tbuckley/cabot-search huggingface dataset:
Somatic mosaicism in the buccal mucosa reflects lifestyle and germline risk factors for esophageal squamous cell carcinoma
Authors: Akira Yokoyama, Koichi Watanabe, Yoshikage Inoue, Tomonori Hirano, Masashi Tamaoki, Kenshiro Hirohashi, Shun Kawaguchi, Yoshihiro Ishida, Yasuhide Takeuchi, Yo Kishimoto, Soo Ki Kim, Chikatoshi Katada, Yasuhito Nannya, Hiroshi Seno, Seishi Ogawa, Manabu Muto, Nobuyuki Kakiuchi
Journal: Science Translational Medicine (2025)

Clones harboring cancer driver mutations can expand in normal tissues, known as somatic mosaicism, and can be influenced by age and environmental and germline factors. Somatic mosaicism in the blood predicts the risk of hematological malignancies; however, the relevance of somatic mosaicism to solid tumors remains unclear, in part because of limited sample availability. Lifestyle habits, including alcohol consumption and tobacco smoking, and pathogenic germline variants increase the risk of developing esophageal squamous cell carcinoma (ESCC). Because somatic mosaicism in the esophagus is known to be associated with aging and lifestyle habits and considering the contiguity of squamous epithelium from the esophagus to the oral cavity, we noninvasively collected buccal mucosa samples from patients with and without ESCC using swabs of different sizes and conducted deep error-corrected sequencing of 26 cancer driver genes to obtain comprehensive landscapes of tissue remodeling by driver-mutant clones. We found that the number of mutations increased with drinking, but only in individuals with germline risks. Moreover, across positively selected genes in the buccal mucosa, mutations increased with age and smoking regardless of germline risks, whereas drinking affected only those with germline risks. The buccal mucosa of patients with ESCC was extensively remodeled, and models predicting the presence of ESCC demonstrated high accuracy with smaller swab sizes, possibly because of their higher sensitivity in detecting small mutant clones. In conclusion, we showed that buccal mucosal remodeling reflects lifestyle and germline risks, as well as age, which might be exploited for noninvasive risk assessment of ESCC.
Under (Genetic Selection) Pressure: Human Tumors and Human Populations in Hypoxia
Authors: Frank S. Lee
Journal: Cancer Discovery (2025)

Summary: Arenillas and colleagues report that pheochromocytomas and paragangliomas in the setting of chronic hypoxia due to cyanotic congenital heart disease harbor, at high frequency, somatic gain-of-function mutations in the EPAS1 gene, which encodes for one of the oxygen-labile subunits of the hypoxia-inducible factor complex. Interestingly, germline loss-of-function EPAS1 alleles are under natural selection in human populations subjected to a different chronic hypoxia condition, namely, high altitude. See related article by Arenillas et al., p. 1037
British Society of Gastroenterology guidelines on colorectal surveillance in inflammatory bowel disease
Authors: James Edward East, Morris Gordon, Gaurav Bhaskar Nigam, Vassiliki Sinopoulou, Adrian C Bateman, Shahida Din, Marietta Iacucci, Misha Kabir, Christopher Andrew Lamb, Ana Wilson, Ibrahim Al Bakir, Anjan Dhar, Sunil Dolwani, Omar Faiz, Ailsa Hart, Bu'Hussain Hayee, Chris Healey, Simon John Leedham, Marco R Novelli, Tim Raine, Matthew D Rutter, Neil A Shepherd, Venkataraman Subramanian, Margaret Vance, Ruth Wakeman, Lydia White, Nigel J Trudgill, A John Morris
Journal: Gut (2025)

Patients with inflammatory bowel disease (IBD) remain at increased risk for colorectal cancer and death from colorectal cancer compared with the general population despite improvements in inflammation control with advanced therapies, colonoscopic surveillance and reductions in environmental risk factors. This guideline update from 2010 for colorectal surveillance of patients over 16 years with colonic inflammatory bowel disease was developed by stakeholders representing UK physicians, endoscopists, surgeons, specialist nurses and patients with GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodological support.An a priori protocol was published describing the approach to three levels of statement: GRADE recommendations, good practice statements or expert opinion statements. A systematic review of 7599 publications, with appraisal and GRADE analysis of trials and network meta-analysis, where appropriate, was performed. Risk thresholding guided GRADE judgements.We made 73 statements for the delivery of an IBD colorectal surveillance service, including outcome standards for service and endoscopist audit, and the importance of shared decision-making with patients.Core areas include: risk of colorectal cancer, IBD-related post-colonoscopy colorectal cancer; service organisation and supporting patient concordance; starting and stopping surveillance, who should or should not receive surveillance; risk stratification, including web-based multivariate risk calculation of surveillance intervals; colonoscopic modalities, bowel preparation, biomarkers and artificial intelligence aided detection; chemoprevention; the role of non-conventional dysplasia, serrated lesions and non-targeted biopsies; management of dysplasia, both endoscopic and surgical, and the structure and role of the multidisciplinary team in IBD dysplasia management; training in IBD colonoscopic surveillance, sustainability (green endoscopy), cost-effectiveness and patient experience. Sixteen research priorities are suggested.
Nivolumab plus ifosfamide, carboplatin, and etoposide are a highly effective first salvage regimen in high‐risk relapsed/refractory Hodgkin lymphoma
Authors: Matthew Mei, Joycelynne Palmer, Hun Ju Lee, Iris Isufi, Robert Chen, Ni‐Chun Tsai, Saro Armenian, James Godfrey, Joo Y. Song, John H. Baird, Swetha Thiruvengadam, Yazeed Samara, Jessica Flores, Lacolle Peters, Steven Rosen, Larry Kwak, Stephen J. Forman, Alex F. Herrera
Journal: HemaSphere (2025)

Nivolumab is an anti-PD-1 antibody that is effective in patients with relapsed/refractory (RR) classic Hodgkin lymphoma (cHL). We previously showed PET-adapted sequential nivolumab ± ifosfamide, carboplatin, and etoposide (ICE) chemotherapy as the first salvage in RR cHL was a safe and effective bridge to autologous stem cell transplant (ASCT) (cohort A). We then tested a non-PET-adapted schema where all patients received nivolumab + ICE (cohort B). In this study, we present results from cohort B. Patients with high-risk RR cHL after frontline treatment received 240 mg nivolumab followed by 2-3 cycles of NICE (240 mg nivolumab day 1, standard doses of ICE). High-risk disease was defined as having one of the following: primary refractory cHL, relapse within 1 year of completing frontline therapy, B symptoms at relapse, extranodal disease at relapse, or frontline brentuximab vedotin use. PET/CT was performed after nivolumab × 1 and NICE × 2. Responding patients (complete response [CR] or partial response) were intended to proceed to ASCT. The primary endpoint was CR rate per 2014 Lugano classification. A total of 35 patients were enrolled, all of whom were evaluable for safety and efficacy. Overall response rate and CR were 100% and 86%, respectively; 2-year progression-free survival (PFS) and overall survival (OS) were 88% and 100%, respectively. Thirty-two patients proceeded to ASCT directly after NICE; 2-year post-ASCT PFS and OS were 94% and 100%, respectively. Immune-related toxicities were all grades 1-2, and no patient discontinued treatment for toxicity. Nivolumab/NICE is a highly effective salvage regimen and bridges patients effectively to ASCT.
Recurrence Rates of Barrett’s Esophagus and Dysplasia in Patients Successfully Treated with Radiofrequency Ablation vs Cryoballoon Ablation: a Comparative Study
Authors: Karan Sachdeva, Paras Singh Chandi, Anjul Verma, Ross Dierkhising, D. Chamil Codipilly, Cadman L Leggett, Arvind Julius Trindade, Prasad Iyer
Journal: Endoscopy (2025)

Background and aims Endoscopic eradication therapy (EET) is recommended for the management of dysplastic Barrett's esophagus (BE) and intramucosal adenocarcinoma (IMC). Both radiofrequency (RFA) and cryoballoon ablation (CBA), can induce complete remission of Intestinal metaplasia (CRIM). We aimed to compare long-term durability following CRIM in patients treated with RFA vs. CBA. Methods We conducted a retrospective cohort study to analyze patient outcomes following EET with RFA or CBA at 2 referral centers. We measured and compared the recurrence rate of BE with or without dysplasia after CRIM, using Cox proportional hazard models and propensity score-matched analyses. Our secondary aim was to identify predictors of recurrence. Results: We included 681 patients achieving CRIM (RFA: 610 and CBA: 71). Median follow-up was 4.1 years following RFA and 4.4 years following CBA. A multivariable model revealed a higher risk of any recurrence with RFA (HR, 2.19; 95 % CI, 1.18- 4.06; P= 0.013), but not dysplastic recurrence (RFA vs. CBA: HR, 0.88; 95 % CI, 0.39- 1.97; P= 0.75). However, a comparable risk of "any recurrence" (RFA vs CBA, HR, 1.18; 95% CI, 0.61-2.30, p=0.62) was observed after excluding IM-GEJ. Propensity score-matched analysis (54 CBA and 54 RFA cases) showed that RFA and CBA groups had comparable recurrence risk. Baseline maximal BE length was associated with a higher risk of any (HR 1.07; P < 0.01) and dysplastic recurrence (HR 1.11; P = 0.001). Conclusions: The rates of any and dysplastic BE recurrence were comparable with both modalities in this non-randomized study.
Development of a Bio-inspired Soft Robotic System for Teleoperated Endoscopic Surgery
Authors: Kefan Zhu, Chi Cong Nguyen, Bibhu Sharma, Phuoc Thien Phan, Trung Thien Hoang, James Davies, Adrienne Ji, Emanuele Nicotra, Jingjing Wan, Patrick Pruscino, Sumeet Walia, Tat Thang Vo-Doan, Soo Jay Phee, Shing Wong, Nigel H. Lovell, Thanh Nho Do
Journal: Cyborg and Bionic Systems (2025)
An Automated Frailty Index and Loss to Follow-Up Among Patients With Diabetic Retinopathy
Authors: Manuela Gutierrez Velez, Logan Bearfield, Alicia Chen, Margaret Havunjian, Heidi Whiteside, Kathryn Callahan, Joseph Rigdon, Sally S. Ong
Journal: JAMA Network Open (2025)

This cohort study examines whether patients with diabetic retinopathy who are frail according to an electronic frailty index have higher rates of loss to follow-up compared with less-frail patients.
A Neuroimmune Modulator for Alcohol Use Disorder
Authors: Lara A. Ray, Lindsay R. Meredith, Erica N. Grodin, Malia A. Belnap, Steven J. Nieto, Wave A. Baskerville, Suzanna Donato, Steven J. Shoptaw, Artha J. Gillis, Michael R. Irwin, Karen Miotto, Craig K. Enders
Journal: JAMA Network Open (2025)

Importance The neuroimmune system represents a promising target for novel medications for alcohol use disorder (AUD). Ibudilast is a neuroimmune modulator which selectively inhibits phosphodiesterases (PDE) 3, PDE4, PDE10, and PDE11, and macrophage migration inhibitory factor (MIF). Objective To test the efficacy of ibudilast for AUD compared with placebo. Design, Setting, and Participants This randomized clinical trial was a double-masked, phase 2 trial conducted at an academic research center between October 2018 and April 2023. Eligible participants were adults seeking treatment for moderate or severe AUD. After completing the 12-week treatment period, participants were followed up for an additional 4 weeks. Interventions Ibudilast taken twice daily in 50 mg doses for 12 weeks vs placebo. Main Outcomes and Measures Percentage of heavy drinking days; secondary efficacy outcomes included drinks per day, drinks per drinking day, and percentage of days abstinent. Registered exploratory analyses tested whether the effects of ibudilast of drinking outcomes were moderated by baseline depressive symptomatology. Registered exploratory analyses also tested whether ibudilast reduced inflammation compared with placebo, as indicated by circulating levels of proinflammatory markers over the 12-week trial. Additionally, a post hoc exploratory analysis investigated whether sex moderated the effect of ibudilast on drinking outcomes. Data were analyzed between October 2018 and April 2023. Results A total of 102 participants were enrolled in the study (mean [SD] age, 44.3 [10.8] years; 61 male [59.8%]; 24 Black [23.5%], 32 Hispanic [31.4%], 52 White [51.0%]). Baseline demographic characteristics and alcohol use patterns did not significantly differ between the 2 medication conditions. There was no significant difference between ibudilast vs placebo on percentage of heavy drinking days (β = 0.06, SE = 0.08 [95% CI, −0.09 to 0.21]; P = .46). There were no significant differences between ibudilast vs placebo on registered secondary outcomes. There were no significant effects of ibudilast compared with placebo on peripheral markers of inflammation. Moderation analyses found that baseline depressive symptomology (time 2 for drinks per drinking day: β = 0.25, SE = 0.11 [95% CI, 0.03 to 0.48]; P = .03) and sex (β = −2.48, SE = 1.07 [95% CI, −4.59 to −0.37]; P = .02) may moderate the effects of ibudilast. Conclusions and Relevance In this randomized clinical trial of ibudilast for the treatment of AUD, there was no support for the efficacy of ibudilast over placebo; additionally, no effect of ibudilast on markers of peripheral inflammation was observed. As novel treatments for AUD are developed for novel molecular targets, their effects may depend on mechanisms and moderators of efficacy. Trial Registration ClinicalTrials.gov Identifier: NCT03594435
Surgical Performance Metrics for 1-Year Patient-Reported Outcomes After Radical Prostatectomy
Authors: John R. Heard, Umar Ghaffar, Runzhuo Ma, Cherine H. Yang, Melissa Assel, Christian Wagner, Geoffrey A. Sonn, Alvin C. Goh, Shady Saikali, Vipul Patel, Andrew Vickers, Jim C. Hu, Andrew J. Hung
Journal: JAMA Surgery (2025)

Importance There is a dearth of surgical performance measures that accurately predict long-term patient outcomes. Objective To develop surgical performance measures collected at the time of surgery that accurately predict future outcomes. Design, Setting, and Participants In this cohort study, surgical video of 157 patients undergoing robotic-assisted radical prostatectomy by 28 surgeons from 4 tertiary referral hospitals across the US and 1 hospital in Germany was analyzed. Four trained and blinded raters annotated video clips of the bilateral nerve-sparing step using standardized tools for identifying surgical gestures and assessing technical skills. Patients were prospectively enrolled from July 2016 to January 2023 and followed up for 12 months postoperatively. Data were analyzed from April to August 2024. Patients with clinically localized prostate cancer undergoing robotic-assisted radical prostatectomy were eligible. Inclusion criteria included adequate erectile function prior to surgery and access to complete surgical video. Interventions/Exposures Robotic-assisted radical prostatectomy Main Outcomes and Measures Performance metrics were compared between patients who recovered erectile function and those who did not. Erectile function recovery was defined as achieving erections sufficient for intercourse measured using the Sexual Health Inventory for Men. Results Fifty-three patients (34%) recovered erectile function at 12 months after surgery. The median age was 64 (IQR, 59-68) years and median body mass index was 28 (IQR, 26-30). In total, 80 957 surgical gestures were annotated and 2568 technical skills scores were evaluated. The impact of performance factors on erectile function recovery was evaluated using univariate logistic regression. Recovery was associated with a greater proportion of peel/push gestures (odds ratio [OR], 1.72; 95% CI, 1.24-2.42, per 0.1 increase; P = .001), lower proportion of energy gestures applied to the neurovascular bundle (OR, 0.35; 95% CI, 0.13-0.81, per 0.1 increase; P = .03), and less gestures grabbing the neurovascular bundle (OR, 0.02; 95% CI, 0.00-0.47, per 0.1 increase; P = .02). Erectile function recovery was associated with higher tissue handling skill scores (OR, 3.43; 95% CI, 1.23-10.90, P = .03). On multivariable regression the association between peel/push gestures and erectile function recovery remained significant (OR, 1.66; 95% CI, 1.18-2.39, per 0.1 increase; P = .005). Conclusions and Relevance Surgical performance can be assessed from data collected during surgery and used to predict erectile function 12 months later. This was not previously feasible due to a lack of quantitative methods for assessing surgical performance. Combining surgical gestures and skills assessment demonstrates a novel opportunity for advancing surgical performance.
Generalizability of FDA-Approved AI-Enabled Medical Devices for Clinical Use
Authors: Daniel Windecker, Giovanni Baj, Isaac Shiri, Pooya Mohammadi Kazaj, Johannes Kaesmacher, Christoph Gräni, George C. M. Siontis
Journal: JAMA Network Open (2025)

Importance The primary objective of any newly developed medical device using artificial intelligence (AI) is to ensure its safe and effective use in broader clinical practice. Objective To evaluate key characteristics of AI-enabled medical devices approved by the US Food and Drug Administration (FDA) that are relevant to their clinical generalizability and are reported in the public domain. Design, Setting, and Participants This cross-sectional study collected information on all AI-enabled medical devices that received FDA approval and were listed on the FDA website as of August 31, 2024. Main Outcomes and Measures For each AI-enabled medical device, detailed information and key characteristics relevant for the generalizability of the devices at the time of approval were summarized, specifically examining clinical evaluation aspects, such as the presence and design of clinical performance studies, availability of discriminatory performance metrics, and age- and sex-specific data. Results In total, 903 FDA-approved AI-enabled medical devices were analyzed, most of which became available in the last decade. The devices primarily related to the specialties of radiology (692 devices [76.6.%]), cardiovascular medicine (91 devices [10.1%]), and neurology (29 devices [3.2%]). Most devices were software only (664 devices [73.5%]), and only 6 devices (0.7%) were implantable. Detailed descriptions of development were absent from most publicly provided summaries. Clinical performance studies were reported for 505 devices (55.9%), while 218 devices (24.1%) explicitly stated no performance studies were conducted. Retrospective study designs were most common (193 studies [38.2%]), with only 41 studies (8.1%) being prospective and 12 studies (2.4%) randomized. Discriminatory performance metrics were reported in 200 of the available summaries (sensitivity: 183 devices [36.2%]; specificity: 176 devices [34.9%]; area under the curve: 82 devices [16.2%]). Among clinical studies, less than one-third provided sex-specific data (145 studies [28.7%]), and only 117 studies (23.2%) addressed age-related subgroups. Conclusions and Relevance In this cross-sectional study, clinical performance studies at the time of approval were reported for approximately half of AI-enabled medical devices, yet the information was often insufficient for a comprehensive assessment of their clinical generalizability, emphasizing the need for ongoing monitoring and regular re-evaluation to identify and address unexpected performance changes during broader use.
Tiered Clinician Vaccine Communication Strategy to Improve Childhood Vaccine Uptake
Authors: Douglas J. Opel, Jeffrey D. Robinson, Chuan Zhou, Kathryn Colborn, Heather Spielvogle, Anna Furniss, Christine Spina, Cathryn Perreira, Sean T. O’Leary
Journal: JAMA Network Open (2025)

Importance No experimental studies to date have tested the effectiveness of clinician communication strategies to improve vaccine uptake among children of parents with negative vaccine attitudes. Objective To evaluate the effect of a tiered vaccine communication strategy on children of parents with negative vaccine attitudes. Design, Setting, and Participants This cluster randomized clinical trial was conducted from September 1, 2019, to March 31, 2023, at primary care pediatric clinics in Colorado (n = 12) and Washington State (n = 12). Parents with negative vaccine attitudes who had infants 2 months or younger and were receiving health supervision at a participating clinic during the intervention period were eligible for the study. Intervention Tiered strategy in which clinicians initiated vaccine discussions with all parents using a presumptive format and then used motivational interviewing with parents who verbally resisted recommended vaccines. Clinicians at intervention clinics received training on the tiered vaccination strategy, whereas clinicians at control clinics practiced usual care. Main Outcomes and Measures Child vaccination status at 19 months of age characterized as percentage of days underimmunized (DU) in receiving recommended doses of 8 routinely recommended vaccines, with 0% DU described as up to date (UTD) on time. Results A total of 937 parent-child dyads (intervention: n = 586; control: n = 351) were included in analysis; 434 (46.3%) had an annual household income greater than $75 000 and 682 (72.8%) had some college, a 2-year degree, or more education. In bivariable analyses, more intervention (vs control) participants were UTD on time (130 [22.2%] vs 64 [18.2%]), but intervention (vs control) participants had higher mean (SD) percentage of DU (32.1% [37.9%] vs 23.7% [32.4%]). Variation was observed across states, with intervention participants in Washington (vs Colorado) having a lower mean (SD) percentage of DU (22.4% [31.8%] vs 39.6% [40.1%]) and more infants who were UTD on time (77 [30.0%] vs 53 [16.1%]). In multivariable regression models, there was no difference between intervention and control arms in mean (SD) percentage of DU (adjusted incidence rate ratio, 1.06; 95% CI, 0.69-1.63) or UTD on time (adjusted odds ratio, 1.45; 95% CI, 0.69-3.04), although there were increased odds of being UTD on time among Washington intervention (vs control) participants (adjusted odds ratio, 2.47; 95% CI, 1.09-5.59). Conclusions and Relevance In this cluster randomized clinical trial of a tiered vaccine communication strategy, vaccine uptake of children of parents with negative vaccine attitudes did not improve, although state-specific effects were observed. Trial Registration ClinicalTrials.gov ID: NCT03885232