tbuckley/cabot-search huggingface dataset:
Serum Type I Interferon Score predicts clinically meaningful disease progression in limited cutaneous Systemic Sclerosis
Authors: Stefano Di Donato, Rebecca Ross, Ranjitha Karanth, Vishal Kakkar, Enrico De Lorenzis, Lesley‐Anne Bissell, Kristina Clark, Philip Yee, Christopher P. Denton, Francesco Del Galdo
Journal: Arthritis & Rheumatology (2025)

Objective To assess the value of serum Type I Interferon (IFN) score in predicting clinically meaningful progression in limited cutaneous systemic sclerosis (lcSSc) using a novel composite endpoint adopted from the MINIMISE clinical trial. Methods A retrospective, longitudinal lcSSc cohort was identified within a national, multicentre observational cohort. The MINIMISE combined Morbi‐mortality endpoint was used as clinical outcome for a time to clinical worsening (TTCW) design. IFN score was calculated from the serum concentration of CCL2, CCL8, CCL19, CXCL9, CXCL10, and CXCL11 on patients and age‐ and sex‐matched healthy controls (HC). “High” IFN score was defined as two standard deviations above HC mean. The association of the IFN score with TTCW was assessed using Cox Proportional Hazard regressions and Kaplan‐Meier curves. The potential improvement in risk stratification when combining IFN score with lcSSc clinical features was explored. Results A total of 149 patients were included in the analysis, 67 “High” IFN and 82 “Low”. “High” IFN patients presented a shorter TTCW (74.7 months [95% C.I. 70.1‐79.3] vs 110.6 [95% C.I. 107.2‐114.0], p&lt;0.001) and met the endpoint in higher proportion compared to “Low” IFN (55% vs 12%, p&lt;0.001). “High” IFN score conferred 5.5 (95% C.I. 2.7‐11.3) Hazard Ratio (HR) for TTCW compared to “Low” IFN and IFN score as a continuous variable conferred 2.38 (95% C.I. 1.4‐4.0) HR for TTCW independently of clinical variables. Pulmonary Arterial Hypertension, Interstitial Lung Disease, Digital Ulcers, and modified Rodnan Skin Score were associated to TTCW. An exploratory analysis showed that these clinical features improve risk stratification over time in combination with IFN score. Conclusion Serum assessment of Type I IFN activity is a valuable predictor of clinically meaningful outcomes in lcSSc. The combination of serum IFN score with sentinel clinical features can improve stratification strategies in clinical trials and patient management. image
Long-term follow up from the Harvard Alumni Health Study: collegiate sport participation in males is associated with higher physical activity throughout midlife
Authors: Meagan M Wasfy, Uzair Tahamid Siam, Sarah K Gustus, Kevin S Boyd, Adam S Tenforde, Howard Sesso, I-Min Lee
Journal: British Journal of Sports Medicine (2025)

To compare physical activity (PA) over midlife between (1) former collegiate athletes and non-athletes and (2) among athletes in different sports. The Harvard Alumni Health Study (HAHS) is a prospective cohort study of male undergraduates who completed serial questionnaires regarding PA and health status between 1962 and 1993. PA was categorised by intensity (<3 METs, light; 3 to <6 METs, moderate; ≥6 METs, vigorous), and energy expenditure (kilocalories (kcal)/week) was estimated at each intensity and in total. HAHS data were merged with university athletics records. Mixed linear models, adjusted for graduating class, survey date, age and smoking, were compared with PA between relevant groups. 22 201 participants completed 38 448 surveys when 30-65 years old, of which 1533 (6.9%) participants were athletes completing 2733 (7.1%) surveys. The age at the first survey was 46.8±9.7 years. Athletes were more active than non-athletes throughout midlife (p<0.001), from age 35 (total PA: +856.8 [704.6 to 1009.1] kcal/week) to age 65 (+524.2 [359.1 to 689.4] kcal/week). Total PA levels converged with older age, and differences resulted from more vigorous intensity PA in athletes. Multisport collegiate athletes were more active than single sport athletes (+544.6 [196.5 to 892.7] kcal/week, p=0.002). Compared with other athletes, PA in midlife was higher in tennis (+750.1 [223.9 to 1276.2] kcal/week, p=0.005) and basketball (+373.6 [28.7 to 718.5] kcal/week, p=0.03) players. Collegiate sport participation, particularly participation in multiple sports, is associated with higher midlife PA levels in males. These results underscore the importance of early life sport exposure in supporting health-promoting levels of later life PA.
Sensitivity to Environmental Stress and Adversity and Lung Cancer
Authors: Yingxi Chen, Qing Lan, Jing Yu, Devika Godbole, Jinyoung Byun, Christopher I. Amos, Haoyu Zhang
Journal: JAMA Network Open (2025)

Importance Sensitivity to environmental stress and adversity may influence lung cancer risk, highlighting a critical link between psychosocial factors and cancer etiology. Objective To evaluate whether genetically estimated sensitivity to environmental stress and adversity is associated with lung cancer risk. Design, Setting, and Participants Data were obtained from a genome-wide association study identifying 37 independent genetic variants strongly associated with sensitivity to environmental stress and adversity and a cross-ancestry genome-wide meta-analysis from the International Lung Cancer Consortium. Data were extracted between October 2023 and January 2024 and analyzed between February 2024 and June 2024. Exposures Genetically estimated sensitivity to environmental stress and adversity. Main Outcomes and Measures The main outcome was lung cancer risk, and odds ratios and 95% CIs were used to assess the association between sensitivity to environmental stress and adversity with lung cancer risk. This genetic association study used a 2-sample Mendelian randomization (MR) to estimate the association between genetically estimated sensitivity to environmental stress and adversity and lung cancer risk across different histologic types. Results Using data from 351 827 individuals from the UK Biobank and a cross-ancestry genome-wide analysis of 61 047 lung cancer cases and 947 237 controls from the International Lung Cancer Consortium, sensitivity to environmental stress and adversity was significantly associated with an increased risk of lung cancer among individuals of European ancestry (OR, 1.49; 95% CI, 1.13-1.98; P = .005) and in the cross-ancestry analysis (OR, 1.45; 95% CI, 1.13-1.85; P = .004). There were heterogeneities in the observed associations across histologic subtypes among different population ancestries. Among individuals of European ancestry, a significant association was noted among squamous cell carcinoma (OR, 1.69; 95% CI, 1.06-2.70; P = .03). Among individuals of East Asian ancestry, an increased risk was observed for adenocarcinoma (OR, 2.04; 95% CI, 1.00-4.18; P = .05). Associations were not observed across any of the 3 histologic subtypes among individuals of African ancestry. Conclusions and Relevance In this genetic association study, sensitivity to environmental stress and adversity was associated with lung cancer risk. These results underscore the necessity for further research into the nuanced association between psychosocial stress and cancer risk, with a particular focus on diverse populations.
Cervical Cancer Screening in Women With Physical Disabilities
Authors: Alexandra H. Vinson, Corrianne Norrid, Elizabeth K. Haro, Susan Ernst, Christelle El Khoury, Martha L. Alves, Autumn Kieber-Emmons, Ashwini Kamath Mulki, Emma A. Butcher, Claire Kalpakjian, Michael M. McKee, Diane M. Harper
Journal: JAMA Network Open (2025)

Cervical cancer screening is a crucial public health intervention, but screening disparities exist for women with physical disabilities (WWPD). To explore the experiences of WWPD with both traditional speculum examination-based screening and at-home self-sampling for cervical cancer screening. This qualitative study enrolled 56 WWPD to test self-sampling kits, provide feedback via a survey, and participate in a qualitative interview. An interprofessional team conducted semistructured interviews with 16 key informants and 40 pilot participants for 56 WWPD from November 1, 2021, through April 30, 2023. All completed a self-administered quantitative survey. Key informants' experiences with 4 self-sampling devices helped determine which 2 self-sampling kits would be offered to participants in a pilot study. A coding scheme was developed to represent inductive codes generated through preliminary coding and deductive codes representing domains from the Theoretical Domains Framework. This coding scheme was used to conduct a 2-pass thematic analysis. Of the 56 WWPD (mean [SD] age, 45.4 [9.1] years) who participated in the study, 28 (50.0%) were up to date with cervical cancer screening. Participants described accessibility barriers and clinician ableism that made speculum-based in-office examinations difficult, leading some participants to delay or avoid screening. In contrast, participants described self-screening as more comfortable and convenient, regardless of whether they prefer future speculum-based screening. Their responses also allowed for the exploration of how screening preferences may impact future screening behavior. Interviews with WWPD suggested that access to self-sampling screening options would be more comfortable for cervical cancer screening participation. Understanding participants' experiences with self-sampling devices generates insights into improving screening experiences for WWPD.
Use of Body Armor by EMS Clinicians, Workplace Violence, and Racial and Ethnic Disparities in Care
Authors: Sarayna S. McGuire, Fernanda Bellolio, Matthew D. Sztajnkrycer, Michael J. Sveen, Chad P. Liedl, Aidan F. Mullan, Casey M. Clements
Journal: JAMA Network Open (2025)

Importance There is a clear benefit to body armor against firearms; however, it remains unclear how these vests may influence day-to-day patient encounters when worn by emergency medical services (EMS). Objective To determine the association of ballistic vests worn by EMS clinicians with workplace violence (WPV) and disparities in care among racial and/or ethnic minority patients. Design, Setting, and Participants Prospective cohort study of a volunteer-based sample of EMS clinicians at a large, multistate EMS agency encompassing 15 ground sites across the Midwest from April 1, 2023, to March 31, 2024. Data were analyzed from May to June 2024. Exposure External ballistic armor being used by a group of self-selected clinicians on every run. Main Outcomes and Measures Prevalence and characteristics associated with WPV and with declines of treatment and/or transport compared between crews with 1 or more vested vs no vested members. Results A total of 156 of 415 staff (37.6%) opted in to wear the vests, including 77 male participants (49.4%). Prevalence of WPV was higher for vested crews (1.11 vs 0.85 cases per 100 runs; adjusted risk ratio [aRR], 1.28; 95% CI, 1.10 to 1.50; P = .001) and was due to higher rates of verbal abuse. The presence of 1 or more vested crew members increased the likelihood of all patients declining EMS treatment and/or transport; however, effect size was highest among patients with an unknown race and/or ethnicity (2234 [21.1%] vs 2134 [16.5%] patients; aRR, 1.19; 95% CI, 1.10 to 1.27; P &amp;amp;lt; .001), followed by racial and/or ethnic minority patients (708 [16.7%] vs 399 [13.8%] patients; aRR, 1.18; 95% CI, 1.05 to 1.33; P = .01). Analyses of individual minority groups revealed a significant increase only in Black or African American patients declining treatment and/or transport by vested crews (461 [17.6%] vs 223 [13.7%] patients; RR, 1.28; 95% CI, 1.10 to 1.49; P = .002). Conclusions and Relevance In this cohort study, vested crews experienced increased prevalence of WPV compared with nonvested crews. Use of vests increased the frequency of all patients declining EMS treatment and/or transport. Among minority groups, there was a significant increase in Black or African American patients declining treatment and/or transport. Agencies should consider benefits and unintended consequences of EMS clinicians wearing body armor.
Mental Health Disparities by Sexual Orientation and Gender Identity in the All of Us Research Program
Authors: Junjie Anderson Lu, Shamsi Soltani, S. Bryn Austin, David H. Rehkopf, Mitchell R. Lunn, Marvin E. Langston
Journal: JAMA Network Open (2025)

Importance Limited research explores mental health disparities between individuals in sexual and gender minority (SGM) populations and cisgender heterosexual (non-SGM) populations using national-level data. Objective To explore mental health disparities between SGM and non-SGM populations across sexual orientation, sex assigned at birth, and gender identity within the All of Us Research Program. Design, Setting, and Participants This cross-sectional study used survey data and linked electronic health records of eligible All of Us Research Program participants from May 31, 2017, to June 30, 2022. Exposure Self-identified SGM status. Main Outcomes and Measures Prevalence of common mental health conditions identified from linked electronic health records. Logistic regression adjusted for age, race and ethnicity, educational level, income, employment status, and geographic region was used to assess the association between SGM status and mental health conditions. Results Among 413 457 participants, 269 947 (65.3%) were included in the analysis (median age, 59 [IQR, 43-70] years), with 22 189 (8.2%) self-identified as SGM. Men with cisgender sexual minority identity had higher odds of bipolar disorder (adjusted odds ratio [AOR], 1.87; 95% CI, 1.70-2.56) compared with cisgender heterosexual men. Women with cisgender sexual minority identity had higher odds of bipolar disorder (AOR, 2.09; 95% CI, 1.95-2.25) compared with cisgender heterosexual women. Gender diverse people assigned female sex at birth had higher odds of posttraumatic stress disorder (PTSD) compared with both cisgender heterosexual men (AOR, 3.67; 95% CI, 2.99-4.50) and cisgender heterosexual women (AOR, 2.77; 95% CI, 2.26-3.40). Gender diverse individuals assigned male sex at birth had higher odds of bipolar disorder (AOR, 2.35; 95% CI, 1.66-3.33) compared with cisgender heterosexual men and higher odds of attention-deficit/hyperactivity disorder (AOR, 2.19; 95% CI, 1.48-3.23) compared with cisgender heterosexual women. Transgender men had higher odds of depression (AOR, 2.11; 95% CI, 1.80-2.49) compared with cisgender heterosexual men, while transgender women had higher odds of any personality disorder (AOR, 2.71; 95% CI, 1.84-3.99) compared with cisgender heterosexual women. Conclusions and Relevance In this cross-sectional study of participants in the All of Us Research Program, there were significant mental health disparities between participants in SGM and non-SGM groups. These findings underscore the need for tailored mental health interventions to improve the well-being of SGM populations, while noting that the associations do not imply causality but reflect the stigma and minority stress experienced by these individuals.
Default Bulk Ordering and Text Messaging to Enhance Outreach for Lipid Screening
Authors: Catherine Pollak, Andrew Parambath, Samantha Coratti, Laurie Norton, Anthony Girard, Catherine Reitz, Christopher K. Snider, Lin Xu, Zakiya Walker, Aileen John, Mary E. Putt, Kevin G. Volpp, Shivan J. Mehta
Journal: JAMA Cardiology (2025)

Importance A comprehensive lipid panel is recommended by guidelines to evaluate atherosclerotic cardiovascular disease risk, but uptake is low. Objective To evaluate whether direct outreach including bulk orders with and without text messaging increases lipid screening rates. Design, Setting, and Participants Pragmatic randomized clinical trial conducted from June 6, 2023, to September 6, 2023, at 2 primary care practices at an academic health system among patients aged 20 to 75 years with at least 1 primary care visit in the past 3 years who were overdue for lipid screening. Data analysis was performed from September 2023 to May 2024. Interventions Eligible patients were randomized in a 1:2:2 ratio to usual care (group 1), direct outreach and bulk orders (group 2), and bulk order outreach with additional text message reminders for scheduling assistance (group 3). In group 3, participants received an initial, follow-up, and reminder text message. Patients with electronic portal accounts were encouraged to schedule through them, while others received laboratory contact information. Any participant inquiries were answered either with automated responses for common questions or with study team support. Main Outcomes and Measures Proportion of patients who completed a lipid panel within 3 months. Results Among the 1000 participants, the median (IQR) age was 38 (28-55) years; 470 (47.0%) were female; and 22 (2.3%) were Asian, 38 (3.9%) were Black, 32 (3.2%) were Hispanic or Latino, and 862 (88.6%) were White (race and ethnicity were based on self-reported data). At 3 months, a lipid panel was completed by 12 of 202 patients (5.9%; 95% CI, 3.4% to 10.1%) receiving usual care (group 1) vs 62 of 394 patients (15.7%; 95% CI, 12.5% to 19.7%) receiving direct outreach and bulk order (group 2), a difference of 9.8 percentage points (95% CI, 4.6 to 15.0; P = .001). The panel was completed by 73 of 404 patients (18.1%; 95% CI, 14.6% to 22.1%) receiving outreach, bulk order, and text message reminders (group 3), for a difference of 2.4 percentage points (95% CI, −3.1 to 7.8; P = .43) vs outreach with bulk order alone (group 2). At 6 months, there were no significant differences in lipid screening between either group 1 vs group 2 or group 2 vs group 3. Conclusions and Relevance Lipid screening among participants receiving bulk orders and outreach letters increased significantly compared with usual care at 3 months. However, there was no difference at 6 months. More than 80% of patients did not follow through with lipid screening despite the intervention, and there was no additional increase in lipid testing at 3 months among participants receiving bulk ordering and supplemental text messaging. Trial Registration ClinicalTrials.gov Identifier: NCT05724615
Replication-Poison Treatment in BRCA1-Deficient Breast Cancer Causes MRE11 Over-Resection that Induces Single-Stranded DNA Accumulation and Mitotic Catastrophe
Authors: Imene Tabet, Esin Orhan, Ermes Candiello, Lise Fenou, Carolina Velázquez, Beatrice Orsetti, Geneviéve Rodier, William Jacot, Cyril Ribeyre, Claude Sardet, Charles Theillet
Journal: Cancer Research (2025)

BRCA1 deficiency is observed in approximately 25% of triple-negative breast cancer (TNBC). BRCA1, a key player of homologous recombination (HR) repair, is also involved in stalled DNA replication fork protection and repair. Here, we investigated the sensitivity of BRCA1-deficient TNBC models to the frequently used replication chain terminator gemcitabine, which does not directly induce DNA breaks. A large fraction of BRCA1-deficient cells was sensitive to gemcitabine, in contrast to their isogenic BRCA1-proficient counterparts. Gemcitabine treated BRCA1-deficient cells accumulated massive levels of single strand DNA (ssDNA) and presented no RPA or RAD51 nuclear foci. The gemcitabine-induced accumulation of ssDNA in BRCA1-deficient cells was strongly diminished by targeting MRE11 with inhibitors and by siRNA attenuation. In contrast, treatment with the PARP1/2 inhibitor olaparib did not result in MRE11 dependent over-resection. Furthermore, a fraction of gemcitabine treated BRCA1-deficient cells that showed massive ssDNA accumulation slipped into mitosis, producing mitotic bridges and strongly stained BrdU and γH2AX micronuclei (MN). The BrdU-positive MN and DNA bridges also stained positively for cGAS. In conclusion, these data suggest that gemcitabine treatment in BRCA1-deficient TNBC exposes unprotected nascent DNA linked to replication fork reversal, which leads to MRE11 over-resection and ssDNA accumulation. Therefore, the observed hypersensitivity to gemcitabine indicates that it could be a beneficial addition to BRCA1-deficient TNBC treatment.
Improved Outcomes and Resource Use With Normothermic Machine Perfusion in Liver Transplantation
Authors: Michelle C. Nguyen, Chi Zhang, Yu-Hui Chang, Xingjie Li, Stephanie Y. Ohara, Kayla R. Kumm, Christopher P. Cosentino, Bashar A. Aqel, Blanca C. Lizaola-Mayo, Peter E. Frasco, Raphael Nunez-Nateras, Winston R. Hewitt, Jack W. Harbell, Nitin N. Katariya, Andrew L. Singer, Adyr A. Moss, Kunam S. Reddy, Caroline Jadlowiec, Amit K. Mathur
Journal: JAMA Surgery (2025)

Importance Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. Objective To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). Design, Setting, and Participants This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. Exposure DBD and DCD livers preserved on NMP or SCS. Main Outcomes and Measures The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. Results A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) ( P &amp;amp;lt; .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P &amp;amp;lt; .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P &amp;amp;lt; .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) ( P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P &amp;amp;lt; .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P &amp;amp;lt; .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). Conclusions and Relevance In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.