bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blink rates in patients with schizophrenia compared to healthy controls: A meta-analysis
Authors: Nielsen Johannes Reinau Windelborg , Dietz Martin , Jefsen Oskar Hougaard 
Published: October 2024

AbstractBackgroundEyeblink rates vary with cognitive states and may be related to dopaminergic activity. Early reports have found elevated blink rates in patients with schizophrenia, possibly related to hyperdopaminergia, but findings appear inconsistent. We performed a systematic review and meta-analysis to evaluate the evidence regarding blink rates in patients with schizophrenia compared to healthy controls and the impact of medication.MethodsWe registered a protocol for the review on PROSPERO. We searched PubMed, SCOPUS, and Embase, performed title- and abstract-screening, full-text screening, data extraction, and risk-of-bias assessment. We calculated meta-level effect sizes, assessed effect size heterogeneity, and tested for small-study effects.ResultsWe included 22 studies in the systematic review and of those, 19 in the meta-analysis. The studies included a total of 632 patients and 791 healthy controls. The risk of bias was high in all but two studies, particularly due to the lack of blinding and confounding by medication. Meta-analysis revealed an elevated blink rate in patients with schizophrenia (irrespective of medication status) compared to healthy controls (Hedges’g= 0.48; 95% CI [0.13,0.82]). Stratified meta-analyses revealed elevated blink rates in unmedicated patients with schizophrenia compared with healthy controls (Hedges’g= 0.83; 95% CI [0.34, 1.31]), but not in medicated patients compared with controls (Hedges’g= -0.09; 95% CI [-0.64, 0.46]).ConclusionBlink rates are elevated in unmedicated, but not medicated, patients with schizophrenia compared with healthy controls. These findings motivate further study of the link between blink rates, central dopamine, and schizophrenia.
Developing Del2Phen: a novel phenotype description tool for chromosome deletions
Authors: Rraku Eleana , Medina Tyler D. , van Ravenswaaij-Arts Conny M.A. , Slofstra Mariska K. , Swertz Morris A. , Dijkhuizen Trijnie , Johansson Lennart F. , Engwerda Aafke 
Published: October 2024

AbstractInformation on the health-related consequences of rare chromosome disorders is often limited, posing challenges for both patients and their families. The Chromosome 6 Project aims to bridge this knowledge gap for structural aberrations involving chromosome 6 by providing parents of affected children with information on the expected phenotypes of their child. To achieve this, detailed phenotype and genotype data is collected directly from parents worldwide and supplemented with data from literature reports, resulting thus far in a dataset of over 500 individuals. This comprehensive data pool was used to develop Del2Phen, a software tool introduced in this paper that generates aberration-specific phenotype information for chromosome disorders. Del2Phen identifies individuals with a deletion or duplication similar to that of a new patient (index) and produces a clinical description for the index based on phenotypic features observed in these genotypically similar individuals. Genotypic similarity is determined using existing knowledge on the haploinsufficiency effect of genes and established gene-phenotype relationships. The optimal genotypic similarity parameters for chromosome 6 deletions were evaluated, which lead to thorough and reliable clinical descriptions based on sufficiently large groups of individuals with highly similar deletions. Although currently applied to and optimized for chromosome 6 deletions, Del2Phen can be used on deletions involving other chromosomes and is easily adapted for use on duplications, provided sufficient data is available. Del2Phen can already be used to expedite data analysis for chromosome disorders, thus aiding healthcare professionals in providing clinical care. Lastly, this tool will also be integrated into an interactive website aimed at parents of children with a chromosome 6 aberration, providing them with essential health information in an efficient and timely manner.
CardioBrain: A Novel User-Friendly Software for Assessing Dynamic Cerebral Autoregulation and Cardiovascular Interactions
Authors: Pecanha Tiago , Bartels Rhenan , Rodrigues Gabriel Dias 
Published: October 2024

AbstractCerebral autoregulation (CA) is a critical mechanism that maintains cerebral blood flow (CBF) relatively stable despite fluctuations in arterial blood pressure (ABP), ensuring protection against ischemia and hyperperfusion. Alterations in CA are linked to adverse outcomes in various conditions, highlighting the need for precise and accessible methods to analyse CA.CardioBrainis a freely available user-friendly software developed to assess dynamic CA by performing Transfer Function Analysis (TFA) on continuously recorded ABP and CBF data. The software utilizes the Welch method for spectral density and cross-spectral analysis. Following TFA, the software calculates different dCA metrics as gain, phase, and coherence across various frequency bands (VLF, LF, HF).CardioBrainallows users to easily manipulate signal processing parameters, visualize data, and export results, making it suitable for both research and clinical settings without requiring advanced programming skills. Additionally, the software includes tools to address signal misalignments, such as a temporal shift feature, and ensures adherence to recommended standards for TFA analysis. Future development will focus on incorporating user feedback, validating the software against simulated and real-world data, and expanding its functionality for a broader range of regulatory analyses.
Estimating the Prevalence of Generative AI Use in Medical School Application Essays
Authors: Spies Nicholas C. , Ratts Valerie S. , Hagemann Ian S. 
Published: October 2024

AbstractBackgroundGenerative artificial intelligence (AI) tools became widely available to the public in November 2022. The extent to which these tools are being used by aspiring medical school applicants during the admissions process is unknown.MethodsWe retrospectively analyzed 6,000 essays submitted to a U.S. medical school in 2021– 2022 (baseline, before wide availability of AI) and in 2023–2024 (test year) to estimate the prevalence of AI use and its relation to other application data. We used GPTZero, a commercially available detection tool, to generate a metric for the likelihood that each essay was human-generated, Phuman, ranging from 0 (entirely AI) to 1 (entirely human).ResultsFully human-generated negative controls demonstrated a median Phumanof 0.93, while AI-generated positive controls demonstrated a median Phumanof 0.01. Personal Comments essays submitted in the ‘23–‘24 cycle had a median human-generated score of 0.77 (95% confidence interval 0.76–0.78), versus 0.83 (95% CI 0.82–0.85) during the ‘21–‘22 cycle. Approximately 12.3 and 2.7% of essays were evaluated as having Phuman< 0.5 in the test and baseline year, respectively. Secondary essays demonstrated lower Phumanthan Personal Comments essays, suggesting more AI use. In multivariate analysis, younger age, visa requirement, and higher GPA were significantly associated with lower Phuman. No differences were observed in gender, MCAT score, undergraduate major, or socioeconomic status. Phumanwas not predictive of admissions outcomes in uni- or multivariate analyses.ConclusionsAn AI detection algorithm estimated significantly increased use of generative AI in 2023-2024 medical school admission applications, as compared to the 2021-2022 baseline. Estimated AI use demonstrated no significant differences in admissions decisions. While these results provide information about the applicant pool as a whole, AI detection is imperfect. We recommended exercising caution before deploying any AI detection tools on individual applications in live admissions cycles.DescriptionMedical school applicants increased their use of generative AI to write application essays in the most recent admissions cycle, but this use did not confer an admissions advantage.
Genetic and other omics-based information in the most-cited recent clinical trials
Authors: Russo Luigi , Siena Leonardo M. , Farina Sara , Pastorino Roberta , Boccia Stefania , Ioannidis John P.A. 
Published: October 2024

AbstractImportanceGenetics and other -omics’ technologies have long been proposed for medical research use.ObjectiveTo assess how genetics and other -omics information’ are used in the most cited recent clinical trials, and to evaluate industry involvement and transparency patterns.Design, Setting, ParticipantsMeta-research evaluation using a previously constructed database of the 600 most cited clinical trials published from 2019 to 2022.Main Outcome(s) and Measure(s)Utilization of genetic or other -omics information in the trial design, analysis, and results; industry involvement and transparency.Results132 (22%) trials used genetic or other -omics information, predominantly for detection of cancer mutations (n=101). Utilization included eligibility criteria (n=59), subgroup analysis (n=82), and stratification factor in randomization (n=14). Authors addressed the relevance in the conclusions in 82 studies (62%). 102 studies (77%) provided data availability statements and 6 had data already available. Most studies had industry funding (n=111 [84.0%]). Oncology trials were more likely to be industry-funded (90.1% vs 64.5%, p=0.001), to have industry-affiliated analysts (43.6% vs 22.6%, p=0.036) and to favor industry-sponsored interventions (83.2% vs 58.1% p=0.004). When compared to other trials, genetic and other -omics trials were more likely to be funded by industry (84% vs 63.9%, p<0.001) and tended to be less likely to have full protocols (p=0.018) and statistical plans (p=0.04) available.Conclusions and RelevanceOur study highlights the current underutilization of genetic and other-omics technologies beyond testing for cancer mutations. Industry involvement in these trials appears to be more substantial and transparency is more limited, raising concerns about potential bias.Key PointsQuestionHow are genetics and other -omics information used in highly impactful clinical trials, and what is the involvement of the industry in their development?Findings22% of the trials employed genetic or -omics information, with the vast majority being oncology-related and focusing on testing for mutations. Industry was more heavily involved in the funding and in the design of these trials, in particular for oncology trials.MeaningThe use of genetics and -omics is limited and needs to become more common in non-oncology trials. Industry involvement is intense in this context, highlighting the need for improvements in transparency and independence.
ToxoplasmaInfection and Its Sequential Impact on Physical Health, Stress, and Anxiety: A Large Cross-Sectional Study Testing the Stress-Coping Hypothesis
Authors: Flegr Jaroslav , Latifi Ashkan , Kaňková Šárka 
Published: October 2024

AbstractIntroductionLatent toxoplasmosis, affecting approximately one-third of people worldwide, was once thought to be asymptomatic. However, studies in the last three decades have revealed that it can cause significant psychological and behavioral changes in humans. The observation that the behavioral impacts of toxoplasmosis manifest in opposite directions in men and women has led to the development of the Stress-Coping Hypothesis. This hypothesis posits that health degradation from toxoplasmosis results in chronic stress, with gender-specific coping strategies explaining the divergent behavioral responses observed between men and women.MethodsThis study, conducted on 1,768 individuals who had previously been tested for toxoplasmosis or borreliosis, sought to examine this hypothesis through a survey that included the Perceived Stress Scale and the State-Trait Anxiety Inventory.ResultsConfirmed poorer health, higher stress, and anxiety levels amongToxoplasma-infected participants. Path analysis showed that toxoplasmosis directly negatively impacts physical health, which in turn directly increases stress and anxiety among infected individuals, thereby negatively affecting cognitive performance. This pattern was not seen with borreliosis, serving as a negative control, underscoring the unique impact of toxoplasmosis on human physical health, well-being, and cognition.ConclusionsOur findings strongly suggest that the cognitive impairments associated with toxoplasmosis are primarily side effects of chronic stress resulting from the compromised health of infected individuals.Key PointsChronic stress mediates the negative effects of toxoplasmosis on cognition, stemming from the impaired health of infected individuals.This effect was not observed with the negative control, borreliosis.Our results support the side effects hypothesis and contradict the parasite manipulation hypothesis.
Change in Acetylcholinesterase Activity from Childhood to Young Adulthood
Authors: Suarez-Lopez Jose R. , Gould Carlos F. , Vashishtha Devesh , Bradman Asa , Suarez-Torres Jose , Lopez-Paredes Dolores , Martinez Danilo , Moore Raeanne M. 
Published: October 2024

AbstractObjectiveAcetylcholinesterase (AChE) is an enzyme that metabolizes acetylcholine, an essential neurotransmitter, and is frequently used to monitor adult agricultural workers for exposure to cholinesterase inhibitor pesticides. Yet, there are no clear standards for AChE activity in children and adolescents, which prohibits evaluations of dangerous pesticide exposures in younger populations.MethodsWe measured AChE activity from a single finger stick blood sample data from 746 participants ages 4 to 26 years across 3,100 observations who resided in an agricultural county in Ecuador. We used generalized estimating equations to predict AChE activity levels in one year age increments from 5 to 25 years, accounting for nonlinear aging patterns and survey wave specific effects. We also decomposed variation in observed AChE activity levels into aging effects, differences in our recruited participants, and participant-specific aging patterns.ResultsAverage AChE activity levels across all observations were 3.88 U/mL (standard deviation [sd] = 0.67). AChE activity levels increased nonlinearly as participants aged. We found that males had higher AChE activity levels than females and that those levels established themselves later in age than females. AChE activity levels increased essentially linearly from ages 5 to 12 or 18 years, depending on sex, at which point levels did not meaningfully change with age. Most variation observed in AChE activity levels were due to aging effects.ConclusionOur findings provide reference levels for AChE activity across childhood, adolescence, and into early adulthood that can be used by clinicians and researchers in the context of assessing neurodevelopment and potential exposure to neurotoxicants.
Virus testing optimisation using Hadamard pooling
Authors: Beddard Godfrey S. , Yorke Briony A. 
Published: October 2024

AbstractPooled testing is an established strategy for efficient surveillance testing of infectious diseases with low prevalence. Pooled testing works by combining clinical samples from multiple individuals into one test, where a negative result indicates the whole pool is disease free and a positive result indicates that individual testing is needed. Here we present a straightforward and simple method for pooled testing that uses the properties of Hadamard matrices to design optimal pooling strategies. We show that this method can be used to efficiently identify positive specimens in large sample sizes by simple pattern matching, without the requirement of complex algorithms.
Community-based interventions to address depression in older adults: a systematic scoping review
Authors: Restrepo-Escudero Laura , Jaimes Maria Alejandra , Arango Isabela , Santos Sofia , Ramírez Valentina , Uribe Daniel , Muñoz Jenny , Ballesteros Lina Maria González 
Published: October 2024

AbstractDepression is a prevalent psychiatric disorder among adults aged 65 and older, significantly impacting their well-being. With an aging global population, effective community-based interventions are vital to combat this issue. This review provides an overview of the characteristics of community-based interventions addressing depression in the elderly, identifying knowledge gaps by synthesizing current data. The search strategy entails a systematic database search. Results show that interventions have been effective in reducing depressive symptoms and enhancing social interaction, mainly those that include physical activity, social engagement, or mental health education. Success depends on factors such as participant engagement, adherence, and the sociocultural environment. Addressing these barriers requires a comprehensive understanding of local contexts and innovative service delivery approaches. Improving recruitment by overcoming cultural and logistical challenges could expand the reach and accessibility of these programs, thereby increasing their overall impact on older adults mental health and quality of life.
N-Palmitoyl glycine activates transient receptor potential channel 5 and increases the risk of Brugada syndrome
Authors: Xu Hongxuan , Li Bingxun , Chen Ying , Lin Yanyun , Zhang An , Wu Lin 
Published: October 2024

AbstractBackgroundBrugada syndrome (BrS) is an arrhythmic disorder associated with an increased risk of sudden cardiac death; however, current treatment options are limited due to their side effects and variable efficacy.MethodsIn this study, we first employed Mendelian randomization analysis utilizing proteomic, transcriptomic, and metabolomic data to identify potential therapeutic targets for BrS. Ex vivo perfused heart models were used to assess the effects of the potential targets on action potentials and QT intervals. Calcium indicators were employed to evaluate calcium homeostasis in primary cardiomyocytes, and patch-clamp techniques were used to investigate the impact on Nav1.5 and TRPC5 channels.ResultsOur findings indicate that N-palmitoyl glycine (PalGly) is linked to an increased risk of BrS and interacts with BrS-associated proteins, demonstrating moderate binding affinities for DCC, CR1, CTSB, NAAA, DEFB1, EPHA1, IGF1/IGFBP3/ALS, and LTA. Electrophysiological experiments showed that although PalGly does not interact with Nav1.5, it enhances calcium sparks in ventricular cardiomyocytes. We determined that the calcium-modulating effect of PalGly is mediated by its binding to and activation of the transient receptor potential channel 5 (TRPC5) channel. Furthermore, PalGly was found to shorten the QT interval and action potential duration in Langendorff-perfused rabbit hearts and isolated rabbit cardiomyocytes. Transcriptomic and lipidomic analyses of PalGly-treated neonatal rat cardiomyocytes revealed significant negative modulation of immune pathways, akin to the effects observed with agonizing TRPC5.ConclusionOur study underscores the involvement of PalGly, TRPC5, and inflammation-related proteins in the pathophysiology of BrS.
Engineering Resilient Gene Drives Towards Sustainable Malaria Control: Predicting, Testing and Overcoming Target Site Resistance
Authors: Morianou Ioanna , Phillimore Lee , Khatri Bhavin S. , Marston Louise , Gribble Matthew , Burt Austin , Bernardini Federica , Hammond Andrew M. , Nolan Tony , Crisanti Andrea 
Published: October 2024

ABSTRACTCRISPR-based gene drives are selfish genetic elements with the potential to spread through entire insect populations for sustainable vector control. Gene drives designed to disrupt the reproductive capacity of females can suppress laboratory populations of the malaria mosquito. However, any suppressive intervention will inevitably exert an evolutionary pressure for resistance. Here, we present a pipeline for the accelerated discovery, engineering, and testing of both natural and drive-induced variants that could reverse gene drive spread. We applied our method to stress-test a highly effective gene drive that has evaded resistance in all laboratory-contained releases to date, known as Ag(QFS)1. We showed that previously undetected resistant alleles can arise at low frequency, and discovered novel, partially resistant alleles that can perturb drive-invasion dynamics. We then engineered next-generation gene drives that can actively remove resistant alleles by targeting several highly conserved and non-overlapping sites in the female-specific exon of thedoublesexgene. Our models predict that such gene drive designs could suppress large, natural populations of the malaria mosquito in the field.
Differential enrichment of retinal ganglion cells underlies proposed core neurodegenerative transcription programs
Authors: Watkins Trent A. 
Published: October 2024

SummaryIn a published Correction1, a revised analysis updated two “core transcription programs” proposed to underlie axon injury-induced retinal ganglion cell (RGC) neurodegeneration. Though extensive, the Correction purported to leave the two principal conclusions of its parent study2unaltered. The first of those findings was that a core program mediated by the Activating Transcription Factor-4 (ATF4) and its likely heterodimeric partner does not include numerous canonical ATF4 target genes stimulated by RGC axon injury. The second was that the Activating Transcription Factor-3 (ATF3) and C/EBP Homologous Protein (CHOP) function with unprecedented coordination in a parallel program regulating innate immunity pathways. Here those unexpected findings are revealed to instead reflect insufficient knockout coupled with differences in RGC enrichment across conditions. This analysis expands on the published Correction’s redefinition of the purported transcription programs to raise foundational questions about the proposed functions and relationships of these transcription factors in neurodegeneration.
COmapper: High-resolution mapping of meiotic crossovers by long-read sequencing inArabidopsis
Authors: Byun Dohwan , Son Namil , Kim Heejin , Kim Jaeil , Park Jihye , Park Sang-jun , Kim Hyein , Kim Jaebeom , Kim Juhyun , Lee Seula , Hyun Youbong , Ziolkowski Piotr A. , Henderson Ian R. , Choi Kyuha 
Published: October 2024

AbstractMeiotic crossovers rearrange existing genetic variation between homologous chromosomes, profoundly affecting genomic diversity. Crossovers are typically constrained to 1–3 events per chromosome pair, and their distribution is shaped by chromatin accessibility and DNA polymorphisms. Genome-wide crossover maps can be generated in plants by high-throughput short-read sequencing or linked-read sequencing. Here, we use long-read nanopore sequencing technology to develop a crossover mapping pipeline, COmapper, for high-resolution mapping of genome-wide crossovers from pooled DNA of F1hybrid pollen and F2recombinant seedlings derived from a cross betweenArabidopsis thalianaaccessions Col and Ler. We validate the high accuracy of COmapper by applying nanopore long-read sequencing to pooled DNA ofArabidopsisF2individuals with crossovers mapped by short-read sequencing. Using the COmapper, we constructed high-resolution genomic maps of crossovers using F1hybrid pollen and F2seedlings in wild type and crossover-elevatedrecq4a recq4bmutant, showing results comparable to short-read sequencing. Crossovers were enriched at gene-proximal promoters in wild type and increased but reshaped by high polymorphism density inrecq4a recq4b. We propose that COmapper will be widely applicable for exploring the effects of genetic, epigenetic and environmental changes on the crossover patterns across diverse plant species.