bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of skin disorders and associated factors among patients with celiac disease: a cross-sectional study
Authors: Tajabadi Zohreh , Ekhlasi Golnaz , Daneshpazhooh Maryam , Fakheri Hafez , Tavakoli Tahmine , Ahmadi Bizhan , Ganji Azita , Niknam Ramin , Pashaei Mohammad Reza , Ghadir Mohammad Reza , Shahbazi Shaahin , Ghanaei Fariborz Mansour , Alavinejad Pezhman , Shirmohamadi Masoud , Aflatoonian Majid , Bakhshipour Alireza , Masoudi Sahar , Shahbazkhani Bijan 
Published: January 2025

AbstractBackgroundWhile celiac disease (CD) ordinarily presents with gastrointestinal manifestations, extraintestinal appearances may also happen. Although cutaneous manifestations are one of the most common extraintestinal manifestations of CD, little is known about their prevalence and associated factors. This study aims to determine the prevalence of cutaneous manifestations and related factors in CD patients.MethodsThis cross-sectional study enrolled CD patients referred to the National Celiac Registry, for whom a diagnosis of CD was confirmed through clinical examination, serological testing, and intestinal biopsy. Data on demographic characteristics, CD staging, clinical manifestations, underlying comorbidities, and family history (FH) of diseases were collected. Data were analyzed using SPSS version 25.0. Ap-value less than 0.05 was considered significant.ResultsOf the 4357 enrolled CD patients (male 65.7%), 18.20% had cutaneous manifestations, with eczema (3.73%), dermatitis herpetiformis (3.46%), and psoriasis (0.71%) being the most common disorders. The FH of skin disorders (Odds ratio (OR)=7.99, 95% confidence interval (CI) 2.44-26.13,p=0.00), osteoarthritis (OR=6.15, 95% CI 1.15-32.78,p=0.03), Sjögren syndrome (OR=4.82, 95% CI 1.98-11.73,p=0.00), mouth aphthae (OR=3.10, 95% CI 1.80-5.32,p=0.00), thalassemia (OR=2.78, 95% CI 1.19-6.50,p=0.01), constipation (OR =1.62, 95% CI 1.10-2.38,p=0.01), and iron deficiency anemia (IDA) (OR=1.54, 95% CI 1.05-2.24,p=0.02) were independent predictors, and type I diabetes mellitus (OR=0.20, 95% CI 0.05-0.81,p=0.02) was a protective factor for skin diseases.ConclusionConsidering the higher probability of cutaneous manifestations in CD patients, regular clinical evaluation of these patients is recommended for timely diagnosis and management of underlying skin diseases.
Upper extremity joint tenderness as a practical indicator for assessing presenteeism in rheumatoid arthritis patients
Authors: Naito Ryota , Taniguchi Masashi , Onizawa Hideo , Nakajima Tomoya , McCracken Kayo , Mori Masato , Hiwa Ryosuke , Nakamura Takuji , Onishi Akira , Matsuda Shuichi , Morinobu Akio , Hirose Shinji , Shinkawa Yutaka , Umehara Hisanori , Tanaka Masao 
Published: January 2025

AbstractObjectiveRheumatoid arthritis (RA) causes chronic polyarthritis and joint dysfunction, reducing work productivity. This reduction is mainly due to presenteeism, characterized by impaired work performance despite being present at work. This study aims to investigate the impact of specific joint involvement, particularly in the upper extremities, on work disability in RA patients.MethodsAnnual surveys assessing work disability were conducted among RA outpatients enrolled in the Nagahama Riumachi Cohort at Nagahama City Hospital, using the Work Productivity and Activity Impairment Questionnaire (WPAI). A multivariate regression analysis was performed to examine the cross-sectional and longitudinal associations between presenteeism and the tender joint count (TJC) in the extremities across two WPAI surveys.ResultsThe analysis included 201 patients, 52% of whom reported presenteeism. Cross-sectional analysis revealed a significant positive correlation between three or more TJCs of the upper extremity and presenteeism, with a regression coefficient (β) = 17.9 (95% confidence interval [CI]: 9.85–25.9). Among the joints evaluated, the sum of TJCs in the shoulder area (β = 9.55, CI: 5.39–13.7) and the fingers (β = 1.60, CI: 0.35–2.85) were significantly correlated with presenteeism. Additionally, change in presenteeism were significantly correlated with change in upper extremity TJCs (β = 1.41, CI: 0.05–2.77).ConclusionsThe upper extremity TJC is strongly associated with presenteeism in RA patients. The TJC of the upper extremities serves as a valuable indicator for clinicians, helping them effectively assess a patient’s underlying work disability.
Smooth pursuit eye movements contribute to long-latency reflex modulation in the lower extremity
Authors: Sinha Oindrila , Bertucco Matteo , Kurtzer Isaac , Singh Tarkeshwar 
Published: January 2025

ABSTRACTSomatosensory mediated reactions play a fundamental role in adapting to environmental changes, particularly through long-latency responses (LLRs). We investigated how smooth pursuit eye movements (SPEM), which are slow eye movements used to track moving objects, influence LLRs of the upper and lower limb during mechanical interactions with moving objects. Seventeen participants stabilized their limb in anticipation of a collision with a virtual object approaching at 25 cm/s while standing. This task occurred while subjects either visually pursued the object or fixated a central location. Mechanical perturbations were applied at two time points: approximately 200ms and 60ms before the anticipated collision. On a random subset of trials, the robot applied a mechanical perturbation either 200ms (early) or 60ms (late) before the anticipated collision. As in previous studies LLRs were observed in leg muscles to upper limb displacement. Moreover, the leg LLRs were modulated by gaze, being larger during pursuit than fixation but only during late perturbations. This timing-specific modulation aligns with previous reports of policy transitions in feedback control roughly 60ms before impact. Upper limb LLRs were not impacted by gaze indicating a prioritization on postural control circuits. This work extends our understanding of the neural mechanisms underlying sensorimotor integration and highlights the sophisticated nature of the human motor control system in coordinating eye movements with whole-body postural responses.NEW and NOTEWORTHYWe show for the first time that smooth pursuit eye movements contribute to modulation of long-latency reflexes in the lower limb during virtual object interactions in upright stance. Smooth pursuit eye movements are used to track moving objects. These findings suggest a neurophysiological link between control of eye movements and posture stabilization.
Explainable artificial intelligence for neuroimaging-based dementia diagnosis and prognosis
Authors: Martin Sophie A. , Zhao An , Qu Jiongqi , Imms Phoebe , Irimia Andrei , Barkhof Frederik , Cole James H. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

AbstractINTRODUCTION: Artificial intelligence and neuroimaging enable accurate dementia prediction, but ‘black box’ models can be difficult to trust. Explainable artificial intelligence (XAI) describes techniques to understand model behaviour and the influence of features, however deciding which method is most appropriate is non-trivial. Vision transformers (ViT) have also gained popularity, providing a self-explainable, alternative to traditional convolutional neural networks (CNN). METHODS: We used T1-weighted MRI to train models on two tasks: Alzheimer’s disease (AD) classification (diagnosis) and predicting conversion from mild-cognitive impairment (MCI) to AD (prognosis). We compared ten XAI methods across CNN and ViT architectures. RESULTS: Models achieved balanced accuracies of 81% and 67% for diagnosis and prognosis. XAI outputs highlighted brain regions relevant to AD and contained useful information for MCI prognosis. DISCUSSION: XAI can be used to verify that models are utilising relevant features and to generate valuable measures for further analysis.
Metabolomic insight into the link of Intermuscular Fat with Cognitive Performance: The Health ABC Study
Authors: Xu Richard , Tian Qu , Marron Megan M. , Ferrucci Luigi , Yao Shanshan , Kim Seyoung , Shah Ravi V. , Murthy Venkatesh L. , Newman Anne B. , Miljkovic Iva , Rosano Caterina 
Published: January 2025

AbstractThere is growing evidence that higher intermuscular fat (IMF) is associated with worse processing speed, measured by the digit symbol substitution test (DSST) in older adults. However, the underlying biological mechanisms are not well understood. Considering that both muscle and the brain are metabolically active organs, we sought to identify metabolites that may explain the IMF-DSST association. We assessed 613 plasma metabolites in 2388 participants from the Health, Aging and Body Composition Study (mean age ± SD: 74.7 ± 2.9 years, 50% men, 63% white), using liquid chromatography-mass spectrometry. We found that higher IMF was associated with worse DSST scores (standardized beta (95% CI): -0.08 (-0.12, -0.03), p<0.001). Sixty-six metabolites were significantly associated with both IMF and DSST. Four of the 66 metabolites attenuated the association by ≥10%: higher levels of adrenic acid (polyunsaturated fatty acid), and lower levels of C20:5 lysophosphatidylcholine (lysophospholipid), 1-methylnicotinamide (vitamin B3-related myokine), and maslinic acid (triterpene) were associated with higher IMF and worse DSST. Together, they explained 41% of the IMF-DSST association. Pathway enrichment analyses identified two significant shared pathways: unsaturated fatty acid metabolism and the citrate (TCA) cycle. This study provides hypothesis-generating evidence that a set of circulating metabolites related to unsaturated fatty acids, energy metabolism, and myokines may partially explain the inverse association of IMF with processing speed. The findings, if further confirmed by independent studies, advance our understanding of molecular pathways underlying muscle-brain crosstalk and raise the possibility of metabolites as potential predictive biomarkers and/or therapeutic targets.
The engineered monoclonal antibody tobevibart enhances HBsAg capture by Fc receptor positive cells leading to activation of HBV-specific T cells
Authors: Vincenzetti Lucia , Wong Rachel , Marzi Roberta , Guarino Barbara , Stefanutti Erin , Gupta Sneha V. , Rosen Laura E. , Belnap David M. , Wang Li , Chen Yi-Pei , di Iulio Julia , Momin Amin , Tracy Karen E. , Deshpande Sharvari , Errico John M. , Sprugasci Nicole , Peter Alessia , Seu Lillian , Cloutier Daniel , Tay Chin H. , Snell Gyorgy , Czudnochowski Nadine , Lempp Florian A. , Havenar-Daughton Colin , Benigni Fabio , Lanzavecchia Antonio , Agarwal Kosh , Yuen Man-Fung , Wedemeyer Heiner , Gane Ed , Arvin Ann , Corti Davide , Schmid Michael A. 
Published: January 2025

AbstractBackground & AimsImmune targeting is likely required for functional cure of chronic hepatitis B (CHB). Tobevibart, a human monoclonal antibody against hepatitis B virus (HBV) surface antigen (HBsAg), neutralizes HBV and hepatitis delta virus (HDV). This study aimed to characterize effects of the engineered GAALIE Fc of tobevibart on HBV immune responses.MethodsWe studied tobevibart and its equivalent HBC34*-GAALIEin vitrousing electron microscopy, FcγR reporter cells, and primary human or mouse immune cells to assess HBsAg binding, dendritic cell (DC) activation, and T cell stimulation. Tobevibart-mediated binding of HBsAg to immune cells was evaluated also in a phase 1 clinical trial in patients with CHB.ResultsThe GAALIE Fc of tobevibart mediated gain of function in FcγR signaling in immune complexes (ICs) with HBsAg compared to wild-type (WT) Fc and increased binding of HBsAg to neutrophils and monocytesin vitro. Similarly, dosing of 300 mg tobevibart in patients with CHB mediated binding of HBsAg to these cellsin vivo, concomitant with reducing HBsAg in circulation.In vitro, ICs of HBC34*-GAALIE and HBsAg activated human DCs significantly more than HBC34*-WT. These DCs presented antigen and stimulated HBsAg-specific human T cells. Similarly, ICs of HBC34*-GAALIE and HBsAg activated DCs from mice transgenic for human FcγRs and stimulated CD4+ T cells from immunized animals more than ICs with HBC34*-WT.ConclusionsWe demonstrate that tobevibart combines the advantages of potent neutralization of HBV and HDV, FcγR-mediated reduction of HBsAg, and Fc-dependent enhancement of T cell responses. Tobevibart is currently under clinical investigation alone or in combination with other agents to treat patients with chronic hepatitis delta and to induce functional cure of patients with CHB.Impact and ImplicationsChronic infection with hepatitis B virus (HBV) or co-infection with hepatitis delta virus (HDV) can cause severe liver disease and cancer. We previously showed that the monoclonal antibody tobevibart potently neutralizes HBV and HDV. Here we show that the engineered Fc region of tobevibart effectively interacted with several immune cell typesin vitro, which may support the rapid removal of damaging virus proteins from circulation, potentially activating T cell responses that may control HBV infection long term.
The quarantine hospital strategy as a way to reduce both community and nosocomial transmission in the context of a COVID-like epidemic
Authors: Pinettes Théo , Leclerc Quentin J. , Jean Kévin , Temime Laura 
Published: January 2025

AbstractNosocomial infections of both patients and healthcare workers (HCWs) in hospitals may play an important part in the overall dynamics of a viral pandemic, as evidenced by the recent COVID-19 experience. A strategy to control this risk consists in dedicating some hospitals to the care of infected patients only, with HCWs alternating between shifts of continuous stay within these hospitals and periods of isolation. This strategy has been implemented locally in various settings and generalized in Egypt. Here, using a mathematical model coupling hospitals and community, we assess the impact of this strategy on overall epidemic dynamics. We find that quarantine hospitals may significantly reduce the number of cumulative cases, as well as the peak incidence. These benefits are highest when effective control strategies are in place in the community and symptomatic HCWs comply with self-isolation recommendations. Our results, which are robust to variations in assumed biological characteristics of the virus, suggest that the quarantine hospital strategy should be considered in future pandemic contexts to best protect the entire population.
Facilitators and Barriers to Patient-Caregiver Dyadic Recruitment in Transplantation
Authors: Koons Brittany , Lehman Rachel , Riegel Barbara , Buck Harleah 
Published: January 2025

AbstractBackgroundDespite growing awareness of the dyadic role in transplant care and a mandate for patient–caregiver dyads for transplant listing, the integration of dyadic science into transplantation research is lacking. Recruiting transplant patient-caregiver dyads has unique challenges that need to be considered when designing and conducting dyadic studies in transplantation.ObjectivesTo present 1) the barriers and facilitators to dyadic recruitment in a patient-caregiver transplant population that we encountered and 2) strategies developed to overcome these challenges.MethodsWe used the Social Marketing Mix framework to guide this methodological report of patient-care dyadic recruitment strategies employed during a post-lung transplant psychometric study of 50 patient-caregiver dyads.ResultsWe identified several facilitators of dyadic recruitment in the lung transplant population including: 1) conducting a study of high relevance to both patients and caregivers, which helped to facilitate maximum engagement of participants, 2) using remote recruitment and data collection strategies to improve accessibility to participation and to minimize the amount of time or energy required to participate, 3) conducting patient and caregiver study visits independently from one another, which allowed for scheduling flexibility, and helped improve participation among dyad members who do not live together, and 4) establishing clinical partnerships and having acquired clinical experience with the target population. We also identified barriers to dyadic recruitment that require careful planning in future studies including: 1) high health care utilization, which can delay the recruitment timeline, 2) recruiting patients and caregivers independently within relevant timeframes, 3) gatekeeping, when the patient or the caregiver block researcher access to the other dyad member, 4) establishing contact with the participant via the phone, and 5) limited study staffing that reduced recruitment and study visit scheduling flexibility.DiscussionTo our knowledge, this is the first methodological report to present the barriers and facilitators to dyadic recruitment in a patient-caregiver transplant population. Our experience and lessons learned can be used to inform future research teams to successfully design and conduct much needed dyadic research in organ transplantation.
Ptpn14Knockout Mice Reveal Critical Female-Specific Roles for the Hippo Pathway
Authors: McCrea Edel M. , Makrides Neoklis , Tabata Takako , Vogel Hannes , Howitt Brooke , Reineking Wencke , Vilches-Moure José G. , Wang Mengxiong , Zhang Xin , Attardi Laura D. 
Published: January 2025

ABSTRACTThe Hippo pathway regulates many physiological processes, including development, tumor suppression, and wound healing. One understudied Hippo pathway component is PTPN14, an evolutionarily conserved tyrosine-phosphatase that inhibits YAP/TAZ. While an established tumor suppressor, PTPN14’s role in tissue homeostasis has remained unclear. We thus generatedPtpn14-deficient mice and found that only ∼60% ofPtpn14-/-mice survived postnatally, highlighting the importance of PTPN14 for viability, while also enabling the discovery of PTPN14 physiological functions.Ptpn14-/-mice developed debilitating corneal lesions and the uterus defect, hydrometra, as well as heart and kidney abnormalities.Ptpn14-deficiency precipitated an impaired injury response in the cornea and dysregulated YAP signaling in the uterus. Notably, these phenotypes were female-specific, revealing sexually-dimorphic Hippo pathway function through PTPN14. Finally, analysis of humanPTPN14variants suggested that PTPN14’s essential roles are conserved in humans, underscoring the importance of our insights for designing therapies to improve women’s health.
Development of FAP-targeted theranostics discovered by next-generation sequencing-augmented mining of a novel immunized VNAR library
Authors: Gunaratne Gihan S. , Gallant Joseph P. , Ott Kendahl L. , Broome Payson L. , Celada Sasha , West Jayden L. , Mixdorf Jason C. , Aluicio-Sarduy Eduardo , Engle Jonathan W. , Boros Eszter , Meimetis Labros , Lang Joshua M. , Zhao Shuang G. , Hernandez Reinier , Kosoff David , LeBeau Aaron M. 
Published: January 2025

AbstractCancer-associated fibroblasts (CAFs) in the stroma of solid tumors promote an immunosuppressive tumor microenvironment (TME) that drives resistance to therapies. The expression of the protease fibroblast activation protein (FAP) on the surface of CAFs has made FAP a target for development of therapies to dampen immunosuppression. Relatively few biologics have been developed for FAP and none have been developed that exploit the unique engagement properties of Variable New Antigen Receptors (VNARs) from shark antibodies. As the smallest binding domain in nature, VNARs cleverage unique geometries and recognize epitopes conventional antibodies cannot. By directly immunizing a nurse shark with FAP, we created a large anti-FAP VNAR phage display library. This library allowed us to identify a suite of anti-FAP VNARs through traditional biopanning and also by anin silicoapproach that did not require any prior affinity-based enrichmentin vitro. We investigated four VNAR-Fc fusion proteins for theranostic properties and found that all four recognized FAP with high affinity and were rapidly internalized by FAP-positive cells. As a result, the VNAR-Fc constructs were effective antibody-drug conjugatesin vitroand were able to localize to FAP-positive xenograftsin vivo. Our findings establish VNAR-Fc constructs as a versatile platform for theranostic development that could yield innovative cancer therapies targeting the TME.
dlmoR: An open-source R package for the dim-light melatonin onset (DLMO) hockey-stick method
Authors: Thalji Salma M. , Spitschan Manuel 
Published: January 2025

AbstractThe dim-light melatonin onset (DLMO) is a commonly used circadian phase marker indicating the start time of evening melatonin synthesis in humans. Several quantitative techniques have been developed to determine DLMO from melatonin time-series, including fixed- or variable-threshold techniques and the hockey-stick method developed by Danilenko and colleagues (2014). Here, we introducedlmoR, an open-source implementation of the hockey-stick method implemented in the R programming language and licensed under the permissive MIT License. Our clean-room implementation followed the algorithm description from the original article, supported by iterative validation against the existing binary executable software. We benchmark our implementation using a total of 112 melatonin time-series data sets from two different studies (Blume et al, 2024; Heinrichs and Spitschan, 2024), and find high agreement between our implementation and the reference implementation. The mean DLMO point discrepancy between implementations was −2.1 ± 11.1 minutes for the Blume et al. (2024) dataset and −1.482 ± 21.7 for the Heinrichs and Spitschan (2024) dataset. Circular correlation coefficients were 0.986 and 0.964, respectively, and paired t-tests (p >0.05) were not significant, suggesting no systematic difference or bias between the methods.dlmoRallows for the programmatic and batchable analysis of evening melatonin concentration data, enabling transparency and reproducibility of analytic techniques.