tbuckley/cabot-search huggingface dataset:
Harnessing Type II Cytokines to Reinvigorate Exhausted T Cells for Durable Cancer Immunotherapy
Authors: Wenle Zhang, Yanwen Wang, Bin Li
Journal: Genomics Proteomics & Bioinformatics (2024)

Count of references: 10Cancer immunotherapy has made significant strides in developing immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-based cellular therapies in recent years.Despite these advancements, the immunosuppressive nature of the tumor microenvironment (TME) and its metabolic complexity continue to present substantial challenges.Within this hostile environment, tumor-infiltrating T cells often experience severe functional impairment and reduced cytotoxic potential.One of the main barriers to effective and long-lasting tumor control is T cell exhaustiona state characterized by diminished effector functions, impaired proliferation, and sustained expression of inhibitory receptors like PD-1, TIM-3 and LAG-3.Although CAR-T cell therapy has revolutionized the treatment of hematological malignancies, relapse was constantly reported and limited efficacy was observed in treating solid tumors, largely due to the hostile TME and rapid onset of CAR-T cell exhaustion.To better understand mechanisms behind sustained CAR-T cell responses, a large-scale single-cell multi-omics study profiled over one million pre-infusion CAR T cells collected from 82 acute lymphoblastic leukemia patients, with clinical follow-up extending up to 10 years [1].The analysis highlighted that elevated type II cytokine activity in CAR-T cell infusion products was linked to patients maintaining 8-year leukemia remission.At the chromatin level, higher increased accessibility was found at the loci of GATA3, while the IFNG, STAT1, STAT4 and TBX21 showed negligible differences.Remarkably, the study also identified that this small
COCOA: A Framework for Fine-scale Mapping Cell-type-specific Chromatin Compartments with Epigenomic Information
Authors: Kai Li, Ping Zhang, Jinsheng Xu, Zi Wen, Junying Zhang, Zhike Zi, Li Li
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Chromatin compartmentalization and epigenomic modification are crucial in cell differentiation and diseases development. However, precise mapping of chromatin compartmental patterns requires Hi-C or Micro-C data at high sequencing depth. Exploring the systematic relationship between epigenomic modifications and compartmental patterns remains challenging. To address these issues, we present COCOA, a deep neural network framework using convolution and attention mechanisms to infer fine-scale chromatin compartment patterns from six histone modification signals. COCOA extracts 1-D track features through bi-directional feature reconstruction after resolution-specific binning epigenomic signals. These track features are then cross-fused with contact features using an attention mechanism and transformed into chromatin compartment patterns through residual feature reduction. COCOA demonstrates accurate inference of chromatin compartmentalization at a fine-scale resolution and exhibits stable performance on test sets. Additionally, we explored the impact of histone modifications on chromatin compartmentalization prediction through in silico epigenomic perturbation experiments. Unlike obscure compartments observed with 1 kb resolution high-depth experimental data, COCOA generates clear and detailed compartmental patterns, highlighting its superior performance. Finally, we demonstrated that COCOA enables cell-type-specific prediction of unrevealed chromatin compartment patterns in various biological processes, making it an effective tool for gaining chromatin compartmentalization insights from epigenomics in diverse biological scenarios. The COCOA python code is publicly available at https://github.com/onlybugs/COCOA.
Before the Ailments
Authors: Tarek Zieneldien
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Sociodemographic Factors and Utilization of Pediatric Oncology Satellite Clinics in Ontario, Canada
Authors: Maria Chiu, Abbas Ali, Felicia Leung, Chaoran Dong, Petros Pechlivanoglou, David Hodgson, Paul Gibson
Journal: JAMA Network Open (2024)

Importance Pediatric cancer care services in high-income nations are mainly centralized in metropolitan cities. To allow treatments closer to home, patients across Ontario, Canada, a geographically large province, are offered decentralized care via satellite clinics; however, it is unclear whether the utilization of these pediatric oncology satellite clinics differs by area-level sociodemographic factors. Objective To examine whether sociodemographic factors, such as area-level income and rurality, are independently associated with the odds of satellite clinic visit and the hazards of time to first visit among pediatric oncology patients receiving cancer treatment. Design, Setting, and Participants This is a retrospective population-based cohort study of patients aged 0 to 17 years with cancer living in a satellite catchment area in Ontario, Canada (from 2015 to 2022, with follow-up through 2023). The Pediatric Oncology Group of Ontario Networked Information System cancer registry (containing age, sex, diagnosis type, and year information) was linked to satellite, OpenStreetMap, and postal-code databases to ascertain rural or urban dwelling, neighborhood-based income, and driving time saved. Exposures Age, sex, rural or urban dwelling, and neighborhood-level income quintiles. Main Outcomes and Measures The primary outcomes were the odds of satellite clinic attendance within 1 year of diagnosis and the hazards of first clinic visit after starting systemic therapy, derived from multivariable logistic and Cox proportional hazards models, respectively. Results Among the 1280 eligible patients (median [IQR] age, 7.0 [3.0-13.0] years; 753 male [58.8%]), 844 (65.9%) visited a satellite clinic within 1 year of diagnosis with a median (IQR) of 39 (14-67) days to first visit. Driving time saved (&amp;amp;gt;60 minutes) was the factor most associated with satellite use, followed by diagnostic type (with patients with central nervous system tumors least likely to visit). Rural (vs urban) patients had significantly lower odds of satellite visit within a year of diagnosis (odds ratio, 0.48; 95% CI, 0.31-0.74; P = .001) and lower instantaneous likelihood of visiting after start of treatment (hazard ratio, 0.65; 95% CI, 0.53-0.81; P &amp;amp;lt; .001). Living in a lower-income (vs middle-income) area was also associated with significantly lower utilization (odds ratio, 0.53; 95% CI, 0.35-0.80; P = .009; hazard ratio, 0.73; 95% CI, 0.60-0.89; P = .002). Conclusions and Relevance This population-based study of pediatric oncology patients found that satellite clinics, despite being designed to reduce transportation and financial burdens, were disproportionately underutilized by patients living in rural and lower-income areas. Monitoring area-level social determinants of health can help inform interventions to improve timely and equitable access to childhood cancer care closer to home.
Persistence of a Birth Cohort Effect in the US Among the Adult Homeless Population
Authors: Thomas Byrne, Kelly M. Doran, Randall Kuhn, Stephen Metraux, Maryanne Schretzman, Dan Treglia, Dennis P. Culhane
Journal: JAMA Network Open (2024)

This cross-sectional study evaluates the persistence of a birth cohort effect among adults born between 1955 and 1965 in the US homeless population.
Private-Sector Readmissions for Inpatient Surgery in Veterans Health Administration Hospitals
Authors: Mary Vaughan Sarrazin, Yubo Gao, Carly A. Jacobs, Michael A. Jacobs, Susanne Schmidt, Heather Davila, Katherine Hadlandsmyth, Andrea L. Strayer, John Cashy, George Wehby, Paula K. Shireman, Daniel E. Hall
Journal: JAMA Network Open (2024)

The Veterans Health Administration (VHA) reports multiple indicators of hospital surgical performance, including hospital risk-standardized 30-day readmission rates (RSRRs). Currently, most routinely reported measures do not include readmissions that occur outside VHA hospitals. The impact of readmissions outside the VHA on hospital RSRR is not known. To measure the impact of including non-VHA readmissions on VHA hospital performance rankings for 30-day readmission. This retrospective cohort study included patients aged at least 65 years from 2013 to 2019 from the Veterans Affairs Surgical Quality Improvement Program linked to patient-level data from the VHA and Medicare. Data were limited to patients with VHA and Medicare enrollment during the year prior to surgery. Data were analyzed from November 2023 through July 2024. The main outcome was readmissions to acute care VHA or non-VHA hospitals within 30 days of discharge. VHA hospital-level RSRRs were estimated using separate generalized linear mixed-effects risk adjustment models that alternatively included VHA-only or VHA plus non-VHA readmissions. VHA hospitals were then stratified into quintiles based on RSRRs derived using VHA-only or VHA plus non-VHA readmissions. Changes in hospital performance quintiles with the addition of non-VHA readmissions were calculated, and characteristics of VHA hospitals most impacted by including non-VHA readmissions were evaluated. The eligible cohort included 108 265 patients (mean [SD] age, 72.2 [6.5] years; 105 661 [97.6%] male) who underwent surgery in 104 VHA hospitals. The combined readmission rate was 14.0%. The proportion of readmissions occurring outside the VHA ranged from 0% to 55.3% across the 104 VHA hospitals (median, 20.9%). Using VHA and non-VHA readmissions, 24 VHA hospitals (23.1%) improved performance and 23 hospitals (22.1%) worsened performance, defined as a decrease or increase, respectively, of 1 or more RSRR quintiles. Improvements in hospital performance rank were associated with larger surgical volume (-7.48; 95% CI, -11.33 to 03.64; P < .001), urban location, greater surgical complexity (-9.86; 95% CI, -16.61 to -3.11; P = .005), and lower proportion of readmissions outside the VHA (-8.15; 95% CI, -12.75 to -3.55; P < .001). In this cohort study, VHA hospitals whose readmission performance metric improved by including non-VHA readmissions had higher patient volume, higher complexity, and lower proportion of care outside the VHA. Thus, improving continuity of care may have a paradoxical effect of worsening VHA performance metrics.
A Novel Targeted Long-read Sequencing Approach Boosts Transcriptomic Profiling
Authors: Xiaolong Tian, Rong Fan
Journal: Genomics Proteomics & Bioinformatics (2024)

TEQUILA-seq (Transcript Enrichment and Quantification Utilizing Isothermally Linear-Amplified probes in conjunction with long-read sequencing) [1], a novel targeted alternative isoform variation sequencing technique.This method enables the economical profiling of fulllength transcriptomic landscapes with high sensitivity and fidelity, facilitating the discovery of a wide array of novel transcripts and the elucidation of RNA-associated mechanisms, like tumor suppressor gene inactivation.Such capabilities hold significant implications for a broad range of basic, translational, and clinical applications.Mechanisms such as splicing, polyadenylation, alternative promoter usage, or RNA editing significantly diversify gene output.Hence, characterizing transcript isoforms remains a challenge when using short-read RNA sequencing.Although long-read sequencing reveals complete
Immunotherapy Benefit Over Best Supportive Care in Hepatocellular Cancer With Child-Pugh B Dysfunction
Authors: Manuel David Gil-Sierra, María del Pilar Briceño-Casado, Cristina Moreno-Ramos
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Dissection of Progressive Disease Patterns for a Modified Classification for Immunotherapy
Authors: Jonas Saal, Markus Eckstein, Manuel Ritter, Peter Brossart, Julian Luetkens, Jörg Ellinger, Viktor Grünwald, Michael Hölzel, Niklas Klümper
Journal: JAMA Oncology (2024)

Importance Progressive disease (PD) in patients treated with immune checkpoint inhibitors (ICIs) varies widely in outcomes according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Efforts to modify RECIST for ICI treatment have not resolved the heterogeneity in PD patterns, posing a clinical challenge. Objective To develop and validate a modified PD classification based on PD patterns and evaluate its association with postprogression survival (PPOS) in patients treated with the programmed cell death protein ligand 1 antibody atezolizumab across various solid tumors. Design, Setting, and Participants This study analyzed data from 5 phase 3 trials (IMmotion151, IMvigor211, OAK, Impower133, and IMspire150) involving patients treated with atezolizumab for renal cell carcinoma (RCC), urothelial carcinoma, small cell lung cancer, non–small cell lung cancer, and melanoma. This post hoc analysis was conducted from March to September 2024. Exposure Treatment with atezolizumab. Main Outcomes and Measures The primary outcome was the association of PD patterns with PPOS. Seven PD patterns were identified based on the enlargement of target and nontarget lesions or new lesions and their combinations. Results A total of 1377 patients were analyzed across the 5 trials. In RCC, 7 PD patterns significantly affected prognosis. The 6-month PPOS probability ranged from 26% for progression in target and nontarget lesions plus new lesions to 90% for progression in either target or nontarget lesions alone. A modified PD classification was developed that categorized PD into 3 risk levels: low risk (progression of existing lesions), intermediate risk (new lesions without progression of existing lesions), and high risk (progression of existing lesions plus new lesions). This score was associated with PPOS in ICI-treated RCC, with hazard ratios of 0.23 (95% CI, 0.13-0.41; P &amp;amp;lt; .001) and 0.39 (95% CI, 0.23-0.66; P &amp;amp;lt; .001) for low-risk and intermediate-risk PD compared with high-risk PD, respectively. Validation in additional trials confirmed the score’s applicability across various tumors. Conclusions and Relevance In this study, a survival score was developed based on PD patterns. The risk classification was associated with PPOS across various solid tumors treated with immunotherapy and may therefore enhance prognostication and clinical decision-making, potentially providing a valuable tool for treating patients with PD who are receiving immunotherapy.
Single Cell Sequencing Traces Mitochondrial Transfers
Authors: Mengying Wu, Weilin Pu, Zhenglong Gu
Journal: Genomics Proteomics & Bioinformatics (2024)

Mitochondrial transferMitochondrial transfer, encompassing the transfer of whole mitochondria and mitochondrial DNA, manifests under specific biological conditions, and it holds potential to exert profound effects on various cellular functions, such as proliferation, differentiation, and metabolism.A pivotal discovery in 2006 illuminated that the active mitochondrial transfer from both adult stem cells and somatic cells could restore aerobic respiration in mammalian cells afflicted by nonfunctional mitochondria [1].Moreover, adipocytes were found to transfer mitochondria to macrophages in white and brown adipose tissues to maintain metabolic homeostasis [2].In addition, it has been elucidated that astrocytes can release functional mitochondria, which could be subsequently integrated into neurons following cerebral ischemia, contributing to the activation of endogenous neuroprotective and neurorecovery processes [3].In the controlled environment of in vitro studies, it has been revealed that Rho0 cells, characterized by the absence of functional mitochondria, display the capacity to capture exogenous mitochondria sourced from supernatants or other cells.Remarkably, these captured mitochondria are harnessed by the Rho0 cells to restore deficiencies in aerobic
Prolonged vs Intermittent Infusions of β-Lactam Antibiotics
Authors: Huayang Pang, Hao Sun
Journal: JAMA (2024)

To the Editor We have several concerns about the recent meta-analysis conducted by Dr Abdul-Aziz and colleagues,1 which investigated the efficacy of prolonged vs intermittent infusions of β-lactam antibiotics in adults with sepsis or septic shock.
Suicide Risk Among Veterans Who Receive Evidence-Based Therapy for Posttraumatic Stress Disorder
Authors: Kevin G. Saulnier, Stuart Brabbs, Benjamin R. Szymanski, Ilan Harpaz-Rotem, John F. McCarthy, Rebecca K. Sripada
Journal: JAMA Network Open (2024)

Importance Suicide rates are increased for veterans with posttraumatic stress disorder (PTSD). To inform Veterans Health Administration (VHA) operations, it is important to assess whether suicide risk for veterans differs by receipt of evidence-based treatments. Objective To assess suicide risks among veterans in VHA care with new PTSD diagnoses who initiated or received an adequate course of evidence-based psychotherapy (cognitive processing therapy or prolonged exposure [CPT/PE]). Design, Setting, and Participants This cohort study of veterans in VHA care evaluated suicide risk through 2020 for veterans with initial PTSD diagnoses during 2016-2019. Data collection and analyses were performed from March 22 to November 22, 2023. The population consisted of veterans who received an initial PTSD diagnosis (preceded by at least 12 months without a PTSD diagnosis) in 2016-2019. Exposures Following the index PTSD diagnosis, receipt of a CPT/PE encounter and receipt of an adequate course of therapy (≥8 CPT/PE encounters). Main Outcome and Measure Suicide mortality, per death certificate data from the Veterans Affairs/Department of Defense Mortality Data Repository. Results Of the population-based sample of 847 217 US veterans, most were male (735 974 [86.9%]); the mean (SD) age was 50.1 (16.3) years. From initial PTSD diagnosis through 2020, there were 1552 suicides. Multivariable proportional hazards regression indicated that initiation of CPT/PE treatment was associated with a 23% lower suicide risk compared with those who did not initiate CPT/PE (hazard ratio [HR], 0.77; 95% CI, 0.59-0.99). Receipt of an adequate course was not associated with suicide (HR, 0.80; 95% CI, 0.55-1.18). Similar results were observed when limiting the cohort to those who received any psychotherapy (n = 552 742; CPT/PE initiation: HR, 0.73; 95% CI, 0.56-0.95; adequate course: HR, 0.77; 95% CI, 0.52-1.12). Conclusions and Relevance The findings of this study suggest that, among veterans in VHA care with new PTSD diagnoses, CPT/PE initiation was associated with lower suicide risk. However, for those who initiated CPT/PE, receipt of 8 or more sessions was not associated with added benefit.
Clinical Implications of Trauma-Focused Therapy for Veterans
Authors: Shannon Wiltsey Stirman
Journal: JAMA Network Open (2024)

Kevin G. Saulnier, PhD; Stuart Brabbs, MPH; Benjamin R. Szymanski, PhD, MPH; Ilan Harpaz-Rotem, PhD; John F. McCarthy, PhD, MPH; Rebecca K. Sripada, PhD
Care
Authors: Austin M. Parsons
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