bluuebunny/crossref_metadata_2025_split huggingface dataset:
PERCEPTIVE: an R Shiny pipeline for the prediction of epigenetic modulators in novel species
Authors: Small Eric M. , Steadman Christina R. 
Published: November 2024

ABSTRACTEpigenetic processes play key roles in regulating gene expression, genome stability, and metabolic output in organisms across the tree of life. Yet, the role epigenetics plays in regulating genomes and behaviors remains underdeveloped for microalgae, particularly as new species are identified and characterized. This is likely due to the cumbersome nature and species-dependent attributes of epigenetic wet-lab methodologies, which preclude the rapid identification of epigenetic modifications and modulators. However, there is extraordinary conservation of epigenetic processes from budding yeast to humans; in many cases, one may infer how behavior and function are epigenetically regulated in novel species by simply identifying epigenetic modulators, or the proteins responsible for conferring epigenetic modifications. To this end, we have developed a graphical software package, titled PERCEPTIVE (pipelinefor the prediction ofepigenetic modulators in novel species). This novel platform solely uses the genomic sequence of an organism, and preexisting information from model species, to predict the epigenetic modulators and associated modifications in a novel species. Predictions are presented to the user in a graphical interface, which provides literature-based interpretation of results, enabling users to quickly understand potential epigenetic processes in their species of interest and plan follow-up experiments. To test PERCEPTIVE, we predicted epigenetic modulators in several feedstock candidate algae species. To validate these predictions, wet-lab studies were performed, including mass spectrometry; these results underscore the high accuracy of PERCEPTIVE predictions. Overall, PERCEPTIVE represents a powerful tool for the research and manipulation of algal species, which does not requirea prioriknowledge of epigenetics and is accessible to a broad set of investigators.
Diminished gap junction coupling under diabetogenic conditions does not drive loss of functional β-cell sub-populations
Authors: Levitt Claire H , Isaacs Dominic , Hansen Maria S , Kravets Vira , Briggs Jennifer K , Benninger Richard KP 
Published: November 2024

AbstractWithin the islets of Langerhans, gap junction coupling is important for synchronizing oscillatory free-calcium activity ([Ca2+]) and regulating pulsatile insulin release. In islets from multiple models of diabetes, gap junction coupling is disrupted, and [Ca2+] synchronization and pulsatile insulin is lost. Functional sub-populations have been identified within the islet that are linked to driving synchronized [Ca2+] and insulin release. These sub-populations can be disrupted under conditions associated with diabetes such as glucolipotoxicity and inflammatory environments, and their loss may drive islet dysfunction. Here we investigate how loss of gap junction coupling influences functional subpopulations under diabetogenic environments. We treated islets with a cocktail of pro-inflammatory cytokines and specifically recovered gap junction coupling via co-treatment with a Cx36 mimetic peptide S293 that was previously shown to protect gap junction permeability and synchronized [Ca2+] dynamics. We performed calcium imaging and ChR2 stimulation, analyzed islet [Ca2+] dynamics and the presence of functional sub- populations including hubs and first-responders. 1h or 24h cytokine-treatment disrupted gap junction coupling, which was fully recovered by S293 peptide co-treatment. Treatment with pro- inflammatory cytokines decreased the recruitment of [Ca2+] upon ChR2 stimulation, increased the time between first and last responding cells upon glucose stimulation, and reduced the number and consistency of hub cells. When preserving gap junction coupling by S293 during cytokine treatment, the presence and consistency of these sub-populations was only marginally improved. We therefore concluded that restoration of gap junctions alone is not sufficient to recover functional sub-populations and their influence over islet function upon diabetogenic conditions associated with diabetes. Thus, preventing a disruption to intrinsic β-cell properties that define functional subpopulations is likely important for preserving these sub-populations during diabetes.
Testing hypotheses of skull function with comparative finite element analysis: three methods reveal contrasting results
Authors: Mitchell D. Rex , Wroe Stephen , Martin Meg , Weisbecker Vera 
Published: November 2024

ABSTRACTComparative finite element analysis often involves standardising aspects of the models to test equivalent loading scenarios across species. However, in the context of feeding biomechanics of the vertebrate skull, what is considered “equivalent” can depend on the hypothesis. We use 13 skulls from diverse group of marsupial bettongs and potoroos (Potoroidae) to demonstrate that that scaling muscle forces to standardise unique aspects of biting mechanics can produce contrasting results of comparative stress or strain that are differentially suited to test specific kinds of hypotheses. We propose three categories of hypotheses for skull biting mechanics which each involve a unique method of muscle scaling: those comparing (1) the skull’s efficiency in distributing input muscle forces, via standardising input muscle force to size, (2) morphological biting adaptation through standardising mechanical advantage to simulate size-independent, equivalent bites, and (3) feeding ecology affected by size, such as niche partitioning, via standardising bite reaction force.SUMMARY STATEMENTCommon approaches for scaling muscle forces in skull finite element models might not always offer reliable results for all hypotheses. We provide a framework for selecting the appropriate method.
Automatic Phenotyping Using Exhaustive Projection Pursuit
Authors: Moore Wayne A. , Meehan Stephen W. , Meehan Connor , Parks David R. , Walther Guenther , Herzenberg Leonore A. 
Published: November 2024

AbstractOne of the most common objectives in the analysis of flow cytometry data is the identification and delineation of phenotypes, distinct populations of cells with shared characteristics in the measurement dimensions. We have developed an automated tool to comprehensively identify these cell populations by Exhaustive Projection Pursuit (EPP). The method evaluates all two-dimensional projections among the suitable data dimensions and creates an optimized sequence of statistically significant gating regions that identify all phenotypes supported by the data. We evaluate the results of EPP on four well characterized datasets from the literature. The C++ for EPP can be called from any computing environment. We illustrate this with a MATLAB utility that integrates EPP with FlowJo. All source code is freely available.
Recovery and long-term health outcomes of SARS-CoV-2 infection in a prospective cohort in an urban setting, Kenya
Authors: Kisiangani Isaac , Ben Ângela Jornada , Wynberg Elke , Wami Welcome , Iddi Samuel , Kinya Idah , Vassall Anna , Kyobutungi Catherine , Ziraba Abdhalah , Njeru John , Mugenda Olive , Kiguoya-Njau Marion Wangui , Kimondo Mutambuki , Githua Geoffrey , de Jong Menno D. , Mohamed Shukri F. , Asiki Gershim , Schultsz Constance 
Published: November 2024

AbstractBackgroundEvidence on Long COVID remains limited in sub-Saharan countries. This study aimed to explore the occurrence of COVID-19-related symptoms and factors affecting recovery and Long COVID severity in Nairobi, Kenya.MethodsA prospective cohort of individuals testing positive for SARS-CoV-2 between February 2022 and February 2023 were followed until June 2023. COVID-19-related symptoms were assessed every three months. Time to recovery was analyzed using survival analysis, while factors affecting recovery and Long COVID severity using Cox proportional hazard and Poisson regression, respectively.Results42/291 (14%) participants had severe/critical SARS-CoV-2 infection, 59.1% were female and median age was 34. At 6 and 12 months post-positive PCR, 53.1% and 33.5% of participants had ≥1 COVID-19-related symptoms, respectively. Fatigue (40.2%), pain (36.8%), sore throat (36.8%), headaches (36.4%), and loss of strength (31.6%) were the most frequently reported COVID-19-related symptoms. Median time to recovery was longer in symptomatic participants with severe/critical SARS-CoV-2 infection than those with mild/moderate (234 vs 206 days respectively, p=0.016). Participants aged 40-64 years experienced slower recovery than those aged <40 years (aHR=0.635 [95%CI, 0.429;0.941]) and those with tertiary education recovered faster than those with primary education (aHR=1.869 [95%CI, 1.050;3.327]). Long COVID severity was associated with female sex (aIRR=1.413 [95%CI; 1.089;1.833]), tertiary education (aIRR, 0.525 [95%CI, 0.350;0.786]), and ≥1 comorbidity (aIRR=2.540 [95%CI, 1.377;4.687]).ConclusionsOur findings suggest Long COVID presents a substantial, under-researched disease burden in Kenya. Risk factors for Long COVID are similar to those in high-income countries (HICs). Tailored prevention and support strategies for high-risk groups are needed.
Distinct subgroups in gastroparesis defined by simultaneous body surface gastric mapping and gastric emptying breath testing
Authors: Varghese Chris , Huang I-Hsuan , Schamberg Gabriel , Calder Stefan , Andrews Christopher N. , O’Grady Greg , Tack Jan , Gharibans Armen A 
Published: November 2024

AbstractBackgroundGastroparesis is a heterogeneous disorder with several contributing pathophysiologies. In this study we used simultaneous body surface gastric mapping (BSGM) and gastric emptying breath testing (GEBT) to subgroup patients with gastroparesis based on dynamic spectral meal response profiles and emptying rate.MethodsPatients with chronic gastroduodenal symptoms and negative gastroscopy underwent simultaneous BSGM and gastric emptying breath test (GEBT) with 30 minutes fasting and 4 hours postprandial recording. In addition to standard metrics, the BSGM ‘Meal Response Ratio’ (MRR) compared amplitude in the first 2 hours postprandially to the subsequent 2 hours (lagged meal response ≤1).Results143 patients underwent simultaneous BSGM and GEBT (79% female, median age 31 years, median BMI 23 kg/m2). Delayed emptying occurred in 25.2% (n = 36). Those with a lagged meal response had longer T1/2(median 95.0 [IQR 59-373] vs median 78.0 [IQR 31-288], p=0.009) and higher rates of delayed emptying (42.9% vs 16.7% p = 0.03). BSGM phenotypes identified in patients with delayed emptying were: lagged meal response (25%), low gastric amplitude / rhythm stability (30.6%), elevated gastric frequencies (11.1%), and normal BSGM spectral analysis (33.3%). T1/2weakly correlated with worse total symptom burden score (r = 0.18, p = 0.03).ConclusionCombined BSGM and gastric emptying testing defines subgroups of gastroparesis based on contributing disease mechanisms, including a novel group with delayed post-prandial onset of gastric motor activity. Improved patient phenotyping in gastroparesis may enable improved therapeutic targeting through these biomarkers of disease processes.
Comprehensive analysis acrossSMN2excludes DNA methylation as an epigenetic biomarker for spinal muscular atrophy
Authors: Zwartkruis M.M. , Kortooms J.V. , Gommers D. , Elferink M.G. , Signoria I. , van der Sel J. , Hop P.J. , Zwamborn R.A.J. , Geene R. , Green J.W. , van Deutekom H.W.M. , van Rheenen W. , Veldink J.H. , Asselman F. , Wadman R.I. , van der Pol W.L. , van Haaften G.W. , Groen E.J.N. 
Published: November 2024

AbstractSpinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by defects in the survival motor neuron 1 (SMN1) gene. The wide variability in SMA severity is partially explained by an inverse correlation with copy number variation of the second humanSMNgene (SMN2). Nevertheless, significant variability in severity and treatment response remains unexplained, prompting a search for accessible biomarkers that could explain and predict this variability. DNA methylation ofSMN2has been proposed as one such biomarker, but comprehensive evidence and analyses are lacking. Here, we combined long-read nanopore sequencing with targeted bisulfite sequencing to enable high-resolution analysis ofSMN2-specific methylation patterns. We observed tissue-specific variation in DNA methylation across the entire 30 kbSMN2gene in 29 patients analyzed by long-read nanopore sequencing, identifying variable methylation patterns in the promoter, introns, and 3’ UTR. Subsequent targeted analysis of these regions by bisulfite sequencing of blood-derived DNA in 365 SMA patients showed no association betweenSMN2methylation and disease severity or treatment response, excluding blood methylation patterns as predictive biomarkers. However, we discovered significant age-associated variation inSMN2methylation, particularly in intron 1 and the 3’ UTR, highlighting DNA methylation as a possible modifier of SMN expression during development and aging. Our approach provides a broadly applicable strategy for detailed but cost-effective and high-throughput characterization of DNA methylation in other genes and diseases, including complex genetic regions.
Fine-mapping SLE-MHC associations revealed independent contributions of HLA missense variants andC4copy number variations
Authors: Yu Chae-Yeon , Shin Dong Mun , Kim Sung Min , Lee Yui Taek , Jeon Sungwon , Chun Sehwan , Bang So-Young , Lee Hye-Soon , Yin Xianyong , Cui Yong , Zhang Xuejun , Bhak Jong , Yoo Soon Ji , Kim Young Jin , Kim Bong-Jo , Bae Sang-Cheol , Kim Kwangwoo 
Published: November 2024

AbstractSystemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic associations within the major histocompatibility complex (MHC) region. Despite significant advances, precisely pinpointing the genetic variants that contribute to SLE risk within the MHC remains challenging. This study aimed to comprehensively profile SLE-driving variants using a newly developed East Asian MHC imputation reference panel, capable of simultaneously imputing diverse MHC variants, including multi-level variants of HLA genes and copy number variations (CNVs) ofC4elements, with high imputation accuracy. Applying this panel to two SLE genome-wide association study datasets, we uncovered the independent contributions from six amino acid positions altering the epitope-binding surfaces of HLA-DRB1 and HLA-C. Additionally, reducedC4Acopy numbers and increased HERV copy numbers, collectively lowering C4 protein levels, were associated with increased SLE risk, independent of HLA variants. Our refined MHC-SLE association model provided superior explanations for SLE risk over previous association models. In summary, this study enhanced the understanding of HLA andC4in SLE pathogenesis and holds promise for advancing MHC association studies for immune-mediated inflammatory disorders in East Asians using our MHC panel (https://coda.nih.go.kr/usab/kis/intro.do).
Evaluation of the costs of care for pediatric patients hospitalized for RSV: a retrospective cohort study in Belgium
Authors: Tilmanne Anne , Pirson Magali , Leclercq Pol , Van Den Bulcke Julie , Bruyneel Arnaud 
Published: November 2024

AbstractObjectivesThis study aimed to evaluate the costs of respiratory-syncytial virus (RSV)-related hospitalizations in children under 3 years old in Belgium for hospitals and health insurance, and to identify factors influencing costs.Study designThis retrospective cohort study used data from 16 French-speaking hospitals in Belgium, covering January 1, 2018, to December 31, 2019. RSV diagnoses for children under three were identified using International Classification of Diseases-Tenth Revision (ICD-10) codes, resulting in 2,176 hospitalizations analyzed for cost assessment. Hospital and health insurance costs were derived from administrative and billing data, adjusted for inflation, and analyzed using descriptive and inferential statistics, including regression models to assess cost factors.ResultsRSV prevalence among pediatric hospitalizations peaked at 12.9% in 2018 and 10.0% in 2019, with children under 3 years showing a prevalence of 16.7% both years. Of the 2,176 RSV-related hospitalizations, 61.8% were in children under one year, and 28.6% had readmissions within a year. The median length of stay (LOS) was 3.67 days, with a median hospital cost of €2,924 and a median health insurance cost of €2,221 per stay. Factors associated with higher costs included longer LOS, severe diagnosis-related group category, pediatric intensive care unit admission, and non-invasive ventilation use, with costs generally lower for children aged 1-2 years.ConclusionsThis study highlights the significant financial burden of RSV hospitalization in Belgium, with costs exceeding €25 million annually. This emphasizes the need for preventive measures and better resource allocation to reduce the economic impact of RSV on healthcare systems.
A Digital Biomarker Dataset in Hematopoietic Cell Transplantation: A Longitudinal Study of Caregiver-Patient Dyads (dHCT)
Authors: Jalin Aditya , Swatthong Nawat , Rozwadowski Michelle , Kumar Rajnish , Barton Deb , Braun Tom , Carlozzi Noelle , Hanauer David A. , Hassett Afton , Choi Sung Won 
Published: November 2024

AbstractBackgroundHematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for individuals with blood diseases, but involves a challenging recovery process that requires dedicated caregivers. The complex interplay between emotional distress, care partner (or unpaid caregiver) burden, and treatment outcomes necessitates comprehensive physiological and psychological measurements to fully understand these dynamics.FindingsWe collected longitudinal data from 166 HCT caregiver-patient dyads over 120 days post-transplant as part of a randomized controlled trial (NCT04094844). Data were gathered using the Fitbit® Charge 3 device, a custom mood-reporting app with positive psychology-based activities (Roadmap), PROMIS® health measures, and clinical events. The dataset includes minute-level heart rate, daily sleep metrics, step counts, self-reported mood scores, app usage metrics, PROMIS® T-scores (i.e. global health, depression), infection and readmission records, and clinical outcomes (e.g., acute and chronic graft-versus-host disease, relapse, mortality). Physiological data were available for both caregivers and patients. Data validation confirmed high compliance with mood reporting and the presence of physiological patterns between caregivers and patients that differed (i.e., lower activity in patients compared with caregivers across time).ConclusionsThis dataset offered an unprecedented view into the daily fluctuations of caregiver and patient well-being throughout the critical post-HCT period. It provided a valuable resource for researchers investigating the impact of mHealth app interventions, including emotional distress and physiological markers on treatment course and clinical outcomes. Our unique dataset informs interventions that may address caregiver support, patient care, or dyadic-focused strategies and enable novel analyses of single member or dyadic dynamics in HCT treatment.
Relation between motor competence and academic achievement: the mediating role of fitness and cognition in boys and girls
Authors: Fernández-Sánchez Antonio , Ruiz-Hermosa Abel , Redondo-Tébar Andrés , Díez-Fernández Ana , Martínez-Vizcaíno Vicente , Visier-Alfonso María Eugenia , Sánchez-López Mairena 
Published: November 2024

ABSTRACTIntroductionGood motor competence is linked to better academic achievement in schoolchildren, potentially mediated by fitness and cognition. However, the relative impact of these factors and whether they differ by sex remains unclear. The aim of the present study was to assess the mediating role of fitness components and executive function on this relationship, with a particular focus on sex differences.MethodsThis cross-sectional study included 562 schoolchildren (9-11 years, 293 girls) from Cuenca, Spain. We assessed gross motor competence (MABC-2 battery), fitness components (ALPHA battery), executive function (Toolbox battery), academic achievement (mean of language and mathematics grades), weight, height, and sociodemographic variables. Serial multiple mediation models between gross motor competence to AA through fitness and cognition were conducted using the Hayes’ PROCESS SPSS macro, both for the total sample and by sex.ResultsBoth fitness and executive function partially mediated the relationship between gross motor competence and AA. In the total sample, the direct effect explained most of the total effect (51.22% to 72.68%), followed by the cognitive path (19.51% to 30.73%), fitness path (10.84% to 19.02%), and multiple path (4.43% to 9.27%). In boys, only the cognitive path mediated the relationship (56.35% to 68.91%), while in girls, the fitness path (for cardiorespiratory fitness and speed/agility, 19.08% and 20.27%), the cognitive path (limited to upper body strength, 14.92%), and the multiple path (for cardiorespiratory fitness, speed/agility, and lower body strength, 4.93%, 8.31% and 9.43%) were partial mediators.ConclusionsOur results suggest that part of the effect found between gross motor competence and academic achievement in children occurs from improvements in fitness and executive function. These findings emphasize the need for motor competence programs that target both fitness (especially cardiorespiratory fitness and speed/agility) and executive function to boost academic achievement in children aged 9-11. Additionally, interventions should consider sex-specific differences.
Research on the Structural Characteristics and Evolution of China’s Medical and Health Innovation Cooperation Network Based on the Chinese Medical Science and Technology Awards
Authors: Xiaoqian Li , Fan Zhang , Junliang Zhang , Zhengfang Wang , Yue Yu , Huizheng Chen 
Published: November 2024

AbstractCooperative innovation is an important means to promote the development of medical and health undertakings. Based on the award data of the Chinese Medical Science and Technology Award from 2003 to 2022, this paper constructs an innovation cooperation network and uses social network analysis to explore the structure and evolution characteristics of China’s medical and health innovation cooperation network. The research shows that China’s medical and health innovation cooperation continues to increase, but the development of regional cooperation is not balanced; the scale of the network is expanding, and the small world effect is obvious, but the network density is relatively low, and there is still a large space for development of institutional innovation cooperation; Hospitals and universities play an important role in the network; The medical and health innovation cooperation network has the characteristics of community. Finally, policy suggestions are put forward from the aspects of strengthening regional balanced development, giving play to the radiation role of core institutions in the innovation cooperative network, and promoting diversified innovation cooperation, to form a balanced development innovation cooperation system, a robust innovation cooperation network ecology, and a stable innovation cooperation network structure.