tbuckley/cabot-search huggingface dataset:
Detection Bias in EHR-Based Research on Clinical Exposures and Dementia
Authors: Jingxuan Wang, Minhyuk Choi, Peter Buto, J. Daniel Kelly, Renaud La Joie, John Kornak, Scott C. Zimmerman, Ruijia Chen, Eva Raphael, Catherine A. Schaefer, Deborah Blacker, M. Maria Glymour
Journal: JAMA Network Open (2025)

Importance Detection bias occurs when an exposure is associated with a systematic difference in outcome ascertainment or diagnosis. For dementia research, diagnosed health conditions that bring patients into frequent interaction with health care may increase the chance that an individual receives a dementia diagnosis. Objective To evaluate potential detection bias or misdiagnosis bias in evaluation of clinical factors associated with dementia using electronic health record (EHR) data. Design, Setting, and Participants This prospective cohort study used data from 2 population-based volunteer cohorts: UK Biobank (UKB) and All of Us (AOU). Participants were aged 55 years or older, were dementia-free at baseline, and had linked EHRs. Participants in UKB were followed up from baseline (2006-2010) until December 2022, and in AOU, from baseline (2017-2022) until July 2022. Data were analyzed from November 2023 through February 2025. Exposures Diagnoses of type 2 diabetes, depression, hypertension, urinary tract infection, kidney stones, forearm fracture, and gastrointestinal (GI) bleeding. Main Outcomes and Measures Rate of incident all-cause dementia diagnosis from EHRs and associations between clinical exposures and incident dementia diagnosis, assessed using Cox proportional hazards regression models. Results Among 228 392 participants from UKB (n = 137 374; mean [SD] age at baseline, 62.5 [4.1] years; 53.8% female) and AOU (n = 91 018; mean [SD] age at baseline, 66.9 [7.8] years; 57.1% female), those with a history of a clinical exposure at baseline had higher dementia incidence rates compared with those without such history. For example, among participants with a history of GI bleeding, the dementia incidence rates were 3.0 (UKB) and 7.7 (AOU) per 1000 person-years compared with 2.2 (UKB) and 2.4 (AOU) per 1000 person-years among those without a history of GI bleeding. All exposures were significantly associated with incident dementia, with hazard ratios (HRs) ranging from 1.18 (95% CI, 1.00-1.40) to 3.51 (95% CI, 3.08-4.01). Risk of incident dementia was typically highest in the first year following exposure diagnosis and attenuated thereafter. For example, in the first year after GI bleeding, there were larger elevations in risk of incident dementia (HR, 2.17 [95% CI, 1.46-3.22] in UKB; HR, 2.56 [95% CI, 1.62-4.04] in AOU) compared with 1 to 5 years after bleeding (HR, 1.46 [95% CI, 1.15-1.86] in UKB; HR, 2.14 [95% CI, 1.63-2.81] in AOU). Conclusions and Relevance In this cohort study of 2 large datasets, diagnoses of several conditions associated with varying risks of dementia were associated with a higher short-term likelihood of dementia diagnosis. This finding suggests that diagnostic bias or misdiagnoses may lead to spurious associations between conditions requiring clinical care and subsequent dementia diagnoses.
Cutaneous <i>Mycobacterium marinum</i> Treated With Photodynamic Therapy Alone and Combined With Antibiotics
Authors: Wenlong Hu, Qiunan Yao, Yue Mou, Chaochao Ji, Wenhao Cheng, Renqiong Chen, Jiaqi Liu, Xudong Mou, Di Cao, Hong Ren
Journal: JAMA Dermatology (2025)

This cohort study evaluated the effectiveness and safety of photodynamic therapy (PDT) alone and combined with antibiotics for the treatment of cutaneous Mycobacterium marinum infections.
Cuffless Blood Pressure Measurement Devices—International Perspectives on Accuracy and Clinical Use
Authors: Eugene Yang, Aletta E. Schutte, George Stergiou, Fernando Stuardo Wyss, Yvonne Commodore-Mensah, Augustine Odili, Ian Kronish, Hae-Young Lee, Daichi Shimbo
Journal: JAMA Cardiology (2025)

Importance Hypertension is a primary modifiable risk factor for cardiovascular death and disability. Accurate blood pressure (BP) measurement is essential for the diagnosis and treatment of hypertension. Conventional BP measurement with cuff devices is recommended but difficult for patients to perform due to inconvenience, discomfort, and challenges with appropriate cuff sizing and measurement protocols. The emergence of cuffless BP devices provides an opportunity to address many of these problems, including inconvenience, patient comfort, positional requirements, and continuous measurement. Observations Cuffless BP measurement devices are appealing to patients and clinicians, but validation of these technologies is essential before they can be deployed for clinical use. Key issues that remain include accuracy with risk of undertreatment or overtreatment, equitable access for low- and middle-income countries and minoritized populations, data privacy concerns, and how the devices will be deployed in clinical practice. Conclusions Clinicians and patients should only use validated BP cuff devices until cuffless BP measurement devices are appropriately tested and validated.
Long-Term Postoperative Outcomes by Surgeon Gender and Patient-Surgeon Gender Concordance in the US
Authors: Ryo Ikesu, Hiroshi Gotanda, Tara A. Russell, Melinda Maggard-Gibbons, Marcia McGory Russell, Ryu Yoshida, Ruixin Li, Alexandra Klomhaus, Christian de Virgilio, Yusuke Tsugawa
Journal: JAMA Surgery (2025)

Importance Evidence suggests that physician gender and patient-physician gender concordance have the potential to improve patient outcomes, especially for female patients. However, whether long-term outcomes differ by surgeon gender and patient-surgeon gender concordance has not been studied in the US. Objective To compare long-term postoperative outcomes by surgeon gender and patient-surgeon gender concordance. Design, Setting, and Participants A population-based cross-sectional study was conducted based on 100% Medicare fee-for-service claims data from 2016 through 2019. Data analysis was performed between October 17, 2023, and January 28, 2025. The study took place at acute care hospitals in the US. Participants included Medicare fee-for-service beneficiaries aged 65 to 99 years who underwent 1 of 14 elective or emergent surgeries. Exposures Surgeon gender and patient-surgeon gender concordance. Main Outcomes and Measures Ninety-day and 1-year postoperative mortality, readmission, and complication rates were compared by surgeon gender and patient-surgeon gender concordance. The study team adjusted for patient and surgeon characteristics and hospital fixed effects, effectively comparing patients within the same hospital. Results Among 2 288 279 patients who underwent surgery, 129 528 were operated on by female surgeons (5.7%) and 2 158 751 were by male surgeons (94.3%). Patients treated by female surgeons experienced a lower long-term mortality rate compared with those treated by male surgeons (adjusted 90-day mortality rates, 2.6% for female surgeons vs 3.0% for male surgeons; adjusted risk difference [aRD], −0.3 percentage points [pp]; 95% CI, −0.5 pp to −0.2 pp; P &amp;amp;lt; .001), similarly for both female and male patients. For female patients, the patient-surgeon gender concordance was associated with lower long-term readmission (adjusted 90-day readmission rates, 7.3% vs 7.7%; aRD, −0.4 pp; 95% CI, −0.7 pp to −0.2 pp; P = .001) and complication rates (adjusted 90-day complication rates, 12.2% vs 12.8%; aRD, −0.5 pp; 95% CI, −0.9 pp to −0.2 pp; P = .005). For male patients, long-term readmission and complication rates did not differ between patients treated by female vs male surgeons. Similar patterns were found between 90-day and 1-year patient outcomes. Conclusions and Relevance In this study, both female and male patients treated by female surgeons experienced lower long-term postoperative mortality rates compared with those treated by male surgeons. Patient-surgeon gender concordance was associated with lower long-term readmission and complication rates for female patients, but not for male patients. These patterns were observed only for elective procedures and may not be generalizable to other populations, such as younger patients.
Cumulative Life’s Essential 8 Scores and Cardiovascular Disease Risk
Authors: James Walker, Daniel Won, James Guo, Jamal S. Rana, Norrina B. Allen, Hongyan Ning, Donald M. Lloyd-Jones
Journal: JAMA Cardiology (2025)

Importance Most literature on the association between cardiovascular health (CVH) and incident cardiovascular disease (CVD) and mortality has relied on single midlife measurements. Understanding how cumulative CVH over time influences later-life CVD and mortality may aid early prevention. Objective To determine whether cumulative CVH, as measured by the American Heart Association Life’s Essential 8 (LE8) from age 18 to 45 years, is associated with incident CVD and mortality in midlife. Design, Setting, and Participants This cohort study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, collected CVH data for participants from 4 US centers from 1985 to 2020. Multivariate Cox proportional hazard models assessed the associations of (1) cumulative LE8 score by quartile, (2) cumulative LE8 score and score at age 45 years, and (3) cumulative LE8 score and LE8 score slope from age 18 to 45 years with incident CVD and mortality after age 45 years. Main Outcomes and Measures Incident CVD and all-cause mortality. Cumulative LE8 score was calculated as the area under the curve of the LE8 score (0-100, higher is better CVH) over time from age 18 to 45 years. Results There were 4832 CARDIA participants (2690 [55.7%] female and 2142 [44.3%] male) with a mean (SD) cumulative LE8 score from age 18 to 45 years of 2018.8 (95.0) point × years. Compared with quartile 1 (Q1, ie, lowest CVH), Q2, Q3, and Q4 had significantly lower hazards for CVD (Q2 HR, 0.44; 95% CI, 0.32-0.61; Q3 HR, 0.26; 95% CI, 0.18-0.38; Q4 HR, 0.12; 95% CI, 0.07-0.21) and mortality (Q2 HR, 0.51; 95% CI, 0.36-0.71; Q3 HR, 0.38; 95% CI, 0.26-0.55; Q4 HR, 0.29; 95% CI, 0.18-0.45) after age 45 years. When cumulative LE8 score from age 18 to 45 years and LE8 score at age 45 years were in the model together, both were significantly associated with lower risk for CVD. Likewise, both cumulative LE8 score and positive slope of (improving) LE8 score from age 18 to 45 years were significantly associated with lower hazards for incident CVD after age 45 years. Conclusions and Relevance Greater cumulative CVH and improvement in CVH during young adulthood, as well as better CVH in middle age, were all independently associated with lower risk for incident CVD in midlife. These results emphasize the importance of maintaining and improving CVH throughout young adulthood.
Cannabis Use and Misuse Following Recreational Cannabis Legalization
Authors: André J. McDonald, Amanda Doggett, Kyla Belisario, Jessica Gillard, Jane De Jesus, Emily Vandehei, Laura Lee, Jillian Halladay, James MacKillop
Journal: JAMA Network Open (2025)

Importance An increasing number of jurisdictions have legalized recreational cannabis for adults, but most evaluations have used repeated cross-sectional designs, preventing examination of within-person and subgroup trajectories across legalization. Objective To examine changes in cannabis use and misuse in the 5 years following legalization in Canada both overall and by prelegalization cannabis use frequency using a longitudinal design. Design, Setting, and Participants This prospective cohort study included data from community-dwelling adults who participated in up to 11 biannual assessments from September 2018 to October 2023 in Ontario, Canada. Data were analyzed from November 2023 to January 2024. Exposure Five years of recreational cannabis legalization (baseline wave was immediately prior to legalization). Main Outcome and Measures Primary outcomes were cannabis use frequency and cannabis misuse, assessed using Cannabis Use Disorder Identification Test – Revised (CUDIT-R) score. Prelegalization cannabis use frequency, age, and sex were examined as moderators. Secondary outcomes included changes in cannabis product preferences over time. Results The final cohort included 1428 community-dwelling adults aged 18 to 65 years (859 [60.2%] female; mean [SD] age, 34.5 [13.9] years). Mean retention was 90% across all waves. Linear mixed-effects modeling found a significant increase in cannabis use frequency, such that the mean proportion of days using cannabis increased by 0.35% (95% CI, 0.19% to 0.51%) per year ( P &amp;amp;lt; .001) in the overall sample (1.75% over 5 years). In contrast, CUDIT-R scores (on scale of 0 to 32) decreased significantly overall (β = −0.08 [95% CI, −0.10 to −0.06] per year; −0.4 over 5 years; P &amp;amp;lt; .001), most notably with the onset of the COVID-19 pandemic. Interaction analyses indicated that prelegalization cannabis use frequency significantly moderated changes for both outcomes ( P &amp;amp;lt; .001). Specifically, cannabis use and misuse decreased among prelegalization frequent consumers and modestly increased among occasional users and nonusers. Cannabis product preferences shifted away from dried flower, hashish, concentrates, oil, tinctures, and topicals to edibles, liquids, and vape pens. Conclusions and Relevance In this prospective cohort study of community-dwelling adults in Canada, cannabis use frequency increased modestly in the 5 years following legalization, while cannabis misuse decreased modestly. These changes were substantially moderated by prelegalization cannabis use, with more frequent consumers of cannabis before legalization exhibiting the largest decreases in both outcomes. Although longer-term surveillance is required, these results suggest Canadian recreational cannabis legalization was associated with modest negative and positive consequences among adults.
Helminth reshapes host gut microbiota and immunoregulation by deploying an antimicrobial program of innate immunity
Authors: Yang Zou, Lixia Pu, Aijiang Guo, Yaqi Li, Yihui Liu, Yugui Wang, Yingying Ding, Xiaowei Du, Xiaola Guo, Shaohua Zhang, Xuepeng Cai, Shuai Wang
Journal: Gut Microbes (2025)

Helminths can manipulate their host's gut microbiota, with the expansion of the lactobacilli population being a common feature. This process profoundly influences host immunoregulation, yet the underlying mechanisms remain almost unknown. Using a tissue-dwelling helminth model (larval Echinococcus multilocularis) while validating key findings from other helminth infections, we show that helminths harness the antibacterial program of host innate immunity to transform the host gut microbiome and control gut microbiota-mediated immunity. Using multifaceted techniques, we elucidate that cathelicidin-related antimicrobial peptide (CRAMP), derived from the expanded CD11b+CD206+ macrophages rather than the intestinal epithelial cells, is the key component that enters into the gut ecological system and enhances the fitness of Lactobacillus by selectively killing gram-negative microbes like enterobacteria. Furthermore, through in vitro cell culturing and in vivo dietary intervention experiments, we demonstrate that this regulation from innate immunity is boosted via toll-like receptor signaling by helminth's secretory products, which could be sufficiently tuned down by dietary vitamin D through its receptor and cyp27b1. Importantly, using microbiota-targeted treatment methods, we prove that this signaling bolsters gut microbiota-mediated host intestinal Foxp3+ Treg cell expansion and parasite survival and that therapies targeting this signaling are effective in treating infection. We outline a dietary micronutrient-dependent mechanism by which helminths leverage host innate immunity to edit the host gut microbiome and thereby control immunosuppression precisely.
Microglia and CD8+ T cell activation precede neuronal loss in a murine model of spastic paraplegia 15
Authors: Aleksej Frolov, Hao Huang, Dagmar Schütz, Maren Köhne, Nelli Blank-Stein, Collins Osei-Sarpong, Maren Büttner, Tarek Elmzzahi, Mukhran Khundadze, Marina Zahid, Michael Reuter, Matthias Becker, Elena De Domenico, Lorenzo Bonaguro, Axel Kallies, Helen Morrison, Christian A. Hübner, Kristian Händler, Ralf Stumm, Elvira Mass, Marc D. Beyer
Journal: The Journal of Experimental Medicine (2025)

In central nervous system (CNS) diseases characterized by late-onset neurodegeneration, the interplay between innate and adaptive immune responses remains poorly understood. This knowledge gap is exacerbated by the prolonged protracted disease course as it complicates the delineation of brain-resident and infiltrating cells. Here, we conducted comprehensive profiling of innate and adaptive immune cells in a murine model of spastic paraplegia 15 (SPG15), a complicated form of hereditary spastic paraplegia. Using fate-mapping of bone marrow–derived cells, we identified microgliosis accompanied by infiltration and local expansion of T cells in the CNS of Spg15−/− mice. Single-cell analysis revealed an expansion of disease-associated microglia (DAM) and effector CD8+ T cells prior to neuronal loss. Analysis of potential cell–cell communication pathways suggested bidirectional interactions between DAM and effector CD8+ T cells, potentially contributing to disease progression in Spg15−/− mice. In summary, we identified a shift in microglial phenotypes associated with the recruitment and expansion of T cells as a new characteristic of Spg15-driven neuropathology.
Use of 68Ga-labeled Macroaggregated Albumin Particles for Selective Internal Radiation Therapy (SIRT) Dosimetry and Treatment Planning
Authors: Christian Goetz, Michael Christian Doppler, Mohamed Aymen Omrane, Wibke Uller, Philipp Tobias Meyer
Journal: Clinical Nuclear Medicine (2025)

In October 2024, Europe again experienced a period of shortage of technetium-labeled tracers. In order not to delay time-critical treatments of liver tumors, we turned to 68 Ga-labeled macroaggregated albumin particles ([ 68 Ga]Ga-MAA) as already used for lung perfusion PET imaging for selective internal radiation therapy (SIRT) dosimetry and treatment planning. Labeling was performed under GMP conditions and could be applied for SIRT planning in one patient. Post-therapy dosimetry based on [ 90 Y]microsphere PET/CT demonstrated excellent agreement. Dosimetry and treatment planning with [ 68 Ga]Ga-MAA should be considered as a viable alternative to [ 99m Tc]Tc-MAA SPECT/CT and could be considered for routine use.
Prevalence of Elevated Lipoprotein(a) and its Association With Subclinical Atherosclerosis in 2.9 Million Chinese Adults
Authors: Sailimai Man, Yining Zu, Xiaochen Yang, Yuhan Deng, Dan Shen, Yuan Ma, Jingzhu Fu, Jing Du, Canqing Yu, Jun Lv, Gang Li, Bo Wang, Liming Li
Journal: Journal of the American College of Cardiology (2025)
Dual αVβ8 Integrin and PD-1 Blockade Overcomes TGFβ-Mediated B-Cell Suppression to Enhance Anti-Glioma Immunity
Authors: David Hou, Si Wang, Brandyn A Castro, Joshua L Katz, Mark Dapash, Victor A Arrieta, Gustavo I Vazquez-Cervantes, Hanxiao Wan, Leah K Billingham, Rebecca Du, Alina R Murphy, Aurora Lopez-Rosas, Yu Han, Ronit V Patel, Tzu-Yi Chia, Crismita C Dmello, Peng Zhang, Dean Sheppard, Adam M Sonabend, Jason M Miska, Maciej S Lesniak, Dieter Henrik Heiland, Catalina Lee-Chang
Journal: Neuro-Oncology (2025)

ABSTRACT Background Immunotherapy has revolutionized cancer treatment but has yet to be translated into brain tumors. Studies in other solid tumors suggest a central role of B-cell immunity in driving immune checkpoint blockade efficacy. In glioblastoma (GBM), tumor B-cells are driven into a regulatory B-cell state that suppresses immune activation and T-cell function. Methods We used spatially resolved transcriptomics and multiplex immunofluorescence to characterize B-cell neighborhoods within GBM and identify enhanced TGFβ-signaling between myeloid and B cells. We generated conditional knockouts to investigate the effects of TGFβ signaling on B-cell function and survival in vivo. Additionally, we combined TGFβ blockade with PD-1 inhibition to evaluate their combined anti-glioma efficacy. Results Our findings reveal that myeloid cells are the primary interactors with B-cells in GBM through the TGFβ pathway. Pharmacological or genetic TGFβ blockade expanded intratumoral B-cells and synergized with PD-1 inhibition to enhance survival (60% tumor eradication in dual-treated mice). Therapeutic efficacy critically depended on B-cells, as their depletion abolished survival benefits. Dual αVβ8/PD-1 blockade reduced B-cell-mediated suppression of CD8⁺ T-cell cytotoxicity and increased plasmablast differentiation, while partial efficacy in RagKO mice implicated ancillary roles for innate immunity. Conclusion Targeting TGFβ signaling using an anti-αVβ8 blocker can impact anti-tumor immunity through different possible mechanisms, of which we highlight the rescuing of B-cell function through synergy with PD-1 checkpoint blockade therapy. Our work underscores the critical role of intratumoral B-cell immunity in enhancing immunotherapy against brain tumors.
Phase Ib study with expansion of ibrutinib, lenalidomide and rituximab in patients with relapsed/refractory CNS lymphoma
Authors: Lauren R Schaff, Anna F Piotrowski, Elena Pentsova, Igor T Gavrilovic, Andrew Lin, Thomas J Kaley, Venissala Wongchai, Laleh Emadi-Paramkouhi, Juli Madzsar, Lillian Quinn, Ashley Gonzalez, Laura Breakey, Sarah S Tang, Joe S Mendez, Rachna Malani, Craig Nolan, Vaios Hatzoglou, Robert J Young, Lisa M DeAngelis, Anne S Reiner, Katherine S Panageas, Jasmine H Francis, Ingo K Mellinghoff, Christian Grommes
Journal: Neuro-Oncology (2025)

Abstract Background Treatment options for recurrent/refractory CNS lymphoma are limited but the Bruton’s tyrosine kinase inhibitor ibrutinib has shown promise.. To increase efficacy and reduce resistance, ibrutinib was combined with lenalidomide in a pre-clinical study and rituximab (R2I) in a phase Ib trial with expansion. Methods Ibrutinib 560mg (dose level 1) or 840mg (levels 2-4) was administered daily; lenalidomide was dosed day 1-21 at 10mg (level 1 + 2), 15mg (level 3), or 20mg (level 4) daily; rituximab 500mg/m2 was administered every 28 days. Rituximab was given for 6 cycles, lenalidomide 12 cycles, and ibrutinib ongoing. Results 25 patients were enrolled (3 each into dose level 1-3; 6 into level 4; 10 into expansion cohort at level 4). Median age was 67 years (range 41-85) and median ECOG 1 (range 0-2). Patients had a median of 2 prior regimens (range 1-5). Common adverse events were thrombocytopenia, rash, and lymphopenia. No aspergillosis or grade 5 toxicities were observed. After 12.8 months median follow-up, 20/25 (80%) showed a response with a median time to best response 60 days (range, 25-615). Median progression-free survival (PFS) was 4.3 months (95% CI: 2.4-not reached) with a PFS12m of 37% (95% CI: 22%-63%). Median overall survival has not been reached. Patients with rash during treatment had improved PFS (HR: 0.17, 95% CI: 0.05-0.55, p-value=0.003). Conclusions R2I was tolerated well with high response rates and short time to best response. Median PFS was limited but 1/3 of patients had durable response &amp;gt;12 months. This trial was registered at www.clincialtrails.gov (NCT03703167).