tbuckley/cabot-search huggingface dataset:
Physicians’ Electrocardiogram Interpretations
Authors: Jean Jacques Noubiap, Joseph Kamtchum-Tatuene
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Loss of TGFβ signaling increases alternative end-joining DNA repair that sensitizes to genotoxic therapies across cancer types
Authors: Qi Liu, Luis Palomero, Jade Moore, Ines Guix, Roderic Espín, Alvaro Aytés, Jian-Hua Mao, Amanda G. Paulovich, Jeffrey R. Whiteaker, Richard G. Ivey, George Iliakis, Daxian Luo, Anthony J. Chalmers, John Murnane, Miquel Angel Pujana, Mary Helen Barcellos-Hoff
Journal: Science Translational Medicine (2021)

Among the pleotropic roles of transforming growth factor-β (TGFβ) signaling in cancer, its impact on genomic stability is least understood. Inhibition of TGFβ signaling increases use of alternative end joining (alt-EJ), an error-prone DNA repair process that typically functions as a "backup" pathway if double-strand break repair by homologous recombination or nonhomologous end joining is compromised. However, the consequences of this functional relationship on therapeutic vulnerability in human cancer remain unknown. Here, we show that TGFβ broadly controls the DNA damage response and suppresses alt-EJ genes that are associated with genomic instability. Mechanistically based TGFβ and alt-EJ gene expression signatures were anticorrelated in glioblastoma, squamous cell lung cancer, and serous ovarian cancer. Consistent with error-prone repair, more of the genome was altered in tumors classified as low TGFβ and high alt-EJ, and the corresponding patients had better outcomes. Pan-cancer analysis of solid neoplasms revealed that alt-EJ genes were coordinately expressed and anticorrelated with TGFβ competency in 16 of 17 cancer types tested. Moreover, regardless of cancer type, tumors classified as low TGFβ and high alt-EJ were characterized by an insertion-deletion mutation signature containing short microhomologies and were more sensitive to genotoxic therapy. Collectively, experimental studies revealed that loss or inhibition of TGFβ signaling compromises the DNA damage response, resulting in ineffective repair by alt-EJ. Translation of this mechanistic relationship into gene expression signatures identified a robust anticorrelation that predicts response to genotoxic therapies, thereby expanding the potential therapeutic scope of TGFβ biology.
Publisher Correction: The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens
Authors: Johnathan Canton, Hanna Blees, Conor M. Henry, Michael D. Buck, Oliver Schulz, Neil C. Rogers, Eleanor Childs, Santiago Zelenay, Hefin Rhys, Marie-Charlotte Domart, Lucy Collinson, Andres Alloatti, Cara J. Ellison, Sebastian Amigorena, Venizelos Papayannopoulos, David C. Thomas, Felix Randow, Caetano Reis e Sousa
Journal: Nature Immunology (2021)
A Moving Target: Inactivating BTK Mutations as Drivers of Follicular Lymphoma
Authors: Jumana Afaghani, Justin Taylor
Journal: Clinical Cancer Research (2021)

Abstract Drugs that target Bruton tyrosine kinase (BTK) have been highly successful and changed the landscape of therapies in B-cell lymphomas. However, their lower rates of effectiveness in follicular lymphoma are unexplained. Recent work describes inactivating BTK mutations that show that at least some follicular lymphomas do not require BTK. See related article by Hu et al., p. 2301
Role of Neurogenic Inflammation, especially Calcitonin Gene-related Peptide (CGRP), in Anaphylactic Reaction of Children with Food Allergy
Authors: Kenichi Tokuyama, Shunichi Ogawa, Takeshi Koga, Keisuke Okada, Yutaka Ueda, Eiji Morita, Toshiko Itazawa
Journal: Journal of Allergy and Clinical Immunology (2021)
4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial
Authors: Peter Hoskin, Biliana Popova, Oliver Schofield, Caroline Brammer, Martin Robinson, A Murray Brunt, Krishnaswamy Madhavan, Tim Illidge, Eve Gallop-Evans, Isabel Syndikus, Laura Clifton-Hadley, Amy A Kirkwood
Journal: The Lancet Oncology (2021)
Viral Loads of SARS-CoV-2 in Young Children
Authors: Arnaud G. L’Huillier, Stéphanie Baggio, Isabella Eckerle
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Chronic dapsone use causing methemoglobinemia with oxidative hemolysis and dyserythropoiesis
Authors: Christian Aledia Gallardo, Bingwen Eugene Fan, Kian Guan Eric Lim, Ponnudurai Kuperan
Journal: American Journal of Hematology (2021)

An 82-year-old Chinese female known to have erythrodermic pemphigus with background of psoriasis was started on dapsone for 4 months prior to admission. She was then admitted due to delirium and desaturation. On admission, oxygen saturation was 89% on room air, which subsequently improved with high flow oxygen therapy. The full blood count showed hemoglobin 11.2 g/dL (reference range: 13.6–16.6 g/dL), white blood cells 23.9 × 109/L (reference range: 4.0–9.6 × 109/L), platelets 362 × 109/L (reference range: 150–360 × 109/L) and reticulocyte counts 220.8 × 109/L (reference range: 25–85 × 109/L). Markers of hemolytic anemia were present, including an elevated LDH at 730 U/L (reference range: 270–550 U/L), elevated total bilirubin 54 mmol/L (reference range: 5–30 mmol/L) and low haptoglobulin at <30 mg/dL (reference range: 36–200 mg/dL) but direct Coombs test was negative. Peripheral blood film showed significant numbers of irregularly contracted red cells, bite cells and fragmented cells, suggestive of oxidative hemolysis. There were also Howell-Jolly bodies and Papenheimer bodies seen suggestive of possible dyserythropoiesis. Blood methemoglobin level was elevated at 8.2%. Her G6PD assay was normal. In view of clinical findings of oxidative hemolysis and methemoglobinemia, dapsone was stopped. She was then started on folic acid and vitamin C at 1 gram twice a day. Two days after, her oxygen saturation improved, and a repeat blood methemoglobin level improved to 1.8%. Dapsone is known as a cause of drug induced hemolytic anemia and methemoglobinemia due to N-hydroxylation to a hydroxylamine derivative that is directly toxic to RBCs.1, 2 The amine metabolites of dapsone are capable of oxidation of heme iron, resulting in acquired methemoglobinemia and hemoglobin denaturation forming Heinz bodies which are removed by splenic macrophages, forming bite cells and irregularly contracted cells.3 In addition, given the chronic consumption of dapsone for 4 months, compounded with the long standing oxidative hemolysis, the features observed in the patient's blood film such as the presence of Howell-Jolly and Pappenheimer bodies probably represent dyserythropoiesis secondary to erythroid stress. None. None. Data is available on request from the corresponding author.
Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC
Authors: Marius Ilié, Julien Mazières, Emmanuel Chamorey, Simon Heeke, Jonathan Benzaquen, Brice Thamphya, Jacques Boutros, Angélica Tiotiu, Julien Fayada, Jacques Cadranel, Michel Poudenx, Denis Moro-Sibilot, Fabrice Barlesi, Juliette Thariat, Christelle Clément-Duchêne, Pascale Tomasini, Véronique Hofman, Charles-Hugo Marquette, Paul Hofman, Dominique Israel-Biet, Christophe Pison, Denis Moro-Sibilot, Sylvie Lantuejoul, Olivier Stephanov, Meyzenc Juliette, Christophe Mendozat, Manel Zaidi, Sandra Coulouvrat, Edwige Col, Pascal Chanez, Laurent Greillier, Pascale Tomasini, Fabrice Barlesi, Céline Mascaux, Sandrine Jourdan, Aurélie Roger, Julie Biemar, Rondro Randriamampionona, François Chabot, Angélica Tiotiu, Christelle Clement-Duchene, Jean-Michel Vignaud, Stéphanie Lacomme, Sandra Lomazzi, Carine Laurent, Xavier Bulsei, Laura Bischoff, Raymond Rakotonirina, Mehdi Layouni, Gaëtan Deslee, Hervé Mal, Romain Kessler, Jean-Michel Vergnon, Isabelle Pelissier, Antoine Cuvelier, Arnaud Bourdin, Vincent Jounieaux, Nicolas Roche, Stéphane Jouneau, Philippe Bonniaud, Arnaud Scherpereel, Jean François Mornex, François Steenhouwer, Sylvie Leroy, Charles Hugo Marquette, Jonathan Benzaquen, Andrea Mazzette, Bernard Padovani, Paul Hofman, Marius Ilié, Véronique Hofman, Julien Fayada, Elodie Long-Mira, Sandra Lassalle, Johanna Pradelli, Estelle Martinez, Marine Habault, Mélanie Bonnard, Julie Moutarde, Rachida Yatimi, Hakima Labsi, Loïc Gazoppi, Tumorothèque Lpce, Jennifer Griffonnet, Maureen Fontaine, Ariane Guillemart, Catherine Butori, Eric Selva, Michel Poudenx, Josiane Otto, Christophe Hebert, Delphine Botchiellini, Soukaina Boudouf, Margaux Menier, Estelle Occeli, Sophie Bellentani, Carine Pion, Elodie Fournier, Juliette Thariat, Radj Gervais, Karim Hamond, Sylvain Marchand-Adam, Laurent Plantier, Gaelle Fajolle, Mélanie Rayez, Jacques Cadranel, Vincent Fallet, Marie Wislez, Martine Antoine, Jean-François Cote, Nouha Chaabane, Anne Marie Ruppert, Eliane Bertrand, Anita Rodenas, Gwenaëlle Pontdeme, Nathalie Mathiot, Tamazouzt Ribert, Julien Mazières, Nicolas Guibert, Damien Rouviere, Emilie Bousquet, Laurence Bigay-Game, Christophe Hermant, Gavin Plat, Isabelle Rouquette, Solène Evrard, Sandrine Gouin, Estelle Taranchon Clermont, Inge Dormoy, Christelle Coulomb, Anne Pradine, Véronique Lambert, Lilian Laborde, Olivier Castelnau
Journal: Journal of Thoracic Oncology (2021)
Adrenal gland as a sanctuary site for immunotherapy in patients with microsatellite instability-high metastatic colorectal cancer
Authors: Romain Cohen, Vincent Jonchère, Christelle De La Fouchardière, Toky Ratovomanana, Quentin Letourneur, Mira Ayadi, Lucile Armenoult, Adrien Buisson, Matthieu Sarabi, Anna Pellat, Raphael Colle, Francois Paye, Pierre Meeus, Magali Svrcek, Alex Duval, Thierry Andre
Journal: Journal for ImmunoTherapy of Cancer (2021)

Metastatic colorectal cancers (mCRC) harboring microsatellite instability (MSI) are sensitive to immune checkpoint inhibitors (ICIs), but the mechanisms of resistance to ICIs remain unclear. Dissociated responses in patients with ICI-treated cancer suggest that certain organs may serve as sanctuary sites due to the tumor microenvironment. This case series describes five patients with ICI-treated MSI mCRC with disease progression limited to the adrenal glands. At ICI initiation, three patients were free of metastasis in the adrenal glands. Four patients experienced objective response per RECIST (Response Evaluation Criteria in Solid Tumors) while treated with ICI. ICI treatment was discontinued due to progressive disease limited to the adrenal glands (n=3) or toxicity (n=2). The time between ICI initiation and progression in the adrenal glands ranged from 11 to 39 months. Adrenalectomy (n=3) and stereotactic body radiation therapy (n=2) were performed. At the last follow-up, all patients were alive and progression free. Molecular analyses were performed in one patient. A significant impairment of the antigen presentation pathway was observed in the ICI-resistant lesion of the adrenal gland, which could be explained by the presence of glucocorticoids in the adrenal gland microenvironment. We also detected an overexpression of TSC22D3 , a glucocorticoid-target gene that functions as a mediator of anti-inflammation and immunosuppression. This case series suggests that the adrenal glands may be the sanctuary sites for ICI-treated MSI mCRC through the glucocorticoid-induced impairment of the antigen presentation machinery.
Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation
Authors: Philippe B Bertrand, Jessica R Overbey, Xin Zeng, Robert A Levine, Gorav Ailawadi, Michael A Acker, Peter K Smith, Vinod H Thourani, Emilia Bagiella, Marissa A Miller, Lopa Gupta, Michael J Mack, A Marc Gillinov, Gennaro Giustino, Alan J Moskowitz, Annetine C Gelijns, Michael E Bowdish, Patrick T O'Gara, James S Gammie, Judy Hung
Journal: Journal of the American College of Cardiology (2021)
Abstract 14255: Radiomic Analysis of Myocardial Native T1Imaging Discriminates Between Hypertensive Heart Disease and Hypertrophic Cardiomyopathy
Authors: Ulf Neisius, Hossam El-Rewaidy, Shiro Nakamori, Warren J Manning, Reza Nezafat
Journal: Circulation (2018)

Introduction: Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are both associated with increased left ventricular wall thickness (LVWT). Contemporary guidelines define HCM as...
Efficacy and Safety of Crisaborole in Patients With Mild-to-Moderate Atopic Dermatitis With Comorbid Allergic Rhinitis or Asthma
Authors: Jonathan Spergel, Michael Blaiss, Peter Lio, Aharon Kessel, Liza Takiya, John Werth, Michael O'Connell, Chuanbo Zang, Michael Cork
Journal: Journal of Allergy and Clinical Immunology (2021)
Targeting miR-21 with NL101 blocks c-Myc/Mxd1 loop and inhibits the growth of B cell lymphoma
Authors: Shu Li, Xin He, Yichao Gan, Jiawei Zhang, Feiqiong Gao, Limin Lin, Xi Qiu, Teng Yu, Xuzhao Zhang, Panpan Chen, Jiefeng Tong, Wenbin Qian, Yang Xu
Journal: Theranostics (2021)

Background: NL101 has shown activities against multiple myeloma and acute myeloid leukemia, but its anti-lymphoma activity remains unknown. The transcription factor c-Myc is frequently dysregulated in aggressive B cell lymphomas such as double-hit lymphoma, for which the standard of care is still lacking. A novel approach to target c-Myc needs to be explored. Although the role of oncogenic microRNA-21 (miR-21) was well established in an inducible mice model of B cell lymphoma, whether targeting miR-21 could inhibit the growth of B cell lymphoma and its underlying mechanisms is unclear. Methods: We used MTT assay and flow cytometry to determine the inhibitory effect of NL101 on the cell proliferation of B cell lymphoma in vitro. The lymphoma xenograft mice models were generated to evaluate the anti-lymphoma function in vivo. Western blot and qPCR were applied to measure the expression levels of protein and microRNA, respectively. To investigate the mechanisms of action in NL101, we used genechip to profile differentially-expressed genes upon NL101 induction. Luciferase reporter system and chromatin immunoprecipitation were used for the validation of target gene or miRNA. Results: Nl101 significantly inhibited B cell lymphoma proliferation through induction of cell cycle arrest and apoptosis. NL101 suppressed the growth of B cell lymphoma in vivo and prolonged the survival of lymphoma xenograft models. Gene expression profiling revealed that miR-21 was significantly decreased upon the induction of NL101 in B cell lymphoma. The miR-21 level was associated with the sensitivity of NL101. miR-21 inhibited Mxd1 expression via directly combining to Mxd1 3'-UTR; c-Myc activated miR-21 expression by directly binding to the miR-21 promoter. Conclusion: NL101 significantly inhibited the growth of B cell lymphoma in vitro and in vivo. The novel c-Myc/miR-21/Mxd1 positive-feedback loop is critical for the maintenance of B cell lymphoma survival. Targeting miR-21 to block c-Myc/miR-21/Mxd1 loop represents a novel potential strategy of c-Myc-directed therapy.
PD-L1 as a biomarker of response to immune-checkpoint inhibitors
Authors: Deborah Blythe Doroshow, Sheena Bhalla, Mary Beth Beasley, Lynette M. Sholl, Keith M. Kerr, Sacha Gnjatic, Ignacio I. Wistuba, David L. Rimm, Ming Sound Tsao, Fred R. Hirsch
Journal: Nature Reviews Clinical Oncology (2021)
Bendamustine and Bortezomib-Containing Regimens Produce Higher Response Rates and More Durable Responses Versus Cyclophosphamide-Based Therapy in Frontline Waldenstrom Macroglobulinemia
Authors: Jorge J. Castillo, Joshua Gustine, Kirsten Meid, Toni Dubeau, Patricia Severns, Steven P Treon
Journal: Blood (2017)
Comorbidities Among Young Adults with Congenital Heart Defects: Results from the Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG — Arizona, Arkansas, and Metropolitan Atlanta, 2016<b>–</b>2019
Authors: Matthew E. Oster, Aspen P. Riser, Jennifer G. Andrews, Elijah H. Bolin, Maureen K. Galindo, Wendy N. Nembhard, Charles E. Rose, Sherry L. Farr
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

An estimated 1.4 million adults in the United States live with congenital heart defects (CHDs), yet their health outcomes are not well understood (1). Using self-reported, cross-sectional data from 1,482 respondents in the 2016-2019 Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) (2), CDC and academic partners estimated the prevalence of comorbidities among adults with CHDs aged 20-38 years born in Arizona (AZ), Arkansas (AR), and metropolitan Atlanta, Georgia (GA) compared with the general population (aged 20-38 years) from the National Health and Nutrition Examination Survey (NHANES) during 2015-2018 (3) and the AZ, AR, and GA Behavioral Risk Factor Surveillance Systems (BRFSS) during 2016-2018 (4). Adults with CHDs were more likely than those in the general population to report cardiovascular comorbidities, such as a history of congestive heart failure (4.3% versus 0.2%) and stroke (1.4% versus 0.3%), particularly those with severe CHDs (2). Adults with CHDs were more likely to report current depressive symptoms (15.1% versus 8.5%), but less likely to report previous diagnoses of depression (14.2% versus 22.6%), asthma (12.7% versus 16.9%), or rheumatologic disease (3.2% versus 8.0%). Prevalence of noncardiovascular comorbidities was similar between adults whose CHD was considered severe and those with nonsevere CHDs. Public health practitioners and clinicians can encourage young adults with CHDs to seek appropriate medical care to help them live as healthy a life as possible.
Mast cells cultured from human peripheral blood and bone marrow: a phenotypic and functional comparison
Authors: Jessy Elst, Didier Ebo, Margaretha Faber, Athina Van Gasse, Ine Decuyper, Chris Bridts, Leander De Puysseleyr, Marie-Line Van Der Poorten, Christel Mertens, Margo Hagendorens, Anke Verlinden, Vito Sabato
Journal: Journal of Allergy and Clinical Immunology (2021)
Causes and Consequences of Bacteriophage Diversification via Genetic Exchanges across Lifestyles and Bacterial Taxa
Authors: Jorge A Moura de Sousa, Eugen Pfeifer, Marie Touchon, Eduardo P C Rocha
Journal: Molecular Biology and Evolution (2021)

Bacteriophages (phages) evolve rapidly by acquiring genes from other phages. This results in mosaic genomes. Here, we identify numerous genetic transfers between distantly related phages and aim at understanding their frequency, consequences, and the conditions favoring them. Gene flow tends to occur between phages that are enriched for recombinases, transposases, and nonhomologous end joining, suggesting that both homologous and illegitimate recombination contribute to gene flow. Phage family and host phyla are strong barriers to gene exchange, but phage lifestyle is not. Even if we observe four times more recent transfers between temperate phages than between other pairs, there is extensive gene flow between temperate and virulent phages, and between the latter. These predominantly involve virulent phages with large genomes previously classed as low gene flux, and lead to the preferential transfer of genes encoding functions involved in cell energetics, nucleotide metabolism, DNA packaging and injection, and virion assembly. Such exchanges may contribute to the observed twice larger genomes of virulent phages. We used genetic transfers, which occur upon coinfection of a host, to compare phage host range. We found that virulent phages have broader host ranges and can mediate genetic exchanges between narrow host range temperate phages infecting distant bacterial hosts, thus contributing to gene flow between virulent phages, as well as between temperate phages. This gene flow drastically expands the gene repertoires available for phage and bacterial evolution, including the transfer of functional innovations across taxa.
Comparison of Demand for Drugs Used for COVID-19 Treatment and Other Drugs During the Early Phase of the COVID-19 Pandemic in Italy
Authors: Adriana Ammassari, Aurora Di Filippo, Maria Paola Trotta, Giuseppe Traversa, Andrea Pierantozzi, Francesco Trotta, Nicola Magrini
Journal: JAMA Network Open (2021)

This cross-sectional study compares demand for drugs for treatment of coronavirus disease 2019 (COVID-19) between the period directly before the COVID-19 outbreak in Italy and the early period of the outbreak.