bluuebunny/crossref_metadata_2025 huggingface dataset:
Capillary-induced bundling of biopolymer networks via protein condensates
Authors: Feigeles Carolyn A. , Brasovs Artis , Puchalski Adam , Laukat Olivia , Kornev Konstantin G. , Weirich Kimberly L.
Published: January 2025

Within the cell, biopolymers form self-organized assemblies that regulate cellular processes. These assemblies can be constructed through either protein interactions or phase separation. It is known that actin filaments, which form the mechanical structure of cells, are assembled into networks and bundles by protein cross-linkers. Different network and bundle microstructures support different physiological functions. Recently, there is evidence that protein condensates interact with biopolymers to create bundles. Here, we show that protein condensates colocalize with actin filaments and form networks of bundles. The condensates absorb on actin bundles and relax into a barrel shaped droplet on bundles, evocative of drops of simple liquids on fibers. We investigate the condensate spreading and measure contact angle that condensates make with bundles. Condensates at the intersection of bundles cause capillary bridges which induce network remodeling. Our results suggest that network formation, bundling, and remodeling in biopolymer assemblies could be induced by capillary interactions due to condensates. Understanding this bundling mechanism could expand our toolkit for making self-assembled fiber-based soft materials.
On the duality of pain and pleasure processing: Why two dimensions of valence may be better than one
Authors: Dulberg Zack , Cohen Jonathan D.
Published: January 2025

Reinforcement learning treats reward maximization as a single objective, such that pain avoidance is implicit in pleasure seeking. However, humans appear to have distinct neural systems for processing pain and pleasure. This paper investigates the computational advantages of this separation through grid-world experiments. We demonstrate that modular architectures employing distinctmaxandminoperators for value propagation outperform monolithic models in non-stationary environments. This separation allows agents to simultaneously grow and shrink learned values without interference, enabling both efficient reward collection and punishment avoidance. Additionally, these separate systems can be dynamically arbitrated using a mood-like mechanism for rapid adaptation. Our results suggest that separate pain and pleasure systems may have evolved to enable safe and efficient learning in changing environments.

Nature has placed mankind under the governance of two sovereign masters, pain and pleasure

Jeremy Bentham
Text Mining miRNA-gene Interactions for the mx-plore Platform
Authors: Joppich Markus , Klein Samuel , Zimmer Ralf
Published: January 2025

miRNAs are post-transcriptional regulators which bind to the specific mRNA of expressed genes and induce increased mRNA degradation, thereby reducing the gene expression of their target genes. miRNAs perform their regulatory functions in a context-specific manner. Several databases contain collections of miRNA-target interactions, which are either experimentally validated, derived from high-throughput experiments, or computationally predicted or captured from existing literature. For most databases, the specific context of the miRNA-target interaction is unknown or missing in these databases. mx-plore is not only a database of text-dervied miRNA-gene interactions, but it enhances the found interactions including detailed context information from scientific publications. To derive the entries in the mx-plore database, a newly developed text mining strategy combining dependency graph analysis and rule-based systems has been used. The mx-plore platform makes miRNA-gene interactions accessible and searchable on various levels, such as by cell type, disease or involved processes. The platform is available athttps://rest.bio.ifi.lmu.de/mxploreand corresponding source code is deposited on GitHub.

Author summary

The mx-plore platform is a comprehensive database of miRNA:target interactions as described in the scientific literature.

mx-plore is a new text-mining approach to extract context-dependent miRNA interactions from Pubmed abstracts and PMC full texts.

mx-plore allows to query the comprehensive database in a context-specific manner, both on- and off-line.
UNICORN: Towards Universal Cellular Expression Prediction with an Explainable Multi-Task Learning Framework
Authors: Liu Tianyu , Huang Tinglin , Lin Yingxin , Ying Rex , Zhao Hongyu
Published: January 2025

Sequence-to-function analysis is a challenging task in human genetics, especially in predicting cell-type-specific multi-omic phenotypes from biological sequences such as individualized gene expression. Here, we present UNICORN, a new method with improved prediction performances than the existing methods. UNICORN takes the embeddings from biological sequences as well as external knowledge from pre-trained foundation models as inputs and optimizes the predictor with carefully-designed loss functions. We demonstrate that UNICORN outperforms the existing methods in both gene expression prediction and multi-omic phenotype prediction at the cellular level and the cell-type level, and it can also generate uncertainty scores of the predictions. Moreover, UNICORN is able to link personalized gene expression profiles with corresponding genome information. Finally, we show that UNICORN is capable of characterizing complex biological systems for different disease states or perturbations. Overall, embeddings from foundation models can facilitate the understanding of the role of biological sequences in the prediction task, and incorporating multi-omic information can enhance prediction performances.
Low Field Magnetic Resonance Imaging to Detect Acute Kidney Injury
Authors: Kishimoto Shun , Horie Kazumasa , Devasahayam Nallathamby , Yamashita Kota , Gadisetti Chandramouli , Yamamoto Kazutoshi , Brender Jeffrey R. , Mitchell James B. , Krishna Murali C. , Linehan W. Marston , Crooks Daniel R.
Published: January 2025

Renal oxygenation is essential for maintaining kidney function. Disruptions in oxygen delivery can lead to renal hypoxia, which can exacerbate kidney injury through multiple pathways, including inflammation, oxidative stress, and ischemia-reperfusion injury. Despite the recognized importance of oxygenation in renal pathology, non-invasive and reliable methods for assessing kidney oxygen levels are limited. Current techniques either lack sensitivity or involve invasive procedures, restricting their use in routine monitoring. Therefore, there is a pressing need for innovative approaches to assess renal oxygenation, particularly in kidney injury. This study evaluated Electron Paramagnetic Resonance (EPR)-based oxygen imaging using the paramagnetic tracer Ox071 to assess kidney oxygen levels in mice with cyclophosphamide-induced kidney injury. Urine pO2 was also assessed as a potential surrogate marker. EPR oximetry accurately measured kidney oxygen distribution, revealing a temporary increase in pO2 post-injury. Urine oximetry, however, did not reliably reflect changes in kidney oxygenation. Furthermore, EPR oximetry provided high-resolution spatial mapping of oxygen levels within the kidney, allowing for a detailed understanding of the impact of hypoxia on renal tissue. EPR oximetry is a promising, non-invasive tool for monitoring renal oxygenation, offering high-resolution mapping and longitudinal assessment. Its ability to provide detailed information about oxygen distribution within the kidney makes it a valuable tool for studying the pathophysiology of renal diseases and for developing novel therapeutic strategies.

Translational Statement: Quantitative spatially resolved measurement of renal oxygenation has the potential to guide clinical decision making in renal disorders such as acute kidney injury. In this study we demonstrate the utility of electron paramagnetic resonance imaging to provide non-invasive and quantitative high-resolution mapping of kidney oxygen concentrations.
Spatially explicit capture–recapture models for relative density
Authors: Efford M. G.
Published: January 2025

Spatially explicit capture–recapture (SECR) methods are used widely to estimate animal population density and related parameters. Maximum likelihood has been applied to two flavors of SECR model - a full model that includes absolute density as a spatially varying parameter, and a model conditional on the number of detected individuals that assumes uniform density. We show how the conditional model may be extended to estimate relative density as a function of habitat and other spatial variables. The conditional model has the major advantage of seamlessly including individual covariates of detection. It is also faster to fit than the full model and more robust with an ‘identity’ link. The spatial absolute density surface may be derived from the conditional model fit. We demonstrate this with a spline surface fitted to data on American black bears (Ursus americanus). The relative density formulation also allows an adjustment for spatially selective prior marking. The problem arises when fish are caught and implanted with transponders, such as acoustic tags, and later monitored intensively with passive recorders. The confounding spatial effect of undocumented initial sampling may be removed from spatial analyses of the monitoring data by including an offset proportional to the smoothed sampling effort.
Plasmid copy number variation impacts pathogenicity and quantification ofCurtobacterium flaccumfacienspv.flaccumfaciensinfecting mung bean
Authors: Saad Ahmed , Vaghefi Niloofar , Poudel Barsha , Young Anthony J. , Kelly Lisa A. , Knight Noel L.
Published: January 2025

In bacteria, plasmids can confer the ability to cause disease. Although they can potentially vary in copy number, little has been reported on the dynamics of plasmids in plant pathogenic bacteria. Pathogenicity of the bacteriumCurtobacterium flaccumfacienspv.flaccumfaciens(Cff), which causes foliar disease on leguminous crops, including mung bean (Vigna radiata), has previously been linked to a plasmid. This study explored the variation in plasmid copy number among a genetically diverse collection of 25Cffisolates using purposely designed quantitative PCR assays for chromosomal and plasmid DNA targets. Pathogenicity and virulence of sixCffisolates, including one plasmid-free isolate, were assessed on the susceptible mung bean cultivar Opal-AU using visual symptoms, trifoliate dry weights andCffDNA quantities following stem inoculation. Plasmid copy numbers varied significantly (p<0.001) among plasmid-carrying isolates, ranging from 1.37 to 2.74. For subsequent quantificationin planta, the single-copy chromosomal PCR target gene, gyrase b, was selected. Mung beans inoculated with plasmid-carrying isolates exhibited significant variation in visual symptoms (p<0.001), while trifoliate dry weights andCffDNA quantities did not significantly differ. The treatment using a plasmid-free isolate was not significantly different from the negative control for each of the disease traits. Knowledge of plasmid dynamics inCffpopulations lays a foundation for improved understanding of the inheritance and impact of plasmid-related traits. The quantification assays will be useful for monitoringCffpopulations and the demonstrated variation in pathogenicity and virulence can assist efforts to breed host plant germplasm with reduced susceptibility toCff.
SMTdb: A comprehensive spatial meta-transcriptome resource in cancer
Authors: Zhou Weiwei , Yang Qingyi , Guo Jiyu , Li Si , Su Minghai , Leng Feng , Rong Tingyu , Shi Jingyi , Gao Yueying , Jiang Tiantongfei , Xu Juan , Li Yongsheng
Published: January 2025

Microbes have been found in various tumors and the research of tumor microbiome has been garnering increased attention. However, it remains challenge to investigate the microbiome in cancer at spatial resolution. The rapid advent of spatially resolved transcriptomics techniques has given rise to map transcripts at single-cell resolution in various types of cancer. Here, we constructed a comprehensive spatial meta-transcriptome resource by manually curating 203 fresh frozen (FF) slices from 20 cancers encompassing 334,253 spots and 1,908,646 cells. SMTdb (http://bio-bigdata.hrbmu.edu.cn/SMTdb/) was constructed to provide comprehensive insights into the abundance, distribution and enriched TME regions of 1218 microbiota in spatial tissue slices. SMTdb enables vast interactive data exploration of spatial distribution and expression of microbiota, host gene modules associated with certain microbiota and co-occurrence between microbiota and immune cells within tumor microenvironment. The atlas resource serves as a one-stop and time-effective platform to investigate the interactions among microbial ecosystems and hosts in cancer.
Shared molecular regulation of quiescence in neural and glioma stem cells reveals therapeutic vulnerabilities
Authors: Choudhury Chandra , Singleton Matthew , Brauer Stephanie , Friess Dana , Hart Jessica , Skarne Niclas , Pullela Karthik , Mao Likai , Day Bryan W , Harris Lachlan
Published: January 2025

Quiescence, a reversible state of cell-cycle arrest, is an adaptive feature of many adult tissue stem cells, including those in the adult brain. In gliomas, brain tumour stem cells that reside in a quiescent state preferentially survive chemotherapy and radiotherapy, highlighting their critical role in therapy resistance and disease progression. To date, it remains unclear whether the molecular programs governing these states are functionally conserved between neural stem cells and brain tumour stem cells. Here, we establish novelin vitromodels to study quiescence and find that glioma stem cells are markedly more resistant to entering quiescence than neural stem cells, suggesting that glioma stem cell quiescence more closely resembles a slow-cycling phenotype or shallow quiescence. Nonetheless, direct comparison of quiescent neural stem cells and quiescent/slow-cycling glioma stem cells, as they transition towards proliferation, reveals conserved gene expression trajectories, indicating shared molecular mechanisms. Furthermore, we find that pathways influencing quiescence in neural stem cells exert similar effects in glioma stem cells, underscoring the functional parallels between these populations. Finally, we identify that inhibition of TGF-β signalling might provide an avenue to improve current standard-of-care treatments by targeting quiescent glioma stem cells.
How immigration affects the burden of tuberculosis among foreign-born Canadians: estimates with dynamic models
Authors: Chiu Jeremy , Ruth William , Rutherford Alexander , Wijaya Kezia , Lee Timothy , Williams JF , Wong Albert
Published: January 2025

Despite only comprising about a quarter of the total population of Canada, foreign-born individuals bear about three-quarters of the burden of active tuberculosis (TB) cases. New immigrants arriving in Canada are screened for active TB, but generally not latent TB infection (LTBI); thus the burden of LTBI among foreign-born Canadians is not well understood.

To investigate the impact of immigration on the burden of TB among foreign-born Canadians, we develop an SEIR-compartment model that distinguishes between actively infected, latently infected, and uninfected individuals. Unknown parameters are calibrated to reports on the incidence and prevalence of active TB in Canada. We validate our model by comparing model computed quantities to other reports of tuberculosis burden among foreign-born Canadians, such as our estimate of the prevalence of LTBI among immigrants entering Canada.

If the profile and number of immigrants arriving into Canada in the next decade is similar to the past decade, our model predicts that Canada will not meet the End TB 2035 goal of reducing incidence by 90% compared to 2015. Even if Canada were to limit immigration only to the WHO geographic region with the lowest incidence (Americas), we would still fail to meet the target.

Author summary

Our model examines how immigration affects the burden of tuberculosis among foreign-born Canadians. We fit a compartment model to calibration data, then find a feasible parameter set based on validation data. We forecast the incidence of TB in 2035 and demonstrate that if the number of immigrants entering Canada in the next decade is similar to the past decade, regardless of which WHO geographic region they originate from, Canada will fail to meet the WHO End TB’s 2035 incidence goal (90% less than 2015).
Current status and expectations of medical interns in the advanced phase of the DES (specialized medical studies) in medical gynecology regarding medical theses
Authors: Poisson Aurelie , Jochum Floriane , Gougis Paul , Savarino Raphaelle , Coussy Florence , Sonigo Charlotte , Laas Enora , Roux Damien , Reyal Fabien , Rousset-Jablonski Christine , Hamy Anne-Sophie
Published: January 2025

Introduction

In France, Writing and defending a medical thesis are mandatory components of medical education curriculum to obtain the degree of Doctor of Medicine. The expectations of medical interns in medical gynecology regarding their medical thesis have not been evaluated.

Methods

A 10-question form was distributed during the national teaching of the advanced phase of the specialized medical studies (DES) in medical gynecology (corresponding to the 2ndand 3rdyear of internship). Responses were collected using the Wooclap* software.

Results

A total of 131 interns participated in the survey out of 170 interns solicited. Approximately two-thirds of the surveyed students had a medical thesis topic at the time of the survey. Among students with a thesis topic, thesis supervisors were most often university practitioners (MCU-PH/PH-U/PU-PH, 37.4%), followed by hospital practitioners (22.8%). The quality of supervision by the thesis supervisor was rated at 6.9/10, and the quality of supervision by the university was rated at 3.3/10. Overall, 53.4% of students wished to leverage their work through scientific publication. Nearly all students (94%) wished for guidance on at least one of the following topics: writing scientific articles (83%), basic statistics (83%), basic data collection (75%), training in the use of Pubmed (68%), Excel (65%), Zotero (63%), project management (53%), Word (15%).

Conclusion

Support for medical interns in medical gynecology for their medical thesis could be improved, particularly through modules on scientific publication, bibliography, and office automation.
Partial loss ofFITM2function causes hereditary spastic paraplegia
Authors: Salazar-Villacorta Ainara , Bond Laura M. , Kim Leehyeon , Anagnostopoulou Katherine , Scardamaglia Annarita , Filippakopoulou Eugenia , Ververi Athina , Efthymiou Stephanie , Dinopoulos Argirios , Murphy David , Karadima Georgia , Koutsis Georgios , Kaliakatsos Marios , Houlden Henry , Walther Tobias C. , Farese Robert V.
Published: January 2025

FITM2encodes fat-storage inducing transmembrane protein 2 (FIT2), a lipid diphosphatase in the ER that cleaves acyl-CoAs and is crucial for ER homeostasis. In humans, homozygous null mutations inFITM2are associated with a syndrome characterized by deafness and dystonia. Here, we report two families with hereditary spastic paraplegia (HSP) in whom exome sequencing revealed compound heterozygosity forFITM2mutations. In each family, the affected probands carry one putative null allele and one G100R missense allele. Functional analyses demonstrated that the G100R allele is hypomorphic, with FIT2 protein levels reduced to 20% of wild type, leading to proportionately decreased enzyme activity. The occurrence of similar HSP disease phenotypes and the same hypomorphic mutation in these families suggests that the G100R mutation and its associated reduced enzyme activity represent a newly recognized clinical manifestation ofFITM2mutations, expanding the spectrum of conditions associated with this gene.
Accuracy of rapid antigen testing for COVID-19 in shelter settings
Authors: Garad Yasmin , Manea Andreea A. , Pak Negin , Barker Bronwyn , Kasperavicius Danielle , Danok Lames , Baral Stefan , Orkin Aaron M. , Siddiqui Amna , Straus Sharon E. , Fahim Christine
Published: January 2025

Background

The COVID-19 pandemic disproportionally affected congregate living settings, including shelters. COVID-19 transmission can have more adverse outcomes in these settings due to the vulnerability of residents. Point of care rapid antigen testing (RAT) represents a strategy with potential benefits for COVID-19 detection in shelters, including rapid results, ease of use, cost-effectiveness, and early detection.

Objectives

Our primary objective was to assess the real-world test accuracy of RAT for COVID-19 using the Quidel Sofia 2 Flu + SARS Antigen fluorescent immunoassay (Sofia RAT) compared to polymerase chain reaction (PCR) testing among shelter residents in Ontario, Canada.

Study Design

A consecutive sample of 102 residents across six shelters who were symptomatic for, or exposed to COVID-19 were included. The RAT and PCR samples were taken on the same day for each participant. Results from the Sofia RAT were compared to PCR test results to determine test accuracy. Participant demographic data could not be collected due to workforce constraints.

Results

We reported our methods and findings using the QUality Assessment tool of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Sofia 2 RAT specificity was 97.9% (95% CI: 92.7% to 99.7%) for COVID-19 compared to PCR. Due to a lack of true positive cases, sensitivity could not accurately be calculated (0.00% (95% CI: 0.00% to 52.2%)).

Conclusion

These data suggest that the Sofia RAT is a highly specific test for COVID-19.
Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Upper Limb Function After Stroke: A Systematic Review and Meta-Analysis
Authors: Russo Nazzareno , Hunt Thomas , McMullin Alex , Payard Timothy , Gane Elise , Sale Martin
Published: January 2025

Functional recovery of motor deficits post-stroke is improved with physical therapy, however functional recovery is often incomplete. Non-invasive brain stimulation may enhance functional recovery post-stroke. This systematic review explored the effectiveness of high-frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) to improve upper limb motor function post-stroke. A database search was conducted within PubMed, CINAHL, Embase and Cochrane Library. Criteria for inclusion: randomised controlled trials employing HF-rTMS on the affected hemisphere of adults post-stroke, and using the Fugl-Meyer Assessment (FMA) tool. Sixteen articles were included in the review. There was significant improvement in FMA-UL scores immediately post-intervention (mean difference = 3.53 [95% CI 1.82 to 44.58]) and 1-3 months post-intervention (8.95 [5.95 to 11.95]) for patients who commenced treatment within 1-month of their stroke. Based on the FMA, excitatory rTMS may provide more favourable effects on motor recovery when applied in the first-month post-stroke, however a variety of heterogeneous application parameters limit the certainty of effectiveness.
Multi-Night Home testing with portable EEG shows Improvement in Sleep Quality after Starting CPAP for Obstructive Sleep Apnoea
Authors: Lee Kieran O. , Bekinschtein Tristan A. , Smith Ian E.
Published: January 2025

Obstructive sleep apnoea (OSA) impacts sleep quality and has considerable night to night variability. This study explored the use of low-density EEG headbands to evaluate changes in sleep architecture and sleep features in the patients’ own homes over multiple nights both Pre and Post treatment with continuous positive airway pressure (CPAP). Seven participants recorded 144 high-quality EEG sessions (84 Pre-CPAP, 60 Post-CPAP). Comparing Pre and Post-CPAP there were significant reductions in N1 (P < 0.0001) and N2 (P < 0.0001) sleep, increases in N3 (P < 0.0001) and REM (P < 0.0001) sleep and fewer sleep stage shifts (P < 0.0001), micro-arousals (P < 0.0001) and awakenings (P < 0.0001). Total sleep time did not change. Strength testing identified that one participant (who had the most severe OSA, and produced the most EEG recordings), was a major driver of the effects, however, improvements in REM, shifts, and micro arousals remained when this participant was excluded. These results suggest low-density EEG devices can be used for multi-night monitoring, potentially advancing OSA research and personalised care.

Statement of Significance

OSA is a highly prevalent condition, with increasing global demand for care resources. Current OSA diagnostic and follow-up methods face two significant limitations: they do not capture night-to-night variability in sleep quality, and polysomnography, the current gold-standard measurement of sleep quality, requires substantial resources and is usually performed in a laboratory, which will not always reflect sleep quality achieved at home. This study collected 144 high-quality sleep recordings from seven participants using low-density EEG headbands in a community setting, both Pre and Post-CPAP. Results showed significant improvements in multiple measures of sleep quality after initiating CPAP. These findings demonstrate the feasibility of portable EEG headbands for OSA and suggest potential for enhancing clinical monitoring and advancing research through multi-night frameworks.
Real-world smartphone data predicts mood after cerebrovascular symptoms and may constitute digital endpoints
Authors: Zawada Stephanie , Acosta Jestrii , Collins Caden , Dumitrascu Oana , Harahsheh Ehab , Hagen Clint , Ganjizadeh Ali , Mahmoudi Elham , Erickson Bradley , Demaerschalk Bart
Published: January 2025

Though depression is prevalent in patients with cerebrovascular dysfunction, screening for symptoms is not routine and is often limited via subjective patient-reported surveys. Using smartphone sensors, we sought to evaluate the performance of objective behavior measures and self-report surveys at predicting depression severity in patients with cerebrovascular syndromes. Among enrolled participants (n = 54), 35 patients with ischemic stroke or transient ischemic attack symptoms were monitored in real-world settings using the Beiwe app for 8 or more weeks with adequate compliance. Depression symptoms were tracked via weekly Patient Health Questionnaire-8 (PHQ-8) surveys, monthly personnel-administered Montgomery-Asberg Depression Rating Scale (MADRS) assessments, and passive smartphone sensors. Across weeks, several passive measures were significantly associated with PHQ-8 scores. Personnel-assessed depression severity moderately correlated with self-reported scores. To estimate MADRS, we applied linear mixed models using passive data and PHQ-8 scores. Using antecedent PHQ-8 scores and demographic data, average root-mean-squared error (RMSE) for depression severity prediction across models was 1.54 with accelerometer data, 1.40 also including global position system (GPS) data, and 1.33 also including PHQ-8 open survey duration. Though future research should validate this decentralized approach in a larger cohort, real-world monitoring with active and passive data may triage cerebrovascular patients for efficient depression screening and provide novel mobility and response time outcome measures.
Intracranial Photobiomodulation In De Novo Parkinson’s Patients: preliminary data of an ongoing randomized controlled trial
Authors: Chabardès Stéphan , Thobois Stéphane , Mitrofanis John , Beaudoin-Gobert Maude , Anglade Daniel , Aubert Nicolas , Auboiroux Vincent , Bleuet Pierre , Costecalde Thomas , De Schlichting Emmanuel , Faivre Olivier , Mastrosimone Marine , Molet Jenny , Poizat Adrien , Renault Sarah , Torres Napoleon , Chabrol Claude , Moro Cecile , Benabid Alim Louis
Published: January 2025

Parkinson’s disease (PD) is a progressive neurodegenerative disorder and current treatment options only tackle symptoms. We aimed to evaluate the effect of intracranial photobiomodulation (iPBM) on dopaminergic neurons and its consequences on motor symptoms in de novo PD patients.

This randomised open label study included 6 de novo PD patients, 3 served as control and 3 were treated by chronic iPBM during 2 years. Researcher analysing the PET data was unaware of patients’ iPBM status but clinical examinator was aware of it. Data analysis was performed on June 2024.

De novo PD patients were recruited and randomized (1:1) to receive iPBM or medical treatment alone for 4 years. PD diagnosis was < 2 years, and no medication was allowed at inclusion. PET scan was performed at baseline and at 1 year

Primary outcome was safety. The secondary outcome measure was the evolution at 2 years of motor scales using the MDS-UPDRS part III and the evolution of PET scan (using the [11C]-PE2I ligand) at 1 year.

Six patients (1f, 5m) were recruited with a mean age (SD) of 55.3 years (7.6). We showed that iPBM was feasible and safe on the first 3 operated patients. The first novelty of the study was that iPBM improved motor scores in average at 2 years whereas the control group followed the natural clinical decline. Mean (SD) clinical outcome with iPBM was -6.2% (32.9%) improvement on the MDS-UPDRS (part III) compared to baseline versus +130% (143%) for control group. The second novelty was that in the iPBM group, [11C]-PE2I PET scans showed an unusual mean increase in tracer binding within the caudate +21.3%(15.9), nucleus accumbens +22.2%(23.7%), pallidum +89.7% (94.8%) and putamen +26.1%(34%). in the control group, as expected, tracer binding was decreased (SD) on average in the caudate - 16.9%(−16.3%), nucleus accumbens -27.5%(−28.4%), and putamen -19.5%(−11.4%), but slightly increased in the pallidum +10.7%(+39.6%). Because of the small number of patients, no statistical test was performed at this stage.

Conclusions

iPBM was feasible and safe in this small group of patients. It showed an unusual improvement of motor scores at 2 years that was associated with striking increase of dopamine transporter in the basal ganglia observed on the [11C]-PE2I PET. These preliminary data suggest a possible modifying disease effect related to iBPM. A larger number of patients with longer follow up is mandatory to validate our preliminary results.

Trial Registration

the EvNIR study is registered atClinicalTrials.gov(NCT04261569).
A Structural Equation Model Predicts Chronic Wound Healing Time Using Patient Characteristics and Wound Microbiome Composition
Authors: Ancira Jacob , Gabrilska Rebecca , Tipton Craig , Miller Clint , Stickley Zachary , Omeir Khalid , Wakeman Catherine , Little Todd , Wolcott Joseph , Philips Caleb D.
Published: January 2025

Wound etiology, host characteristics, and the wound microbiome contribute to chronic wound development. Yet, there is little accounting for the relative importance of these factors to predict wound healing. Here, a structural equation model was developed to provide such an explanatory and predictive framework. Chronic wounds from 565 patients treated at a clinic practicing biofilm-based wound care were included. Patient information included DNA sequencing-based wound microbiome clinical reports corresponding to initial clinical visit. Wound microbiome data was integrated into the SEM as a latent variable using a pre-modeling parcel optimization routine presented herein for the first time (available as R libraryparcelR). A microbiome latent construct associated with improved healing was validated, and the final SEM included this latent construct plus three species associated with diminished healing (Anaerococcus vaginalis, Finegoldia magna, Pseudomonas aeruginosa), as well as smoking, wound volume, slough, exudate, edema, percent granulation, and wound etiology This model explained 46% of variation in healing time with the microbiome contributing the largest proportion of variance explained. Model validity was confirmed with an independent cohort (n = 79) through which ∼60% of variation in healing time was predicted. This model can serve as foundation for development of a predictive tool that may have clinical utility.
Neural Correlates of Non-Suicidal Self-Injury Functions: Neurobiological Vulnerabilities and Psychosocial Risks in Psychiatric Disorders
Authors: Li Mingzhu , Xiao Yang , Ge Yuqi , Yan Huiru , Li Xueni , Yue Weihua , Yan Hao
Published: January 2025

Background

Non-suicidal self-injury (NSSI) is common in adolescents and young adults, especially among psychiatric disorders. It arises from neurobiological and psychosocial factors, yet its underlying mechanisms remain unclear.

Methods

A total of 304 inpatients (aged 16–25 years) with NSSI and psychiatric diagnoses (major depressive disorder [MDD], bipolar disorder [BD], and eating disorders [ED]) were assessed using the Ottawa Self-Injury Inventory. Resting-state functional magnetic resonance imaging were collected from 163 of them. Functional factors, representing motivations of NSSI, were identified using orthogonal projection non-negative matrix factorization. These factors were then linked to brain functional connections (FC) via canonical correlation analysis and used to classify patients into subtypes through fuzzy C-means clustering. Differences in FC and psychosocial characteristics were analyzed across subtypes.

Results

Two NSSI functional factors were identified: self-related and social-related. Self-related factor was associated with an amygdala-centered cortico-limbic network and prevalent in affective disorders (MDD and BD). Social-related factor correlated with frontoparietal and frontotemporal networks, prominent in ED. Clustering identified three NSSI functional subtypes. Subtype 1 was primarily driven by self-related functions. Subtype 2 was influenced by both self- and social-related functions with greater exposure to psychosocial risks. Subtype 3 remained undifferentiated. No subtype exclusively driven by social-related function was observed.

Conclusion

This study establishes the neural correlates of a “self-social” functional model of NSSI. Self-related functions are underpinned by emotional regulation networks, while social-related functions synergize with psychosocial risks via cognitive-emotional regulation pathways. These findings highlight the need for tailored psychological and neuromodulatory interventions targeting specific functional subtypes.
A Systematic Literature Review of Randomized Trials Comparing In-Person and Digital Interventions for Type 2 Diabetes Prevention
Authors: Riera-Serra Pau , Morales-Hernández David , Fiol-deRoque Maria Antonia , Zamanillo-Campos Rocío , Ricci-Cabello Ignacio
Published: January 2025

Background

Digital and in-person lifestyle interventions to prevent type 2 diabetes (T2DM) are being increasingly implemented in some countries, particularly in the United States. However, their comparative effectiveness remains unclear, partly due to variability in intervention designs and limited robust evidence from randomized controlled trials (RCTs). Understanding their relative impacts is critical for informing evidence-based implementation in diverse healthcare settings.

Aim

To compare the effectiveness of digital versus in-person interventions for preventing T2DM.

Methods

We conducted a systematic literature review, following Cochrane methodology to identify and synthesize evidence from RCTs. Searches were conducted in EMBASE, MEDLINE, and Cochrane CENTRAL from inception to December 2024, including completed and ongoing trials published in English or Spanish. Studies comparing purely digital and in-person interventions were eligible. Meta-analyses were performed where appropriate, and narrative syntheses were provided for remaining outcomes. The GRADE approach was used to assess the certainty of evidence.

Results

Eight RCTs met the inclusion criteria, including six completed trials with published results and two ongoing trials. The completed trials encompassed a total of 2,450 participants across various healthcare settings. At 12 months, digital interventions were associated with significantly greater weight loss than in-person interventions (mean difference: –1.38 kg [95% CI: –2.34 to –0.43]), with moderate certainty of evidence. At shorter (3 and 6 months) and longer (>12 months) time points, no relevant differences were observed for weight, body mass index, or glycosylated haemoglobin levels between the modalities, with the certainty of evidence rated as low to very low. Evidence about cost-effectiveness was scarce. No trials evaluated key outcomes such as incidence of T2DM or health-related quality. For adverse events, no significant differences were found between modalities (RR: 1.06 [95% CI: 0.45 to 2.50]).

Conclusions

This systematic review highlights that while digital and in-person interventions can both be effective for T2DM prevention, their relative benefits depend on follow-up duration and contextual factors. The limited certainty of evidence and the absence of trials addressing critical outcomes, such as T2DM incidence, underscore the need for further well- designed RCTs. Future research should prioritize equivalence in intervention intensity, longer follow-up durations, and standardized reporting of outcomes to better inform public health decision-making.
Understanding the causes and consequences of low statin adherence: evidence from UK Biobank primary care data
Authors: Türkmen Deniz , Liang Xiaoran , Masoli Jane A H , Gill Dipender , Pilling Luke C , Bowden Jack
Published: January 2025

Background

Statins are commonly prescribed to lower LDL cholesterol. Clinical guidelines recommend 30-50% reduction within 3 months, yet many patients do not achieve this. We investigated the impact of patient characteristics and genetics on LDL-c reduction, treatment adherence, and adverse clinical outcomes.

Methods

We analysed 76,000 UK Biobank participants prescribed atorvastatin or simvastatin in primary care: 41,000 had LDL-c measurements before statin initiation (median=16 days prior, IQR=28) and within a year of starting treatment (median=89 days, IQR=125). Adherence was defined as the “proportion of days covered” (PDC). We estimated associations between PDC within one year of statin initiation, genetic factors, post-treatment LDL reduction, and clinical adverse outcomes. For 13,000 patients with ≥3 LDL-c measures, we used inverse probability weighting methods to estimate the effect of sustained adherence intervention on LDL-c reduction longitudinally.

Results

Predictors of LDL-c reduction following statin initiation included the time until the 1stmeasurement, PDC, and the pharmacogenetic variantSLCO1B1*5. LDL-c reduction was greater in those with high adherence versus lower adherence (38% reduction when PDC>95% [high] vs. 15% when PDC<50% [low]). Longitudinal causal modelling showed that the most recent PDC measure exerted the largest influence on overall LDL-c reduction, followed by the initial PDC.

Genetic predictors of reduced PDC included liability to schizophrenia (Coeftop20%-1.94, 95%CI -2.69 to -1.19), whilst genetic liability to cardiovascular diseases increased PDC (Coeftop20%1.30, 95%CI 0.55 to 2.05). High PDC was associated with increased risk of incident iron deficiency anaemia (HR 1.30, 95%CI 1.09-1.54) and cataract (HR 1.20, 95%CI 1.07-1.34), and decreased risk of incident coronary heart disease (HR 0.78, 95%CI 0.73-0.84).

Conclusion

We identify substantial variability in the time to first on-treatment LDL measurements and also in adherence to statin medication, highlighting a gap between NHS guidelines, LDL monitoring and statin adherence. We show its subsequent impact on long term health, demonstrating the potential effect of targeted interventions to improve adherence. We identify important predictors of reduced statin effectiveness, including pharmacogenetic variants, polygenic scores, but most of all, adherence. Tailored statin therapy strategies with patient education on statin indication and adherence could optimise treatment efficacy, safety, and long-term clinical outcomes.
Assessment of SARS-CoV2 genome sequence recovery from four lateral flow device products available in the UK
Authors: Lewandowski Kuiama , Stokes Matthew , Alexandridou Alexandra , Fenwick Abigail , White Mia L. , Crook Jack , Rogers-Broadway Karly-Rai , Ryan Catherine , Williamson Deborah A. , Vipond Richard , Pullan Steven T.
Published: January 2025

Lateral flow tests have played a key role in the response to the COVID-19 pandemic and are likely to be a major component of diagnostic strategies to combat future outbreaks of infectious disease. One challenge posed by widescale use of lateral flow tests in the community is the loss of sequence information to track virus evolution and epidemiology.

Beyond their primary diagnostic function, it has been demonstrated that recovery of viral RNA for genome sequencing purposes is possible, from positive lateral flow devices (LFDs).

To assess the robustness and broader applicability of this process, we assessed SARS-CoV-2 RNA recovery and sequencing from the four major LFDs in use in the UK.

Testing both cultured virus and residual clinical nasal swab samples demonstrated that sequencing from LFD eluates is possible, at clinically relevant titres, within a reasonable processing time frame post-use, and gave sequences concordant with routine methods, but results varied across the four devices used.

This highlights the requirement for refinement of existing LFDs or of second–generation LFD design, where sequencing is an intended output from positive LFDs.
Approach-Avoidance Tendencies Influence the Relationship Between Fear of Movement and Physical Activity in Osteoarthritis
Authors: Goubran Miriam , Zammar Christian , Tellez Alvarez Santiago , Héran Élodie , Proulx Sara , Bilodeau Martin , Boisgontier Matthieu P.
Published: January 2025

Purpose

Almost twice as many people with arthritis report being physically inactive compared to people without arthritis. The objective of this study was to examine whether psychological processes including fear of movement, explicit attitudes, and approach-avoidance tendencies toward physical activity, are associated with lower physical activity levels in people with arthritis.

Methods

An online observational study was conducted in 197 participants, including 68 with osteoarthritis and 13 with rheumatoid arthritis. Arthritis, fear of movement, usual level of physical activity, and explicit attitudes were assessed using questionnaires. Approach-avoidance tendencies, an indicator of implicit attitudes, was derived from reaction times in an approach-avoidance task.

Results

Results showed that higher fear of movement was associated with lower physical activity levels in participants with osteoarthritis than in those without osteoarthritis. This association was moderated by approach-avoidance tendencies toward physical activity, with a significant effect only in participants with an automatic tendency to avoid physical activity or a weak tendency to approach it. In addition, contrary to our hypothesis, higher fear of movement was associated with a stronger tendency to approach physical activity and avoid sedentary behaviors, suggesting that people who were most fearful of movement may also be those who unconsciously internalized the importance of physical activity the most.

Conclusion

This study suggests that in adults with osteoarthritis, the detrimental effect of fear of movement on usual physical activity levels may be mitigated by strong automatic tendencies to approach physical activity. Since these tendencies result from the automatic activation of affective memories, health professionals should consider not only promoting physical activity but also ensuring its association with positive emotional experiences.
Changes in public perception of AI in healthcare after exposure to ChatGPT
Authors: Isaksen Anders Aasted , Schaarup Jonas Rosborg , Bjerg Lasse , Hulman Adam
Published: January 2025

Background

Artificial intelligence (AI) is expected to become an integral part of healthcare services, and the widespread adoption of AI tools in all areas of life is making AI accessible to the general public. Public perception of the benefits and risks of AI in healthcare is key to large-scale acceptance and implementation, and is increasingly influenced by first-hand experiences of AI. The aim of this study was to assess how exposure to ChatGPT changed public perception of AI in healthcare.

Methods

We used baseline and follow-up data from 5,899 survey participants, who reported their perception of AI in 2022 and 2024, and ChatGPT use in 2024. Administrative and healthcare data from nationwide Danish registers was used for weighting and adjustment. Multinomial multivariate logistic regression was used to model how exposure to ChatGPT use affected changes in perception of AI.

Results

At baseline (before ChatGPT’s launch) 2,236 individuals (37%) were unsure of the benefits and risks of AI in healthcare, 2,384 (40%) perceived net benefits, 1,083 (18%) perceived benefits and risks as equal, and 196 (3.3%) perceived net risks. At follow-up, 1,195 individuals (20%) had been exposed to ChatGPT use, which was associated with higher odds of changing perception of AI to benefits (OR 3.21 [95% CI: 2.34-4.40]) among individuals who were unsure at baseline, and lower odds of changing to uncertainty from more defined baseline perceptions (from benefits (OR 0.32 [0.24-0.42]), equal (OR 0.47 [0.32-0.69]) and risks (OR 0.27 [0.08-0.98])).

Conclusion

Exposure to ChatGPT was associated with a change towards positive perception of benefits and risks of AI in healthcare among individuals who were uncertain prior to exposure, and individuals with more defined perceptions of AI were less likely to become uncertain after exposure to ChatGPT.
Network meta-analysis combining survival and count outcome data: A simple frequentist approach
Authors: Noma Hisashi , Maruo Kazushi
Published: January 2025

Network meta-analysis for survival outcome data often involves several studies only reported dichotomized outcomes (i.e., the numbers of events and sample sizes of individual arms). To avoid the reporting biases via eliminating these studies in the syntesis analyses, Woods et al. (2010;BMC Med Res Methodol10:54) proposed a Bayesian approach to combine the survival and dichotomized outcome data using hierarchical models. However, the Bayesian methods require complicated computations involving the Markov Chain Monte Carlo and the technical aspects are generally difficult to handle by non-statisticians (e.g., the convergence diagnostics). Besides, frequentist approaches have been alternative standard methods for statistical analyses of network meta-analysis. The methodology has been well established, and several effective software packages have been developed (e.g.,netmetapackage in R). In this article, we propose a simple method to synthesis the survival and dichotomized outcome data within the frequentist framework using the contrast-based models. We also provide a R packagesurvNMA(https://doi.org/10.32614/CRAN.package.survNMA) to calculate hazard ratio statistics from the dichotomized outcome data that can be directly used for implementing general analyses of network meta-analysis usingnetmetapackage of R.