tbuckley/cabot-search huggingface dataset:
Neoantigen landscape in metastatic nasopharyngeal carcinoma
Authors: Mei Lin, Xiao-Long Zhang, Rui You, Qi Yang, Xiong Zou, Kai Yu, You-Ping Liu, Ru-Hai Zou, Yi-Jun Hua, Pei-Yu Huang, Jin Wang, Qi Zhao, Xiao-Bing Jiang, Jun Tang, Yang-Kui Gu, Tao Yu, Gui-Ping He, Yu-Long Xie, Zhi-Qiang Wang, Ting Liu, Si-Yuan Chen, Zhi-Xiang Zuo, Ming-Yuan Chen
Journal: Theranostics (2021)

Background: Reportedly, nasopharyngeal carcinoma (NPC) patients with MHC I Class aberration are prone to poor survival outcomes, which indicates that the deficiency of tumor neoantigens might represent a mechanism of immune surveillance escape in NPC. Methods: To clearly delineate the landscape of neoantigens in NPC, we performed DNA and RNA sequencing on paired primary tumor, regional lymph node metastasis and distant metastasis samples from 26 patients. Neoantigens were predicted using pVACseq pipeline. Subtype prediction model was built using random forest algorithm. Results: Portraying the landscape of neoantigens in NPC for the first time, we found that the neoantigen load of NPC was above average compared to that of other cancers in The Cancer Genome Atlas program. While the quantity and quality of neoantigens were similar among primary tumor, regional lymph node metastasis and distant metastasis samples, neoantigen depletion was more severe in metastatic sites than in primary tumors. Upon tracking the clonality change of neoantigens, we found that neoantigen reduction occurred during metastasis. Building a subtype prediction model based on reported data, we observed that subtype I lacked T cells and suffered from severe neoantigen depletion, subtype II highly expressed immune checkpoint molecules and suffered from the least neoantigen depletion, and subtype III was heterogenous. Conclusions: These results indicate that neoantigens are conducive to the guidance of clinical treatment, and personalized therapeutic vaccines for NPC deserve deeper basic and clinical investigations to make them feasible in the future.
A NATIONWIDE ANALYSIS OF THE EXTERNAL APPLICABILITY OF THE COMPASS TRIAL IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS SURGERY
Authors: Salil Deo, Jayakumar Sahadevan, Muhammad Adil Sheikh, Padmini Selvaganesan, Shrikrishna Madan Mohan, Richard Josephson, Joseph Rubelowsky, Yakov Elgudin, Brian Cmolik, Salah Altarabsheh, Piroze Davierwala, Varun Sundaram
Journal: Journal of the American College of Cardiology (2021)
Endometrial membrane organoids from human embryonic stem cell combined with the 3D Matrigel for endometrium regeneration in asherman syndrome
Authors: Xiuxiu Jiang, Xingmiao Li, Xiangwei Fei, Jiajie Shen, Jianhua Chen, Meijun Guo, Yangyang Li
Journal: Bioactive Materials (2021)

Asherman's syndrome (AS), a leading cause of uterine infertility worldwide, is characterized by scarring of the uterine surfaces lacking endometrial epithelial cells, which prevents endometrial regeneration. Current research on cell therapy for AS focuses on mesenchymal and adult stem cells from the endometrium. However, insufficient number, lack of purity, and rapid senescence of endometrial epithelial progenitor cells (EEPCs) during experimental processes restrict their use in cell therapies. In this study, we induced human embryonic stem cells-9 (H9-ESC) into EEPCs by optimizing the induction factors from the definitive endoderm. EEPCs, which act as endometrial epithelial cells, accompanied by human endometrial stromal cells provide a niche environment for the development of endometrial membrane organoids (EMOs) in an in vitro 3D culture model. To investigate the function of EMOs, we transplanted tissue-engineered constructs with EMOs into an in vivo rat AS model. The implantation of EMOs into the damaged endometrium facilitates endometrial regeneration and angiogenesis. Implanting EMOs developed from human embryonic stem cells into the endometrium might prove useful for "endometrial re-engineering" in the treatment of Asherman's syndrome.
Does the Association Between Hemoglobin A1c and Risk of Cardiovascular Events Vary by Residential Segregation? The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Doyle M. Cummings, Shivajirao P. Patil, D. Leann Long, Boyi Guo, Andrea Cherrington, Monika M. Safford, Suzanne E. Judd, Virginia J. Howard, George Howard, April P. Carson
Journal: Diabetes Care (2020)

OBJECTIVE To examine if the association between higher A1C and risk of cardiovascular disease (CVD) among adults with and without diabetes is modified by racial residential segregation. RESEARCH DESIGN AND METHODS The study used a case-cohort design, which included a random sample of 2,136 participants at baseline and 1,248 participants with incident CVD (i.e., stroke, coronary heart disease [CHD], and fatal CHD during 7-year follow-up) selected from 30,239 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants originally assessed between 2003 and 2007. The relationship of A1C with incident CVD, stratified by baseline diabetes status, was assessed using Cox proportional hazards models adjusting for demographics, CVD risk factors, and socioeconomic status. Effect modification by census tract-level residential segregation indices (dissimilarity, interaction, and isolation) was assessed using interaction terms. RESULTS The mean age of participants in the random sample was 64.2 years, with 44% African American, 59% female, and 19% with diabetes. In multivariable models, A1C was not associated with CVD risk among those without diabetes (hazard ratio [HR] per 1% [11 mmol/mol] increase, 0.94 [95% CI 0.76–1.16]). However, A1C was associated with an increased risk of CVD (HR per 1% increase, 1.23 [95% CI 1.08–1.40]) among those with diabetes. This A1C-CVD association was modified by the dissimilarity (P &amp;lt; 0.001) and interaction (P = 0.001) indices. The risk of CVD was increased at A1C levels between 7 and 9% (53–75 mmol/mol) for those in areas with higher residential segregation (i.e., lower interaction index). In race-stratified analyses, there was a more pronounced modifying effect of residential segregation among African American participants with diabetes. CONCLUSIONS Higher A1C was associated with increased CVD risk among individuals with diabetes, and this relationship was more pronounced at higher levels of residential segregation among African American adults. Additional research on how structural determinants like segregation may modify health effects is needed.
Abstract 11641: C2 and Association With New Onset of Type 2 Diabetes Mellitus: The MESA Study
Authors: Daniel A Duprez, Nketi I Forbang, Matthew A Allison, Carmen A Peralta, Christina L Wassel, Steven Shea, David R Jacobs
Journal: Circulation (2018)

Introduction: Microvascular abnormalities delay the access of glucose and insulin to target tissues, which may lead to insulin resistance, a major mechanism underlying type 2 diabetes (DM). C2, der...
Ischemic Events After Intracerebral Hemorrhage
Authors: Graeme J. Hankey
Journal: JAMA Neurology (2021)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 2023 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 Neurology journal
Environmental and sex-specific molecular signatures of glioma causation
Authors: Elizabeth B Claus, Vincent L Cannataro, Stephen G Gaffney, Jeffrey P Townsend
Journal: Neuro-Oncology (2021)

The relative importance of genetic and environmental risk factors in gliomagenesis remains uncertain.Using whole-exome sequencing data from 1105 adult gliomas, we evaluate the relative contribution to cancer cell lineage proliferation and survival of single-nucleotide mutations in tumors by IDH mutation subtype and sex. We also quantify the contributions of COSMIC cancer mutational signatures to these tumors, identifying possible risk exposures.IDH-mutant tumors exhibited few unique recurrent substitutions-all in coding regions, while IDH wild-type tumors exhibited many substitutions in non-coding regions. The importance of previously reported mutations in IDH1/2, TP53, EGFR, PTEN, PIK3CA, and PIK3R1 was confirmed; however, the largest cancer effect in IDH wild-type tumors was associated with mutations in the low-prevalence BRAF V600E. Males and females exhibited mutations in a similar set of significantly overburdened genes, with some differences in variant sites-notably in the phosphoinositide 3-kinase (PI3K) pathway. In IDH-mutant tumors, PIK3CA mutations were located in the helical domain for females and the kinase domain for males; variants of import also differed by sex for PIK3R1. Endogenous age-related mutagenesis was the primary molecular signature identified; a signature associated with exogenous exposure to haloalkanes was identified and noted more frequently in males.Cancer-causing mutations in glioma primarily originated as a consequence of endogenous rather than exogenous factors. Mutations in helical vs kinase domains of genes in the phosphoinositide 3-kinase (PI3K) pathway are differentially selected in males and females. Additionally, a rare environmental risk factor is suggested for some cases of glioma-particularly in males.
SP0051 CASE 2 DISCUSSANT: DISCUSSION OF HOW A LARGE PROPORTION OF PEOPLE DO NOT BECOME ACTIVE AFTER JOINT REPLACEMENT DESPITE ADEQUATE PAIN RELIEF, REASONS, NEGATIVE CONSEQUENCES OF REDUCED ACTIVITY AND POSSIBLE APPROACHES
Authors: Thea Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The literature on the effect of total hip and knee arthroplasty (THA and TKA) on the amount of physical activity is scanty, with various studies suggesting that physical activity levels do not increase after surgery. These results raise several questions, such as: Are patients who will undergo or underwent THA or TKA more or less physically active than the general population? And, if not, should they become more physically active, what are barriers and facilitators for physical activity levels, what would be the potential benefits? Who are the stakeholders that should be involved in the promotion of physical activity in this patient group? These, and other questions will be highlighted in an interactive discussion with the attendees of the session. <h3>References:</h3> [1] Pellegrini CA, et al. Disabil Rehabil. 2018;40:2004-2010. [2] Naylor JM, et al. Arthritis Care Res (Hoboken). 2019;71:207-217. [3] Hodges A, et al. Clin Rehabil. 2018;32:1271-1283. <h3>Disclosure of Interests:</h3> None declared
IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy
Authors: Karan Kohli, Lu Yao, Theodore Scott Nowicki, Shihong Zhang, Ralph Graeme Black, Brett A Schroeder, Erik A Farrar, Jianhong Cao, Heather Sloan, Dawn Stief, Lee D Cranmer, Michael J Wagner, Douglas S Hawkins, Venu G Pillarisetty, Antoni Ribas, Jean Campbell, Robert H Pierce, Edward Y Kim, Robin L Jones, Stanley R Riddell, Cassian Yee, Seth M Pollack
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1–specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression. Method We performed a phase I clinical trial evaluating the safety of NY-ESO-1–specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15. Results Four patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1–specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor–based products at other centers. Conclusions ETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1–specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.
SEVERE OBESITY IS ASSOCIATED WITH HDL PROTEOME CHANGES THAT RESOLVE WITH BARIATRIC SURGERY
Authors: Ariya Chaloemtoem, Tomas Vaisar, Marcin Falis, Ruina Zhang, BingXue Lin, Manish Parikh, Jake Wimberger, Carissa Thornock, Jeffrey Berger, Edward Fisher, Florencia Schlamp
Journal: Journal of the American College of Cardiology (2021)
Appropriate Use of High-Flow Nasal Oxygen in Hospitalized Patients for Initial or Postextubation Management of Acute Respiratory Failure: A Clinical Guideline From the American College of Physicians
Authors: Amir Qaseem, Itziar Etxeandia-Ikobaltzeta, Nick Fitterman, John W. Williams, Devan Kansagara
Journal: Annals of Internal Medicine (2021)

Description: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of high-flow nasal oxygen (HFNO) in hospitalized patients for initial or postextubation management of acute respiratory failure. It is based on the best available evidence on the benefits and harms of HFNO, taken in the context of costs and patient values and preferences. Methods: The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of HFNO. The patient-centered health outcomes evaluated included all-cause mortality, hospital length of stay, 30-day hospital readmissions, hospital-acquired pneumonia, days of intubation or reintubation, intensive care unit (ICU) admission and ICU transfers, patient comfort, dyspnea, delirium, barotrauma, compromised nutrition, gastric dysfunction, functional independence at discharge, discharge disposition, and skin breakdown. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Target Audience and Patient Population: The target audience is all clinicians, and the target patient population is adult patients with acute respiratory failure treated in a hospital setting (including emergency departments, hospital wards, intermediate or step-down units, and ICUs). Recommendation 1a: ACP suggests that clinicians use high-flow nasal oxygen rather than noninvasive ventilation in hospitalized adults for the management of acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence). Recommendation 1b: ACP suggests that clinicians use high-flow nasal oxygen rather than conventional oxygen therapy for hospitalized adults with postextubation acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence).
DIASTOLIC FUNCTION: MEASURING LEFT VENTRICULAR UNTWISTING AS A DAMPED HARMONIC OSCILLATOR
Authors: Forrest Gamble, Rifqi Aufan, Oleg F. Sharifov, Lamario J. Williams, Shane Reighard, David Calhoun, Himanshu Gupta, Louis Dell’Italia, Thomas Denney, Steven Lloyd
Journal: Journal of the American College of Cardiology (2021)
CHEST PAIN WITH TRANSIENT ST SEGMENT ELEVATION DO WE NEED CORONARY ANGIOGRAM
Authors: Gunjan S. Joshi, Amudhan Jyothidasan, William Sanchez-Garcia, Haitham Mazek, Sylvester Ejeh, Divyang Patel, Amol Bahekar, Manoj Bhandari
Journal: Journal of the American College of Cardiology (2021)
Sustained Care Smoking Cessation Intervention for Individuals Hospitalized for Psychiatric Disorders
Authors: Richard A. Brown, Haruka Minami, Jacki Hecht, Christopher W. Kahler, Lawrence H. Price, Kimberly L. Kjome, Erika Litvin Bloom, Douglas E. Levy, Kelly M. Carpenter, Ashleigh Smith, Jasper A. J. Smits, Nancy A. Rigotti
Journal: JAMA Psychiatry (2021)

Smoking among individuals with serious mental illness (SMI) represents a major public health problem. Intervening during a psychiatric hospital stay may provide an opportunity to aid engagement in smoking cessation treatment and facilitate success in quitting. To examine the effectiveness of a multicomponent, sustained care (SusC) smoking cessation intervention in adults with SMI receiving inpatient psychiatric care. The Helping HAND 3 randomized clinical trial compared SusC with usual care (UC) among individuals with SMI who smoked daily and were receiving inpatient psychiatric care in Austin, Texas, in a single hospital. The study was conducted from July 2015 through August 2019. The UC intervention involved brief smoking cessation information, self-help materials and advice from the admitting nurse, and an offer to provide nicotine replacement therapy during hospitalization. The SusC intervention included 4 main components designed to facilitate patient engagement with postdischarge smoking cessation resources: (1) inpatient motivational counseling; (2) free transdermal nicotine patches on discharge; (3) an offer of free postdischarge telephone quitline, text-based, and/or web-based smoking cessation counseling, and (4) postdischarge automated interactive voice response calls or text messages. The primary outcome was biochemically verified 7-day point-prevalence abstinence at 6-month follow-up. A secondary outcome was self-reported smoking cessation treatment use at 1, 3, and 6 months after discharge. A total of 353 participants were randomized, of whom 342 were included in analyses (mean [SD] age, 35.8 [12.3] years; 268 White individuals [78.4%]; 280 non-Hispanic individuals [81.9%]; 169 women [49.4%]). They reported smoking a mean (SD) of 16.9 (10.4) cigarettes per day. Participants in the SusC group evidenced significantly higher 6-month follow-up point-prevalence abstinence rates than those in the UC group (8.9% vs 3.5%; adjusted odds ratio, 2.95 [95% CI, 1.24-6.99]; P = .01). The number needed to treat was 18.5 (95% CI, 9.6-306.4). A series of sensitivity analyses confirmed effectiveness. Finally, participants in the SusC group were significantly more likely to report using smoking cessation treatment over the 6 months postdischarge compared with participants in the UC group (74.6% vs 40.5%; relative risk, 1.8 [95% CI, 1.51-2.25]; P < .001). The findings of this randomized clinical trial provide evidence for the effectiveness of a scalable, multicomponent intervention in promoting smoking cessation treatment use and smoking abstinence in individuals with SMI following hospital discharge. ClinicalTrials.gov Identifier: NCT02204956.
Polypharmacy, inappropriate prescribing, and deprescribing in older people: through a sex and gender lens
Authors: Paula A Rochon, Mirko Petrovic, Antonio Cherubini, Graziano Onder, Denis O'Mahony, Shelley A Sternberg, Nathan M Stall, Jerry H Gurwitz
Journal: The Lancet Healthy Longevity (2021)
A RARE CASE OF CHEMOTHERAPY-INDUCED TAKOTSUBO'S CARDIOMYOPATHY COMPLICATED BY LVOT OBSTRUCTION WITH EVIDENCE OF BROCKENBROUGH-BRAUNWALD MORROW'S SIGN
Authors: Adhiraj Bhattacharya, Mahesh Golla, Uyen Lam, Tariq Bhat
Journal: Journal of the American College of Cardiology (2021)
EFFICACY AND SAFETY OF LOW-DOSE RIVAROXABAN IN SYMPTOMATIC PAD PATIENTS UNDERGOING REVASCULARIZATION CURRENTLY SMOKING: INSIGHTS FROM VOYAGER PAD
Authors: Justin Morrison, William Hiatt, Manesh Patel, Sonia Anand, E. Sebastian Debus, Mark Nehler, Connie Hess, Warren H. Capell, Taylor Bracken, Scott Berkowitz, Eva Muehlhofer, Lloyd Haskell, Rupert Bauersachs, Marc Bonaca
Journal: Journal of the American College of Cardiology (2021)
Be aware: new rules for corticosteroids!
Authors: Lars Engebretsen
Journal: British Journal of Sports Medicine (2021)

A paper in this issue on ‘ A novel approach to improve detection of glucocorticoid doping in sport with new guidance for physicians prescribing for athletes’ by Ventura et al 1 is important for every practising physician and physical therapist who is treating high level athletes. As of 2022 (remember; prior to the Games in Beijing), new rules will be in effect, and you need to be aware of them. This review evaluates the current glucocorticoid (GC) anti-doping regulations as defined by the WADA and presents a novel approach for defining permitted and prohibited use of GCs in sport based on the potential for performance enhancement and risk to health. Revised and substance-specific laboratory reporting values are presented in this paper to better distinguish between prohibited and permitted use in sport.2 In addition, washout periods are presented to enable clinicians to avoid the risk of athletes testing positive on a doping test.

The systemic effect of GCs following injectable and other routes of administration presents a potential both to improve performance and to cause harm to health in athletes. This paper presents a novel approach to a ‘contentious’ subject in anti-doping—GCs injections. GCs have been ‘contentious’ in sport for years. When the systemic …
CAN ARTIFICIAL INTELLIGENCE QUANTIFY LV EJECTION FRACTION INSTANTLY AND ACCURATELY FROM POINT-OF-CARE ECHOCARDIOGRAMS PERFORMED BY MEDICAL RESIDENTS ON CRITICALLY-ILL PATIENTS?
Authors: Jason Feinman, Solomon Bienstock, Ashton Lai, Rajeev Samtani, Nikola Kocovic, Frans Beerkens, Michal Yaacobi, Stéphane Gatesoupe, Lori Croft, Samuel Acquah, Martin Goldman
Journal: Journal of the American College of Cardiology (2021)
Covid-19: Uptake of testing does not reflect chances of positive test, study finds
Authors: Barbara Kermode-Scott
Journal: BMJ (2021)

Social determinants of health and certain health conditions are associated with testing and with testing positive for SARS-CoV-2, a study published in the Canadian Medical Association Journal has found.1

And it is important to understand these factors in managing the response to the pandemic, the researchers suggest, after they conducted an observational study using cross sectional analyses among nearly 14.7 million community dwelling people in Ontario, Canada.

Researchers analysed data on 14 695 579 people in Ontario from March to June 2020, of whom 758 691 were tested for SARS-CoV-2 and 25 030 (3.3%) tested positive.

The research team explored the potential for collider or selection bias …
GUIDELINE CONCORDANT ANTIPLATELET REGIMENS IN PATIENTS WHO UNDERWENT CAROTID ARTERY REVASCULARIZATION: INSIGHTS FROM THE VASCULAR QUALITY INITIATIVE REGISTRY
Authors: Zain Ahmed, Megan Lee, Jiaming Huang, Aaron Brice, Ahmad Arham, Yulanka Castro Dominguez, Edouard Aboian, Sameer Nagpal, Kim Smolderen, Carlos Mena Hurtado
Journal: Journal of the American College of Cardiology (2021)