bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Single-Cell Chromatin and Transcriptomic Profiling of Peripheral Immune Cells in Non-Segmental Vitiligo
Authors: Gay-Mimbrera Jesus , Lozano-Ojalvo Daniel , Gómez-Arias Pedro J , Rivera-Ruiz Irene , Aguilar-Luque Macarena , Mochón-Jiménez Carmen , Andújar Pulido Eloísa , Pérez-Alegre Mónica , Guttman-Yassky Emma , Ruano Juan 
Published: January 2025

Abstract

Introduction
Non-segmental vitiligo (NSV) is an autoimmune condition characterized by melanocyte loss. While skin-specific mechanisms are well-studied, systemic immune dysregulation contributing to NSV pathogenesis remains unclear.

Objective
This study employs a multi-omic single-cell approach to investigate circulating immune cells in NSV, integrating transcriptional and chromatin accessibility data.

Methods
An integrative scRNA-seq/scATAC-seq analysis was conducted on PBMCs from NSV patients (n=11) and controls (n=5), identifying transcriptional markers, cell-cell interactions, chromatin accessibility, and transcription factor (TF) dynamics. Key findings were validated in an expanded cohort (NSV, n=16; controls, n=9) using spectral flow cytometry, with additional stratification by sex, age, disease activity, severity, and duration.

Results
Analysis of 59,192 PBMCs identified 8,204 gene expression markers and 13,925 ATAC peaks across 25 immune cell subtypes. A broadly activated immune response was observed, characterized by cytotoxicity, antigen presentation, cell exhaustion, and stress, predominantly in monocytes, NK cells, CD8+ T cells, and dendritic cells (DCs). Multi-omic integration revealed Th1/Th17 polarization and dysfunctional regulatory T cell (Treg/mTreg) responses. Chromatin accessibility highlighted enriched TF binding sites for FOXO3, SP1, AP1, STAT1/STAT3, IRF1, and IRF4, regulating pathways linked to cytotoxicity, antigen processing, NF-κB, Toll-like receptor, and JAK-STAT signaling.
Flow cytometry validated these findings, showing that disease activity and shorter duration were associated with heightened immune dysregulation. Robust TCR activation drove Th1/Th17 polarization and elevated IFN-γ and TNF-α production in CD4+ and CD8+ T cells. CLA+ skin-homing Th1/Th17-polarized CD4+ T cells, CD8+ T cells, and mTregs exhibited persistent activation, marked by basal PD1+ expression. OX40/OX40L-mediated interactions between monocytes and effector T cells amplified inflammation. Regulatory dysfunction, including reduced IL-4 and IL-13 production in mTregs, was prominent in moderate-severe and active disease.

Conclusion
This is the first multi-omic single-cell study in PBMCs of NSV patients, revealing systemic immune dysregulation driven by cytotoxicity, antigen presentation, exhaustion, and regulatory failure. Disease severity, activity, and evolution influence these pathways, highlighting the OX40/OX40L axis as a potential therapeutic target to mitigate immune dysregulation and relapse risk.
Research progress on the role of fascia in skin wound healing
Authors: Xu Jiamin , Zhang Hongyan , Ye Haifeng 
Published: January 2025

Abstract
The skin, the human body’s largest organ, is perpetually exposed to environmental factors, rendering it vulnerable to potential injuries. Fascia, a vital connective tissue that is extensively distributed throughout the body, fulfils multiple functions, including support, compartmentalization, and force transmission. The role of fascia in skin wound healing has recently attracted considerable attention. In addition to providing mechanical support, fascia significantly contributes to intercellular signalling and tissue repair, establishing itself as a crucial participant in wound healing. This review synthesises the latest advancements in fascia research and its implications for skin wound healing.
Combination of white-light imaging–based and narrow-band imaging–based artificial intelligence models during colonoscopy in patients with ulcerative colitis
Authors: Kuroki Takanori , Maeda Yasuharu , Kudo Shin-Ei , Ogata Noriyuki , Takabayashi Kaoru , Takenaka Kento , Kawashima Jiro , Kawabata Yurie , Iwasaki Shunto , Shiina Osamu , Morita Yuriko , Kouyama Yuta , Sakurai Tatsuya , Ogawa Yushi , Baba Toshiyuki , Mori Yuichi , Iacucci Marietta , Ogata Haruhiko , Ohtsuka Kazuo , Misawa Masashi 
Published: January 2025

Abstract

Background and Aims
The long-term treat-to-target (T2T) approach in ulcerative colitis (UC) aims for endoscopic remission, but variability among endoscopists and a lack of precision in relapse prediction both limit its clinical usefulness. A recently reported white-light imaging (WLI) artificial intelligence (AI) model helps standardize diagnosis, although challenges remain. Therefore, we attempted to combine a narrow-band imaging (NBI) AI model with the WLI AI model to determine whether these challenges can be overcome.

Methods
This post hoc analysis of a prospective study evaluated the efficacy of combining AI-assisted WLI and NBI models in predicting clinical relapse in patients with UC over a 12-month follow-up period. A total of 102 patients with UC in clinical remission were included, and the combined AI models were used during colonoscopy to assess relapse risk.

Results
The study found that within the same AI-based Mayo endoscopic subscore category, patients with vascular activity were more likely to experience clinical relapse than those with vascular healing. Compared with the WLI model alone, the specificity of the combined method significantly increased from 42.2% (95% confidence interval [CI]: 32.1%–52.9%) to 61.5% (95% CI: 50.7%–71.2%) (P = .013) with its sensitivity being maintained.

Conclusions
The sequential use of WLI and NBI AI models can provide better stratification of relapse risk compared with using either model alone, offering a more accurate and personalized approach to treatment intensification. This dual-model AI approach aligns with the T2T approach in UC management.
Estrogenic activity of alkylcyclohexanones and alkylcyclohexanols in rainbow trout estrogen receptor binding and liver slices Vtg mRNA expression assays
Authors: Tapper Mark A , Denny Jeffrey S , Sheedy Barbara R , Kolanczyk Richard C , Saari Gavin , Hammermeister Dean E , Backe Will , Serrano Jose 
Published: January 2025

Abstract
Alkylcyclohexanones and alkylcyclohexanols are industrial chemicals produced in large volumes. Little is known regarding estrogenic activity of these chemicals in aquatic species. A series of para-alkyl subsituted hexanones and hexanols with varying chain length and branching were tested in a suite of in vitro rainbow trout binding assays and in an ex vivo rainbow trout liver slice/vitellogenin (Vtg) expression assay to assess estrogenic potential. Furthermore, the extent of biotransformation of these chemicals under test conditions was monitored. Cyclohexane, cyclohexanol, and 4-ethylcyclohexanol had no detectable estrogenic activity in these assays. Para substituted alkylcyclohexanones and alkylcyclohexanols with side chains containing three to six carbons were active in both assays. Alkylcyclohexanones and alkylcyclohexanols with other than para substitution were also estrogenic when tested in these assays. The binding affinity relative to estradiol in cytosol of active chemicals was low, ranging from 0.0016 to 0.000029%. Biotransformation of alkylcyclohexanones to alkylcyclohexanols occurred in the cytosol binding assay and in the liver slice assay, thus making those exposures a mixture of alcohol and ketone forms. Biotransformation did not occur in rainbow trout nuclear extract and recombinant binding assays, thus the exposure in these assays was to only the dosed chemical. Both alkylcyclohexanones and alkylcyclohexanols bound to the estrogen receptor in these metabolically limited assays. Significant induction of Vtg mRNA expression was seen in slice exposed to chemicals with measurable binding affinities. Often the induction levels were below maximum efficacy and occurred at concentrations slightly lower than toxic concentrations. Therefore, while these chemicals produced an estrogenic effect, it is considerably weaker than that of the endogenous hormone and occurred at concentrations close to those which produce toxicity.
Investigating the role of adipose tissue in mobility and aging: design and methods of the Adipose Tissue ancillary to the Study of Muscle, Mobility and Aging (SOMMA-AT)
Authors: Yeo Reichelle X , Mau Theresa , Ross Zana M , Edenhoffer Nicholas P , Liu Jingfang , Barnes Haley N , Lui Li-Yung , Adkins Joshua N , Sanford James A , Seldin Marcus M , Viesi Carlos H , Zhou Mingqi , Gregory Heather L , Toledo Frederico G S , Stefanovic-Racic Maja , Lyles Mary , Wood Ashlee N , Mattila Polly E , Blakley Elizabeth A , Miljkovic Iva , Cawthon Peggy M , Newman Anne B , Kritchevsky Stephen B , Cummings Steven R , Goodpaster Bret H , Justice Jamie N , Kershaw Erin E , Sparks Lauren M 
Published: January 2025

Abstract

Background
Age-related changes in adipose tissue impact chronic medical diseases and mobility disability but mechanism remains poorly understood. The goal of this study is to define methods for phenotyping unique characteristics of adipose tissue from older adults.

Methods
Older adults enrolled in Study of Muscle, Mobility and Aging selected for the adipose tissue ancillary (SOMMA-AT; N=210, 52.38% women, 76.12±4.37 years) were assessed for regional adiposity by whole-body magnetic resonance (AMRA) and underwent a needle-aspiration biopsy of abdominal subcutaneous adipose tissue (ASAT). ASAT biopsies were flash frozen, fixed, or processed for downstream applications and deposited at the biorepository. Biopsy yields, qualitative features, adipocyte sizes, and concentration of adipokines secreted in ASAT explant conditioned media were measured. Inter-measure Spearman correlations were determined.

Results
Regional, but not total, adiposity differed by sex: women had greater ASAT mass (8.20±2.73kg, p&lt;0.001) and biopsy yield (3.44±1.81g, p&lt;0.001) than men (ASAT=5.95±2.30kg, biopsy=2.30±1.40g). ASAT mass correlated with leptin (r=0.54, p&lt;0.001) and not resistin (p=0.248) and adiponectin (p=0.353). Adipocyte area correlated with ASAT mass (r=0.34, p&lt;0.001), BMI (r=0.33, p&lt;0.001), adiponectin (r=-0.22, p=0.005) and leptin (r=0.18, p=0.024) but not with resistin (p=0.490).

Conclusion
In addition to the detailed ASAT biopsy processing in this report, we found that adipocyte area correlated with ASAT mass, and both measures related to some key adipokines in the explant conditioned media. These results, methods, and biological repositories underscore the potential of this unique cohort to impact the understanding of aging adipose biology on disease, disability, and other aging tissues.
Olfactory Function and Frailty in Older Adults
Authors: Pleasants Hannah , Yuan Yaqun , Chamberlin Keran , Li Chenxi , Couper David , Shrestha Srishti , Kamath Vidyulata , Deal Jennifer A , Mosley Thomas H , Palta Priya , Pinto Jayant M , Chen Honglei , Kucharska-Newton Anna 
Published: January 2025

Abstract
This study investigated the relationship between olfactory impairment and frailty among 5,231 (mean age 75.3 (SD 5.0), 59% women, 22% Black) participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort located in the U.S.. Olfactory function, assessed from the 12-item Sniffin' Sticks Odor Identification Test at Visit 5 (2011-2013), was categorized as poor (0-8), moderate (9-10) and good (11-12). Frailty was assessed using both the Fried Frailty Phenotype and the Cumulative Frailty Index. Findings revealed that good olfaction was significantly associated with lower odds of frailty (OR=0.29, 95% CI [0.22, 0.39]) and prefrailty (OR= 0.52, 95% CI [0.45, 0.61]) in cross-sectional analyses. Results were robust to adjustment for all covariates. Longitudinal analyses, including 1,519 participants who were robust at study baseline, similarly showed a dose-response pattern, with improved olfaction associated with decreased odds of experiencing prefrailty (OR=0.63 95% CI [0.48, 0.83]) or frailty (OR=0.50, 95% CI [0.25, 1.02]). Further research is needed to elucidate the mechanisms linking olfaction and frailty and explore potential interventions.
Employment Status: The Death Throes of the Tests of Mutuality of Obligation and Control
Authors: Collins Hugh , Freedman Judith 
Published: January 2025

ABSTRACT
The UK Supreme Court in HMRC v Professional Game Match Officials Ltd answered two contentious issues about the identification of contracts of employment for the purpose of tax law. The first rejected the claim that ‘mutuality of obligation’ is a necessary feature of contracts of employment unless it is interpreted to mean the same as ‘consideration’, an essential requirement for all legally binding contracts. The second interpreted the meaning of the necessary requirement of control exercised by the employer to require no more than authority granted by a contractual framework backed up with the possibility of imposing sanctions for poor performance. Although the case concerned a question of tax law, the Supreme Court intermingled case law from employment law as well, so that the case is the leading authority on mutuality of obligation and control for employment law as well.
Question and answers on long-acting therapy with cabotegravir and rilpivirine in people with HIV
Authors: Taramasso Lucia , Bonora Stefano , Cingolani Antonella , Di Biagio Antonio , Gianotti Nicola , Guaraldi Giovanni , Lo Caputo Sergio , Madeddu Giordano , Maggi Paolo , Marchetti Giulia , Nozza Silvia , Rusconi Stefano , Maggiolo Franco 
Published: January 2025

Abstract
Modern ART is evolving, allowing the use of new drug formulations and alternative routes of administration to oral therapy. Long-acting (LA) cabotegravir and rilpivirine, the first fully injectable antiretroviral regimen approved for clinical use, is a test case for this new route of administration, and an innovation with implications for the quality of life of people with HIV (PWH). However, its use requires a reorganization of outpatient clinics and outpatient services, and a number of issues remain to be defined regarding the management of PWH on LA drugs, including the correct selection of people who can be treated with LA cabotegravir and rilpivirine. There is also ongoing debate about the best way to monitor both efficacy and tolerability of LA treatment and whether the management of virological failures and blips should be different from that reserved for oral regimens. The present article reviews the data on the use and management of LA cabotegravir and rilpivirine in different settings, with a review of clinical trial data and also the first available real-life experiences. The article focuses on the following: the reasons for the use of LA drugs; the implementation of their use in clinical practice; and the monitoring of treated people over time.
Experimental investigation and simulation of SEM image intensity behaviors for developing thickness-controlled S/TEM lamella preparation via FIB-SEM
Authors: Uzuhashi Jun , Yao Yuanzhao , Ohkubo Tadakatsu , Sekiguchi Takashi 
Published: January 2025

Abstract
High-quality thin lamellae are essential for state-of-the-art scanning transmission electron microscopy (S/TEM) analyses. While the preparation of S/TEM lamellae using focused ion beam (FIB) scanning electron microscopy has been established since the early twenty-first century, two critical factors have only recently been addressed: precise control over lamella thickness and a systematic understanding of FIB-induced damage. This study conducts an experimental investigation and simulation to explore how the intensities of backscattered and secondary electrons (BSEs and SEs, respectively) depend on lamella thickness for semiconductor (Si), insulator (Al2O3), and metallic (stainless-steel) materials. The BSE intensity shows a simple linear relationship with the lamella thickness for all materials below a certain thickness, whereas the relationship between the SE intensity and thickness is more complex. In conclusion, the BSE intensity is a reliable indicator for accurately determining lamella thickness across various materials during FIB thinning processing, while the SE intensity lacks consistency due to material and detector variability. This insight enables the integration of real-time thickness control into S/TEM lamella preparation, significantly enhancing lamella quality and reproducibility. These findings pave the way for more efficient, automated processes in high-quality S/TEM analysis, making the preparation method more reliable for a range of applications.
Academic Freedom, Education and the ‘Trans Debate’: A Response to Suissa and Sullivan
Authors: Bliss Iris , Gatley Jane 
Published: January 2025

Abstract
Judith Suissa and Alice Sullivan’s 2021 paper ‘The Gender Wars, Academic Freedom and Education’ holds that activism associated with the slogan ‘trans women are women’ harms progress towards the goals of shared learning and knowledge production. They hold that shared learning and knowledge production ground the value of the university. In response, we point out that academic freedom is not absolute, and that its contribution to learning and knowledge production is only part of a host of academic goods. Given the hostile environment faced by trans people in the United Kingdom, absolute academic freedom in relation to questions about sex, gender and gender identity should not be taken for granted. The focus of this paper is on the following: (1) Academic freedom is not absolute and should be responsibly curtailed when it causes harm, or hinders other educational goods; (2) public perceptions of ‘gender debates’ in the United Kingdom cause harm and hinder other educational goods; (3) academic debates about sex, gender and gender identity could contribute to this harm and hindrance and should be undertaken only with care.
Nocturnal hemoglobin desaturation (NHD) in chronically transfused adults with sickle cell disease: a retrospective study
Authors: Obadina Mofiyin A , Owens Iman , Chang Ada , Miller Vanessa , Little Jane A 
Published: January 2025

Unstructured Abstract
High risk sickle cell disease may be managed with chronic red blood cell exchange transfusions. We examined the prevalence of sleep-associated hypoxemia (≥5 minutes at SpO2 ≤88%), or nocturnal hemoglobin desaturation in chronically transfused adults with sickle cell disease. Of 41 identified participants, 15 (36.6%) had tested positive for nocturnal hemoglobin desaturation at some point prior to enrollment. The median duration of desaturation (SpO2 ≤88%) in those that tested positive was 88.3 minutes (IQR 27.9-226.0 minutes). Participants with and without nocturnal hemoglobin desaturation were compared using non-parametric statistical tests. Compared to participants without nocturnal hemoglobin desaturation, those with nocturnal hemoglobin desaturation had higher absolute reticulocyte counts (p = 0.018) and white blood counts (p = 0.05) and tended to be older. They had more anemia (p = 0.11) and higher lactate dehydrogenase levels (p = 0.072). Older age at initiation of chronic red blood cell transfusions associated the strongest with a longer duration of nocturnal hemoglobin desaturation (ρ =  0.4253, p = 0.0067), while prior history of cerebrovascular events associated with a shorter duration of NHD (p = 0.0315). Our results demonstrate that nocturnal hemoglobin desaturation is common in adults being treated with red blood cell exchange for high-risk sickle cell disease, and associates with laboratory evidence of increased disease activity. Increased awareness of this complication and appropriate screening may provide an additional simple, low cost and physiologically relevant treatment intervention ie oxygen therapy.
What Is Fueling FinTech Lending? The Role of Banking Market Structure
Authors: Balyuk Tetyana , Berger Allen N , Hackney John 
Published: January 2025

Abstract
We study the broad question about the sources of FinTech lending growth by examining a specific representative product for which the technologies of both FinTech and the incumbent competitors can be identified and compared—small business lending. We test whether the presence of incumbents employing different technologies affects FinTech penetration, and find more FinTech lending where large/out-of-market banks are more prevalent. Using stress test exposures and Community Reinvestment Act examinations as instruments, we find that FinTech credit more often substitutes for loans by large/out-of-market banks than small/in-market banks. Results are consistent with FinTech advantages in processing hard information, rather than hardening soft information. (JEL G21, G23, O33)
Corticosteroids in Cardiogenic Shock: A Retrospective Analysis of the Medical Information Mart for Intensive Care-IV Database
Authors: Haddad Ghazal , Maslove David M. , Mbuagbaw Lawrence , Belley-Côté Emilie P. , Rochwerg Bram 
Published: January 2025

IMPORTANCE:
While corticosteroid administration in septic shock has been shown to result in faster shock reversal and lower short-term mortality, the role of corticosteroids in the management of cardiogenic shock (CS) remains unexplored.

OBJECTIVES:
Determine the impact of corticosteroid administration on 90-day mortality (primary outcome) in patients admitted to a critical care unit with CS.

DESIGN, SETTING, AND PARTICIPANTS:
In this retrospective cohort study, we used the critical care database of Medical Information Mart for Intensive Care-IV, and included all adult patients diagnosed with CS excluding repeated admissions, patients with adrenal insufficiency, those receiving baseline corticosteroids, and those requiring extracorporeal life support. We considered exposure based on receiving systemic corticosteroids from 6 hours before to 24 hours post-critical care admission.

MAIN OUTCOMES AND MEASURES:
We calculated Cox proportional hazards using multivariate analysis for 90-day mortality (primary outcome). We also explored the association of corticosteroid use with hospital length of stay, ventilator-free days (VFDs), vasopressor-free days, ventilator-associated pneumonia, central-line-associated bloodstream infections, and hyperglycemia.

RESULTS:
We included 2000 eligible patients, with 143 (7.2%) receiving systemic corticosteroids. Corticosteroid-treated patients were younger (67.7 vs. 71.2 yr; p = 0.006), had higher Sequential Organ Failure Assessment scores at baseline (9.4 vs. 7.8; p < 0.001), and more often required vasopressors (78% vs. 63%; p < 0.001), and invasive mechanical ventilation (73% vs. 45%; p < 0.001). Corticosteroid use was associated with increased 90-day mortality in multivariate analysis (hazard ratio, 1.60; 95% CI, 1.25–2.05) and fewer VFDs (2.8 d fewer; 95% CI, 0.35–5.26) with no effect on other secondary outcomes.

CONCLUSIONS AND RELEVANCE:
Use of corticosteroids may be associated with increased mortality and a reduction in VFDs in patients admitted to critical care with CS. These findings suggesting potential harm of corticosteroids in CS might reflect unmeasured confounding and require corroboration through additional observational studies and ultimately randomized clinical trials.