tbuckley/cabot-search huggingface dataset:
Update on Cancer and Central Nervous System Tumor Surveillance in Pediatric NF2-, SMARCB1-, and LZTR1-Related Schwannomatosis
Authors: Melissa R. Perrino, Marjolijn C. J. Jongmans, Gail E. Tomlinson, Mary-Louise C. Greer, Sarah R. Scollon, Sarah G. Mitchell, Jordan R. Hansford, Kris Ann P. Schultz, Wendy K. Kohlmann, Jennifer M. Kalish, Suzanne P. MacFarland, Anirban Das, Kara N. Maxwell, Stefan M. Pfister, Rosanna Weksberg, Orli Michaeli, Uri Tabori, Gina M. Ney, Philip J. Lupo, Jack J. Brzezinski, Douglas R. Stewart, Emma R. Woodward, Christian P. Kratz
Journal: Clinical Cancer Research (2025)

Abstract Schwannomatoses (SWN) are distinct cancer predisposition syndromes caused by germline pathogenic variants in the genes NF2, SMARCB1, or LZTR1. There is significant clinical overlap between these syndromes with the hallmark of increased risk for cranial, spinal and peripheral schwannomas. Neurofibromatosis type 2 was recently renamed as NF2-related SWN and is the most common SWN syndrome with increased risk for bilateral vestibular schwannomas, intradermal schwannomas, meningiomas and less commonly ependymoma. SMARCB1-related SWN is a familial SWN-syndrome associated with peripheral and spinal schwannomas and an increased risk for meningiomas and malignant peripheral nerve sheath tumors, even in the absence of radiation. These individuals do not develop bilateral vestibular schwannomas. Finally, patients with LZTR1-related SWN typically present with peripheral schwannomas, and unilateral vestibular schwannomas have been reported. The following perspective is intended to highlight the clinical presentation and international tumor surveillance recommendations across these SWN-syndromes.
Epistasis of <i>ERAP1</i> With 4 Major Histocompatibility Complex Class I Alleles in Frontal Fibrosing Alopecia
Authors: Tuntas Rayinda, Nick Dand, Sheila M. McSweeney, Evangelos Christou, Chuin Ying Ung, Catherine M. Stefanato, David A. Fenton, Matthew Harries, Ioulios Palamaras, Alice Tidman, Susan Holmes, Anastasia Koutalopoulou, Michael Ardern-Jones, Manjit Kaur, Sofia Papanikou, Vasiliki Chasapi, Sergio Vañó-Galvan, David Saceda-Corralo, Ana Melián-Olivera, Carlos Azcarraga-Llobet, Alejandro Lobato-Berezo, Mariona Bustamante, Jordi Sunyer, Michela Valeria Rita Starace, Bianca Maria Piraccini, Isabel Pupo Wiss, Maryanne Makredes Senna, Rashmi Singh, Kathrin Hillmann, Varvara Kanti-Schmidt, Ulrike Blume-Peytavi, John A. McGrath, Michael A. Simpson, Christos Tziotzios
Journal: JAMA Dermatology (2025)

Importance Frontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets. Objective To identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci. Design, Setting, and Participants Four genome-wide association studies were combined using an SE-weighted meta-analysis. Within the major histocompatibility complex (MHC) locus, stepwise conditional analysis was undertaken to determine independently associated classical MHC class I alleles. Statistical tests for epistatic interaction were performed between risk alleles at the MHC and endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) loci. Main Outcomes and Measures Genome-wide significant locus associated with FFA and nonadditive effects on genetic risk between susceptibility loci. Results Of 6668 included patients, there were 1585 European female individuals with FFA and 5083 controls. Genome-wide significant associations were identified at 4 genomic loci, including a novel susceptibility locus at 5q15, and the association signal could be fine-mapped to a single nucleotide substitution (rs10045403) in the 5′ untranslated region of ERAP1 (rs10045403; odds ratio, 1.30; 95% CI, 1.19-1.43; P = 3.6 × 10 −8 ). Within the MHC, FFA risk was statistically independently associated with HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01. FFA risk was affected by genetic variation at the ERAP1 locus only in individuals who carried at least 1 of the MHC class I risk alleles. Conclusions and Relevance In this genome-wide meta-analysis, a supra-additive effect of genetic variation was found that affected peptide trimming and antigen presentation on FFA susceptibility. Patients with FFA may benefit from emerging therapeutic approaches that modulate ERAP-mediated processes.
Management of Perforated Peptic Ulcer
Authors: Seyed A. Arshad, Patrick Murphy, Jon C. Gould
Journal: JAMA Surgery (2025)

Importance Perforated peptic ulcer disease (PUD) affects 4 million people annually worldwide, with a lifetime prevalence of 5% to 10%. Of those affected, 5% will progress to the point of perforation. Despite advances in the understanding and treatment, perforated PUD continues to have a high rate of morbidity (50%) and mortality (30%). This review summarizes the current evidence on management of perforated PUD, including management of failed repairs. Observations Approaches for repair include primary closure and omental patch closure. Omental patch may be most useful in large perforations with friable tissue. Minimally invasive surgery is the preferred approach in perforated PUD, with improved outcomes compared with open techniques. Leak from the ulcer after repair is seen in approximately 12% to 17% of cases. Approaches to releak include expectant management, radiologic and/or endoscopic intervention, and repeat surgery. Morbidity and mortality after releak are especially high, and complete healing of the leak may take time. Conclusions and Relevance Despite advances in medical management and surgical techniques, perforated PUD continues to have a relatively high rate of morbidity and mortality. Minimally invasive surgery is the current preferred treatment approach.
Delicious Oranges—Mental Health, Poetry, and the Non Sequitur
Authors: Rafael Campo
Journal: JAMA (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Patient Enrollment for Cardiovascular Clinical Trials in the United States
Authors: Muhammad Shahzeb Khan, Adeena Jamil, Muteia Shakoor, Stephen J. Greene, Gregg C. Fonarow, Deepak L. Bhatt, J. Michael DiMaio, Michael J. Mack, Javed Butler
Journal: JAMA Cardiology (2025)

This cross-sectional study evaluates enrollment trends in recent cardiovascular clinical trials.
Making Progress in Clinical Trials for Suicide Prevention
Authors: Samuel T. Wilkinson, Craig J. Bryan, Larry D. Alphs, Carla M. Canuso, Michael J. Ostacher, Rebecca B. Price, Michael H. Bloch, Carlos A. Zarate, Taeho Greg Rhee
Journal: JAMA Psychiatry (2025)

Importance Suicide is a public health crisis, and despite renewed efforts to confront this problem, suicide rates continue to rise in the US. While suicide prevention encompasses a broad array of strategies, treatment development is lagging. Within this realm, clinical trials are the criterion standard for evaluating safety and efficacy of new treatments. Observations Most clinical trials conducted among patients with mental illness have excluded patients at risk of suicide. Historical reasons for this include regulatory challenges, liability concerns, ethical questions, discomfort working directly with high-risk patients, and the belief that research is too risky for individuals at elevated risk for suicide. Conclusions and Relevance Several considerations are provided for investigators in the design of trials targeting at-risk populations, including thoughtful selection of study outcome, use of time-to-event design and analysis (which may simultaneously satisfy ethical concerns and scientific aims), enrolling an enriched sample (eg, among patients recently discharged from the hospital), and provision of usual care in the comparator group. Caution should be exercised to avoid excessive or unreasonable safety requirements, which may lead participants to minimize self-report of suicidal ideation or to drop out of trials. Where possible, regulatory bodies (institutional review boards [IRBs] and data and safety monitoring boards) should consult with or include as members those with direct clinical experience with this high-risk population. An important ethical principle for IRB members and other regulators to consider is that suicide-related events are expected in this clinical population.
Research Domain Criteria in NIMH Grants Characterized Using Large Language Models
Authors: Roy H. Perlis
Journal: JAMA Network Open (2025)

Importance Over the past decade, the leadership of the National Institute of Mental Health (NIMH) has emphasized the importance of a transdiagnostic approach to psychiatric investigation using Research Domain Criteria (RDoC) mapping more closely to neurobiology. Objective To investigate whether research support from the NIMH for individual RDoC domains and for transdiagnostic investigation has changed over time and has had differential impact in terms of publication, citations, or patent filings. Design, Setting, and Participants In this longitudinal cohort study, all R01, R21, and R03 studies funded by the NIMH between January 2003 and December 2023 were identified via the National Institutes of Health RePORTER database. Their abstracts were characterized in terms of RDoC domains (negative valence, positive valence, cognition, social, arousal, and sensorimotor) using a large language model. Main Outcomes and Measures Primary outcomes were publications, citation impact estimated at 5 years from the index year of funding, and patents, examined using regression models adjusted for other grant characteristics. Results Among 8897 R01, R03, and R21 projects, reflecting $17.7 billion of investment, abstracts of 3141 (35.3%) reflected negative valence; 1344 (15.1%), positive valence; 2781 (31.3%), cognition; 1607 (18.1%), social; 343 (3.9%), arousal; and 571 (6.4%), sensorimotor domains. A total of 1793 (20.2%) incorporated a transdiagnostic perspective. Positive and social domains were associated with fewer publications (difference, −1.13 [95% CI, −2.11 to −0.15] and −2.23 [95% CI, −3.15 to −1.30], respectively) and lesser citation impact (difference, −0.47 [95% CI, −0.75 to −0.18] and −1.19 [95% CI, −1.46 to −0.91], respectively) at 5 years. Social (adjusted odds ratio [AOR], 0.11; 95% CI, 0.04-0.23) and cognitive (AOR, 0.66; 95% CI, 0.48-0.89) domains and transdiagnostic proposals (AOR, 0.37; 95% CI, 0.21-0.60) were associated with lower likelihood of patent filing. Conclusions and Relevance In this study of NIMH funding, grants reflecting different RDoC domains differed substantially in their scientific impact in terms of publications, citations, and patent generation. The findings suggest that large language models represent a promising approach to characterizing research proposals at scale, which may be useful in guiding resource allocation to maximize scientific return on investment.
Aortic Valve Replacement for Asymptomatic Severe Aortic Stenosis—The Time Has Come
Authors: Brian R. Lindman, Eugene Braunwald, Patricia A. Pellikka
Journal: JAMA Cardiology (2025)

This Viewpoint advocates for prompt aortic valve replacement (rather than clinical surveillance) as the default strategy for patients with asymptomatic severe aortic stenosis.
AZD8701, an Antisense Oligonucleotide Targeting FOXP3 mRNA, as Monotherapy and in Combination with Durvalumab: Phase I trial in Patients with Advanced Solid Tumors
Authors: Lillian L. Siu, Sophie Postel-Vinay, Rafael Villanueva-Vázquez, Guillermo de Velasco, Eduardo Castanon Alvarez, Christos E. Kyriakopoulos, Melissa Johnson, Kaïssa Ouali, Stephen McMorn, Helen K. Angell, Felicia Ng, Shashank Saran, Mahdiye Bayat, Teresa Collins, Archana Roy, Arthur W. Lambert, Song Cho, Neil Miller, Michele Petruzzelli, John Stone, Christophe Massard
Journal: Clinical Cancer Research (2025)

Abstract Purpose: AZD8701 uses next-generation antisense oligonucleotide (ASO) technology to selectively reduce human forkhead box P3 (FOXP3) expression in regulatory T cells, reversing their immunosuppressive function. FOXP3 ASOs alone or with programmed cell death protein (ligand) 1 (PD-[L]1) inhibition attenuated tumor growth in mice. We report a phase I study of AZD8701 alone or combined with durvalumab in patients with advanced solid tumors. Methods: Eligible patients had solid tumors and had received prior standard-of-care treatment including anti-PD-(L)1 therapy. Patient cohorts were treated with AZD8701 intravenously (IV) weekly at escalating doses, either alone (60–960 mg) or combined (240–720 mg) with durvalumab 1,500 mg IV every 4 weeks. The primary objective was safety and tolerability, with the aim of determining the maximum tolerated dose. Results: Forty-five patients received AZD8701 monotherapy and 18 received AZD8701 with durvalumab. One dose-limiting toxicity (increased alanine aminotransferase [ALT]) occurred with AZD8701 960 mg. The most common adverse events (AEs) related to AZD8701 monotherapy were fatigue (22.2%), asthenia, pyrexia, and increased ALT (20%, each); the safety profile was similar when combined with durvalumab. With AZD8701 monotherapy, 24.4% and 15.6% of patients had stable disease for ≥16 and ≥24 weeks, respectively; one patient treated with AZD8701 720 mg and durvalumab had a partial response. FOXP3mRNA changes were heterogeneous (8/13 patients showed reduction), with no clear dose relationship. ASO accumulated in the tumor epithelium and stroma. Conclusions: This study demonstrates the clinical feasibility of ASO therapy, with generally manageable AEs, FOXP3 knockdown, and ASO delivery to the tumor.
<i>JAMA Dermatology</i> Editorial Fellowship—What We Have Learned
Authors: Maria Teresa García-Romero, Andrea D. Maderal
Journal: JAMA Dermatology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Pilot Randomized Trial of an Educational Intervention About Immunotherapy for Patients With Advanced Cancer and Their Caregivers
Authors: Laura A. Petrillo, Kelly Hsu, Kedie Pintro, Dustin J. Rabideau, Ashley Z. Zhou, Roshni Sarathy, An Tran, Ryan Sullivan, Kerry L. Reynolds, Areej El-Jawahri, Angelo Volandes, Joseph A. Greer, Jennifer S. Temel
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Immune checkpoint inhibitors (ICIs) are widely used cancer drugs. We developed “UPLIFT,” a video and question prompt list (QPL) intervention to educate patients about ICI risks and benefits. Patients and Methods: We conducted a randomized controlled trial of UPLIFT versus usual care among 130 adults initiating ICIs and caregivers. Dyads were randomized 1:1 to receive UPLIFT or usual care prior to ICI initiation. Participants completed surveys at enrollment, 72 hours, and 6 weeks post-ICI initiation. The primary outcomes were feasibility (≥70% enrollment of eligible patients and ≥80% of UPLIFT patients reviewing the video and QPL) and ICI knowledge (8 items, scored as % correct). We also assessed acceptability of UPLIFT (3 items), anxiety (6-item State-Trait Anxiety Inventory), and patient activation (number of questions asked in oncology visit). We used descriptive statistics, analysis of covariance (ANCOVA), and negative binomial models. Results: We enrolled 130 of 178 eligible patients (73%) and 56 caregivers. Patients (mean age, 67 years [range, 31–92]) had diagnoses of melanoma (41%), lung cancer (26%), or other cancers. All UPLIFT patients (100%) watched the video; 47% used the QPL. Nearly all patients (61/65; 94%) felt “somewhat” or “very comfortable” with UPLIFT. ICI knowledge improved among UPLIFT patients versus controls at 72 hours (difference in adjusted mean % correct at 72 hours, 9% [95% CI, 3%–16%]). The change in anxiety at 72 hours did not significantly differ and there was no difference in knowledge or anxiety change at 6 weeks across groups. UPLIFT patients asked more questions (ratio, 1.27 [95% CI, 0.97–1.66]). Conclusions: A novel educational intervention about ICI risks and benefits was feasible to deliver, deemed acceptable, and shows promise in improving knowledge and activation to ask questions without increasing anxiety. A future study evaluating UPLIFT’s efficacy in these and other outcomes, including severe ICI toxicity, is warranted.
NCCN Guidelines® Insights: Head and Neck Cancers, Version 2.2025
Authors: A. Dimitrios Colevas, Anthony J. Cmelak, David G. Pfister, Sharon Spencer, Douglas Adkins, Andrew C. Birkeland, David M. Brizel, Paul M. Busse, Jimmy J. Caudell, Greg Durm, Carole Fakhry, Thomas Galloway, Jessica L. Geiger, Maura L. Gillison, Christine Glastonbury, Robert I. Haddad, Wesley L. Hicks, Ying J. Hitchcock, Antonio Jimeno, Aditya Juloori, Michael Kase, Debra Leizman, Ellie Maghami, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, Katharine Price, James W. Rocco, Cristina P. Rodriguez, David Schwartz, Jatin P. Shah, David Sher, Maie St. John, He Wang, Gregory Weinstein, Francis Worden, Justine Yang Bruce, Sue S. Yom, Weining Zhen, Sarah Montgomery, Susan D. Darlow
Journal: Journal of the National Comprehensive Cancer Network (2025)

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses, as well as occult primary cancer, salivary gland cancer, and mucosal melanoma (MM). The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of nasopharynx cancer and ongoing research in this area.
Stress About Eviction or Loss of Housing and Child Mental Health
Authors: Jamie L. Hanson
Journal: JAMA Network Open (2025)

Importance Eviction and housing loss are pressing public health concerns. Understanding how caregivers’ stress about eviction or loss of housing is associated with specific childhood psychiatric issues across development is important. Objective To examine associations between stress about eviction or loss of housing and caregiver-reported child depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and behavioral problems, while adjusting for sociodemographic factors. Design, Setting, and Participants This cross-sectional study analyzed data from the 2022 National Survey of Children's Health, a nationally representative survey of caregivers and children in the US. Data were collected between July 2022 and January 2023. Exposure Eviction or loss of housing. Main Outcomes and Measures Caregiver-reported child depression, anxiety, ADHD, and behavioral problems. Generalized linear mixed models were used to test associations with stress about eviction or loss of housing. Results From a sample of 54 103 families, 36 638 were included in the analytic sample (analytic sample mean [SD] age: 9.91 [4.62] years; sex assigned at birth, 18 901 male [52%]). In this study, stress about eviction or loss of housing was associated with depression in children (adjusted odds ratio [aOR], 1.10; 95% CI, 1.02-1.18). Stress about eviction or loss of housing was significantly associated with higher odds of reported anxiety in the base model (aOR, 1.26 (95% CI, 1.22-1.31) but not in the stringently adjusted model (aOR, 1.04; 95% CI, 1.00-1.08]). Associations were sometimes moderated by age, with stronger associations for younger children. Stress about eviction or loss of housing was not associated with ADHD or behavioral problems after adjustment. Conclusions and Relevance This study found that stress about eviction or loss of housing was associated with increased odds of internalizing issues, such as depression and anxiety, among children. Prospective longitudinal research is still needed to fully understand these complex associations over time. These findings underscore the importance of policies and interventions to address housing instability and its mental health consequences for children.
Disparities in Substance Use Disorder Telehealth Services
Authors: Lauryn Saxe Walker, Manying Cui, Jonathan Cantor, Melody Craff, Cheryl L. Damberg, John N. Mafi, Katherine L. Kahn
Journal: JAMA Network Open (2025)

This cross-sectional study evaluates whether telehealth utilization is associated with changes in payer-based and rural-urban disparities in substance use disorder treatment.