tbuckley/cabot-search huggingface dataset:
G6PD functions as a metabolic checkpoint to regulate granzyme B expression in tumor-specific cytotoxic T lymphocytes
Authors: Chunwan Lu, Dafeng Yang, John D Klement, Yolonda L Colson, Nicholas H Oberlies, Cedric J Pearce, Aaron H Colby, Mark W Grinstaff, Han-Fei Ding, Huidong Shi, Kebin Liu
Journal: Journal for ImmunoTherapy of Cancer (2022)

Granzyme B is a key effector of cytotoxic T lymphocytes (CTLs), and its expression level positively correlates with the response of patients with mesothelioma to immune checkpoint inhibitor immunotherapy. Whether metabolic pathways regulate Gzmb expression in CTLs is incompletely understood.A tumor-specific CTL and tumor coculture model and a tumor-bearing mouse model were used to determine the role of glucose-6-phosphate dehydrogenase (G6PD) in CTL function and tumor immune evasion. A link between granzyme B expression and patient survival was analyzed in human patients with epithelioid mesothelioma.Mesothelioma cells alone are sufficient to activate tumor-specific CTLs and to enhance aerobic glycolysis to induce a PD-1hi Gzmblo CTL phenotype. However, inhibition of lactate dehydrogenase A, the key enzyme of the aerobic glycolysis pathway, has no significant effect on tumor-induced CTL activation. Tumor cells induce H3K9me3 deposition at the promoter of G6pd, the gene that encodes the rate-limiting enzyme G6PD in the pentose phosphate pathway, to downregulate G6pd expression in tumor-specific CTLs. G6PD activation increases acetyl-coenzyme A (CoA) production to increase H3K9ac deposition at the Gzmb promoter and to increase Gzmb expression in tumor-specific CTLs converting them from a Gzmblo to a Gzmbhi phenotype, thus increasing CTL tumor lytic activity. Activation of G6PD increases Gzmb+ tumor-specific CTLs and suppresses tumor growth in tumor-bearing mice. Consistent with these findings, GZMB expression level was found to correlate with increased survival in patients with epithelioid mesothelioma.G6PD is a metabolic checkpoint in tumor-activated CTLs. The H3K9me3/G6PD/acetyl-CoA/H3K9ac/Gzmb pathway is particularly important in CTL activation and immune evasion in epithelioid mesothelioma.
Deep learning approaches to non-invasively assess molecular features of gliomas
Authors: Rifaquat Rahman, Raymond Y Huang
Journal: Neuro-Oncology (2021)

The recent 2021 World Health Organization classification of central nervous system tumors has reinforced the role of molecular changes in CNS tumor classification, and they increasingly inform the management of brain tumor patients.1 For example, IDH wild-type status is now required to establish a diagnosis of glioblastoma, and IDH-mutant diffuse astrocytic tumors are a single entity with a numeric (2, 3, or 4) grade. Oligodendrogliomas have been defined by IDH mutation and 1p/19q co-deletion since 2016.2 The identification of key molecular changes, particularly IDH mutation status and 1p/19q co-deletion status is therefore paramount to the classification of CNS tumors and subsequent understanding of prognosis and management of patients. Molecular testing, however, can be a time-consuming process reliant on sufficient surgical tissue. Noninvasive identification of molecular status would be tremendously valuable. Early determination of molecular subgroups could inform clinical trial eligibility or help with decision making of surgical approach or treatment in cases where surgical tissue sampling is not possible.
Abstract P152: Health Informatics: A New Hope for Familial Hypercholesterolemia
Authors: Amy P Joseph, Charles J Mullett, Matthew Armistead, Jeff Cox, Michael Denney, William A Neal, Lee A Pyles
Journal: Circulation (2018)

Introduction: Electronic Health Records (EHRs) benefit record keeping, information collation, error prevention, and charge capture. They provide a large database of clinical information that can be used for research. Sorting vast amounts of data manually is inefficient, hence, an effectual, validated method is required to uncover information from large sets of data and generate knowledge. The U.S., and especially West Virginia, has a tremendous burden of cardiovascular disease (CVD). Undiagnosed Familial Hypercholesterolemia (FH) is an important factor for CVD in the U.S. FH results in elevated levels of LDL from childhood and early atherosclerotic disease. We are interested in better screening processes for FH. One method is to detect adults with coronary artery disease (CAD) and determine if their lipid levels are indicative of FH. Relatives and children can then be screened for FH and treated. Efficient identification of a CAD phenotype from EHRs is an important initial step in this screening process. Hypothesis: We hypothesized that a CAD phenotype detection algorithm that uses discrete data elements from EHRs can be validated as a precursor to detection of FH. Methods: We developed an algorithm to detect a CAD phenotype, which searched through discrete data elements, such as diagnoses lists (ICD-10) and procedure (CPT) codes. Direct inspection of EHR discrete data avoided the need for artificial intelligence, such as natural language processing. The algorithm was applied to a cohort of 1,000 patients with varying characteristics. We then determined which patients had CAD by systematically going through EHRs. Following this, we revised the algorithm by refining the constraints under which it operated. We ran the algorithm again on the same 1,000 patients, and determined the accuracy of the modified algorithm. Results: Manual validation of the 1,000 patients resulted in 413 with CAD and 587 without. The original algorithm distinguished 488 CAD positive patients and 512 CAD negative patients. This was 89% accurate, 96% sensitive, and 85% specific. After revising the algorithm and applying it to the same cohort, it determined that there were 474 CAD patients and 526 without CAD. This was 93% accurate, 99% sensitive, and 89% specific. Conclusion: EHR usage has created a large pool of minable clinical data. However, without an efficient method to obtain inferences from it, the information cannot be effectually utilized. We have created an algorithm that detects CAD on a large scale with high accuracy. It has proven to be useful among a varied patient population. Since the constraints that are used, such as ICD codes and CPT codes, are universal, it can be utilized across many hospital systems; although, local validation is prudent. Using this algorithm can select a population with a propensity for FH, thereby allowing us to screen and manage patients with undiagnosed FH or other familial dyslipidemias.
“Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study.” Rong-Hui Du, Li-Rong Liang, Cheng-Qing Yang, Wen Wang, Tan-Ze Cao, Ming Li, Guang-Yun Guo, Juan Du, Chun-Lan Zheng, Qi Zhu, Ming Hu, Xu-Yan Li, Peng Peng and Huan-Zhong Shi. <i>Eur Respir J</i> 2020; 55: 2000524.
Journal: European Respiratory Journal (2020)
Angiographic findings in non Q vs. Q wave myocardial infarction after thrombolysis for ST segment elevation infarction. Results from the DANAMI trial Peter Clemmensen, Peer Grande, Jan K. Madsen, Walter B. Nielsen, Galen S. Wagner, Kari Saunam�ki, Eli Kassis, Per Thayssen, Klaus Rasmussen, Torsten T. Nielsen, Torben Haghfelt, Stig Haunsoe. The Heart Center, Rigshospitalet, Copenhagen, Denmark
Journal: Journal of the American College of Cardiology (2001)
Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts
Authors: Dimitra Kerdidani, Emmanouil Aerakis, Kleio-Maria Verrou, Ilias Angelidis, Katerina Douka, Maria-Anna Maniou, Petros Stamoulis, Katerina Goudevenou, Alejandro Prados, Christos Tzaferis, Vasileios Ntafis, Ioannis Vamvakaris, Evangelos Kaniaris, Konstantinos Vachlas, Evangelos Sepsas, Anastasios Koutsopoulos, Konstantinos Potaris, Maria Tsoumakidou
Journal: The Journal of Experimental Medicine (2022)

A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. This analysis shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity. Lung apCAFs directly activated the TCRs of effector CD4 T cells and at the same time produced C1q, which acted on T cell C1qbp to rescue them from apoptosis. Fibroblast-specific MHCII or C1q deletion impaired CD4 T cell immunity and accelerated tumor growth, while inducing C1qbp in adoptively transferred CD4 T cells expanded their numbers and reduced tumors. Collectively, we have characterized in the lungs a subset of antigen-presenting fibroblasts with tumor-suppressive properties and propose that cancer immunotherapies might be strongly dependent on in situ MHCII antigen presentation.
BILIARY PERITONITIS
Authors: S. Power
Journal: BMJ (1935)

A recent case of biliary peritonitis recalled to my mind two others, and suggested that the subject is one which is not commonly discussed in the textbooks and is almost ignored in current literature.My three cases are recorded in brief below. Case RecordsMrs. A., aged 65, was admitted with a history of abdominal pain and uniform tenderness and distension, which made one suspect an obstruction.A slight icterus negatived this diagnosis, and as her condition rapidly deteriorated she was not subjected to operation.She had had a cholecystectomy a year previously.At post-mortem examination the abdomen was found to be full of bile, and there were several stones in the common bile duct, though no perforation was discovered; it is not unlikely that it may have eluded the pathologist.Mrs. C. was admitted with symptoms and signs indicating acute spreading cholecystitis.Laparotomy confirmed the diagnosis, but also revealed massive adhesions of old-standing disease and a leakage of bile.No perforation was seen, but circumstances did not favour investigation.Multiple calculi were removed and cholecystostomy performed.The gallbladder was removed at a later date.Mr. S., aged 70, appeared clinically to be a mild case of perforation.Actually he had a tense gall-bladder with ex- travasation.A point of leakage was not seen.Several small stones were present.Cholecystostomy was done.The fistula persisted, and one anticipated the necessity of further inter- ference, but unfortunately a coronary thrombosis carried the patient off.I have seen one other case at operation in which the bile was oozing from a pin-point perforation in the fundus.The haemorrhagic nature of the exudate was quite striking.
Wnt activation promotes memory T cell polyfunctionality via epigenetic regulator PRMT1
Authors: Bo-Yi Sung, Yi-Hsin Lin, Qiongman Kong, Pali D. Shah, Joan Glick Bieler, Scott Palmer, Kent J. Weinhold, Hong-Ru Chang, Hailiang Huang, Robin K. Avery, Jonathan Schneck, Yen-Ling Chiu
Journal: Journal of Clinical Investigation (2022)

T cell polyfunctionality is a hallmark of protective immunity against pathogens and cancer, yet the molecular mechanism governing it remains mostly elusive. We found that canonical Wnt agonists inhibited human memory CD8+ T cell differentiation while simultaneously promoting the generation of highly polyfunctional cells. Downstream effects of Wnt activation persisted after removal of the drug, and T cells remained polyfunctional following subsequent cell division, indicating the effect is epigenetically regulated. Wnt activation induced a gene expression pattern that is enriched with stem cell-specific gene signatures and upregulation of protein arginine methyltransferase 1 (PRMT1), a known epigenetic regulator. PRMT1+CD8+ T cells are associated with enhanced polyfunctionality, especially the ability to produce IL-2. In contrast, inhibition of PRMT1 ameliorated the effects of Wnt on polyfunctionality. Chromatin immunoprecipitation revealed that H4R3me2a, a permissive transcription marker mediated by PRMT1, increased at the IL-2 promoter loci following Wnt activation. In vivo, Wnt-treated T cells exhibited superior polyfunctionality and persistence. When applied to cytomegalovirus (CMV) donor-seropositive, recipient-seronegative patients (D+/R-) lung transplant patient samples, Wnt activation enhanced CMV-specific T cell polyfunctionality, which is important in controlling CMV diseases. These findings reveal a molecular mechanism governing T cell polyfunctionality and identify PRMT1 as a potential target for T cell immunotherapy.
In This Issue
Authors: Ruth Williams
Journal: Circulation Research (2021)

JNK2-Specific Actions in SERCA2 Function and AF (p 455)Yan et al discover that kinase JNK2 has a dual role in promoting arrhythmia.Atrial fibrillation (AF) is the most common form of arrhythmia and increases a person's risk of sudden death, stroke and heart failure, yet the mechanisms underlying the irregular and rapid heartbeat are not fully understood.It's known that older age and binge alcohol drinking can increase AF risk and that both of these also cause increased levels of the kinase JNK2 in the heart's atria.This JNK2 increase leads to leakage of calcium from ryanodine receptors (RyR2) of the cardiomyocyte sarcoplasmic reticulum (SR), in turn prompting arrhythmogenic activity.But, as Yan and colleagues have now found in rabbit atrial myocytes, JNK2 also phosphorylates the SR calcium ATPase SERCA2 and boosts SR calcium uptake, which could theoretically negate the effect of calcium leakage.Despite the opposing effects of increased JNK2, the net result is a promotion of arrhythmia, the authors showed in mice heart tissue.They suggest the JNK2-induced SERCA2 calcium uptake overloads the SR exacerbating the RyR2 leak.Importantly, inhibiting the activity of JNK2 completely normalized SR calcium handling, and suppressed arrhythmia in aged and alcohol-exposed heart cells and tissue.The findings suggest that JNK2 could be a target for future treatment and prevention strategies for AF, say the team.
Parental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring
Authors: Gayan Bowatte, Dinh S. Bui, Sajith Priyankara, Adrian J. Lowe, Jennifer L. Perret, Caroline J. Lodge, Garun S. Hamilton, Bircan Erbas, Paul Thomas, Bruce Thompson, Vivi Schlünssen, David Martino, John W. Holloway, Cecilie Svanes, Michael J. Abramson, E. Haydn Walters, Shyamali C. Dharmage
Journal: Journal of Allergy and Clinical Immunology (2022)
Phase II study of SHR1210 and trastuzumab in combination with CAPOX for neoadjuvant treatment of HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Ning Li, Zhi Li, Qiang Fu, Bin Zhang, Jian Zhang, XiangBin Wan, Chaomin Lu, Jinbang Wang, Wenying Deng, Chen Wei, Yijie Ma, Liangyu Bie, Mengyu Wang, Suxia Luo
Journal: Journal of Clinical Oncology (2022)

296 Background: Perioperative treatments have significantly improved survival in patients with resectable gastric cancer. PANTHERA study had showed a significant tumor shrinkage for HER2 positive advanced gastric cancer treated with anti-PD-1 agent, transtuzumab and chemotherapy. SHR1210, a human IgG4 monoclonal antibody that binds to PD-1, has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the addition of SHR1210 and trastuzumab to CAPOX for neoadjuvant treatment of HER2-positive gastric or GEJ adenocarcinoma. Methods: In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable HER2-positive gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of transtuzumab (loading dose of 8mg/kg, with subsequent doses of 6 mg/kg, q3w) and CAPOX (oxaliplatin 130 mg/m 2 day 1, capecitabine 1000 mg/ m 2 bid po day 1-14, q3w) in combination with 3 cycles of SHR1210 (200mg, iv, d1, q3w), followed by surgery and 4 postoperative cycles of CAPOX. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR). This trial is registered with ClinicalTrials.gov, number NCT03950271. Results: Between Jan 20, 2020, and Sept 15, 2021, 22 patients were enrolled and commenced treatment. Four patients had not completed neoadjuvant treatment. Twopatitents refused surgery. Sixteen patients who experienced D2 resection, 9 (56.3%) achieved MPR, including 5 (31.3%) with pCR (ypT0N0M0). The R0 rese-ction rate was 100%. The ORR was 77.3%. The main grade 3 or 4 treatment-related adverse events (TRAEs) included lymphocytopenia (22.7%), neutropenia(13.6%), thrombocytopenia (13.6%) and anaemia (5%). Most frequent grade 1 or 2 TRAEs were Nausea (68.2%), lymphocytopenia (63.6%), leukopenia (59.1%), Anaemia (59.1%), Thrombocytopenia (50%), Serum aspartate aminotransfe-rase increased (45.5%) and hypothyroidism (31.8%). There was no surgical del-ays or unexpected surgical complications related to drug toxicity. Conclusions: Neoadjuvant combination of SHR1210, transtuzumab and CAPOX is a safe and efficacious treatment option for patients with HER2-positive gastric or GEJ adenocarcinoma. More importantly, 31.3% pCR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: NCT03950271.
Error in Supplement
Journal: JAMA Cardiology (2021)

Akshay S. Desai, MD; Taylor Maclean, MS; Alexander J. Blood, MD; Joshua Bosque-Hamilton, BA; Jacqueline Dunning, PharmD; Christina Fischer, MS; Liliana Fera, MSN; Katelyn V. Smith, PharmD; Kavishwar Wagholikar, MBBS, PhD; David Zelle, BA; Thomas Gaziano, MD; Jorge Plutzky, MD; Benjamin Scirica, MD; Calum A. MacRae, MD, PhD
FINLAND
Journal: JAMA (1952)

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Sex Difference in Bleeding Risk With P2Y12 Inhibitor Agents After Percutaneous Coronary Intervention
Authors: Po-Wei Chen, Cheng-Han Lee, Ping-Yen Liu
Journal: JAMA Cardiology (2022)

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 Cardiology 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 Cardiology journal
Online-Only Abstracts
Authors: W Ibrahim, N Boukhadra, D Nasri-Zoghlami, P Berthelot, S Omar, T Bourlet, B Pozzetto, S Pillet, Y Zhang, H Wang, S Xu, N Mao, Z Zhu, J Shi, G Huang, C Liu, F Bo, D Feng, P Lu, Y Liu, Y Wang, Y Lei, M Chen, H Chen, C Wang, H Fu, C Li, J He, H Gao, S Gu, S Wang, H Ling, Z Ding, Z Ba, Y Feng, H Zheng, X Tang, Y Xiong, W Bellini, P Rota, Y Jee, W Xu, The Measles
Journal: Clinical Microbiology and Infection (2014)
TCT-567 Comparison of vascular response after Everolimus-Eluting Stents and Bare Metal Stents implantation in ST-segment Elevation Myocardial Infarction Assessed by Optical Coherence Tomography
Authors: Yasushi Ino, Takashi Kubo, Tomoyuki Yamaguchi, Hironori Kitabata, Makoto Orii, Yuichi Ozaki, Kunihiro Shimamura, Keisuke Satogami, Yasutsugu Shiono, Yamano Takashi, Takashi Tanimoto, Kumiko Hirata, Atsushi Tanaka, Toshio Imanishi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2013)