tbuckley/cabot-search huggingface dataset:
Area-Level Social Deprivation and Cytomegalovirus Seropositivity at the Time of Solid Organ Transplant
Authors: Maheen Z. Abidi, Rocio Lopez, Susana Arrigain, Adriana Weinberg, Bruce Kaplan, Mara McAdams-DeMarco, Jesse D. Schold, Kristine M. Erlandson
Journal: JAMA Network Open (2024)

Importance Cytomegalovirus (CMV) is associated with significant morbidity and mortality in solid organ transplant (SOT) recipients. The risk factors for CMV seropositivity in SOT recipients, including area-level social deprivation in the US, have not been fully characterized. Objective To (1) evaluate CMV seroprevalence, (2) assess the recipient characteristics associated with CMV seropositivity, and (3) assess the association of area-level social deprivation index (SDI) scores with pretransplant CMV serostatus. Design, Setting, and Participants This retrospective cross-sectional analysis of the Scientific Registry of Transplant Recipients database included all adult (aged ≥18 years) SOT recipients from January 1, 2008, to May 31, 2022. Data were analyzed from April 10 to October 25, 2023. Exposure Recipient characteristics and area-level SDI. Main Outcomes and Measures Multivariable generalized linear models were used to evaluate the association between (1) patient characteristics and CMV and (2) social deprivation (measured by SDI scores, which were assessed in quintiles, from lowest to highest) and CMV seropositivity. In addition, differences based on patient demographics and the transplanted organ(s) were evaluated. Results Among the 389 288 SOT recipients included in the analysis, mean (SD) age was 53.3 (13.0) years; 63.0% were male, 21.4% were Black, 15.2% were Hispanic White, 56.2% were non-Hispanic White, and 62.7% were CMV seropositive. The mean (SD) age was higher among CMV seropositive (54.0 [12.7] years) compared with CMV seronegative (52.0 [13.5] years) patients. Seropositivity for CMV was higher among women (69.9%) than men (58.5%) and among Black (74.8%) and Hispanic White (80.2%) patients compared with non-Hispanic White patients (50.4%). Seropositivity for CMV was highest among kidney (64.5%), liver (63.6%), and kidney and liver (66.2%) recipients. Greater SDI scores were associated with greater CMV seropositivity, ranging from 51.7% for the least deprived to 75.5% for the most deprived quintiles ( P &amp;amp;lt; .001), independent of age, sex, or race. Conclusions and Relevance In this cross-sectional study, an association between SDI and CMV seropositivity was observed among SOT recipients, independent of age, sex, or race and ethnicity. To optimize posttransplant outcomes in CMV seropositive recipients, efforts targeting prevention of CMV reactivation need to be prioritized in these higher-risk populations.
Applicability of epigenetic age models to next-generation methylation arrays
Authors: Leonardo D. Garma, Miguel Quintela-Fandino
Journal: Genome Medicine (2024)

Epigenetic clocks are mathematical models used to estimate epigenetic age based on DNA methylation at specific CpG sites. As new methylation microarrays are developed and older models discontinued, existing epigenetic clocks might become obsolete. Here, we explored the effects of the changes introduced in the new EPICv2 DNA methylation array on existing epigenetic clocks. We tested the performance of four epigenetic clocks on the probeset of the EPICv2 array using a dataset of 10,835 samples. We developed a new epigenetic age prediction model compatible across the 450 k, EPICv1, and EPICv2 microarrays and validated it on 2095 samples. We estimated technical noise and intra-subject variation using two datasets with repeated sampling. We used data from (i) cancer survivors who had undergone different therapies, (ii) breast cancer patients and controls, and (iii) an exercise-based interventional study, to test the ability of our model to detect alterations in epigenetic age acceleration in response to theoretically antiaging interventions. The results of the four epiclocks tested are significantly distorted by the EPICv2 probeset, causing an average difference of up to 25 years. Our new model produced highly accurate chronological age predictions, comparable to a state-of-the-art epiclock. The model reported the lowest epigenetic age acceleration in normal populations, as well as the lowest variation across technical replicates and repeated samples from the same subjects. Finally, our model reproduced previous results of increased epigenetic age acceleration in cancer patients and in survivors treated with radiation therapy, and no changes from exercise-based interventions. Existing epigenetic clocks require updates for full EPICv2 compatibility. Our new model translates the capabilities of state-of-the-art epigenetic clocks to the EPICv2 platform and is cross-compatible with older microarrays. The characterization of epigenetic age prediction variation provides useful metrics to contextualize the relevance of epigenetic age alterations. The analysis of data from subjects influenced by radiation, cancer, and exercise-based interventions shows that despite being good predictors of chronological age, neither a pathological state like breast cancer, a hazardous environmental factor (radiation), nor exercise (a beneficial intervention) caused significant changes in the values of the "epigenetic age" determined by these first-generation models.
Author Correction: Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response
Authors: Christopher J. M. Williams, Allyson M. Peddle, Pashtoon M. Kasi, Jenny F. Seligmann, Campbell S. Roxburgh, Gary W. Middleton, Sabine Tejpar
Journal: Nature Reviews Clinical Oncology (2024)
Feasibility and Performance of a Point-of-Care Hepatitis C RNA Assay in a Community Supervision Cohort
Authors: Leah Harvey, Brendan Jacka, Lauri Bazerman, Aurielle Thomas, Marc Moody, Risha Irvin, Curt G. Beckwith
Journal: JAMA Network Open (2024)

This cross-sectional study examines the feasibility and clinical performance of a fingerstick point-of-care hepatitis C virus (HCV) RNA assay in a community supervision (probation or parole) setting.
Steatotic Liver Disease in Pediatric Obesity and Increased Risk for Youth-Onset Type 2 Diabetes
Authors: Resthie R. Putri, Thomas Casswall, Pernilla Danielsson, Claude Marcus, Emilia Hagman
Journal: Diabetes Care (2024)

OBJECTIVE To assess 1) the association between metabolic dysfunction–associated steatotic liver disease (MASLD) in pediatric obesity and youth-onset type 2 diabetes, 2) the joint effect of MASLD and intermediate hyperglycemia on type 2 diabetes risk, and 3) the effect of obesity treatment on type 2 diabetes risk. RESEARCH DESIGN AND METHODS A cohort study using the Swedish Childhood Obesity Treatment Register (Barnobesitas Registret i Sverige [BORIS]) (1999–2020) linked with national registers was conducted. We included 10,346 children with overweight or obesity and 59,336 matched control individuals. MASLD was defined by transaminases and diagnosis code, separately. Type 2 diabetes was ascertained from national registers. RESULTS In the obesity cohort, median age at type 2 diabetes diagnosis was 16.9 (quartile 1 [Q1], quartile 3 [Q3]: 14.7, 21.4) years, median follow-up was 8.1 (Q1, Q3: 5.1, 11.7) years. Cumulative incidence of type 2 diabetes at age 30 was 22.7% (obesity and MASLD), 9.9% (obesity alone), and 0.7% (control individuals). MASLD was associated with risk for type 2 diabetes (hazard ratio [HR] 2.71 [95% CI 2.14–3.43]), independently of age, sex, degree of obesity, intermediate hyperglycemia, and parental type 2 diabetes. Joint effect of MASLD and intermediate hyperglycemia increased type 2 diabetes risk (HR 9.04 [6.38–12.79]). Optimal response in obesity treatment reduced the risk (HR 0.23 [0.09–0.57]). CONCLUSIONS MASLD, defined by transaminases or diagnosis code, in pediatric obesity is associated with increased risk for youth-onset type 2 diabetes. MASLD interacts synergistically with intermediate hyperglycemia to dramatically increase the risk. Optimal response in obesity treatment reduces type 2 diabetes risk, despite MASLD.
Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists
Authors: Constance H. Fung, Cathy Alessi, Jennifer L. Martin, Karen Josephson, Lara Kierlin, Joseph M. Dzierzewski, Alison A. Moore, M. Safwan Badr, Michelle Zeidler, Monica Kelly, Jason P. Smith, Ian A. Cook, Erin Der-Mcleod, Sara Ghadimi, Saadia Naeem, Lisa Partch, Andrew Guzman, Austin Grinberg, Michael Mitchell
Journal: JAMA Internal Medicine (2024)

Placebo effects are commonly observed in benzodiazepine receptor agonist hypnotic clinical trials. Clinical guidelines recommend discontinuing benzodiazepine receptor agonist hypnotics (particularly in older adults) and administering cognitive behavioral therapy for insomnia (CBTI) as first-line therapy for insomnia. It is unknown whether a novel intervention that masks the daily dose of benzodiazepine receptor agonist during tapering and augments CBTI with novel cognitive and behavioral exercises targeting placebo effect mechanisms improves benzodiazepine receptor agonist discontinuation.
Portal Confidentiality Concerns and Health Information Sharing and Access
Authors: Marianne Sharko, Stephanie Niño de Rivera, Natalie Benda, Meghan Reading Turchioe, Xiaoyue Ma, Ruth Masterson Creber, Erika L. Abramson
Journal: JAMA Pediatrics (2024)

This survey study evaluated whether concerns about parental access to online health information through patient portals altered the amount of sensitive health information by young adults and the likelihood of opening a portal account.
Type I IFN drives unconventional IL-1β secretion in lupus monocytes
Authors: Simone Caielli, Preetha Balasubramanian, Juan Rodriguez-Alcazar, Uthra Balaji, Lauren Robinson, Zurong Wan, Jeanine Baisch, Cynthia Smitherman, Lynnette Walters, Paola Sparagana, Djamel Nehar-Belaid, Radu Marches, Lorien Nassi, Katie Stewart, Julie Fuller, Jacques F. Banchereau, Jinghua Gu, Tracey Wright, Virginia Pascual
Journal: Immunity (2024)
The Lāhainā Wildfires and ‘Āina Connectedness in the Face of Climate Disasters
Authors: Kekoa Taparra, Jeremy Samuel Faust, Kauanoe Batangan
Journal: JAMA Internal Medicine (2024)

This Viewpoint examines the disaster response and climate health concepts following the 2023 Lāhainā wildfires in Maui through the perspective of Native Hawaiian leaders and health care workers.
Testing of New Drugs Approved From 2015 Through 2021 Under the US Pediatric Research Equity Act
Authors: Ian T. T. Liu, Thomas J. Hwang, Aaron S. Kesselheim
Journal: JAMA (2024)

This study uses public US Food and Drug Administration lists to identify new drugs approved from 2015 through 2021 to examine recent estimates of compliance with and timing of pediatric testing requirements after passage of the Pediatric Research Equity Act.
Evaluating Pediatric Macrolide Allergy Using Direct Graded Oral Challenges
Authors: Carly Sillcox, Sofianne Gabrielli, Andrew O’Keefe, Christine McCusker, Elissa M. Abrams, Thomas Eiwegger, Adelle Atkinson, Vy Kim, Ana-Maria Copaescu, Moshe Ben-Shoshan
Journal: JAMA Pediatrics (2024)

This quality improvement study evaluates the use of direct graded oral challenge to confirm suspected macrolide allergy in children.
Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms
Authors: David Koeckerling, Rohin K. Reddy, Joseph Barker, Christian Eichhorn, Pip Divall, James P. Howard, Felix Korell, Michael Schmitt, Peter Dreger, Norbert Frey, Lorenz H. Lehmann
Journal: JAMA Network Open (2024)

The frequency and clinical phenotypes of cardiotoxic events in chimeric antigen receptor (CAR) T-cell recipients remain poorly understood given that landmark approval trials typically exclude patients with high-risk cardiovascular profiles and data from nontrial settings are scarce.
Mast cell modulation: A novel therapeutic strategy for abdominal pain in irritable bowel syndrome
Authors: Samuel Van Remoortel, Hind Hussein, Guy Boeckxstaens
Journal: Cell Reports Medicine (2024)

SummaryIrritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders characterized by recurrent abdominal pain and an altered defecation pattern. Chronic abdominal pain represents the hallmark IBS symptom and is reported to have the most bothersome impact on the patient's quality of life. Unfortunately, effective therapeutic strategies reducing abdominal pain are lacking, mainly attributed to a limited understanding of the contributing mechanisms. In the past few years, exciting new insights have pointed out that altered communication between gut immune cells and pain-sensing nerves acts as a hallmark driver of IBS-related abdominal pain. In this review, we aim to summarize our current knowledge on altered neuro-immune crosstalk as the main driver of altered pain signaling, with a specific focus on altered mast cell functioning herein, and highlight the relevance of targeting mast cell-mediated mechanisms as a novel therapeutic strategy for chronic abdominal pain in IBS patients.Graphical abstract
Evaluating Tools for Assessing Bias in a Meta-Analysis of Clinical Trials on Race and RAS Blockade
Authors: Jianguo Xu, Ya Gao, Jinhui Tian
Journal: JAMA (2024)

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 2024 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
Cannabis Use During Adolescence and Young Adulthood and Academic Achievement
Authors: Olsen Chan, Ahad Daudi, David Ji, Mathias Wang, Jeremy P. Steen, Parsia Parnian, Crystal Li, Annie Xiong, Wei Zhang, Luciane C. Lopes, James MacKillop, Jason W. Busse, Li Wang
Journal: JAMA Pediatrics (2024)

Cannabis use during adolescence and young adulthood may affect academic achievement; however, the magnitude of association remains unclear.
COVID-19 Therapeutics for Nonhospitalized Older Adults
Authors: Pragna Patel, David E. Wentworth, Demetre Daskalakis
Journal: JAMA (2024)

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.
Tissue-based Profiling Techniques to Achieve Precision Medicine in Cancer: Opportunities and Challenges in Melanoma
Authors: Tuba N. Gide, Yizhe Mao, Richard A. Scolyer, Georgina V. Long, James S. Wilmott
Journal: Clinical Cancer Research (2024)

Abstract Immunotherapies targeting the programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) checkpoint receptors have revolutionized the treatment of metastatic melanoma. However, half of the treated patients do not respond to or eventually progress on standard therapies and many experience adverse events as a result of drug toxicity. The identification of accurate biomarkers of clinical outcomes are required in order to move away from the one-size-fits-all treatment approach of standard clinical practice and toward a more personalized approach to enable the administration of the optimal therapy for any given patient and further improve patient outcomes. Recent clinical trials have proven the potential of multiomics analyses, including genomic, gene expression, and tumor immune profiling, of patients’ tumor biopsies, to predict a patient’s response to subsequently administered immunotherapies. However, reproducibility of such multiomics analyses, tissue requirements, and clinical validation have limited the practical application of these approaches in routine clinical workflows. In this review, we discuss several pivotal tissue-based profiling techniques that can be utilized to identify potential genomic, transcriptomic, and immune biomarkers predictive of clinical outcomes following treatment with immune checkpoint inhibitors in melanoma. Furthermore, we highlight the key opportunities and challenges associated with the use of each of these techniques. The development and implementation of multimodal predictive models that combine data derived from these various methods is the future for achieving precision medicine for patients with melanoma.
Evaluating Tools for Assessing Bias in a Meta-Analysis of Clinical Trials on Race and RAS Blockade—Reply
Authors: Li Shen, Pardeep S. Jhund, John J. V. McMurray
Journal: JAMA (2024)

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 2024 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
An RNA damage response network mediates the lethality of 5-FU in colorectal cancer
Authors: Jung-Kuei Chen, Karl A. Merrick, Yi Wen Kong, Anita Izrael-Tomasevic, George Eng, Erika D. Handly, Jesse C. Patterson, Ian G. Cannell, Lucia Suarez-Lopez, Aaron M. Hosios, Anh Dinh, Donald S. Kirkpatrick, Kebing Yu, Christopher M. Rose, Jonathan M. Hernandez, Haeun Hwangbo, Adam C. Palmer, Matthew G. Vander Heiden, Ömer H. Yilmaz, Michael B. Yaffe
Journal: Cell Reports Medicine (2024)

Highlights•5-FU does not synergize with DNA-damaging agents such as oxaliplatin or irinotecan•5-FU incorporation into structured RNAs (primarily rRNA) causes cancer cell death•5-FU drives lysosomal degradation of rRNA and ubiquitylation of ribosomal proteins•Upregulating rRNA transcription enhances tumor killing following 5-FU treatmentSummary5-fluorouracil (5-FU), a major anti-cancer therapeutic, is believed to function primarily by inhibiting thymidylate synthase, depleting deoxythymidine triphosphate (dTTP), and causing DNA damage. Here, we show that clinical combinations of 5-FU with oxaliplatin or irinotecan show no synergy in human colorectal cancer (CRC) trials and sub-additive killing in CRC cell lines. Using selective 5-FU metabolites, phospho- and ubiquitin proteomics, and primary human CRC organoids, we demonstrate that 5-FU-mediated CRC cell killing primarily involves an RNA damage response during ribosome biogenesis, causing lysosomal degradation of damaged rRNAs and proteasomal degradation of ubiquitinated ribosomal proteins. Tumor types clinically responsive to 5-FU treatment show upregulated rRNA biogenesis while 5-FU clinically non-responsive tumor types do not, instead showing greater sensitivity to 5-FU's DNA damage effects. Finally, we show that treatments upregulating ribosome biogenesis, including KDM2A inhibition, promote RNA-dependent cell killing by 5-FU, demonstrating the potential for combinatorial targeting of this ribosomal RNA damage response for improved cancer therapy.Graphical abstract
Barriers to Tofersen Therapy for Variant <i>SOD1</i>-Mediated ALS
Authors: Stanley H. Appel, Jason R. Thonhoff
Journal: JAMA Neurology (2024)

This Viewpoint advocates for the accelerated adoption of tofersen therapy to treat patients with variant SOD1-mediated amyotrophic lateral sclerosis (ALS) and describes the current barriers to treatment.
Determination of MYD88 and CXCR4 mutation for clinical detection and their significance in Waldenström macroglobulinemia
Authors: Yuting Yan, Ying Yu, Wenjie Xiong, Jun Wang, Yao Yao, YUJIAO JIA, Yanshan Huang, Yuxi Li, Tingyu Wang, Rui Lv, Hao Sun, Haoxu Wang, Qi Wang, Wei Liu, Gang An, Weiwei Sui, Yan Xu, Wenyang Huang, Zhen Yu, Dehui Zou, Mu Hao, Zhijian Xiao, Jianxiang Wang, Lugui Qiu, Shuhua Yi
Journal: Clinical Cancer Research (2024)

This study aims to explore the incidence and clinical features of MYD88 and CXCR4 mutations in patients with Waldenström macroglobulinemia (WM) and determine the optimal method for routine clinical practice. Additionally, we seek to evaluate the prognostic significance of these features across various therapeutic backgrounds [cytotoxic group, the Rituximab/Bortezomib-based group, and the Bruton's tyrosine kinase inhibitor (BTKi) group].
Longitudinal Changes in Epigenetic Age Acceleration Across Childhood and Adolescence
Authors: Juan Del Toro, Connor Martz, Colin D. Freilich, Gianna Rea-Sandin, Kristian Markon, Steve Cole, Robert F. Krueger, Sylia Wilson
Journal: JAMA Pediatrics (2024)

Individuals exposed to discrimination may exhibit greater epigenetic age acceleration (ie, cellular indicators of premature aging) over time, but few studies have examined longitudinal changes in epigenetic age acceleration, the heterogeneity in these changes for diverse groups of youths, and contextual explanations (ie, discrimination) for differences by ethnicity or race.
Medication Abortion Through Telehealth Is Safe and Effective
Authors: Nisha Verma, Rachel Neal, Michael A. Belmonte
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine 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 2024 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 Internal Medicine journal