tbuckley/cabot-search huggingface dataset:
COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma
Authors: Mi Yang, Xixi Wu, Jinlong Hu, Yingqiao Wang, Yin Wang, Longshan Zhang, Weiqiang Huang, Xiaoqing Wang, Nan Li, Liwei Liao, Min Chen, Nanjie Xiao, Yongmei Dai, Huazhen Liang, Wenqi Huang, Lu Yuan, Hua Pan, Lu Li, Longhua Chen, Laiyu Liu, Li Liang, Jian Guan
Journal: Journal of Hepatology (2022)

Copper (Cu) is an essential trace element whose serum levels have been reported to act as an effective indicator of the efficacy of radiotherapy. However, little is known about the role of Cu in radiotherapy. In this study we aimed to determine this role and investigate the precise mechanism by which Cu or Cu-related proteins regulate the radiosensitivity of hepatocellular carcinoma (HCC).The expression and function of Cu and copper metabolism MURR1 domain 10 (COMMD10) were assessed via a Cu detection assay, immunostaining, real-time PCR, western blot, a radiation clonogenic assay and a 5-ethynyl-2'-deoxyuridine assay. Ferroptosis was determined by detecting glutathione, lipid peroxidation, malondialdehyde and ferrous ion (Fe) levels. The in vivo effects of Cu and COMMD10 were examined with Cu/Cu chelator treatment or lentivirus modification of COMMD10 expression in radiated mouse models.We identified a novel role of Cu in promoting the radioresistance of HCC cells. Ionizing radiation (IR) induced a reduction of COMMD10, which increased intracellular Cu and led to radioresistance of HCC. COMMD10 enhanced ferroptosis and radiosensitivity in vitro and in vivo. Mechanistically, low expression of COMMD10 induced by IR inhibited the ubiquitin degradation of HIF1α (by inducing Cu accumulation) and simultaneously impaired its combination with HIF1α, promoting HIF1α nuclear translocation and the transcription of ceruloplasmin (CP) and SLC7A11, which jointly inhibited ferroptosis in HCC cells. In addition, elevated CP promoted HIF1α expression by reducing Fe, forming a positive feedback loop.COMMD10 inhibits the HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe homeostasis in HCC. This work provides new targets and treatment strategies for overcoming radioresistance in HCC.Radiotherapy benefits patients with unresectable or advanced hepatocellular carcinoma (HCC), but its effectiveness is hampered by radioresistance. Herein, we uncovered a novel role for copper in promoting the radioresistance of HCCs. This work has revealed new targets and potential treatment strategies that could be used to sensitize HCC to radiotherapy.
Error in Figure Captions
Journal: JAMA Neurology (2022)

Calwing Liao, BSc; Charles-Etienne Castonguay, BSc; Karl Heilbron, PhD; Veikko Vuokila, BSc; Miranda Medeiros, BSc; Gabrielle Houle, BSc; Fulya Akçimen, MSc; Jay P. Ross, BSc; Helene Catoire, PhD; Monica Diez-Fairen, PhD; Jooeun Kang, BSc; Stefanie H. Mueller, PhD; Simon L. Girard, PhD; Franziska Hopfner, PhD; Delia Lorenz; Lorraine N. Clark, PhD; Alexandra I. Soto-Beasley, MSc; Stephan Klebe, PhD; Mark Hallett, MD; Zbigniew K. Wszolek, MD; Manuela Pendziwiat, BSc; Oswaldo Lorenzo-Betancor, MD, PhD; Klaus Seppi, MD; Daniela Berg, MD; Carles Vilariño-Güell, PhD; Ronald B. Postuma, MD, MSc; Geneviève Bernard, MD, MSc; Nicolas Dupré, MD, MSc; Joseph Jankovic, MD; Claudia M. Testa, MD, PhD; Owen A. Ross, PhD; Thomas Arzberger, MD; Sylvain Chouinard, MD; Elan D. Louis, MD, MSc; Paola Mandich, MD, PhD; Carmine Vitale, MD, PhD; Paolo Barone, MD, PhD; Elena García-Martín, PhD; Hortensia Alonso-Navarro, MD, PhD; José A. G. Agúndez, MD, PhD; Félix Javier Jiménez-Jiménez, MD, PhD; Pau Pastor, MD, PhD; Alex Rajput, MD; Günther Deuschl, MD, PhD; Gregor Kuhlenbaümer, MD, PhD; Inge A. Meijer, MD, PhD; Patrick A. Dion, PhD; Guy A. Rouleau, MD, PhD; 23andMe Research Team
Novel machine learning-led discovery of adjuvant drug candidate for allergen immunotherapy using synthetic toll-like receptor 2/6 agonist
Authors: Janice Layhadi, Madison Lenormand, Max Kirtland, Gemma Vilà-Nadal, Oleksandra Fedina, Stephen Durham, Daphne Tsitoura, Mohamed Shamji, Lily Wu
Journal: Journal of Allergy and Clinical Immunology (2022)
Generalized Normolipemic Plane Xanthoma
Journal: JAMA (1963)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Characterizing dermatologic findings among patients with PTEN hamartoma tumor syndrome: Results of a multicenter cohort study
Authors: Frederick C. Morgan, Lamis Yehia, Christine McDonald, Julian A. Martinez-Agosto, Antonio Y. Hardan, Joan Tamburro, Mustafa Sahin, Cheryl Bayart, Charis Eng
Journal: Journal of the American Academy of Dermatology (2022)
Cardiac rehabilitation
Authors: Hasnain M Dalal, Patrick Doherty, Rod S Taylor
Journal: BMJ (2015)

Cardiac rehabilitation is a complex intervention offered to patients diagnosed with heart disease, which includes components of health education, advice on cardiovascular risk reduction, physical activity and stress management.2][3][4][5][6] This review focuses on what cardiac rehabilitation is and the evidence of its benefit and effects on cardiovascular mortality, morbidity and quality of life. Why is cardiac rehabilitation important?Although mortality from coronary heart disease has fallen over recent decades, annually it still claims an estimated 1.8 million lives in Europe, 7 and 785 000 new and 470 000 recurrent myocardial infarctions occur in the US. 8 In the UK, around 110 000 men and 65 000 women have an acute myocardial infarction every year, equivalent to one every three minutes. 9With improved survival and an aging population, the number of people living with coronary heart disease in the UK has increased to an estimated 2.3 million. 9 What is cardiac rehabilitation and who should get it?Various organisations and national bodies have defined cardiac rehabilitation, which is encompassed by: "Cardiac rehabilitation (and secondary prevention) services are comprehensive, long term programmes involving medical evaluation, prescribed exercise, cardiac risk factor modification, education, and counselling.These programmes are designed to limit the physiological and psychological effects of cardiac illness, reduce the risk for sudden death or re-infarction, control cardiac symptoms, stabilise or reverse the atherosclerotic process, and enhance the psychosocial and vocational status of selected patients."Although exercise training is a core component, current practice guidelines consistently recommend "comprehensive rehabilitation" programmes that should include other components to optimise cardiovascular risk reduction, foster healthy behaviours and compliance to these behaviours, reduce disability, and promote an active lifestyle. 5][3][4][5][6][7][8][9][10][11][12] and the core components of cardiac rehabilitation are illustrated in figure 2. 1 Historically, cardiac rehabilitation in the UK, US, and most European countries has been delivered to groups of patients in healthcare or community centres. 13 14Recent guidance from the UK Department of Health 12 refers to a seven stage pathway of care that begins with diagnosis of a cardiac event and is followed by assessment of eligibility, referral, clinical assessment, and core delivery of cardiac rehabilitation before progressing to long term management (fig 1⇓).
Warm up
Journal: British Journal of Sports Medicine (2001)

This study raises the issue of the role of sports and exercise medicine in the broader context of public health.Many of us who see ourselves as "couch potatoes" or "mouse potatoes" to use the appropriate computer jargon, lament the passing of our former fitness.Well, hope is at hand.A study with a remarkable name, the Dallas Bed Rest and Training Study, has found in a 30 year follow up, that just six months of exercise can reverse the decline in cardiovascular capacity associated with aging.However, just three weeks of bed rest has a far more profound negative eVect on cardiac fitness than aging alone.The study findings showed that men who undertook a six month endurance training programme of walking, jogging, or stationary cycling were able to completely recover the aerobic fitness they had lost in the previous 30 years.None of the men had complications from the exercise and all managed to stick to their exercise regimen.Their training level increased weekly until at the end of six months they were exercising four hours per week over four to five sessions.The study focused on five healthy men who at the age of 20 originally took part in the landmark Dallas study, and then participated in the 30 year follow up study.In the 1966 study, they did eight weeks of intensive exercise training after 20 days of bed rest.In the follow up, they were evaluated for the eVects of age on cardiovascular response to exercise testing and cardiovascular adaptation to an exercise programme.Researchers found that 20 days of bed rest at the age of 20 had a far more profoundly negative impact on cardiovascular fitness than did 30 years of aging.Over 30
Macrophage global metabolomics identifies cholestenone as host/pathogen cometabolite present in human Mycobacterium tuberculosis infection
Authors: Pallavi Chandra, Héloise Coullon, Mansi Agarwal, Charles W. Goss, Jennifer A. Philips
Journal: Journal of Clinical Investigation (2022)

Mycobacterium tuberculosis (M. tuberculosis) causes an enormous burden of disease worldwide. As a central aspect of its pathogenesis, M. tuberculosis grows in macrophages, and host and microbe influence each other's metabolism. To define the metabolic impact of M. tuberculosis infection, we performed global metabolic profiling of M. tuberculosis–infected macrophages. M. tuberculosis induced metabolic hallmarks of inflammatory macrophages and a prominent signature of cholesterol metabolism. We found that infected macrophages accumulate cholestenone, a mycobacterial-derived, oxidized derivative of cholesterol. We demonstrated that the accumulation of cholestenone in infected macrophages depended on the M. tuberculosis enzyme 3β-hydroxysteroid dehydrogenase (3β-Hsd) and correlated with pathogen burden. Because cholestenone is not a substantial human metabolite, we hypothesized it might be diagnostic of M. tuberculosis infection in clinical samples. Indeed, in 2 geographically distinct cohorts, sputum cholestenone levels distinguished subjects with tuberculosis (TB) from TB-negative controls who presented with TB-like symptoms. We also found country-specific detection of cholestenone in plasma samples from M. tuberculosis–infected subjects. While cholestenone was previously thought to be an intermediate required for cholesterol degradation by M. tuberculosis, we found that M. tuberculosis can utilize cholesterol for growth without making cholestenone. Thus, the accumulation of cholestenone in clinical samples suggests it has an alternative role in pathogenesis and could be a clinically useful biomarker of TB infection.
Second Report of Private Medical Practice for 1841
Authors: C. Cowan
Journal: BMJ (1843)

ought to be the case if these diseases were identical, on account of the greater frequency of gonorrhma.I shall now remind you of a case we observed in the course of last summer.A man entered the hospital for constitutional symptoms after one chancre oiily, the first he had ever been affected with.But in the course of his life he had had no less tllan thirty-tw-o distinct discharges from the urethra, cured wvithout mercurial treatment, and never followed by secondary symptoms.We will add that, at the presenlt moment, thirty-eight cases of general syphilis exist in our wards, in none of which has gonorrhca had anything to do with the development of the disease.
Trends in suicide mortality among people with HIV after diagnosis during 2012–18: a retrospective, national cohort study in China
Authors: Fangfang Chen, Chang Cai, Shengfeng Wang, Qianqian Qin, Yichen Jin, Dongmin Li, Lin Ge, Peilong Li, Yan Cui, Houlin Tang, Fan Lv
Journal: The Lancet HIV (2022)
Indicators of Nicotine Addiction Among Women— United States, 1991-1992
Journal: JAMA (1995)

An estimated 22 million U.S. women were current smokers in 1993; of these, 73% wanted to quit smoking (1). However, attempts to quit smoking and to remain abstinent are hindered by nicotine addiction and by the subsequent effects of nicotine withdrawal (2). To assess the prevalence of selected indicators of nicotine addiction among U.S. women, CDC analyzed data from the National Household Survey on Drug Abuse (NHSDA) in 1991 and 1992 (3). This report presents the findings of the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Epithelial Gasdermin D shapes the host-microbial interface by driving mucus layer formation
Authors: Jian Zhang, Qianzhou Yu, Danlu Jiang, Kang Yu, Weiwei Yu, Zhexu Chi, Sheng Chen, Mobai Li, Dehang Yang, Zhen Wang, Ting Xu, Xingchen Guo, Kailian Zhang, Hui Fang, Qizhen Ye, Yong He, Xue Zhang, Di Wang
Journal: Science Immunology (2022)

Goblet cells and their main secretory product, mucus, play crucial roles in orchestrating the colonic host-microbe interactions that help maintain gut homeostasis. However, the precise intracellular machinery underlying this goblet cell-induced mucus secretion remains poorly understood. Gasdermin D (GSDMD) is a recently identified pore-forming effector protein that causes pyroptosis, a lytic proinflammatory type of cell death occurring during various pathophysiological conditions. Here, we reveal an unexpected function of GSDMD in goblet cell mucin secretion and mucus layer formation. Specific deletion of Gsdmd in intestinal epithelial cells (ΔIEC) led to abrogated mucus secretion with a concomitant loss of the mucus layer. This impaired colonic mucus layer in GsdmdΔIEC mice featured a disturbed host-microbial interface and inefficient clearance of enteric pathogens from the mucosal surface. Mechanistically, stimulation of goblet cells activates caspases to process GSDMD via reactive oxygen species production; in turn, this activated GSDMD drives mucin secretion through calcium ion-dependent scinderin-mediated cortical F-actin disassembly, which is a key step in granule exocytosis. This study links epithelial GSDMD to the secretory granule exocytotic pathway and highlights its physiological nonpyroptotic role in shaping mucosal homeostasis in the gut.
Capacities and Limitations of Using Polygenic Risk Scores for Reproductive Decision Making
Authors: Dorit Barlevy, Todd Lencz, Shai Carmi, Kristin Marie Kostick-Quenet, Meghna Mukherjee, Stacey Pereira, Gabriel Lázaro-Muñoz
Journal: The American Journal of Bioethics (2022)

This article refers to:Implementing Expanded Prenatal Genetic Testing: Should Parents Have Access to Any and All Fetal Genetic Information?
A Multicentre UK-Based Audit on Acquired C1 Inhibitor Deficiency 2021
Authors: Hadeil Morsi, Alexandros Grammatikos, Cathal Steele, Catherine Stroud, Charu Chopra, Efrem Eren, Emily Moon, Grant Hayman, Harichandana Ghanta, Helen Bourne, John Dempster, Katie Townsend, Manisha Ahuja, Marina Frleta-Gilchrist, Michael Zhang, Moira Thomas, Richard Herriot, Sai Murng, Sara Drinkwater, Suzanne Elcombe, Tanya Coulter, Tariq El-shanawany, Tomaz Garcez, Patrick Yong, Rashmi Jain
Journal: Journal of Allergy and Clinical Immunology (2022)
Medical education reform
Authors: Alfred Gellhorn
Journal: JAMA (1991)

<h3>In Reply. —</h3> Validation of peer review of patients' records to determine compliance with guidelines developed by the pertinent medical specialty societies demonstrates that the process is feasible. Further, the method not only detects substandard practice patterns but identifies deficiencies that, when corrected, will improve the general quality of care and encourage change of physician behavior. The Physician Enhancement Program mentioned by Drs Sherman and Farnsworth, which may be developed in New York, is a model for correction of deficiencies. It is interesting that Dr Suter, a specialist in aviation medicine, takes such violent exception to recredentialing but presumably approves that airplane pilots must undergo periodic physical and skill recertification. Dr Thomas should know that the requirement of standard procedures for monitoring intraoperative anesthesia has led to a reduction in malpractice premiums for many anesthesiologists in many states. Tort reform is unlikely without strong public support based on assurance that
Medical education
Authors: J. P. Callan
Journal: JAMA (1979)

It seems an ironic and troubling commentary on our times that the majority of physicians know so much about medicine and so little about arenas outside the healing arts. Like prevoyage Columbus they may have a suspicion that there is more beyond the boundaries of scientific medicine, yet few physicians possess the drive and purpose to stray from the scientific and narrow path into broader areas. Not all the blame for this can be placed at the doors of present-day practitioners; part must be directed toward our standard method of producing physicians—our singularly minded educational system with its obsessions on scientific didacticism. Throughout college and medical school, emphasis is placed on acquiring and memorizing fact on fact until it seems the world is made up of medical minutiae and nothing else. Art, the humanities, the classics, philosophy, and other studies that might detract from learning the insertion and action of
Predictors of death in COVID-19 vaccine breakthrough infections in Brazil
Authors: Cassia Fernanda Estofolete, Gislaine Fusco Fares, Cecilia Artico Banho, Livia Sacchetto, Guilherme R.F. Campos, Marília M. Moraes, Thayza M.I.L. dos Santos, Gislaine C. Dutra da Silva, Flavia Queiroz, Lina de Moura Mendes, Maria Lúcia Machado Salomão, Andreia Francesli Negri, Michela Dias Barcelos, Mauricio L. Nogueira
Journal: Journal of Infection (2022)
Drug-perturbation-based stratification of blood cancer
Authors: Sascha Dietrich, Małgorzata Oleś, Junyan Lu, Leopold Sellner, Simon Anders, Britta Velten, Bian Wu, Jennifer Hüllein, Michelle da Silva Liberio, Tatjana Walther, Lena Wagner, Sophie Rabe, Sonja Ghidelli-Disse, Marcus Bantscheff, Andrzej K. Oleś, Mikołaj Słabicki, Andreas Mock, Christopher C. Oakes, Shihui Wang, Sina Oppermann, Marina Lukas, Vladislav Kim, Martin Sill, Axel Benner, Anna Jauch, Lesley Ann Sutton, Emma Young, Richard Rosenquist, Xiyang Liu, Alexander Jethwa, Kwang Seok Lee, Joe Lewis, Kerstin Putzker, Christoph Lutz, Davide Rossi, Andriy Mokhir, Thomas Oellerich, Katja Zirlik, Marco Herling, Florence Nguyen-Khac, Christoph Plass, Emma Andersson, Satu Mustjoki, Christof von Kalle, Anthony D. Ho, Manfred Hensel, Jan Dürig, Ingo Ringshausen, Marc Zapatka, Wolfgang Huber, Thorsten Zenz
Journal: Journal of Clinical Investigation (2017)

As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
Impact of COVID-19 Restrictions on Anaphylaxis Presentations to the Emergency Department
Authors: Jordan Trevisonno, Kevin Zhao, Adnan Al Ali, Sofianne Gabrielli, Ann Clarke, Judy Morris, Rod Lim, Edmond Chan, Ran Goldman, Andrew O, Jennifer Gerdts, Julia Upton, Elana Hochstadter, Adam Bretholz, Christine McCusker, Xun Zhang, Shira Benor, Elinor Simons, Elissa Abrams, Jennifer Protudjer, Moshe Ben-Shoshan, Derek Chu
Journal: Journal of Allergy and Clinical Immunology (2022)
A randomized, double-blind placebo-controlled first in human study with mannan-conjugated birch pollen allergoids administered subcutaneously to allergic patients
Authors: Ralph Mosges, Esther Raskopf, Christoph Zeyen, Jaswinder Singh, Cengizhan Acikel, Silke Allekotte, José Luis Subiza, Miguel Casanovas
Journal: Journal of Allergy and Clinical Immunology (2022)
Evaluation of Alopecia
Journal: JAMA (1995)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal