bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep increases broadband fast oscillations in the epileptic focus of patients with focal cortical dysplasia
Authors: Schwoon Nina , Khazali Mohammad F , Brandt Armin , Dümpelmann Matthias , Hegner Yiwen Li , Roehri Nicolas , Altenmüller Dirk-Matthias , Antonio-Arce Victoria San , Reinacher Peter C , Nakagawa Julia M , Doostkam Soroush , Demerath Theo , Urbach Horst , Schulze-Bonhage Andreas , Heers Marcel 
Published: February 2025

AbstractRationaleFocal cortical dysplasia (FCD) is associated with increased seizure-risk during sleep, yet the underlying mechanisms remain unclear. Previous studies report increased oscillatory patterns during sleep in focal epilepsy patients with FCD. We investigated whether fast oscillations (FOs, 14-250 Hz) within the epileptic focus significantly change during sleep compared to wake, hypothesizing that analyzing broad frequency bands provides more comprehensive information than narrow bands alone.MethodsWe retrospectively analyzed intracranial EEG recordings from 22 FCD patients (2010-2023), focusing on contacts within the irritative zone (IZ) and seizure onset zone (SOZ). Using semiautomated detections, we compared FO rates between one-hour wake and sleep epochs across beta (14-40 Hz), gamma (40-80 Hz), and ripple (80-250 Hz) bands. Distance-based Multivariate Analysis of Variance (MANOVA) was applied to integrate the spatial organization of FO changes, enabling simultaneous analysis of individual and combined broadband ranges (BGR) while accounting for neocortical detection rates outside the epileptic focus and eloquent cortex.ResultsAnalysis of 67 ± 28 (median ± standard deviation) bipolar iEEG contact pairs per patient (SOZ: 14 ± 12, IZ: 29 ± 16) revealed distinct sleep-related patterns. In the SOZ, gamma showed significant increases in 10 patients, followed by BGR in seven patients. The IZ exhibited strong changes in both BGR and gamma (13 patients each) with high concordance (12 matches). Beta and ripple bands showed moderate concordance. Notably, gamma oscillation rates in the SOZ specifically increased in patients with sleep-related epilepsy (p < 0.05).ConclusionGamma oscillations showed the most robust sleep-related increases in the SOZ, while both gamma and BGR showed strong changes in the IZ. These findings suggest gamma oscillations, complemented by broadband analysis, may serve as reliable markers for sleep-related changes in FCD patients.FundingYLH (LI1904/2-1) and MH (HE6844/3-1; project ID for both: 468174690) were funded by the German Research Foundation (DFG)Key pointsWithin the seizure onset zone, gamma band oscillations (40-80 Hz) followed by combined broadband BGR (14-250 Hz) show more frequent significant increases from wake to sleep across patientsWithin the irritative zone, gamma band and broadband oscillations BRG show even more frequent increases from wake to sleep across patientsChanges occur simultaneously across multiple frequency bands, supporting the value of multi-band analysisGamma oscillation rates within the seizure onset zone significantly increased from wake to sleep in patients with sleep-related epilepsy (p < 0.05)
Can Chinese Herbal Medicine Be Useful in Treatment of Type 2 Diabetes Mellitus? A Systematic Review of Medicinals Used and Clinical Impact
Authors: Finney Anisa , Conboy Lisa 
Published: February 2025

AbstractPurpose: With Diabetes Mellitus (DM) on the rise, biomedicine has identified its treatment as challenging due to the multitude of interventions necessary for disease management1. Biomedical treatment utilizes a single action approach, placing patients in the care of one specialist at a time. The traditional Chinese Herbal Medical approach can be of great utility to DM patients administered by a single practitioner aiming to address whole body imbalances. This project synthesized available research discussing Chinese Herbal medicine in the treatment of T2DM via PubMed. Methods: Systematic review was used to search PubMed database October 2022-April 2023 leading to eventual retrieved sample of 30 articles. Search terms includedChinese MedicineANDDiabetes MellitusORChinese MedicineANDType 2 Diabeteswith the filters of clinical trial, open access, in English. Results: Thirty articles met the inclusion criteria and were included in this review. Chinese herbal medicines have been extensively researched appearing in multiple forms such as pills, single herbs, granules, and decoctions. Of the 30 studies, the most reported outcomes were reduced fasting blood glucose, reduced HbA1c, and improved glycemic control. Conclusions: Further research is necessary to capture the role of Chinese herbal medicine in the integrative treatment of T2DM patients.
Multi-Modal Disentanglement of Spatial Transcriptomics and Histopathology Imaging
Authors: Maan Hassaan , Ji Zongliang , Sicheri Elliot , Tan Tiak Ju , Selega Alina , Gonzalez Ricardo , Krishnan Rahul G. , Wang Bo , Campbell Kieran R. 
Published: February 2025

AbstractSpatially-resolved expression profiling data has revolutionized biological research with multiple emerging clinical applications. Spatial transcriptomic assays are often jointly measured with histopathology imaging data, which is frequently used for diagnosing and staging various diseases. However, determining the extent to which the spatial transcriptomic and histopathology data represent overlapping or unique sources of variation is challenging, particularly given the myriad of factors influencing both, including expression variation, spatial context, tissue morphology, and batch effects. Here, we view this challenge as multi-modal disentanglement and develop an evaluation framework. We introduce SpatialDIVA, a disentanglement technique for jointly measured spatially resolved transcriptomics and histopathology data. We demonstrate that SpatialDIVA outperforms baseline techniques in disentangling salient factors of variation in curated pathologist-annotated multi-sample colorectal and pancreatic cancer cohorts. Further, SpatialDIVA removes batch effects from multi-modal data, allows for factor covariance analysis, and yields actionable biological insights through a novel conditional multi-modal generation method. The SpatialDIVA model, evaluation code, and datasets are available athttps://github.com/hsmaan/SpatialDIVA.
Controlling the Formation of Multiple Condensates in the Synapse
Authors: Safari Nahid , do Rego Barros Fernandes Lima Maria Augusta , Rossetto Riccardo , Zwicker David , D’Este Elisa , Tetzlaff Christian 
Published: February 2025

AbstractThe postsynaptic density (PSD) is a molecule rich structure that continuously adapts its organization controlling synaptic physiology and transmission. Experimental studies have shown that this organization is dominated by the formation of condensates or (nano)clusters and by the seamless transition in their numbers as response to synaptic plasticity. In this study, we utilize different computational modeling frameworks to show that variations in the level of local protein concentrations together with the modulation of protein binding strengths can be key molecular factors in controlling the formation and number of clusters in the synapse. Comparison to MINFLUX data of spatial localization of PSD95 in the postsynapse under different activity conditions allowed us to derive predictions about the correlation between these two factors across a population of synapses. Co-variations of the factors, to mimic a simple LTP protocol, shows that a PSD containing a single cluster can reorganize to form multiple clusters that persists for long periods of time, providing a potential explanation of recent experimental data of PSD reorganization.
High-throughput MicroED for probing ion channel dynamics
Authors: Gallenito Marc J , Clabbers Max TB , Lin Jieye , Hattne Johan , Gonen Tamir 
Published: February 2025

AbstractIon channels play a crucial role in ion transport and are integral to fundamental physiological processes. Therefore, understanding channel structures is essential for elucidating the mechanisms of ion permeation and selectivity beyond what can be predicted by computational simulations. Visualizing dynamics at high resolution, however, remains a significant challenge by structural techniques. In this study, we apply high-throughput Microcrystal Electron Diffraction (MicroED) to explore the structural dynamics of two ion channels, the non-selective ion channel NaK and its mutant, NaK2CNG. This approach utilizes automated data collection and processing to capture distinct structural substates from a large number of microcrystals, offering a deeper understanding of ion channel mechanisms. From a subset of NaK structures, we observed consistent sodium binding at specific sites. In contrast, NaK2CNG appears more dynamic and undergoes dilation of the selectivity filter upon potassium binding. Further, the conduction state of NaK2CNG appears to be influenced by channel gating. Comparative analysis of these structures reveals that non-selectivity arises from the plasticity of the selectivity filter, allowing dynamic control over ion passage. These studies, demonstrate the potential to employ high-throughput MicroED as a technique to address persistent questions regarding ion channel permeation, complementing current computational molecular dynamics studies. We anticipate that this approach will enhance future computational models, leading to more accurate predictions of ion channel behavior and providing a more comprehensive view of transport dynamics.
Bioinformatics analysis identifies sequence determinants of enzymatic activity for the PHARC associated lipase ABHD12
Authors: Chakraborty Arnab , Devarajan Archit , Kumar Kundan , Rohith C. S. , Madhusudhan M. S. , Ratnaparkhi Girish S. , Kamat Siddhesh S. 
Published: February 2025

ABSTRACTIn humans, PHARC (polyneuropathy,hearing loss,ataxia,retinitis pigmentosa, andcataract) is an early onset autosomal recessive neurological disorder caused by deleterious mutations to ABHD12 (α/β-hydrolase domain protein # 12). Biochemically, ABHD12 functions as a lipase, and catalyzes the hydrolysis of lysophosphatidylserine (lyso-PS) (lyso-PS lipase). By doing so, it controls the concentrations and signaling pathways regulated by this potent signaling lysophospholipid in the mammalian brain. While genetic mapping efforts have identified over 30 mutations in ABHD12 from human PHARC subjects, the biochemical activity of these pathogenic mutants remains unknown. To understand this, here, we performed an exhaustive bioinformatics survey, and collated ABHD12 protein sequences from various organisms across evolution. Next, based on sequence alignments and structural modeling, we identified functionally relevant conserved residues in the ABHD12 protein sequence that are potentially important for its enzymatic activity. To validate thesein silicofindings, we generated numerous mutants of murine ABHD12, including those associated with human PHARC subjects, and assayed them for their enzymatic activity. Taken together, these complementaryin silicoand biochemical studies provide the first thorough sequence-function relationship for mammalian ABHD12, especially relevant in the context of PHARC. Finally, our evolutionary analysis identified CG15111 as an ABHD12 ortholog in the fruit fly (Drosophila melanogaster), and enzymatic assays indeed confirmed that recombinant CG15111 has robust lyso-PS lipase activity. Flies serve as an excellent animal system to model various human neurological diseases, and the identification of CG15111 as aDrosophila melanogasterABHD12 ortholog opens new avenues to study PHARC in fly models.
RESiLIENT (Resilience Enhancement with Smartphone in LIving ENvironmenTs) Trial: The Statistical Analysis Plan for 1-year follow-up data
Authors: Noma Hisashi , Furukawa Toshi A. , Tajika Aran , Toyomoto Rie , Sakata Masatsugu , Luo Yan , Horikoshi Masaru , Akechi Tatsuo , Kawakami Norito , Nakayama Takeo , Kondo Naoki , Fukuma Shingo , Christensen Helen , Kessler Ronald C. , Cuijpers Pim , Wason James 
Published: February 2025

ABSTRACTThe RESiLIENT (Resilience Enhancement with Smartphone in LIving ENvironmenTs) trial is designed as a master protocol study including four 2×2 factorial trials to assess specific efficacies of five cognitive-behavioural therapy (CBT) skills (cognitive restructuring, behavioural activation, problem-solving, assertion training, and behavior therapy for insomnia) using the internet CBT program (BMJ Open 2023;13:e067850). In this document, the statistical analysis plan of 1-year follow-up data of the RESiLIENT trial for the assessments of long-term intervention effects is provided.
Interactions between mechanisms of reproductive isolation
Authors: Blanckaert Alexandre , Sousa Vitor C. 
Published: February 2025

AbstractSpeciation is responsible for the diversity of species observed today and corresponds to the build-up of reproductive isolation between populations. Reproductive isolation can be generated by different mechanisms that have been extensively characterized, yet how their interactions affect speciation remains largely unknown. Here, we explicitly model the interaction of three key mechanisms (local adaptation, mate choice and genetic hybrid incompatibilities) quantifying their relative contribution to the evolution of reproductive isolation. We modeled two populations exchanging migrants using Fisher Geometric Model for local adaptation, phenotype matching for mate choice, and multiple pairs of Bateson-Dobzhansky-Muller Incompatibilities (DMI). All three mechanisms were determined by the same set of loci, creating conditions for interactions between barriers both at the genetic and population levels. We found no cases where the three barriers evolved. Instead, two barriers could evolve depending on the migration rate: either local adaptation and genetic incompatibilities for limited migration, or local adaptation and mate choice for higher migration. Our results showed that local adaptation due to ecological differentiation was the first to evolve and by far the most effective reproductive barrier. Finally, we demonstrated that in a polygenic model, populations could become locally adapted and evolve strict mate choice, yet they would not accumulate incompatibilities provided that there was sufficient gene flow.
Factors Associated with All-cause Mortality and Morbidity of Motorcycle Crash-Related Neurological and Musculoskeletal Injuries: The MOTOR Trial Ancillary Study
Authors: Lule Herman , Mugerwa Micheal , Abio Anne , Oguttu Benson , Kakeeto Andrew , Asiimwe Daniel , Lekuya Harvé Monka , Ssebuufu Robinson , Kyamanywa Patrick , Bärnighausen Till , Wilson Michael Lowery , Posti Jussi P. 
Published: February 2025

ABSTRACTIntroductionThe objective of this study was to examine the factors linked to all-cause mortality and morbidity from neurological and musculoskeletal injuries in motorcycle accidents.MethodsThe study was part of a two-armed, parallel, multi-period, cluster-randomized controlled trial of 1003 motorcycle crash victims. Morbidity was assessed using various scoring systems, and mixed effects regression models were employed for analysis.Results90-day all-cause mortality was 9.2% (82/887). Factors associated with mortality included referral-to-discharge >1 hour [OR 4.215 (1.802-9.858),p=.001), Kampala Trauma Score (KTS) ≤6 [OR 7.696 (1.932-30.653),p=.004], GCS 9-12 [OR 3.432 (1.194-9.870),p=.022], GCS ≤8 [OR 6.919 (2.212-21.645),p=.001], intra-axial lesions [OR 78.647 (9.871-626.587),p<.001], extra-axial lesions [OR 11.933 (1.386-102.750),p=.024], skull fracture [OR 11.366, (1.197-107.977),p=.034], and decompressive craniotomy (DC) [OR 0.260 (.095-.706),p=.008).A proportion of 14.5% had unfavourable Glasgow Outcome Scale (1-3); associated factors included increasing age [OR 1.02, (1.013-1.045,p<.001], multiple injuries [OR 4.559 (1.185-17.531), p=.027], KTS 7-8 [OR 2.755 (1.285-5.906), p=.009], KTS ≤6 [OR 7.551 (2.815-20.255), p=.001], GCS 9-12 [OR 4.07 (1.901-8.719), p=.001], GCS ≤8 [OR 13.779 (5.643-33.645),p<.001], and DC [OR 0.149 (.075-.295),p<.001].Factors associated with unfavourable patient-reported musculoskeletal outcomes included being married [OR 1.984 (1.322–2.976),p=.001], multiple injuries [OR 1.762, (1.001–3.100),p=.049], and enrolment after the onset of the COVID-19 pandemic [OR 2.095 (1.199–3.659), p=.009].ConclusionsThe key determinants of mortality and adverse neurological and musculoskeletal injury outcomes observed in this study are essential for establishing core outcome sets in future research and predictive models.Summary of the Key MessagesExisting Knowledge:Motorcycle crashes in low- and middle-income countries represent significant public health issues, exacerbated by low helmet usage and insufficient trauma care resources.Study Contributions:This MOTOR trial ancillary study investigated factors associated with all-cause mortality and morbidity from motorcycle crashes, emphasizing neurological and musculoskeletal injuries as critical targets for enhancing rural trauma care systems.Implications for Research, Practice, and Policy:Our findings indicate that the anatomical nature, multiplicity and severity of injuries, referral-dispatch intervals, operative interventions, and COVID-19-related social conditions significantly influence injury outcomes. These factors may serve as a foundational outcome set for benchmarking future clinical trials and trauma registries.
Impacts of a relational leadership development program on psychological sense of community
Authors: Islam Naseeha , Wiederholt Senta G. , Park Brian , Tuepker Anaïs , Uchison Elaine Waller , Gordon Leah , Lewis Matthew , Mansour Alexander , Steckler Nicole A. , Edwards Samuel T. 
Published: February 2025

AbstractIntroductionIn a time of increasing employee dissatisfaction and burnout within healthcare, relational leadership approaches have the potential to improve belonging and a sense of community among the workforce.MethodsThe Relational Leadership Institute (RLI) teaches a relationship-based leadership model to help participants enhance interpersonal skills in the healthcare workplace. A survey was conducted of participants to assess their psychological sense of community (PSOC) throughout this leadership program, at baseline, post-program, and 6-months post-program.ResultsOverall mean PSOC was 4.87 (SD 0.68) at baseline, 5.16 (SD 0.77) post-program, and 5.13 (SD 0.72) 6-months post-program, with a significant increase from baseline to post-program (p<0.01) and baseline to 6-months post-program (p=0.01). There was no significant difference between post-program and 6-months post-program PSOC levels (p=0.99). Baseline mean PSOC score was greater among non-white participants (mean 5.00 vs. 4.83 among white participants, p<0.01), and greater among trainees than among working professionals (mean 4.96 vs. 4.82, p<0.01).ConclusionThe RLI intervention has a significant impact on the psychological sense of community among participants, suggesting that similar relationship-based programs could support today’s healthcare workforce.
Effect of the Gut Microbiome on the reduction of uremic toxins in patients with chronic kidney disease: A systematic review & Network meta-analysis
Authors: Cedillo-Flores Renata , Cuevas-Budhart Miguel Angel , Cavero Redondo Iván , Kappes Maria Soledad , Ávila Marcela , Paniagua Ramón 
Published: February 2025

AbstractIntroductionChronic kidney disease (CKD) is associated with increased intestinal barrier permeability, leading to heightened inflammation and oxidative stress. These changes contribute to complications such as cardiovascular disease, anemia, altered mineral metabolism, and CKD progression. Interventions using prebiotics, probiotics, and synbiotics may help mitigate dysbiosis and improve intestinal barrier function.AimThis study conducted a network meta-analysis to evaluate the effectiveness of probiotics, prebiotics, and synbiotics in reducing uremic toxins produced by the gut microbiota in CKD patients.MethodA systematic review and network meta-analysis of randomized clinical trials (RCTs) was performed. The analysis focused on the use of prebiotics, probiotics, and synbiotics in CKD patients at stages 3 to 5, as per KDIGO guidelines, and their association with reductions in uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), urea, and creatinine. The study follows the PRISMA statement.ResultsThe studies included 331 patients, primarily male, across CKD stages 3a to 5. The interventions showed a positive impact on the gut microbiota composition, leading to reductions in both free and total p-cresyl sulfate and indoxyl sulfate.ConclusionThe findings suggest that modulating the gut microbiota through these interventions can effectively reduce specific uremic toxins. However, further trials are necessary to better understand the microbiota modulation and its impact on intestinal bacterial composition.PROSPERO RegistrationCRD42023438901
Sexual health empowerment interventions for migrant women: a systematic review of the literature
Authors: Ouanhnon Lisa , Daumail Laure , Kerihuel Marie , Palmaro Aurore , Dupouy Julie , Durand Marie-Anne 
Published: February 2025

ABSTRACTIntroductionMigrant women are suffering from inequalities in access to care and prevention, quality of care, and in particular, sexual health care. As part of an overall project to develop a primary care intervention aimed at empowering migrant women in sexual health, the first objective will be to review the characteristics of sexual health empowerment interventions targeting migrant women. The second objective will be to assess the effectiveness of these interventions.Methods and analysisA systematic review will be conducted across PubMed, Cochrane, Embase, Psychinfo/ Psycharticles, Web of science, Cairn, as well as grey literature, from inception until 01/01/2023. We will include randomized clinical trials, quasi-experimental, and qualitative studies published in any language before 01/01/2023, assessing the effect of a sexual health empowerment intervention targeted at migrant women and meeting the selection criteria. Screening of articles and data extraction will be conducted by two independent researchers. Disagreements will be resolved by a third reviewer. The quality of all included studies will be assessed using validated tools according to the study design. Results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidlines, and a narrative synthesis will be conducted.Ethics and diffusionThis systematic review will involve only secondary data, so ethical approval was not required for this study. The results will be disseminated in peer-reviewed journals and conferences.