tbuckley/cabot-search huggingface dataset:
Longitudinal Associations Between Baseline Sarcopenia and Knee Osteoarthritis Progression and Risk of Knee Replacement
Authors: Tianxing Wu, Xiaoshuai Wang, Zhuojian Cai, Peihua Cao, Qin Dang, Weijie Zhou, Jiawei Xie, Jie Chen, Taiwei Wang, Gaochenzi Tao, Weiyu Han, Zhaohua Zhu, Jian Wang, David J Hunter, Rocco Barazzoni, Changhai Ding, Jia Li
Journal: Arthritis & Rheumatology (2025)

Objectives Sarcopenia and knee osteoarthritis (KOA) are common conditions in older adults, but the relationship is controversial. We aimed to examine the potential role of sarcopenia in KOA progression and subsequent knee replacement (KR). Methods Using data from the Osteoarthritis Initiative (OAI), baseline sarcopenia was first screened according to the EWGSOP2 algorithm using the SARC‐F questionnaire (screened sarcopenia, Scre‐S), then further assessed combined with the five times chair‐stand‐test (probable sarcopenia, Prob‐S). Radiographic KOA progression was evaluated by changes in Kellgren‐Lawrence Grade (KLG) and Osteoarthritis Research Society International (OARSI) atlas scores from baseline to 24‐ and 48‐month follow‐up. Symptomatic progression was evaluated similarly using the Western Ontario McMaster Osteoarthritis Index (WOMAC). The associations of sarcopenia with radiographic or symptomatic progression and subsequent KR were analyzed before and after adjusting for potential confounders and propensity score (PS)‐matching. Results 4316 participants were included with 27.2% being Scre‐S and 16.8% being Prob‐S. Baseline Scre‐S and Prob‐S were positively associated with both radiographic and symptomatic progression in KOA, over 24 and 48 months. Both Scre‐S and Prob‐S were associated with a higher risk of subsequent KR (HR 3.84, 95% CI 3.18 to 4.62 for Scre‐S and HR 2.29, 95% CI 1.87 to 2.81 for Prob‐S). These results remained significant in the PS‐matched cohort. Conclusions Scre‐S and Prob‐S were significantly and longitudinally associated with both radiographic and symptomatic progression in KOA and subsequent KR. Our findings indicated a potential causal role of sarcopenia in KOA progression, and highlighted its potentially therapeutic effect in KOA management. image
Microscopic In Vivo Description of Dermatoscopic Pigment Network under Magnified Dermoscopy
Authors: Maria Daviti, Nikolaos Chaitidis, Joanna Pogorzelska-Dyrbuś, Roberta Giuffrida, Stefania Guida, Franco Rongioletti, Ch Dorado Cortes, Kenny Velia, Jean-Luc Perrot, Caterina Longo, John Paoli, Efstratios Vakirlis, Eleni Sotiriou, Aimilios Lallas, Elisa Cinotti
Journal: Journal of the American Academy of Dermatology (2025)
Validating Optimal ICD-10 Classification Approaches for Identifying Perioral Dermatitis: A Retrospective Chart Review
Authors: Sherry Ershadi, Ursula Biba, Nora Bensellam, Katherine Sanchez, Debby Cheng, Samantha Gregoire, Nikki Zangenah, Arash Mostaghimi, John S Barbieri
Journal: Journal of the American Academy of Dermatology (2025)
Upadacitinib for Refractory Alopecia Areata Unresponsive to Prior Systemic Therapies: A Retrospective Study
Authors: Qin Wang, Linxia Shen, Yuou Sha, Ke Tao, Jui-Ming Lin, Lijuan Zhou, Sisi Qi, Yue Zhang, Jinran Lin, Wenyu Wu
Journal: Journal of the American Academy of Dermatology (2025)
Biomimicry-Inspired Zwitterionic Polyurethane Used for Vascular Implants Showing Water-induced Stiffening and Preventing Intimal Hyperplasia in Stent
Authors: Ruibo Yang, Chuwen Chen, Wenkai Liu, Ao Wang, Pengjun Jiang, Zhen Li, Feng Luo, Jiehua Li, Hong Tan
Journal: Biomaterials (2025)
TBC1D15 protects alcohol-induced liver injury in female mice through PLIN5-mediated mitochondrial and lipid droplet contacting
Authors: Haixia Xu, Jiayu Shi, Wenjun Yu, Shiqun Sun, Haoxiong Zhou, Lu Wang, Jun Ren, Zhifeng Gu, Qi Lu, Yingmei Zhang
Journal: Metabolism (2025)
Impact of pre-existing anti-polyethylene glycol (PEG) IgM on biodistribution and humoral response of intramuscularly administered PEGylated mRNA loaded lipid nanoparticle
Authors: Shunji Abe, Haruka Takata, Taro Shimizu, Yoshino Kawaguchi, Shoichiro Fukuda, Haruka Yamamoto, Hidenori Ando, Tatsuhiro Ishida
Journal: Journal of Controlled Release (2025)
Associations and Diagnostic Accuracy of Ultrasound Features in Knee Osteoarthritis: Cross‐sectional Results from a Large Community‐based Cohort: comment on the article by Yates <scp>KA</scp> et al.
Authors: Haojie Guan, Haidong Zhou, Hongyu Xu, Hejing Pan
Journal: Arthritis & Rheumatology (2025)
Bioinspired 3D‐Printed NIR‐Responsive MXene‐Based Multifunctional Eutectogel Microneedles for Personalized Infected Wound Healing
Authors: Huan Liu, Aminov Nail, Decheng Meng, Liran Zhu, Xiaohan Guo, Cong Li, Xiaoqing Ye, Huanjun Li
Journal: Advanced Healthcare Materials (2025)

Abstract Infected wound healing remains a significant clinical challenge, demanding innovative therapeutic strategies to simultaneously address bacterial elimination, tissue regeneration, and controlled drug delivery. Inspired by the hierarchical structure of crocodile teeth, a bioinspired, 3D‐printed microneedle patch integrating Mxene nanosheets and a polymerizable deep eutectic solvent (PDES) composed of vinyl pyrrolidone (VP), itaconic acid (IA), and N‐isopropyl acrylamide (NIPAM) is developed. The resulting MXene‐based eutectogel microneedle (MF‐MXene@MN) combines photothermal responsiveness, antioxidant activity, and temperature‐triggered drug release for photothermal conversion and reactive oxygen species (ROS) scavenging. The gradient‐height design inspired by crocodile teeth enhances tissue adhesion, while DLP 3D printing enables personalized wound dressing geometries with &lt;50 µm resolution. In vitro and in vivo studies demonstrated a 94.88% wound closure rate within 10 days, 3.2‐fold increased angiogenesis, 68% reduced bacterial viability ( S. aureus : 32.59%; E. coli : 48.17% under NIR), and pH‐/temperature‐responsive mangiferin release (88.3% cumulative release via 5 NIR cycles). These synergistic functions promote wound healing, offering superior antibacterial ability, tissue regeneration promotion, and drug release control compared to traditional wound dressings and microneedle systems. This multifunctional platform integrates bioinspired design, stimuli‐responsive materials, and additive manufacturing, providing a transformative solution for precision wound management.
BCOR and ZC3H12A suppress a core stemness program in exhausted CD8+ T cells
Authors: Jing Xu, Zeran Jia, Xiaocui Zhao, Lixia Wang, Gang Jin, Zhuoyang Li, Na Yin, Yinqing Li, Min Peng
Journal: The Journal of Experimental Medicine (2025)

In chronic viral infections, sustained CD8+ T cell response relies on TCF1+ precursor-exhausted T cells (TPEX) exhibiting stem-like properties. TPEX self-renew and respond to PD-1 blockade, underscoring their paramount importance. However, strategies for effectively augmenting TPEX remain limited. Here, we demonstrate that ZC3H12A deficiency initiates a stemness program in TPEX but also increases cell death, whereas BCOR deficiency predominantly promotes TPEX proliferation. Consequently, co-targeting of both BCOR and ZC3H12A imparts exceptional stemness and functionality to TPEX, thereby enhancing viral control. Mechanistically, BCOR and ZC3H12A collaboratively suppress a core stemness program in TPEX characterized by heightened expression of ∼216 factors. While TCF1 plays a role, this core stemness program relies on novel factors, including PDZK1IP1, IFIT3, PIM2, LTB, and POU2F2. Crucially, overexpressing POU2F2 robustly boosts TPEX and enhances antiviral immunity. Thus, a core stemness program exists in exhausted T cells, jointly repressed by BCOR and ZC3H12A, robustly controlling TPEX differentiation and providing new targets for addressing T cell exhaustion.
Conversion Therapy Exposure and Elevated Cardiovascular Disease Risk
Authors: James K. Gibb, Joshua M. Schrock, Madison Shea Smith, Richard T. D’Aquila, Thomas W. McDade, Brian Mustanski
Journal: JAMA Network Open (2025)

Importance Sexual orientation and gender identity change efforts (SOGICE), commonly known as conversion therapy, persist across the United States despite having been discredited due to their harmful mental health impact. Understanding the health consequences of SOGICE is critical, particularly for conditions exacerbated by stress, such as cardiovascular disease. Objective To investigate the association between SOGICE exposure and cardiovascular disease risk. Design, Setting, and Participants This cohort study draws on data from the observational cohort study RADAR, which included sexual and gender minority (SGM) young adults assigned male at birth (AMAB) in Chicago, Illinois. All data for this analysis were collected cross-sectionally during the same study visit for each participant between December 1, 2023, and October 31, 2024. Participants who completed SOGICE exposure measures and had cardiovascular health data were eligible; participants with incomplete data were excluded. Exposure SOGICE exposure and duration. Main Outcomes and Measures Primary outcomes were diastolic blood pressure (DBP) and systolic blood pressure (SBP) measured via automatic monitors, systemic inflammation (SI) assessed through plasma biomarkers, and self-reported hypertension or high blood pressure (HHBP) diagnosis. Regression analyses were adjusted for sociodemographic and behavioral covariates. Results Among 703 participants (mean [SD] age, 26.75 [4.60] years), 540 (76.8%) identified as cisgender, and 163 (23.2%) identified as transgender or gender diverse. Seventy-two participants (10.2%) reported exposure to SOGICE. Exposed participants had higher SI levels (β = 0.83; 95% CI, 0.17-1.49; P = .02), increased DBP (β = 3.46; 95% CI, 0.60-6.32; P = .02), elevated SBP (β = 4.28; 95% CI, 0.68-7.87; P = .02), and greater odds of self-reported HHBP diagnosis (odds ratio, 2.86; 95% CI, 2.19-3.54; P = .003) compared with nonexposed participants. Associations remained significant after adjusting for covariates. Conclusions and Relevance In this cohort study of SGM young adults AMAB, exposure to SOGICE was associated with adverse cardiovascular health indicators, including elevated DBP and SBP, increased SI, and higher odds of self-reported HHBP. These findings underscore the need for public health and policy interventions to enforce and strengthen bans on SOGICE practices. Recognizing the cardiovascular health consequences of SOGICE contributes to addressing SGM health disparities and emphasizes the importance of affirmative care approaches that prioritize the well-being of SGM individuals.
Transposable elements as genome regulators in normal and malignant haematopoiesis
Authors: Dmitry Prokopov, Hale Tunbak, Eve Leddy, Bryce Drylie, Francesco Camera, Özgen Deniz
Journal: Blood Cancer Journal (2025)

Abstract Transposable elements (TEs) constitute over half of the human genome and have played a profound role in genome evolution. While most TEs have lost the ability to transpose, many retain functional elements that serve as drivers of genome innovation, including the emergence of novel genes and regulatory elements. Recent advances in experimental and bioinformatic methods have provided new insights into their roles in human biology, both in health and disease. In this review, we discuss the multifaceted roles of TEs in haematopoiesis, highlighting their contributions to both normal and pathological contexts. TEs influence gene regulation by reshaping gene-regulatory networks, modulating transcriptional activity, and creating novel regulatory elements. These activities play key roles in maintaining normal haematopoietic processes and supporting cellular regeneration. However, in haematological malignancies, TE reactivation can disrupt genomic integrity, induce structural variations, and dysregulate transcriptional programmes, thereby driving oncogenesis. By examining the impact of TE activity on genome regulation and variation, we highlight their pivotal roles in both normal haematopoietic processes and haematological cancers.
Radical Treatment for Prostate Cancer in Men With Limited Life Expectancy in Sweden
Authors: Eugenio Ventimiglia, Rolf Gedeborg, Johan Styrke, Andri Wilberg Orrason, Pär Stattin, Marcus Westerberg
Journal: JAMA Network Open (2025)

This cohort study compares rates of radical treatment for prostate cancer, despite current guideline recommendations that discourage its use for men with limited life expectancy, in Sweden and the US.
Plasma proteomic and metabolomic profiling of coronary and carotid atherosclerosis in the SCAPIS study – differences and similarities
Authors: Tove Fall, Anders Gummesson, Ulf Hammar, Håkan Ahlström, Oskar Angerås, Anders Blomberg, John Brandberg, Kenneth Caidahl, Elin Chorell, Jan E Engvall, Per Eriksson, David Erlinge, Bruna Gigante, Ola Hjelmgren, Johan Hultdin, Tomas Jernberg, Johan Kihlberg, Lars Lind, Martin Magnusson, Fredrik H Nyström, Carlo Pirazzi, Alexandru Schiopu, Johan Sundström, Stefan Söderberg, Carl Johan Östgren, Gunnar Engström
Journal: Cardiovascular Research (2025)
A hierarchical model of early brain functional network development
Authors: Wei Gao
Journal: Trends in Cognitive Sciences (2025)

Functional brain networks emerge prenatally, grow interactively during the first years of life, and optimize both within-network topology and between-network interactions as individuals age. This review summarizes research that has characterized this process over the past two decades, and aims to link functional network growth with emerging behaviors, thereby developing a more holistic understanding of the developing brain and behavior from a functional network perspective. This synthesis suggests that the development of the brain's functional networks follows an overlapping hierarchy, progressing from primary sensory/motor to socioemotional-centered development and finally to higher-order cognitive/executive control networks. Risk-related alterations, resilience factors, treatment effects, and novel therapeutic opportunities are also discussed to encourage the consideration of future imaging-assisted methods for identifying risks and interventions.
Cerebrospinal fluid proteome profiling across the Alzheimer’s disease continuum: a step towards solving the equation for ‘X’
Authors: Sophia Weiner, Mathias Sauer, Laia Montoliu-Gaya, Andrea L Benedet, Nicholas J Ashton, Fernando Gonzalez-Ortiz, Joel Simrén, Nesrine Rahmouni, Cecile Tissot, Joseph Therriault, Stijn Servaes, Jenna Stevenson, Ville Leinonen, Tuomas Rauramaa, Mikko Hiltunen, Pedro Rosa-Neto, Kaj Blennow, Henrik Zetterberg, Johan Gobom
Journal: Molecular Neurodegeneration (2025)

Abstract Background While the temporal profile of amyloid (Aβ) and tau cerebrospinal fluid (CSF) biomarkers along the Alzheimer’s disease (AD) continuum is well-studied, chronological changes of CSF proteins reflecting other disease-relevant processes, denoted ‘X’ in the ATX(N) framework, remain poorly understood. Methods Using an untargeted mass spectrometric approach termed tandem mass tag (TMT), we quantified over 1500 CSF proteins across the AD continuum in three independent cohorts, finely staged by Aβ/tau positron emission tomography (PET), fluid biomarkers, or brain biopsy. Weighted protein co-expression network analysis identified clusters of proteins robustly correlating in all three cohorts which sequentially changed with AD progression. Obtained protein clusters were correlated with fluid biomarker measurements (phosphorylated tau (p-tau) species including p-tau 181 , p-tau 217 , and p-tau 205 , as well as Aβ), Aβ/tau PET imaging, and clinical parameters to discern disease-relevant clusters which were modelled across the AD continuum. Results Neurodegeneration-related proteins (e.g . , 14–3-3 proteins, PPIA), derived from different brain cell types, strongly correlated with fluid as well as imaging biomarkers and increased early in the AD continuum. Among them, the proteins SMOC1 and CNN3 were highly associated with Aβ pathology, while the 14–3-3 proteins YWHAZ and YWHAE as well as PPIA demonstrated a strong association with both Aβ and tau pathology as indexed by PET. Endo-lysosomal proteins (e.g., HEXB, TPP1, SIAE) increased early in abundance alongside neurodegeneration-related proteins, and were followed by increases in metabolic proteins such as ALDOA, MDH1, and GOT1 at the mild cognitive impairment (MCI) stage. Finally, later AD stages were characterized by decreases in synaptic/membrane proteins (e.g., NPTX2). Conclusions Our study identified proxies of Aβ and tau pathology, indexed by PET, (SMOC1, YWHAE, CNN3) and highlighted the dynamic fluctuations of the CSF proteome over the disease course, identifying candidate biomarkers for disease staging beyond Aβ and tau.
Rapid and Simultaneous Initiation of Guideline-Directed Kidney Therapies in Patients with CKD and Type 2 Diabetes
Authors: Ahmed Mustafa Rashid, Muhammad Shahzeb Khan, David Z.I. Cherney, Ankit Mehta, Janani Rangaswami, Tariq Shafi, Javed Butler
Journal: Journal of the American Society of Nephrology (2025)

The global incidence of chronic kidney disease (CKD) continues to rise, with type 2 diabetes as a major contributor. At any stage of CKD, patients with concurrent CKD and type 2 diabetes are at heightened cardiovascular risk and have a greater likelihood of dying from cardiovascular causes than progressing to kidney failure. Consequently, the use of ‘four pillars’ of CKD therapy, including renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter 2 inhibitors (SGLT2i), nonsteroidal mineralocorticoid receptor antagonists (ns-MRA), and glucagon-like peptide-1 receptor agonists (GLP1-RAs), has been advocated to reduce cardiovascular-kidney risk. While these therapies can mitigate cardiovascular and kidney events when used individually, the residual risks of these events remain high across major clinical trials testing these therapies separately as well as in real-world clinical settings. This raises the question about when to optimally initiate these therapies, including strategies that start these agents in rapid sequence, or even simultaneously, in order to reduce long-term risk, thereby mirroring best-practices with rapid titration schedules in patients with heart failure. However, initiating all four therapies simultaneously in the setting of CKD has not yet been tested due to lack of data on safety and tolerability in this high risk population. Data regarding the safety profile of rapid sequence initiation remain limited. Therefore, our aim was to review the existing evidence on the safety profiles of guideline-recommended therapies and discuss the challenges associated with rapid sequence initiation of these treatments in patients with CKD.
Proximal Tubule Cells Contribute to the Thin Descending Limb of the Loop of Henle during Mouse Kidney Development
Authors: Eunah Chung, Fariba Nosrati, Mike Adam, Andrew Potter, Mohammed Sayed, Christopher Ahn, Benjamin D. Humphreys, Hee-Woong Lim, Yueh-Chiang Hu, S. Steven Potter, Joo-Seop Park
Journal: Journal of the American Society of Nephrology (2025)

Background: The thin descending limb of the loop of Henle is crucial for urine concentration, as it facilitates passive water reabsorption. Despite its importance, little is known about how this nephron segment forms during kidney development. Methods: We assembled a large single-cell RNA sequencing (scRNA-seq) dataset by integrating multiple datasets of non-mutant developing mouse kidneys to identify developing thin descending limb cells. To test whether those cells originate from proximal tubule cells, we generated a proximal tubule-specific Cre line, Slc34a1eGFPCre , and conducted lineage tracing. Additionally, given that the transcription factor Hnf4a directly binds to the Aqp1 gene, we examined whether the loss of Hnf4a affects Aqp1 expression in thin descending limb cells. Results: From our scRNA-seq dataset, we identified a small cluster of cells distinct from both the proximal tubule and the thick ascending limb of the loop of Henle. Those cells exhibited high expression of thin descending limb marker genes, including Aqp1 and Bst1 . Notably, a subset of proximal tubule cells also expressed thin descending limb marker genes, suggesting that proximal tubule cells may give rise to thin descending limb cells. Using lineage tracing with the Slc34a1eGFPCre line, we found that, at least, a subset of thin descending limb cells are descendants of proximal tubule cells. Furthermore, the loss of Hnf4a, a transcription factor essential for mature proximal tubule cell formation, disrupted proper Aqp1 expression in thin descending limb cells, providing additional evidence of a developmental link between proximal tubule cells and thin descending limb cells. Conclusions: Our findings shed new light on the developmental origin of thin descending limb cells and highlight the importance of Hnf4a in regulating their formation.
Impact of Hematopoietic CD14 on Oxidative Stress during Salt-Sensitive Hypertension and Kidney Injury
Authors: Emily C. Burns-Ray, John Henry Dasinger, Mary Cherian-Shaw, Samuel D. Walton, Kaitlyn E. Baldwin, Ann B. Cormier, Sadaf Hasan, Daniel J. Fehrenbach, Justine M. Abais-Battad, David L. Mattson
Journal: Journal of the American Society of Nephrology (2025)

Background: In high-salt diet-fed Dahl salt-sensitive rats, increased CD14 expression by infiltrating macrophages accompanies hypertension and kidney damage. Interestingly, genetic deletion of CD14 in the Dahl salt-sensitive rat model (SS CD14-/- ) conferred a significant exacerbation of salt-induced hypertension and associated kidney disease in females. We speculated that CD14 may function to modulate the production of reactive oxygen species in macrophages, since previous findings implicated hematopoietic NADPH oxidase 2 (NOX2)-derived superoxide in the pathogenesis of salt-sensitive hypertension. The present study tested the hypothesis that the amplification of salt-sensitive hypertension and kidney damage in salt-sensitive females lacking CD14 is dependent upon NOX2. Methods: A double knockout salt-sensitive rat was bred to lack both CD14 and the critical p67 phox subunit of NOX2 (SS CD14-/-p67phox-/- ). In vivo and ex vivo experiments explored the consequences of CD14 deletion in addition to nonfunctional NOX2 on salt-induced blood pressure, kidney damage, and inflammation. Complementary experiments utilizing diseased human kidneys correlated our findings to humans. Results: We found that SS CD14-/- peritoneal macrophages demonstrated increased NOX2 subunit mRNA and a greater capacity to produce NOX2-superoxide versus Dahl salt-sensitive rats, while SS CD14-/-p67phox-/- macrophages did not produce superoxide. We also showed that SS CD14-/-p67phox-/- females had significantly attenuated salt-induced hypertension, kidney damage, and renal inflammation compared to SS CD14-/- , indicating that NOX2 mediates the exacerbation of disease in CD14 absence. A subsequent total body irradiation/bone marrow transfer approach utilizing Dahl salt-sensitive female recipients and transfer of SS CD14-/-p67phox-/- bone marrow recapitulated these findings demonstrating a clear interplay of CD14 and NOX2 specifically in immune cells. Finally, consistent with observations in the Dahl salt-sensitive rats, immunohistochemical observations in human tissue demonstrated a positive correlation between kidney damage, CD68 + macrophages and CD14 in the kidney. Conclusions: We highlight a novel regulatory pathway whereby hematopoietic CD14 influences NOX2-derived oxidative stress and therefore modulates the progression of hypertension and kidney disease.