bluuebunny/crossref_metadata_2025_split huggingface dataset:
Goal-Directed Learning in Cortical Organoids
Authors: Robbins Ash , Schweiger Hunter E. , Hernandez Sebastian , Spaeth Alex , Voitiuk Kateryna , Parks David F. , van der Molen Tjitse , Geng Jinghui , Sharf Tal , Mostajo-Radji Mohammed A. , Haussler David , Teodorescu Mircea 
Published: December 2024

AbstractExperimental neuroscience techniques are advancing rapidly, with major recent developments in high-density electrophysiology and targeted electrical stimulation. In combination with these techniques, cortical organoids derived from pluripotent stem cells show great promise asin vitromodels of brain development and function. Although sensory input is vital to neurodevelopmentin vivo, few studies have explored the effect of meaningful input toin vitroneural cultures over time. In this work, we demonstrate the first example of goal-directed learning in brain organoids. We developed a closed-loop electrophysiology framework to embody mouse cortical organoids into a simulated dynamical task (the inverted pendulum problem known as ‘Cartpole’) and evaluate learning through high-frequency training signals. Longitudinal experiments enabled by this framework illuminate how different methods of selecting training signals enable improvement on the tasks. We found that for most organoids, training signals chosen by artificial reinforcement learning yield better performance on the task than randomly chosen training signals or the absence of a training signal. This systematic approach to studying learning mechanismsin vitroopens new possibilities for therapeutic interventions and biological computation.
CrossLabFit: A Novel Framework for Integrating Qualitative and Quantitative Data Across Multiple Labs for Model Calibration
Authors: Blanco-Rodriguez Rodolfo , Miura Tanya A. , Hernandez-Vargas Esteban 
Published: December 2024

AbstractThe integration of computational models with experimental data is a cornerstone for gaining insight into biomedical applications. However, parameter fitting procedures often require a vast availability and frequency of data that are challenging to obtain from a single source.Here, we present a novel methodology “CrossLabFit” designed to integrate qualitative data from multiple laboratories, overcoming the constraints of single-lab data collection. Our approach harmonizes disparate qualitative assessments—ranging from different experimental labs to categorical observations—into a unified framework for parameter estimation. By using machine learning algorithms, these qualitative constraints are represented as dynamic “qualitative windows” that capture significant trends to which models must adhere. For numerical implementation, we developed a GPU-accelerated version of differential evolution to navigate in the cost function that integrated quantitative and qualitative data.We validate our approach across a series of case studies, demonstrating significant improvements in model accuracy and parameter identifiability. This work opens a new paradigm for collaborative science, enabling a methodological road to combine and compare findings between studies to improve our understanding of biological systems and beyond.
Simulating big mechanically-active culture systems (BigMACS) using paired biomechanics-histology FEA modelling to derive mechanobiology design relationships
Authors: Schoenborn Sabrina , Yuan Mingyang , Fell Cody A. , Liu Chuanhai , Fletcher David F. , Priola Selene , Chan Hon Fai , Woodruff Mia , Li Zhiyong , Toh Yi-Chin , Allenby Mark C. 
Published: December 2024

AbstractBig mechanically-active culture systems (BigMACS) are promising to stimulate, control, and pattern cell and tissue behaviours with less soluble factor requirements, however, it remains challenging to predict if and how distributed mechanical forces impact single-cell behaviours to pattern tissue. In this study, we introduce a centimetre, tissue-scale, finite element analysis (FEA) framework able to correlate sub-cellular quantitative histology with centimetre-scale biomechanics. Our framework is relevant to diverse bigMACS; media perfusion, tensile-stress, magnetic, and pneumatic tissue culture platforms. We apply our framework to understand how the design and operation of a multi-axial soft robotic bioreactor can spatially control mesenchymal stem cell (MSC) proliferation, orientation, differentiation to smooth muscle, and extracellular vascular matrix deposition. We find MSC proliferation and matrix deposition correlate positively with mechanical stimulation but cannot be locally patterned by soft robot mechanical stimulation within a centimetre scale tissue. In contrast, local stress distribution was able to locally pattern MSC orientation and differentiation to smooth muscle phenotypes, where MSCs aligned perpendicular to principal stress direction and expressed increased α-SMA with increasing 3D Von Mises Stresses from 0 to 15 kPa. Altogether, our new biomechanical-histological simulation framework is a promising technique to derive the future mechanical design equations to control cell behaviours and engineer patterned tissue generation.
Global multi-omics analysis of exerkines in progressive treadmill-exercised rodents
Authors: Taha Hash Brown 
Published: December 2024

AbstractExercise is widely recognized for its comprehensive physiological benefits, attributed largely to the secretion of signaling molecules known as exerkines. These molecules, originating from various tissues like muscles, brain, and liver, facilitate inter-organ communication and enhance metabolic health, immune function, and tissue repair. However, the responsiveness of multiple tissues and exerkines to the same exercise regimen remains poorly understood. To address this issue and elucidate patterns of time-dependent, intensity-related and sex-dimorphic tissue and exerkine responsiveness, we leveraged the publicly available Molecular Transducers of Physical Activity Consortium (MoTrPAC) dataset. Male and female Fischer 344 rats aged 6 months underwent a progressive treadmill training protocol designed to emulate human endurance exercise. Blood (cells and plasma) and 18 solid tissues such as adipose, skeletal muscle and brain were collected and multi-omics analyses, including proteomics and transcriptomics were performed on them. We examined the distribution of 26 known and 2 speculative exerkines across 2 biofluids and 18 solid tissues. Our analysis reveals that brown adipose tissue (BAT), the adrenal gland, and white adipose tissue (WAT) are the most responsive to exercise-induced changes. Fractalkine was the most responsive exerkine, followed by prosaposin (speculative), cathepsin B, and FNDC5/irisin, platelet factor 4, Clusterin and SPARC. Additionally, we found distinct patterns in the responsiveness of tissues and exerkines based on the duration and intensity of exercise, with notable differences between male and female rodents. Future research should investigate whether our findings on tissue exerkine responsiveness vary with age and disease status, and determine if these findings can be extrapolated to human populations.
SevereGBA1variants drive the GBA-PD clinical phenotype: implications for counselling and clinical trials
Authors: Menozzi Elisa , Del Pozo Sara Lucas , Macnaughtan Jane , Mezabrovschi Roxana , Koletsi Sofia , Mitrotti Pierfrancesco , Gallo Luca , Calabrese Rosaria , Toffoli Marco , Loefflad Nadine , Valzania Franco , Cavallieri Francesco , Fioravanti Valentina , Yalkic Selen , Limbachiya Naomi , Blandini Fabio , Avenali Micol , Schapira Anthony HV 
Published: December 2024

AbstractBackgroundVariants in theGBA1gene are the commonest genetic risk factor for Parkinson disease (PD). Genotype- phenotype correlations exist but with conflicting data, particularly in the cognitive domain.ObjectivesComparing clinical phenotypes in a multicentre, international cohort incorporating GBA-PD and idiopathic PD (iPD) patients.MethodsPatients underwent a comprehensive assessment of motor and non-motor functions. Two-group (GBA- PD vs iPD) and multiple-group comparisons (iPD, risk, mild, and severe variant GBA-PD) were performed.ResultsThree hundred eleven PD patients were recruited: 183 iPD, 39 severe GBA-PD, 24 mild GBA-PD, 55 risk GBA-PD, and 10 patients carrying variants of unknown significance. Groups were matched for sex, education, disease duration and medications. Mild and severe GBA-PD were younger and developed PD earlier. Severe GBA-PD had worse depression, cognitive impairment, hyposmia, and motor complications.ConclusionsOnly severe variant GBA-PD have a distinctive, more severe clinical profile.
HP1 binding creates a local barrier against transcription activation and persists during chromatin decondensation
Authors: Weinmann Robin , Udupa Arjun , Nickels Jan Fabio , Frank Lukas , Knotz Caroline , Rippe Karsten 
Published: December 2024

ABSTRACTMouse pericentric repeats form transcriptionally silent and compacted domains known as chromocenters. These prototypic heterochromatin compartments are marked by heterochromatin protein 1 (HP1). However, its contributions to chromocenter structure and function remain debated. We investigated the role of HP1α by recruiting the activators VP16, p65, and VPR to mouse fibroblast chromocenters and analyzed its silencing activity with a transcription reporter. Upon chromocenter decondensation and transcription activation, interactions of HP1α with chromatin and H3K9 trimethylation remained stable, suggesting stoichiometric binding rather than higher-order assembly. HP1α-mediated repression required promoter-proximal binding and effectively suppressed VP16-triggered activation but not the stronger activation by VPR. These observations are explained by a 1D lattice binding model, which conceptualizes chromocenters as arrays of repeat units that can independently switch between silenced and activated states. Our findings provide a quantitative framework that explains how chromocenter organization responds to transcriptional activation while maintaining local heterochromatin features.GRAPHICAL ABSTRACTHIGHLIGHTSHP1α represses transcription at mouse chromocenters and an ectopic reporter when competing with transcriptional activators VP16, p65 and VPRHP1α repression requires promoter-proximal binding and effectively counteracts the weak activator VP16The strong activator VPR overcomes HP1α-mediated repression while HP1α remains bound to chromatinHP1α binding and H3K9me3 persist during chromocenter decondensation and transcriptional activationA 1D lattice binding model explains how independent repeat units transition between silenced and activated states without requiring phase separation
A haplotype-resolved chromosomal reference genome for the porcini mushroomBoletus edulis
Authors: Lamartinière Etienne Brejon , Tremble Keaton , Dentinger Bryn T.M. , Dasmahapatra Kanchon K. , Hoffman Joseph I. 
Published: December 2024

AbstractHaplotype-resolved chromosomal reference genomes are increasingly available for many fungi, offering insights into the evolution of pathogenic and symbiotic lifestyles. However, these resources remain scarce for ectomycorrhizal fungi (EMF), which play crucial roles in forest ecosystems. Here, we used a combination of chromatin conformation capture (Hi-C) and PacBio sequencing to construct a haplotype-resolved chromosomal genome assembly forBoletus edulis, an emerging model for EMF research and a prized edible fungus. Our new reference assembly, “BolEdBiel_h2”, derives from a sporocarp sampled in Bielefeld, Germany. The genome assembly spans 41.8 Mb, with a scaffold N50 of 4.1 Mb, and includes 11 chromosome-level scaffolds, achieving near telomere-to-telomere coverage across multiple chromosomes. We annotated 15,406 genes, with a Benchmarking Universal Single-Copy Orthologs (BUSCO) score of 96.2%. Key genomic features such as mating loci, CAZymes, and effector proteins, were mapped across the assembly. As a first application of this new genomic resource, we mapped whole genome resequencing data from 49 genets to investigate the population structure and genetic diversity of the European lineage ofB. edulis. We identified five distinct genetic clusters and found that high-latitude populations from Iceland and Fennoscandia exhibited greater nucleotide diversity than populations from the United Kingdom and central Europe. Additionally, we discovered a 0.4 Mb inversion on chromosome three and identified several regions of locally elevated nucleotide diversity, which may represent candidates for ecological adaptation. This genomic resource will facilitate a deeper understanding of this ecologically and commercially important wild fungus.
Histone H3 tail modifications required for meiosis inSaccharomyces cerevisiae
Authors: Prichard Amy , Johansson Marnie , Kirkpatrick David T. , Clarke Duncan J. 
Published: December 2024

AbstractHistone tail phosphorylation has diverse effects on a myriad of cellular processes, including cell division, and is highly conserved throughout eukaryotes. Histone H3 phosphorylation at threonine 3 (H3T3) during mitosis occurs at the inner centromeres and is required for proper biorientation of chromosomes on the mitotic spindle. While H3T3 is also phosphorylated during meiosis, a possible role for this modification has not been tested. Here, we asked if H3T3 phosphorylation (H3T3ph) is important for meiotic division by quantifying sporulation efficiency and spore viability inSaccharomyces cerevisiaemutants with a T3A amino acid substitution. The T3A substitution resulted in greatly reduced sporulation efficiency and reduced spore viability. Analysis of two other H3 tail mutants, K4A and S10A, revealed different effects on sporulation efficiency and spore viability compared to the T3A mutant, suggesting that these phenotypes are due to failures in distinct functions. To determine if the spindle checkpoint promotes spore viability of the T3A mutant, theMAD2gene required for the spindle assembly checkpoint was deleted to abolish spindle assembly checkpoint function. This resulted in a severe reduction in spore viability following meiosis. Altogether, the data reveal a critical function for histone H3 threonine 3 that requires monitoring by the spindle checkpoint to ensure successful completion of meiosis.
Extracorporeal shock wave therapy for erectile dysfunction: rethinking study design, implementation, and analysis
Authors: Desai Janak , Huyghe Eric , Maffulli Gayle D. , Nussbaum-Krammer Carmen , Tittelmeier Jessica , Schmitz Christoph 
Published: December 2024

ABSTRACTIntroductionExtracorporeal shock wave therapy (ESWT) for erectile dysfunction (ED) presents a challenging paradox. While numerous clinical studies, systematic reviews, and meta-analyses have been published, indicating a substantial body of evidence supporting the efficacy and safety of ESWT, significant questions remain. Notably, the American Urological Association (AUA) continues to classify ESWT for ED as investigational (Evidence Level: Grade C), suggesting that the true therapeutic effect o f ESWT may differ considerably from current estimates. This review aims to critically assess the evidence and propose strategies to address this unresolved discrepancy.Data sourcesWe systematically searched two electronic databases (PubMed and Ovid/Embase) and published systematic reviews on ESWT for ED and compiled a systematic literature review and meta-analysis based on 87 relevant studies.Areas of agreementThere is clear evidence that ESWT for ED is effective and can therefore be a valuable treatment modality in the management of ED.Areas of controversyCurrent assessments of ESWT for ED as investigational by, e.g., the AUA may not stem from a lack of clinical studies, insufficient related basic science, or an inadequate number of systematic reviews and meta-analyses. Instead, the deficits lie in the area of the scientific quality of the clinical studies published to date.Growing pointsWe hypothesize that this unfortunate situation will only change if the following aspects will be rigorously considered in future clinical studies on ESWT for ED: adequate characterization and reporting of extracorporeal shock waves, appropriate handling of missing data and intercurrent events, and comprehensive classification of ESWT in the overall context of the available treatment options for ED.Areas for developing researchWe are convinced that the consistent implementation of these aspects will significantly contribute to establishing ESWT as the first truly regenerative therapy in the management of ED. This overall aim justifies the corresponding efforts, for the benefit of our patients.
ACCURACY OF COMPUTER-ASSISTED DETECTION IN SCREENING PEOPLE WITH DIABETES MELLITUS FOR ACTIVE TUBERCULOSIS: A SYSTEMATIC REVIEW
Authors: Reagan Emoru Daniel , Mrema Lucy Elauteri , Ntinginya Nyanda Elias , Biraro Irene Andia , van Crevel Reinout , Critchley Julia A 
Published: December 2024

AbstractObjectivesDiabetes mellitus (DM) significantly increases the risk of tuberculosis (TB), and active TB screening of people with DM has been advocated. This systematic review aimed to evaluate the accuracy of computer-assisted detection (CAD) for identifying pulmonary TB among people living with DM.MethodsMedline, Embase, Scopus, Global Health and Web of science were searched from January 2010 to May 2024 supplemented with grey literature (Conference abstracts, Trial registries,MedRxiv.org). Studies evaluating CAD accuracy for identifying TB in populations living with diabetes were included. Two researchers independently assessed titles, abstracts, full texts, extracted data and assessed the risk of bias. Due to heterogeneity and a limited number of studies, a descriptive analysis was performed instead of statistical pooling. Forest plot and Summary Receiver Operating Curves (SROC) were generated using RevMan 5.4.ResultsFive eligible studies, all conducted in Asia between 2013 and 2023 were identified, including a total of 1879 individuals of whom 391 were diagnosed with TB. Four different Computer Assisted Detection (CAD) software algorithms were used. Sensitivities ranged from 0.73 (95%CI: 0.61-0.83) to 1.00 (95%CI:0.59-1.00), while specificities ranged from 0.60 (95%CI:0.53-0.67) to 0.88 (95%CI: 0.84-0.91). Area Under the receiver Operating Curve (AUC) values varied from 0.7 (95%CI: 0.68-0.75) to 0.9(95%CI: 0.91-0.96). False positive rates ranged from 0.24% to 30.5%, while false negative rates were 0-3.2%. The risk of bias assessment of the five studies was generally good to excellent.ConclusionsCAD tools show promise in screening people living with diabetes for active TB, but data are scarce, and performance varies across settings.
Return-to-work for People Living with Long COVID: A Scoping Review of Interventions and Recommendations
Authors: Nagra Gagan , Ezeugwu Victor E. , Bostick Geoff P. , Branton Erin , Dennett Liz , Drake Kevin , Durand-Moreau Quentin , Guptill Christine , Hall Mark , Ho Chester , Hung Pam , Khan Aiza , Lam Grace Y. , Nowrouzi-Kia Behdin , Gross Douglas 
Published: December 2024

ABSTRACTIntroductionLong COVID affects individuals’ labour market participation in many ways. While some cannot work at all, others may return to work (RTW) in a limited capacity. Determining what rehabilitation or related strategies are safe and effective for facilitating RTW is necessary.ObjectivesTo synthesize evidence on RTW interventions for people living with Long COVID and to identify ‘promising’ interventions for enhancing work ability and RTW.MethodsWe followed Arksey & O’Malley’s methodology and the PRISMA extension for scoping reviews. Five electronic bibliographic databases and grey literature were searched. The included various study designs, such as randomized controlled trials (RCT), quasi-experimental designs, and observational studies. Two reviewers conducted screening and data extraction, with disagreements resolved through consensus. Intervention studies were categorized as promising (statistically significant RTW outcomes or ≥ 50% RTW), somewhat promising (20% to < 50% RTW), or not promising (non-statistically significant RTW outcomes or < 20% RTW).ResultsEleven recommendations and eleven intervention studies were identified. Of the intervention studies, 6 were cohort studies, 3 quasi-experimental studies, 1 RCT and 1 case report. Promising interventions included multimodal and interdisciplinary work-focused rehabilitation (1 article), psychoeducation, pacing, and breathing strategies (2 articles), shifting focus from symptom monitoring to optimizing functional outcomes (1 article), and enhanced external CounterPulsation (EECP) inflatable pressure to improve blood flow (1 article).ConclusionMany uncertainties remain regarding which RTW interventions are effective or the optimal characteristics of these interventions.
Accelerating the pace and accuracy of systematic reviews using AI: a validation study
Authors: Zhan Jiada , Suvada Kara , Xu Muwu , Tian Wenya , Cara Kelly C. , Wallace Taylor C. , Ali Mohammed K. 
Published: December 2024

AbstractBackgroundArtificial intelligence (AI) can greatly enhance efficiency in systematic literature reviews and meta-analyses, but its accuracy in screening titles/abstracts and full-text articles is uncertain.ObjectivesThis study evaluated the performance metrics (sensitivity, specificity) of a GPT-4 AI program, Review Copilot, against human decisions (gold standard) in screening titles/abstracts and full-text articles from four published systematic reviews/meta-analyses.Research DesignParticipant data from four already-published systematic literature reviews were used for this validation study. This was a study comparing Review Copilot to human decision-making (gold standard) in screening titles/abstracts and full-text articles for systematic reviews/meta-analyses. The four studies that were used in this study included observational studies and randomized control trials. Review Copilot operates on the OpenAI, GPT-4 server. We examined the performance metrics of Review Copilot to include and exclude titles/abstracts and full-text articles as compared to human decisions in four systematic reviews/meta-analyses. Sensitivity, specificity, and balanced accuracy of title/abstract and full-text screening were compared between Review Copilot and human decisions.ResultsReview Copilot’s sensitivity and specificity for title/abstract screening were 99.2% and 83.6%, respectively, and 97.6% and 47.4% for full-text screening. The average agreement between two runs was 95.4%, with a kappa statistic of 0.83. Review Copilot screened in one-quarter of the time compared to humans.ConclusionsAI use in systematic reviews and meta-analyses is inevitable. Health researchers must understand these technologies’ strengths and limitations to ethically leverage them for research efficiency and evidence-based decision-making in health.