bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic printing and actuation of stretchable muscle tissue
Authors: Demri Noam , Morizur Lise , Dumas Simon , Gropplero Giacomo , Martinat Cécile , Descroix Stéphanie , Wilhelm Claire 
Published: February 2025

AbstractWhile the link between tissue organization, stimulation, and function is now acknowledged as crucial for tissue development, engineering tissues with precise, long-lasting shapes and the capability for mechanical stimulation remains challenging. This study addresses this challenge by developing a next-generation magnetic bioprinting approach to create anisotropic, shape-controlled, scaffold-free, and stretchable skeletal muscle constructs.Murine skeletal muscle cells and human induced pluripotent stem cell-derived skeletal muscle cells, labeled with iron oxide nanoparticles, were magnetically bioprinted into wrench-shaped tissues. Their magnetic properties allowed these tissues to be clipped onto magnetic needles, preserving their shape over two weeks of culture while promoting anisotropic differentiation and myoblast fusion. Additionally, the magnetic tissues could be stretched by up to 100%, enhancing their anisotropy and improving muscle maturation.This magnetic toolbox demonstrates significant advancements in muscle tissue engineering, as evidenced by enhanced indicators of myoblast differentiation, including cell fusion, increased myogenic maturation and contractility. These findings highlight the potential of magnetic-based techniques for developing advanced muscle-on-chip systems and other complex tissue constructs.
Sequencing by Expansion (SBX) – a novel, high-throughput single-molecule sequencing technology
Authors: Kokoris Mark , McRuer Robert , Nabavi Melud , Jacobs Aaron , Prindle Marc , Cech Cynthia , Berg Kendall , Lehmann Taylor , Machacek Cara , Tabone John , Chandrasekar Jagadeeswaran , McGee Lacey , Lopez Matthew , Reid Tommy , Williams Cara , Barrett Salka , Lehmann Alex , Kovarik Michael , Busam Robert , Miller Scott , Banasik Brent , Kesic Brittany , Arryman Anasha , Rogers-Peckham Megan , Kimura Alan , LeProwse Megan , Wolfin Mitchell , Kritzer Svetlana , Leadbetter Joanne , Babazadeh Majid , Chase John , Thiessen Greg , Lint William , Goodman Drew , O’Connell Dylan , Lumanpauw Nadya , Hoffman John , Vellucci Samantha , Collins Kendra , Vellucci Jessica , Taylor Amy , Murphy Molly , Lee Michael , Corning Matthew 
Published: February 2025

AbstractRemarkable advances in high-throughput sequencing have enabled major biological discoveries and clinical applications, but achieving wider distribution and use depends critically on further improvements in scale and cost reduction. Nanopore sequencing has long held the promise for such progress, but has had limited market penetration. This is because efficient and accurate nanopore sequencing of nucleic acids has been challenged by fundamental signal-to-noise limitations resulting from the poor spatial resolution and molecular distinction of nucleobases. Here, we describe Sequencing by Expansion (SBX), a single-molecule sequencing technology that overcomes these limitations by using a biochemical conversion process to encode the sequence of a target nucleic acid molecule into an Xpandomer, a highly measurable surrogate polymer. Expanding over 50 times longer than the parent DNA templates, Xpandomers are engineered with high signal-to-noise reporter codes to enable facile, high-accuracy nanopore sequencing. We demonstrate the performance of SBX and present the specialized molecular structures, chemistries, enzymes and methods that enable it. The innovative molecular and systems engineering in SBX create a transformative technology to address the needs of existing and emerging sequencing applications.
Evaluation of the Irritation and Sensitization Potential of Medical-grade Norway Spruce (Picea abies) Resin Salve: Single-Blind Modified Draize Repeat Insult Patch Test in Healthy Volunteers
Authors: Yamileva Kamilla , Multia Evgen 
Published: February 2025

AbstractBackgroundAbilar® is a wound salve containing 10 % medical-grade Norway spruce (Picea abies) resin, known for its antimicrobial and wound-healing properties. However, isolated reports of allergic contact dermatitis have raised concerns regarding its cutaneous safety profile. Given the increasing use ofPicea abiesresin-based products, it is important to evaluate any potential for skin irritation and sensitization.ObjectivesTo evaluate the irritation and sensitization potential of medical-gradePicea abiesresin salve using a modified Draize Human Repeat Insult Patch Test (HRIPT) in a healthy adult cohort, thereby providing toxicological insights relevant to both clinical applications and consumer safety.MethodsA single-blind study (ClinicalTrial.gov, Identifier:NCT06810856) was conducted with 215 healthy volunteers (207 completed the study). Medical-gradePicea abiesresin salve was applied through cutaneous patches in an induction phase and a challenge phase. Skin reactions were evaluated using modified Draize scoring system, with reactions to both the test material and adhesive being recorded separately.ResultsDuring the induction phase, only 7 of 207 subjects (3.38%) of participants exhibited mild erythema (Grade 1) attributed to the resin salve. Notably, no participant experienced moderate to severe reactions (Grades 2–5). In the subsequent challenge phase, no reactions were observed, and subjects with prior Grade 1 responses reverted to a non-reactive status. These findings indicate that, under the test conditions and repeated exposure regimen, the medical-gradePicea abiesresin salve demonstrates a low potential for inducing cutaneous irritation or sensitization.ConclusionsThe HRIPT findings demonstrate that medical-gradePicea abiesresin salve has a low irritation and sensitization potential under the conditions tested. Although rare cases of allergic contact dermatitis have been documented in literature in predisposed individuals, the data of this study suggests that the overall risk in the general population is low. These findings are also supported by clinical studies and extensive post-market surveillance of Abilar® in wound care for both acute and chronic wounds.Graphical Abstract
Chronic adaptive versus conventional deep brain stimulation in Parkinson’s disease: a blinded randomized pilot trial
Authors: Isaias Ioannis U. , Marceglia Sara , Borellini Linda , Mailland Enrico , Cogiamanian Filippo , Barbieri Sergio , Ampollini Antonella , Pirola Elena , Remore Luigi , Caffi Laura , Palmisano Chiara , Baiata Claudio , Bonvegna Salvatore , Romito Luigi , Eleopra Roberto , Levi Vincenzo , Bentivoglio Anna Rita , Piano Carla , Izzo Alessandro , Zibetti Maurizio , Lopiano Leonardo , Lanotte Michele , Mandat Tomasz , Tamma Filippo , Arlotti Mattia , Conti Costanza , Rossi Lorenzo , Foffani Guglielmo , Lozano Andres , Moro Elena , Volkmann Jens , Locatelli Marco , Priori Alberto 
Published: February 2025

ABSTRACTBackgroundAdaptive deep brain stimulation (aDBS) is becoming a feasible therapeutic option in patients who are candidates for DBS, and implantable devices are now commercially available. We present the results of a blinded, randomized, crossover pilot trial aimed at comparing aDBS with conventional DBS (cDBS).MethodsFifteen patients were implanted with the AlphaDBS device (Newronika SpA, Milan, Italy,NCT04681534). The device replaced a previous Medtronic Activa PC at battery depletion in 11 patients, while the other four were first-time implant patients. Patients underwent two study phases: 1) a two-day, short-term follow-up in the hospital, in which patients received aDBS and cDBS for one day each (in random order); 2) a one-month, long-term follow-up at home, with patients receiving both DBS modes, each for two weeks. Safety endpoints were the occurrence of stimulation-related adverse events and the total electrical energy delivered to the tissue. The clinical endpoints were the Unified Parkinson’s (part III) and Dyskinesia Disease Rating Scales used for in-clinic evaluation, and a three-day diary used for home assessment to estimate good on time without troublesome dyskinesia. At the end of the study, patients blindly decided their preferred stimulation mode.FindingsNo related adverse events were reported. The AlphaDBS device reliably recorded deep brain signals and applied a linear algorithm that changed the stimulation current every minute based on the average local field potential amplitude, calculated in a patient-specific beta frequency range. In the short-term follow-up, aDBS improved patients as much as cDBS, with lower UDysRS scores. In the long-term follow up, considering intra-patient differences, aDBS provided greater benefit than cDBS in 80% of patients. The same percentage of patients preferred and continued with aDBS (mean follow-up 316 days).InterpretationOur results suggest that aDBS is safe and effective and can be applied in a large population of parkinsonian patients who are candidates for DBS. The majority of patients improved more with aDBS than cDBS, who subjectively preferred aDBS in the long term. Further research is needed to better understand the profile of the best responders and the scheduling of aDBS.
A standardised saffron extract improves subjective and objective sleep quality in healthy older adults with sleep complaints: results from the Gut-Sleep-Brain Axis randomised, double-blind, placebo-controlled pilot study
Authors: Lang Leonie , Ditton Annabel , Stanescu Andi , Jainani Vernisse , McArthur Simon , Pourtau Line , Gaudout David , Pontifex Matthew G. , Tsigarides Jordan , Steward Taylor , Sami Saber , Muller Michael , Hornberger Michael , Vauzour David , Lazar Alpar S. 
Published: February 2025

AbstractSleep disorders may increase neurodegenerative diseases risks and alter gut microbiota composition. Saffron (Crocus sativus) supplementation has been linked to sleep improvements and gut microbiome changes, but its effect on sleep quality through gut microbiota-brain axis modulation remains unexplored. A randomised, placebo-controlled pilot study of saffron (30mg/day for 4-weeks) was conducted with 52 older adults (55-85 years) experiencing sleep complaints. Subjective and objective sleep quality were measured using validated questionnaires and electroencephalography-based sleep tracker respectively. A subgroup (n=26) underwent microbiome analysis. Saffron supplementation improved subjective sleep quality (p=0.02) and sleep efficiency (p=0.04). Objective measures showed reduced latency to persistent sleep (p=0.003) and sleep onset latency (p=0.03). Linear discriminant analysis effect size analysis of the microbiome revealed increases inFaecalibacterium(q=0.013),Lachnoclostridium(q=0.045),Prevotella(q=0.022),UBA1819(q=0.020) andOscillibacter(q=0.045), while decreasingDialister(q=0.028). Univariate analysis further indicated increases inLachnospiraceae-UGC-001(p=0.020) andRoseburia(p=0.03), with a decrease inTuricibacter(p=0.045) in the saffron group.OscillibacterandUBA1819correlated with subjective measures of sleep efficiency (r=0.63, p=0.0007) and sleep latency (r=-0.39, p=0.04. Changes inDialister, TuricibacterandUBA1819were correlated with several measures of objective sleep quality including wake duration, latency to persistent sleep and wake-after-sleep-onset. Four-weeks saffron supplementation improved both subjective and objective sleep quality in older adults with sleep complaints, while increasing gut bacteria that produce short-chain fatty acids. These results pave the way for further randomised controlled trials exploring the links between sleep quality and gut health and may help devising new preventative strategies for age-related brain disorders.
Tahoe-100M: A Giga-Scale Single-Cell Perturbation Atlas for Context-Dependent Gene Function and Cellular Modeling
Authors: Zhang Jesse , Ubas Airol A , de Borja Richard , Svensson Valentine , Thomas Nicole , Thakar Neha , Lai Ian , Winters Aidan , Khan Umair , Jones Matthew G. , Tran Vuong , Pangallo Joseph , Papalexi Efthymia , Sapre Ajay , Nguyen Hoai , Sanderson Oliver , Nigos Maria , Kaplan Olivia , Schroeder Sarah , Hariadi Bryan , Marrujo Simone , Salvino Crina Curca Alec , Gallareta Olivares Guillermo , Koehler Ryan , Geiss Gary , Rosenberg Alexander , Roco Charles , Merico Daniele , Alidoust Nima , Goodarzi Hani , Yu Johnny 
Published: February 2025

AbstractBuilding predictive models of the cell requires systematically mapping how perturbations reshape each cell’s state, function, and behavior. Here, we presentTahoe-100M, a giga-scale single-cell atlas of 100 million transcriptomic profiles measuring how each of 1,100 small-molecule perturbations impact cells across 50 cancer cell lines. Our high-throughput Mosaic platform, composed of a highly diverse and optimally balanced “cell village”, reduces batch effects and enables parallel profiling of thousands of conditions at single-cell resolution at an unprecedented scale.As the largest single-cell dataset to date,Tahoe-100Menables artificial-intelligence (AI)-driven models to learn context-dependent functions, capturing fundamental principles of gene regulation and network dynamics. Although we leverage cancer models and pharmacological compounds to create this resource,Tahoe-100Mis fundamentally designed as a broadly applicable perturbation atlas and supports deeper insights into cell biology across multiple tissues and contexts. By publicly releasing this atlas, we aim to accelerate the creation and development of robust AI frameworks for systems biology, ultimately improving our ability to predict and manipulate cellular behaviors across a wide range of applications.
IMPDH Cytoophidia in the Pancreas: Morphological Dynamics and Metabolic Implications
Authors: Huang Yujie , Liu Ji-Long , Zhang Wenchuan 
Published: February 2025

ABSTRACTCytoophidia are filamentous structures formed by metabolic enzymes, playing critical roles in cellular metabolism and regulation. Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo nucleotide synthesis, is known to form cytoophidia and is implicated in cell proliferation, nutrient sensing, and metabolic stress responses. Despite their significance, the behavior of IMPDH cytoophidia under different metabolic conditions, particularly in diabetes, remains poorly understood. This study investigates the distribution, morphology, and assembly patterns of IMPDH cytoophidia in the pancreas of normal and diabetic models. Using immunofluorescence staining, pharmacological interventions (e.g., mycophenolic acid), and glucose tolerance tests, we demonstrate that IMPDH cytoophidia exhibit distinct morphological changes in pancreatic islets under diabetic conditions. Notably, cytoophidia elongation is associated with impaired glucose tolerance, suggesting a potential link between cytoophidia dynamics and metabolic dysfunction. Our findings provide novel insights into the role of IMPDH cytoophidia in metabolic regulation and highlight their potential as therapeutic targets for diabetes and related metabolic disorders.
Progression GWAS followed by functional characterization implicates E3 ubiquitin ligaseTRIM2as a potential genetic modifier of Parkinson’s disease progression
Authors: Kulkarni Ameya S. , Apicco Dan , Tamim Saleh , Gibilisco Lauren , Nahlawi Layan , Lucia Rachel , Ghosh Sujana , Lent Samantha , Liang Yanyu , Khasnavis Saurabh , Smith Laura , Stender Joshua , Vijay Priyanka , Zadikoff Cindy , Davis Justin Wade , Stoehr Jan , Noh Hyun Ji 
Published: February 2025

ABSTRACTParkinson’s Disease (PD) is a progressive neurodegenerative disorder, affecting 10 million people worldwide. While genome-wide association studies (GWAS) have identified many genetic variants associated with PD incidence, the genetics underlying PD progression are poorly understood. Here, we aim to address this gap by performing GWAS on longitudinal clinical metrics from well-defined PD cohorts. Specifically, we identify 8 novel GWAS genes for PD progression, includingTRIM2,which encodes an E3 ubiquitin ligase with loss-of-function mutations that cause neuropathy. Functional genomics data suggest that the GWAS SNPs in the locus ofTRIM2regulate its expression across several PD-relevant brain regions. Further, we show thatTRIM2knockdown and overexpression in primary neurons regulate neurofilament light (NF-L) levels and α-synuclein aggregation-the primary neuropathological hallmark of PD. Peripheral proteomic analysis of a genetically defined PD patient cohort demonstrates increased NF-L protein levels in the plasma and cerebrospinal fluid ofTRIM2SNP carriers, corroborating the role of TRIM2 in NF-L regulation. Overall, by integrating PD progression GWAS with transcriptomic, eQTL analyses, and functional data in PD cellular models, we identify new targets includingTRIM2that may influence the progression rate of PD.
Prevalence of screening HIV among LGBTQ+ at Ramathibodi Hospital
Authors: Chuenpakorn Nunticha , Chaisoksombat Kewalin , Siriyotha Sukanya , Chuenpakorn Nanthiphat , Arunakul Jiraporn , Maude Rapeephan R. 
Published: February 2025

AbstractBackgroundLGBTQ+ individuals face significant barriers in accessing healthcare services, particularly in relation to HIV screening. This study investigates the prevalence of HIV testing among LGBTQ+ individuals and explores factors influencing healthcare-seeking behaviors at Ramathibodi Hospital in Bangkok, Thailand.MethodsA cross-sectional survey was conducted among 300 self-identified LGBTQ+ individuals aged 18 and older who recently utilized outpatient services at Ramathibodi Hospital. Data were collected via an online questionnaire assessing demographic characteristics, sexual behaviors, and attitudes toward public health services. Univariate and multivariate logistic regression analyses were performed to identify factors associated with HIV testing.ResultsHIV testing prevalence among participants was 45%, with significant associations found between HIV testing and gender identity, age, and engagement in sexual activity. Gay participants (OR = 21.73, 95% CI: 4.73–99.90, p < 0.001) and transgender females (OR = 7.51, 95% CI: 2.08–27.34, p = 0.002) were more likely to undergo HIV testing compared to other groups. Those aged 30 years or older (OR = 2.50, 95% CI: 1.43– 4.34, p = 0.001) and those engaging in sexual activity (OR = 4.58, 95% CI: 2.52–8.33, p < 0.001) were also more likely to be tested. Participants reported mixed experiences regarding the inclusivity of healthcare environments, with a desire for improved LGBTQ+ cultural competence among healthcare workers.ConclusionWhile HIV testing rates are relatively high among certain LGBTQ+ subgroups, significant gaps remain, particularly for transgender males. The study highlights the need for targeted outreach and healthcare interventions to increase HIV screening among underserved populations. Expanding LGBTQ+ cultural competency in healthcare settings is crucial to ensure inclusive and respectful care.
Transmission thresholds for the spread of infections in healthcare facilities
Authors: Toth Damon J.A. , Khader Karim , Mitchell Christopher , Samore Matthew H. 
Published: February 2025

AbstractSome infections may be sustained in the human population by persistent transmission among patients clustered in healthcare facilities, including patients colonized with multi-drug-resistant organisms posing a major health threat. A nuanced understanding of facility characteristics that contribute to crossing a threshold for self-sustaining outbreak potential may be crucial to designing efficient interventions for lowering regional disease burden and preventing infections among high-risk patients. Using a mathematical model, we define the facility basic reproduction numberR0, where a single facility can sustain an outbreak without ongoing importation under the threshold conditionR0> 1. We defineR0for a general model with heterogeneous patient states of susceptibility and transmissibility and with generic length-of-stay assumptions, and we provide a software package for numerical calculation of user-defined examples. We estimateR0using published data for carbapenemase–producing Enterobacteriaceae (CPE) in longterm acute-care hospitals (LTACHs) and the effects of interventions onR0, including surveillance, pathogen reduction treatments, and length-of-stay reduction. In a simple model,R0is directly proportional to the sum of the mean and variance-to-mean ratio of the length-of-stay distribution. In intervention models,R0depends on the moment-generating function of the length-of-stay distribution. From the CPE data, we estimatedR0= 1.24 (95% CI: 1.04, 1.45) prior to intervention. Weekly surveillance with 50% transmission reduction of detected patients alone could have reducedR0to 0.85 (0.72, 0.98), with additional reduction if detected patients could be decolonized. Reducing the mean length of stay does not necessarily reduceR0if the variance-to-mean ratio is not also reduced. We conclude thatR0>1 conditions plausibly exist in LTACHs, where CPE outbreaks could be sustained by patients who acquire colonization and subsequently transmit to other patients during the same hospital stay. Our findings illuminate epidemiological mechanisms producing those conditions and their relationship to interventions that could efficiently improve population health.
Synaptotoxic effects of extracellular tau are mediated by its microtubule-binding region
Authors: Ondrejcak Tomas , Hu Neng-Wei , Coode Emily , Campbell Tom , Corbett Grant T. , Doykov Ivan , Mills Kevin , Walsh Dominic M. , Livesey Frederick J. , Rowan Michael J. , Klyubin Igor 
Published: February 2025

AbstractImmunotherapies targeting extracellular tau share the premise that interrupting cell-to-cell spread of tau pathology in Alzheimer’s disease (AD) will slow dementia pathogenesis. How these interventions affect the actions of synaptotoxic, extracellular tau species that may help mediate cognitive impairment is relatively unknown. Here, we assayed synaptic plasticity disruption in anaesthetised live rats caused by intracerebral injection of synaptotoxic tau present either in (a) secretomes of induced pluripotent stem cell-derived neurons (iNs) from people with Trisomy 21, the most common genetic cause of AD, or (b) aqueous extracts of human AD brain. Extracellular tau in iN secretomes was found to include fragments that contain the extended microtubule binding regions of tau, MTBR/R’ and adjacent C-terminal peptides. Immunodepletion or co-injection with antibodies targeting epitopes within these fragments prevented the acute disruption of synaptic plasticity by these patient-derived synaptotoxic tau preparations. Conversely, a recombinant human tau fragment encompassing the core MTBR/R’- region present in tau fibrils, tau297-391 potently mimicked this deleterious action of patient-derived tau. MTBR/R’-directed antibodies also rapidly reversed a very persistent synaptotoxic effect of soluble brain tau. Our findings reveal a hitherto relatively unexplored potential benefit of targeting MTBR/R’.