tbuckley/cabot-search huggingface dataset:
Family History in the Context of CKD
Authors: Francesca Zanoni, Maddalena Marasa, Lucrezia Carlassara, Miguel Verbitsky, Atlas Khan, Chen Wang, Joshua D. Bundy, Pietro A. Canetta, Andrew S. Bomback, Afshin Parsa, Harold I. Feldman, Ali G. Gharavi, Krzysztof Kiryluk
Journal: Journal of the American Society of Nephrology (2025)

Background: A family history of health conditions may reflect shared genetic and/or environmental risk. It is not well known to what extent family history impacts outcomes among patients with chronic kidney disease (CKD). Herein, we studied the associations of family history of CKD, diabetes, and other conditions with common comorbidities and kidney disease progression among patients with CKD. Methods: We carried out an observational study of two prospective CKD cohorts, 2,573 adults and children from the Cure Glomerulopathy Network (CureGN) and 3,939 Chronic Renal Insufficiency Cohort (CRIC) adult participants. Self-reported first-degree family history of CKD, diabetes, and other common diseases were tested for associations with the risk of comorbidities and CKD progression using multivariable models. Results: Family history of common comorbid conditions was associated with higher risk of these conditions in the context of CKD, including approximately by over 3-fold for diabetes (adjusted OR 3.37, 95% C.I. 2.73-4.15), 48% for cancer (adjusted OR 1.48, 95% C.I. 1.05-2.09), and 69% for cardiovascular disease (adjusted OR 1.69, 95% C.I. 1.36-2.10 in combined cohorts). While polygenic risk score for CKD was associated with kidney disease progression (adjusted HR 1.11, 95% C.I. 1.06-1.16 in combined cohorts), family history of kidney disease was not an independent risk factor for disease progression in the context of existing CKD. In contrast, family history of diabetes was significantly associated with a higher risk of CKD progression independently of diabetes occurrence, or polygenic risk score for diabetes (adjusted HR 1.19, 95% C.I. 1.05-1.35 in combined cohorts). Conclusions: Broad collection of family history in the context of CKD improved clinical risk stratification. Family history of diabetes was consistently associated with a higher risk of CKD progression independently of diabetes status or polygenic risk score for diabetes in both cohorts.
Resident T Cells and Intrarenal Inflammation
Authors: Rachel M.B. Bell, Laura Denby
Journal: Journal of the American Society of Nephrology (2025)

Edinburgh Kidney, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom Correspondence: Dr. Laura Denby, email: [email protected] See related article, "ATP-Gated P2X7-Ion Channel on Kidney-Resident Natural Killer T Cells and Memory T Cells in Intrarenal Inflammation," on pages 602–613.
Pharmacologically targeting fatty acid synthase-mediated de novo lipogenesis alleviates osteolytic bone loss by directly inhibiting osteoclastogenesis through suppression of STAT3 palmitoylation and ROS signaling
Authors: Chunmei Xiu, Lei Zhang, Chenxi Zhang, Yuannan Zhang, Xi Luo, Ziyi Zhang, Hangkai Zhao, Kaizhong Ji, Zhiyuan Chen, Guangxu He, Jianquan Chen
Journal: Metabolism (2025)
TET2 suppresses vascular calcification by forming inhibitory complex with HDAC1/2 and SNIP1 independent of demethylation
Authors: Dayu He, Jianshuai Ma, Ziting Zhou, Yanli Qi, Yaxin Lian, Feng Wang, Huiyong Yin, Huanji Zhang, Tingting Zhang, Hui Huang
Journal: Journal of Clinical Investigation (2025)

Osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) has been recognized as the principal mechanism underlying vascular calcification (VC). Runt-related transcription factor 2 (RUNX2) in VSMCs plays a pivotal role because it constitutes an essential osteogenic transcription factor for bone formation. As a key DNA demethylation enzyme, ten-eleven translocation 2 (TET2) is crucial in maintaining the VSMC phenotype. However, whether TET2 involves in VC progression remains elusive. Here we identified a substantial downregulation of TET2 in calcified human and mouse arteries, as well as human primary VSMCs. In vitro gain- and loss-of function experiments demonstrated TET2 regulated VC. Subsequently, in vivo knockdown of TET2 significantly exacerbated VC in both vitamin D3 and adenine-diet-induced chronic kidney disease (CKD) mice models. Mechanistically, TET2 binds to and suppresses the activity of the P2 promoter within the RUNX2 gene, whereas an enzymatic loss-of-function mutation of TET2 has a comparable effect. Furthermore, TET2 forms a complex with histone deacetylases 1/2 (HDAC1/2 ) to deacetylate H3K27ac on the P2 promoter, thereby inhibiting its transcription. Moreover, SNIP1 is indispensable for TET2 to interact with HDAC1/2 to exert inhibitory effect on VC, and knockdown of SNIP1 accelerated VC in mice. Collectively, our findings imply that TET2 might serve as a potential therapeutic target for VC.
Transcriptomic profiling after B-cell depletion reveals central and peripheral immune cell changes in multiple sclerosis
Authors: Jessica Wei, Jeonghyeon Moon, Yoshiaki Yasumizu, Le Zhang, Khadir Raddassi, Nicholas C. Buitrago-Pocasangre, M. Elizabeth Deerhake, Nicolas Strauli, Chun-Wei Chen, Ann Herman, Rosetta Pedotti, Catarina Raposo, Isaiah Yim, Jenna L. Pappalardo, Erin E. Longbrake, Tomokazu S. Sumida, Pierre-Paul Axisa, David A. Hafler
Journal: Journal of Clinical Investigation (2025)

Multiple sclerosis (MS) is a complex genetically mediated autoimmune disease of the central nervous system where anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. While previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic impact on patient immune landscape is unknown. In this study, we explored how B cell depleting therapies modulate the immune landscape using single-cell RNA sequencing (scRNAseq). We demonstrate that B cell depletion leads to cell type-specific changes in the abundance and function of CSF macrophages and peripheral blood monocytes. Specifically, a CSF-specific macrophage population with an anti-inflammatory transcriptomic signature and peripheral CD16+ monocytes increased in frequency post-B cell depletion. This was accompanied by increases in TNFα messenger RNA and protein in monocytes post-B cell depletion, consistent with the finding that anti-TNFα treatment exacerbates autoimmune activity in MS. In parallel, B cell depletion induced changes in peripheral CD4+ T cell populations, including increases in the frequency of TIGIT+ regulatory T cells and marked decreases in the frequency of myelin peptide loaded-tetramer binding CD4+ T cells. Collectively, this study provides an exhaustive transcriptomic map of immunological changes, revealing different cell-type specific reprogramming as a result of B cell depletion treatment in MS.
The Path From Intracranial Pressure to Clinical Outcomes in Pediatric Traumatic Brain Injury
Authors: Jennifer C. Laws, Patrick M. Kochanek, Michael S. Wolf
Journal: JAMA Network Open (2025)

Shu-Ling Chong, MD, MPH; Yanan Zhu, PhD; Quan Wang, MD; Paula Caporal, MPH; Juan D. Roa, MD; Freddy Israel Pantoja Chamorro, MD; Thelma Elvira Teran Miranda, MD; Hongxing Dang, MD; Chin Seng Gan, MD; Qalab Abbas, MD; Ivan J. Ardila, MD; Mohannad Ahmad Antar, MD; Jesús A. Domínguez-Rojas, MD; María Miñambres Rodríguez, PhD; Natalia Zita Watzlawik, MD; Natalia Elizabeth Gómez Arriola, MD; Adriana Yock-Corrales, MD; Rubén Eduardo Lasso-Palomino, MD; Ming Mei Xiu, MD; Jacqueline S. M. Ong, MD; Hiroshi Kurosawa, MD; Gabriela Aparicio, MD; Chunfeng Liu, MD; Rujipat Samransamruajkit, MD; Juan C. Jaramillo-Bustamante, MD; Nattachai Anantasit, MD; Yek Kee Chor, MD; Deborah M. Turina, MD; Pei Chuen Lee, MD; Marisol Fonseca Flores, MD; Francisco Javier Pilar Orive, PhD; Jane Ng Pei Wen, BSc; Sebastián González-Dambrauskas, MD; Jan Hau Lee, MCI; Pediatric Acute and Critical Care Medicine in Asia Network (PACCMAN) and the Red Colaborativa Pediátrica de Latinoamérica (LARed); Yasser M. Kazzaz; Ji Jian ; Suyun Qian ; Lijia Fan ; Olive Pei Ee Lee; Soo Lin Chuah; Kai You; Tao Zhang; Deiby Lasso Noguera; Esteban Cerón ; Andrea Leal Barceló; Susana Beatriz Reyes Domínguez ; Cesia J Ortega Ocas
Cardiovascular Health and Biomarkers of Neurodegenerative Disease in Older Adults
Authors: Anisa Dhana, Charles S. DeCarli, Klodian Dhana, Pankaja Desai, Ted K. S. Ng, Denis A. Evans, Kumar B. Rajan
Journal: JAMA Network Open (2025)

Importance Cardiovascular health (CVH), defined by the American Heart Association as Life’s Simple 7 to promote a healthy lifestyle and manage vascular risk factors, has been associated with a low risk of Alzheimer disease and less vascular dementia. However, the association between CVH and biomarkers of neurodegeneration remains less understood. Objective To investigate the association of CVH with serum biomarkers of neurodegeneration, including neurofilament light chain (NfL) and total tau (t-tau). Design, Setting, and Participants This cohort study was conducted within the biracial, population-based Chicago Health and Aging Project (CHAP) of adults aged 65 years or older between 1993 and 2012. Participants who had measured serum NfL and t-tau levels and data on all components of the CVH score were included. The statistical analysis was conducted from April 10 to September 26, 2024. Exposure The CVH score includes 7 components: a healthy diet; regular exercise; normal body mass index; nonsmoking status; and the absence of dyslipidemia, diabetes, and hypertension. The scores were divided into 3 groups from lowest to highest CVH (0-6 points, 7-9 points, and 10-14 points). Main Outcomes and Measures The main outcome was the association of CVH score with serum biomarkers of NfL and t-tau as measured using linear regression and mixed-effects models. Results A total of 1018 CHAP participants were included in the analysis (mean [SD] age, 73.1 [6.1] years; 625 female [61.4%]; 610 Black or African American [59.9%] and 408 White [40.1%]). Participants with a high CVH score (ie, 10-14 points) were predominantly White (151 [64.3%]) and had a higher education (mean [SD], 13.6 [3.7] years). Compared with participants with low CVH scores (ie, 0-6 points), those with CVH scores of 10 to 14 points had significantly lower serum levels of NfL (relative difference, −18.9%; β = −0.091; SE, 0.025). A higher CVH score was associated with a slower annual increase in NfL levels as participants aged (relative difference in rate, −1.7%; β = −0.008; SE, 0.004). Cardiovascular health was not associated with serum levels of t-tau. Conclusions and Relevance These findings suggest that promoting CVH in older adults may help alleviate the burden of neurodegenerative diseases, particularly among Black adults, who are known to experience a higher prevalence of cardiovascular disease.
Bowel Disorder Incidence and Rectal Spacer Use in Patients With Prostate Cancer Undergoing Radiotherapy
Authors: Michael R. Folkert, Ryoko Sato, James B. Yu, Danielle Vannan, Samir Bhattacharyya, Carrie Noriega, Daniel A. Hamstra
Journal: JAMA Network Open (2025)

Importance The polyethylene glycol-based hydrogel spacer (PHS) system temporarily separates the rectum from the prostate in patients undergoing radiotherapy (RT) for prostate cancer (PCa). Objective To compare incidence of bowel disorders and related procedures in patients receiving RT with and without PHS. Design, Setting, and Participants This retrospective cohort study used 4 datasets: Medicare 5% Standard Analytic Files, Medicare 100% Standard Analytic Files, Merative MarketScan Commercial Database, and Premier Healthcare Database. Participants included adult patients with PCa undergoing RT from 2015 to 2021. Exposure Placement of PHS. Main Outcomes All-cause bowel disorders and related procedures, identified from diagnosis and procedure codes. Results were compared with age-matched male general population without PCa or RT. Results Of 261 906 patients with PCa included in the study, 25 167 (9.6%) received PHS (mean [SD] age, 70.7 [6.5] years) and 236 739 did not (mean [SD] age, 71.1 [7.5] years). One year prior to RT, patients who received PHS had a lower mean (SD) Charlson Comorbidity Index score than those who did not (2.48 [1.08] vs 3.14 [1.95]; P &amp;amp;lt; .001). Stereotactic RT was more common in patients who received PHS (2743 [10.9%] vs 8810 [3.7%]; P &amp;amp;lt; .001), while intensity-modulated RT was less common (12 755 [50.7%] vs 142 402 [60.2%]; P &amp;amp;lt; .001). After 4 years post RT, patients who received PHS had a 25% lower hazard of bowel disorders (hazard ratio [HR], 0.75 [95% CI, 0.72-0.78]; P &amp;amp;lt; .001) and a 46% lower hazard of related procedures (HR, 0.54 [95% CI, 0.47-0.62]; P &amp;amp;lt; .001) than patients who did not receive PHS. Patients without PHS had higher hazard compared with an age-matched general population (disorders: 17.1% [95% CI, 17.3%-17.6%] vs 10.3% [95% CI, 10.1%-10.5%]; HR, 1.35 [95% CI, 1.32-1.37]; P &amp;amp;lt; .001; procedures: 2.0% [95% CI, 1.9%-2.1%] vs 0.7% [95% CI, 0.7%-0.8%]; HR, 1.92 [95% CI, 1.79-2.06]; P &amp;amp;lt; .001), while patients who received PHS did not (disorders: 12.4% vs 10.3%; HR, 1.00 [95% CI, 0.98-1.05]; P = .82; procedures: 1.1% [95% CI, 1.0%-1.3%] vs 0.7% [95% CI, 0.7%-0.8%]; HR, 1.11 [95% CI, 0.96-1.29]; P = .15). Common procedures included colonoscopy, sigmoidoscopy, and rectal resection. Conclusions and Relevance In this cohort study of patients with PCa receiving RT, those receiving a PHS had a significantly lower incidence of all-cause bowel disorders and related procedures compared with patients who did not receive a PHS over the 4-year follow-up. The incidence among patients with PHS was similar to the general population. These findings are consistent with prior phase 3 trial results, where patients receiving PHS experienced no decline in bowel quality of life.
Tissue‐Resident Memory CD8+ T Cells: Differentiation, Phenotypic Heterogeneity, Biological Function, Disease, and Therapy
Authors: Luming Xu, Lilin Ye, Qizhao Huang
Journal: MedComm (2025)

ABSTRACT CD8+ tissue‐resident memory T cells (TRM) are strategically located in peripheral tissues, enabling a rapid response to local infections, which is different from circulating memory CD8+ T cells. Their unique positioning makes them promising targets for vaccines designed to enhance protection at barrier sites and other organs. Recent studies have shown a correlation between CD8+ TRM cells and favorable clinical outcomes in various types of cancer, indicating their potential role in immune checkpoint blockade (ICB) therapies. However, the dual nature of CD8+ TRM cells presents challenges, as their inappropriate activation may lead to autoimmunity and chronic inflammatory conditions. This review highlights significant advancements in the field, focusing on the differentiation pathways and phenotypic heterogeneity of CD8+ TRM cells across different tissues and disease states. We also review their protective roles in various contexts and the implications for vaccine development against infections and treatment strategies for tumors. Overall, this comprehensive review outlines the common features of CD8+ TRM cell differentiation and biological functions, emphasizing their specific characteristics across diverse tissues and disease states, which can guide the design of therapies against infections and tumors while minimizing the risk of autoimmune diseases.
PTPσ-mediated PI3P regulation modulates neurodegeneration in C9ORF72-ALS/FTD
Authors: Zhe Zhang, Xiujuan Fu, Noelle Wright, Weiren Wang, Yingzhi Ye, Julie Asbury, Yini Li, Chengzhang Zhu, Rong Wu, Shaopeng Wang, Shuying Sun
Journal: Neuron (2025)
Tumor-specific surface marker-independent targeting of tumors through nanotechnology and bioorthogonal glycochemistry
Authors: Hyesun Hyun, Bo Sun, Mostafa Yazdimamaghani, Albert Wielgus, Yue Wang, Stephanie Ann Montgomery, Tian Zhang, Jianjun Cheng, Jonathan S. Serody, Andrew Z. Wang
Journal: Journal of Clinical Investigation (2025)

Biological targeting is crucial for effective cancer treatment with reduced toxicity but is limited by the availability of tumor surface markers. To overcome this, we developed a nanoparticle-based, Tumor-specific suRfACE maRker-independent (TRACER) targeting approach. Utilizing the unique biodistribution properties of nanoparticles, we encapsulated Ac4ManNAz to selectively label tumors with azide reactive groups. Surprisingly, while NP-delivered Ac4ManNAz was cleared by the liver, it did not label macrophages, potentially reducing off-target effects. To exploit this tumor-specific labeling, we functionalized anti-4-1BB antibodies with dibenzocyclooctyne (DBCO) to target azide-labeled tumor cells and activate the immune response. In syngeneic B16F10 melanoma and orthotopic 4T1 breast cancer models, TRACER enhanced anti-4-1BB's therapeutic efficacy, increasing median survival time. Immunofluorescence analyses revealed increased tumor infiltration of CD8+ T and NK cells with TRACER. Importantly, TRACER reduced hepatotoxicity associated with anti-4-1BB, resulting in normal serum ALT and AST levels and decreased CD8+ T cell infiltration in the liver. Quantitative analysis confirmed a 4.5-fold higher tumor-to-liver ratio of anti-4-1BB accumulation with TRACER compared to conventional anti-4-1BB antibodies. Our work provides a promising approach for developing targeted cancer therapies that circumvent limitations imposed by the paucity of tumor-specific markers, potentially improving efficacy and reducing off-target effects to overcome liver toxicity associated with anti-4-1BB.
RNA Modification in Metabolism
Authors: Yadi Liu, Zhongyan Sun, Dingkun Gui, Yonghua Zhao, Youhua Xu
Journal: MedComm (2025)

ABSTRACT Epigenetic regulation in disease development has been witnessed within this decade. RNA methylation is the predominant form of epigenetic regulation, and the most prevalent modification in RNA is N6‐methyladenosine (m 6 A). Recently, RNA modification has emerged as a potential target for disease treatment. RNA modification is a posttranscriptional gene expression regulation that is involved in both physiological and pathological processes. Evidence suggests that m 6 A methylation significantly affects RNA metabolism, and its abnormal changes have been observed in a variety of diseases. Metabolic diseases are a series of diseases caused by abnormal metabolic processes of the body, the common metabolic diseases include diabetes mellitus, obesity, and nonalcoholic fatty liver disease, etc.; although the pathogenesis of these diseases differs from each other to the current understanding, most recent studies suggested pivotal role m 6 A in modulating these metabolic diseases, and m 6 A‐based drug development has been on the agenda. This paper reviewed recent understanding of RNA modification in metabolic diseases, hoping to provide systematic information for those in this area.
Impact of Work on Personal Relationships—The Missing Workplace Well-Being and Quality Indicator
Authors: Mickey T. Trockel, Tait D. Shanafelt
Journal: JAMA Network Open (2025)

Corey Obermiller, MStat; Richa Bundy, MPH; Lauren Witek, MStat; Adam Moses, MHA, PMP; Lindsey Carlasare, MBA; Gary Rosenthal, MD; Christine Sinsky, MD; Ajay Dharod, MD
Preventive Services for Food Insecurity
Authors: Elizabeth A. O’Connor, Elizabeth M. Webber, Allea M. Martin, Michelle L. Henninger, Michelle L. Eder, Jennifer S. Lin
Journal: JAMA (2025)

Importance An estimated 12.8% of US households experienced food insecurity in 2022. Objective To review the evidence on benefits and harms of screening and interventions for food insecurity in health care settings. Data Sources MEDLINE, CINAHL, and the Cochrane Central Registry of Controlled Trials through October 11, 2022; references of existing reviews; surveillance through January 24, 2025. Study Selection English-language randomized clinical trials (RCTs), nonrandomized studies of interventions, and pre-post studies conducted in US health care settings that examine the impact of screening or interventions for food insecurity; instrument accuracy studies of brief screening tools. Data Extraction and Synthesis Single extraction, verified by a second reviewer. Results were narratively summarized. Main Outcomes and Measures Food insecurity; dietary, physiologic, quality of life, health outcomes; sensitivity and specificity of screening tools. Results One RCT (n = 789) examined the impact of screening for food insecurity and found no difference in food insecurity after 6 months (29.6% in the intervention group vs 29.8% with usual care). Ten accuracy studies (n = 123 886) compared 1-, 2-, and 6-item subsets of the US Department of Agriculture Household Food Security Survey (HFSS) with the full HFSS. Sensitivity was typically above 95% and specificity above 82%, although most studies did not administer the screener separately from the reference standard, potentially overstating the accuracy. Twenty-nine studies (n = 74 292) examined interventions to address food insecurity, but 27 were rated as poor quality for the outcomes of interest for this review. Of the 2 fair-quality studies, 1 randomized crossover study (n = 44) found that home delivery of medically tailored meals was associated with reduced food insecurity (41.9% while “on meals” vs 61.5% while “off meals,” P = .05). The other fair-quality propensity-matched cohort study found a smaller increase in body mass index among children whose families participated in a mobile food bank than those who did not after 6 months (mean difference in change, −0.68 [95% CI, −1.2 to −0.2]). The remaining studies found wide-ranging effect sizes for change in food security status but generally trended in the direction of benefit. Conclusions and Relevance Brief screening tools likely have sufficient sensitivity to identify people with food insecurity in health care settings, but most studies of interventions to improve food insecurity had high risk of bias, limiting the ability to draw firm conclusions.