the juvenile critical period for ocular dominance plasticity in the mouse primary visual cortex. Previously, we showed that transplantation of cortical interneurons derived from the medial ganglionic eminence (MGE) opens a robust period of ocular dominance plasticity 33-35 days after transplantation into neonatal host visual cortex. The plasticity can be induced by transplanting either PV or SST MGE-derived cortical interneurons; it requires transplanted interneurons to express the vesicular GABAergic transporter; and it is manifested by changes to the host visual circuit. Here, we show that transplantation of MGE-derived cortical interneurons into the adult host visual cortex also opens a period of ocular dominance plasticity. The transplanted interneurons must be active to induce plasticity, and the neuronal activity and tuning of visually evoked responses in transplanted and host PV and SST interneurons are modulated by the locomotor state of the host. We also show that changes in activity over the period of plasticity induction are different between PV and SST interneurons but similar between host and transplanted interneurons of each type. The present findings demonstrate that the transplant-induced plasticity generated in adult visual cortex has many features in common with the role of these interneurons during the normal, juvenile critical period.
ThermoPlex: An Automated Design Tool for Target-specific Multiplex PCR Primers based on DNA Thermodynamics
Authors: Agmata Altair , Labrador Kevin , Palermo Joseph Dominic , Pante Maria Josefa 
Published: December 2024

AbstractMultiplex PCR-based assays are indispensable platforms for rapid and cost-effective DNA-based multi-target detection. The success of such an assay highly depends on the accurate design of oligonucleotide primers, arguably its most vital component. In this study, the ThermoPlex design tool is introduced, offering an automated design pipeline for target-specific multiplex PCR primers motivated by DNA thermodynamics. From a sequence alignment of all relevant target and non-target sequences, ThermoPlex automatically designs multiplex PCR primer candidates in just a matter of minutes. The software also offers tools for thermodynamic calculations that can either be used apart from the automated primer screening routine or in conjunction with other existing primer design tools, depending on the on the needs of the user. Evidences presented here in this study provide insights on the performance of the software through theoretical and experimental analyses, serving to establish the reliability of its framework.