tbuckley/cabot-search huggingface dataset:
Next Generation-Targeted Amplicon Sequencing (NG-TAS): an optimised protocol and computational pipeline for cost-effective profiling of circulating tumour DNA
Authors: Meiling Gao, Maurizio Callari, Emma Beddowes, Stephen-John Sammut, Marta Grzelak, Heather Biggs, Linda Jones, Abdelhamid Boumertit, Sabine C. Linn, Javier Cortes, Mafalda Oliveira, Richard Baird, Suet-Feung Chin, Carlos Caldas
Journal: Genome Medicine (2019)

Circulating tumour DNA (ctDNA) detection and monitoring have enormous potential clinical utility in oncology. We describe here a fast, flexible and cost-effective method to profile multiple genes simultaneously in low input cell-free DNA (cfDNA): Next Generation-Targeted Amplicon Sequencing (NG-TAS). We designed a panel of 377 amplicons spanning 20 cancer genes and tested the NG-TAS pipeline using cell-free DNA from two HapMap lymphoblastoid cell lines. NG-TAS consistently detected mutations in cfDNA when mutation allele fraction was > 1%. We applied NG-TAS to a clinical cohort of metastatic breast cancer patients, demonstrating its potential in monitoring the disease. The computational pipeline is available at https://github.com/cclab-brca/NGTAS_pipeline .
Review: In noncardiac surgery, amiodarone, β-blocker, or statin prophylaxis reduces postoperative AF
Authors: Sabina Sayeed, Adrian F. Hernandez
Journal: Annals of Internal Medicine (2018)

ACP Journal Club17 July 2018Review: In noncardiac surgery, amiodarone, β-blocker, or statin prophylaxis reduces postoperative AFSabina Sayeed, MA, Adrian F. Hernandez, MDSabina Sayeed, MADuke–National University of Singapore Medical School and Duke University School of Medicine, Durham, North Carolina, USA (S.S., A.F.H.)Search for more papers by this author, Adrian F. Hernandez, MDDuke–National University of Singapore Medical School and Duke University School of Medicine, Durham, North Carolina, USA (S.S., A.F.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-2-007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationOesterle A, Weber B, Tung R, et al. Preventing postoperative atrial fibrillation after noncardiac surgery: a meta-analysis. Am J Med. 2018;131:795-804. https://pubmed.ncbi.nlm.nih.gov/29476748Clinical Impact RatingsGIM/FP/GP: Cardiology: References1 Riber LP, Larsen TB, Christensen TD. Postoperative atrial fibrillation prophylaxis after lung surgery: systematic review and meta-analysis. Ann Thorac Surg. 2014;98:1989-97. [PMID: 25283696] Google Scholar2 Devereaux PJ, Yang H, Leslie K, et al. 1-year outcomes of perioperative beta-blockade in patients undergoing cardiac surgery. Presented at: ACC 2018, Orlando, Florida. 12 Mar 2018. Google Scholar Author, Article, and Disclosure InformationAffiliations: Duke–National University of Singapore Medical School and Duke University School of Medicine, Durham, North Carolina, USA (S.S., A.F.H.)This article was published at Annals.org on 3 July 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 July 2018Volume 169, Issue 2Page: JC7KeywordsDrugsMortalityOrthopedic surgeryProphylaxisRelative riskSafetyStatinsSurgeryThoracic surgeryVascular surgery ePublished: 17 July 2018 Issue Published: 17 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Myointimal Cells as a Possible Source of Replacement for Endothelial Cells in the Rabbit
Authors: Chung-Hsints'ao
Journal: Circulation Research (1968)

Regeneration of damaged endothelium has been studied by means of mechanical injury to rabbit abdominal aorta and inferior vena cava. Ultrastructural evidence suggests that myointimal cells can become endothelial cells. It is postulated that such a myogenic replacement of endothelial cells may occur under normal circumstances in the aorta. Injury to blood vessels merely accelerates this process.
MicroRNA-451 Exacerbates Lipotoxicity in Cardiac Myocytes and High-Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway
Authors: YasuhideKuwabara, TakahiroHorie, OsamuBaba, ShinWatanabe, MasatakaNishiga, ShunsukeUsami, MasayasuIzuhara, TetsushiNakao, TomohiroNishino, KinyaOtsu, ToruKita, TakeshiKimura, KohOno
Journal: Circulation Research (2015)

Rationale:In some patients with type 2 diabetes mellitus (DM) without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed diabetic cardiomyopathy. To date, microRNA (miRNAs or miR) functions in diabetic cardiomyopathy remain to be elucidated. Objective:To clarify the functions of miRNAs involved in diabetic cardiomyopathy caused by type 2 DM. Methods and Results:C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 DM. miRNA microarray analyses and real-time polymerase chain reaction revealed that miR-451 levels were significantly increased in the type 2 DM mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in neonatal rat cardiac myocytes. Calcium-bi...
Measles outbreak linked to insufficient vaccination coverage in Nouvelle-Aquitaine Region, France, October 2017 to July 2018
Authors: Anne Bernadou, Cyril Astrugue, Matthieu Méchain, Valérie Le Galliard, Catherine Verdun-Esquer, France Dupuy, Julia Dina, Fatima Aït-Belghiti, Denise Antona, Stéphanie Vandentorren
Journal: Eurosurveillance (2018)

On 30 October 2017, an outbreak of measles started in the Nouvelle-Aquitaine (NA) region in France among Bordeaux University students before spreading to other regions. Until 1 July 2018, 1,101 cases were reported in NA, including 98 complications and two deaths. Cases were related to clusters (e.g. students, healthcare workers) in 16%; 81% of cases were not vaccinated against measles as recommended. Vaccination coverage above herd immunity threshold remains the main preventative outbreak measure.
Management of anemia in patients who decline blood transfusion
Authors: Aryeh Shander, Lawrence Tim Goodnough
Journal: American Journal of Hematology (2018)

Abstract Declining a treatment modality should not be considered the same as refusal of medical care as illustrated by the management of Jehovah's Witness patients who do not accept transfusions. Over the years, a comprehensive set of strategies have been developed to meet the specific needs of these patients and these strategies are collectively called “Bloodless Medicine and Surgery” (BMS). The focus in BMS is to optimize the patients' hematopoietic capacity to increase hemoglobin (Hgb) level, minimize blood loss, improve hemostasis, and provide supportive strategies to minimize oxygen consumption and maximize oxygen utilization. We present 3 case reports that illustrate some of the challenges faced and measures available to effectively treat these patients. Under BMS programs, patients with extremely low hemoglobin levels, not conducive to survival under ordinary conditions, have survived and recovered without receiving allogeneic transfusions. Additionally, the valuable experience gained from caring for these patients has paved the way to develop the concept of Patient Blood Management as a standard care to benefit all patients, and not only those for whom blood is not an option.
The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis
Authors: Robert J Commons, Julie A Simpson, Kamala Thriemer, Georgina S Humphreys, Tesfay Abreha, Sisay G Alemu, Arletta Añez, Nicholas M Anstey, Ghulam R Awab, J Kevin Baird, Bridget E Barber, Isabelle Borghini-Fuhrer, Cindy S Chu, Umberto D'Alessandro, Prabin Dahal, André Daher, Peter J de Vries, Annette Erhart, Margarete S M Gomes, Lilia Gonzalez-Ceron, Matthew J Grigg, Aliehsan Heidari, Jimee Hwang, Piet A Kager, Tsige Ketema, Wasif A Khan, Marcus V G Lacerda, Toby Leslie, Benedikt Ley, Kartini Lidia, Wuelton M Monteiro, Francois Nosten, Dhelio B Pereira, Giao T Phan, Aung P Phyo, Mark Rowland, Kavitha Saravu, Carol H Sibley, André M Siqueira, Kasia Stepniewska, Inge Sutanto, Walter R J Taylor, Guy Thwaites, Binh Q Tran, Hien T Tran, Neena Valecha, José Luiz F Vieira, Sonam Wangchuk, Timothy William, Charles J Woodrow, Lina Zuluaga-Idarraga, Philippe J Guerin, Nicholas J White, Ric N Price
Journal: The Lancet Infectious Diseases (2018)

Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings.
2018 IAS-USA Recommendations for the Use of Antiretroviral Therapy for HIV
Authors: James Riddell
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Phase I Trial of ALT-803, A Novel Recombinant IL15 Complex, in Patients with Advanced Solid Tumors
Authors: Kim Margolin, Chihiro Morishima, Vamsidhar Velcheti, Jeffrey S. Miller, Sylvia M. Lee, Ann W. Silk, Shernan G. Holtan, Andreanne M. Lacroix, Steven P. Fling, Judith C. Kaiser, Jack O. Egan, Monica Jones, Peter R. Rhode, Amy D. Rock, Martin A. Cheever, Hing C. Wong, Marc S. Ernstoff
Journal: Clinical Cancer Research (2018)

Abstract Purpose: IL15 induces the activation and proliferation of natural killer (NK) and memory CD8+ T cells and has preclinical antitumor activity. Given the superior activity and favorable kinetics of ALT-803 (IL15N72D:IL15RαSu/IgG1 Fc complex) over recombinant human IL15 (rhIL15) in animal models, we performed this first-in-human phase I trial of ALT-803 in patients with advanced solid tumors. Patients and Methods: Patients with incurable advanced melanoma, renal cell, non–small cell lung, and head and neck cancer were treated with ALT-803 0.3 to 6 μg/kg weekly intravenously or 6 to 20 μg/kg weekly subcutaneously for 4 consecutive weeks, every 6 weeks. Immune correlates included pharmacokinetics, immunogenicity, and lymphocyte expansion and function. Clinical endpoints were toxicity and antitumor activity. Results: Twenty-four patients were enrolled; 11 received intravenous and 13 received subcutaneous ALT-803. Of these patients, nine had melanoma, six renal, three head and neck, and six lung cancer. Although total lymphocyte and CD8+ T-cell expansion were modest, NK cell numbers rose significantly. Neither anti–ALT-803 antibodies nor clinical activity were observed. Overall, ALT-803 was well tolerated, with adverse effects including fatigue and nausea most commonly with intravenous administration, whereas painful injection site wheal was reported most commonly with subcutaneous ALT-803. Conclusions: Subcutaneous ALT-803 produced the expected NK cell expansion and was well tolerated with minimal cytokine toxicities and a strong local inflammatory reaction at injection sites in patients with advanced cancer. These data, together with compelling evidence of synergy in preclinical and clinical studies, provide the rationale for combining ALT-803 with other anticancer agents. Clin Cancer Res; 24(22); 5552–61. ©2018 AACR.
Primary Biliary Cholangitis in Medicare Population: The Impact on Mortality and Resource Use
Authors: Mehmet Sayiner, Pegah Golabi, Maria Stepanova, Issah Younossi, Fatema Nader, Andrei Racila, Zobair M. Younossi
Journal: Hepatology (2018)

Primary biliary cholangitis (PBC) is a disease of small bile ducts, which can lead to morbidity and mortality. Our aim was to assess recent trends in mortality and healthcare use of PBC patients in the Medicare program. Data from Medicare beneficiaries between 2005 and 2015 (5% random samples) were used. The diagnosis of PBC was established with International Classification of Diseases‐9 code 571.6 used for both primary and secondary diagnoses. Mortality was assessed by Medicare‐linked death registry. Healthcare use included episodes of care, length of stay, and total charges/payments. Independent predictors of outcomes were evaluated in multiple generalized linear or logistic regression models. The study cohort included a total of 6,375 inpatient/outpatient Medicare beneficiaries (mean age 69.8 years, 17% male, 88% white, and 18% with disability). Over the study period, 1‐year mortality remained stable (9.1% to 14.3%, P = 0.11). Independent predictors of 1‐year mortality were older age, male gender, black race, the presence of ascites, encephalopathy, hepatocellular carcinoma, and higher Charlson score. Outpatient total yearly charges and payments per beneficiary with PBC increased from $3,065 and $777 (2005) to $5,773 and $967 (2014), respectively. Similarly, inpatient total yearly charges and payments per beneficiary with PBC increased from $59,765 and $19,406 (2007), to $98,941 and $27,948 (2013), respectively (P < 0.05). The presence of ascites, portal hypertension, and higher Charlson score were independent predictors of higher payments for both inpatient and outpatient resource use, and the presence of hepatic encephalopathy was an additional predictor of higher inpatient resource use (all P < 0.02). Conclusion: The prevalence of PBC among the Medicare beneficiaries has increased. Despite stable mortality rates, resource use for Medicare patients with PBC continues to rise.
AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation
Authors: Sophie Lepropre, Shakeel Kautbally, Marie Octave, Audrey Ginion, Marie-Blanche Onselaer, Gregory R. Steinberg, Bruce E. Kemp, Alexandre Hego, Odile Wéra, Sanne Brouns, Frauke Swieringa, Martin Giera, Victor M. Darley-Usmar, Jérôme Ambroise, Bruno Guigas, Johan Heemskerk, Luc Bertrand, Cécile Oury, Christophe Beauloye, Sandrine Horman
Journal: Blood (2018)
Basophil counts in PBMC populations during childhood acute wheeze/asthma are associated with future exacerbations
Authors: Jonatan Leffler, Anya C. Jones, Elysia M. Hollams, Franciska Prastanti, Peter N. Le Souëf, Patrick G. Holt, Anthony Bosco, Ingrid A. Laing, Deborah H. Strickland
Journal: Journal of Allergy and Clinical Immunology (2018)
Enhancing Mitochondrial Ca2+ Uptake in Myocytes From Failing Hearts Restores Energy Supply and Demand Matching
Authors: TingLiu, BrianO'Rourke
Journal: Circulation Research (2008)

Mitochondrial ATP production is continually adjusted to energy demand through coordinated increases in oxidative phosphorylation and NADH production mediated by mitochondrial Ca2+([Ca2+]m). Elevated cytosolic Na+ impairs [Ca2+]m accumulation during rapid pacing of myocytes, resulting in a decrease in NADH/NAD+ redox potential. Here, we determined 1) if accentuating [Ca2+]m accumulation prevents the impaired NADH response at high [Na+]i; 2) if [Ca2+]m handling and NADH/NAD+ balance during stimulation is impaired with heart failure (induced by aortic constriction); and 3) if inhibiting [Ca2+]m efflux improves NADH/NAD+ balance in heart failure. [Ca2+]m and NADH were recorded in cells at rest and during voltage clamp stimulation (4Hz) with either 5 or 15 mmol/L [Na+]i. Fast [Ca2+]m transients and a rise in diastolic [Ca2+]m were observed during electric stimulation. [Ca2+]m accumulation was [Na+]i-dependent; less [Ca2+]m accumulated in cells with 15 Na+ versus 5 mmol/L Na+ and NADH oxidation was evident at 1...
Liver Metastases From Gastric Adenocarcinoma Mimicking Multinodular Hepatocellular Carcinoma
Authors: Álvaro Díaz‐González, Ester Monclús, Anna Darnell, Manel Solé, Jordi Bruix
Journal: Hepatology (2018)

Díaz‐González, Álvaro; Monclús, Ester; Darnell, Anna; Solé, Manel; Bruix, Jordi Author Information
Abstract 19586: Impact of Dyspnea: From Validity Indices to the Clinical Utility of the French-canadian Version of the Modified Dyspnea Index
Authors: Michel Dore, Maria-Cecilia Gallani, Steeve Provencher, Paul Poirier, Camille Gagné, Céline Gélinas
Journal: Circulation (2014)

Introduction: Dyspnea is a cardinal symptom among patients with respiratory and cardiovascular diseases. Its underlying mechanisms are complex, including pathophysiological as well as psychological and environmental factors. There is no gold standard to its evaluation and it has been recognized that multidimensional tools could provide a more comprehensive evaluation of the symptom. Hypothesis: The purpose of this study was to examine the validation of the scores of the French-Canadian version of the Modified Dyspnea Index(MDI), a multidimensional measure of dyspnea, among chronic cardiovascular and pulmonary patients. Methods: This study includes 137 patients: 79 with pulmonary arterial hypertension and 58 with interstitial lung disease. The cross-cultural adaptation and reliability of the MDI were already reported. The hypothesis guiding the test of convergent validity were that the final score of MDI, which reflects the intensity of dyspnea and its functional impact, would have correlations with: pulmonary function (forced vital capacity-FVC and FVC%), physical capacity (6 Minutes Walk Test-6MWT and Veterans Specific Activity Questionnaire-VSAQ), the practice of physical activity (Godin-Shephard Leisure-Time Physical Activity Questionnaire - GSLTPAQ) and quality of life (SF-12). Partial correlations were performed controlling theses variables: diagnosis, age, sex, BMI, and schooling. Results: The following correlations were observed between the total score of MDI and the reference variables: FVC 0.36 ( p&lt;0.001 ); FVC% 0.29 ( p=0.008 ); 6MWT 0.58 ( p&lt;0.001 ); VSAQ 0.77 ( p&lt;0.001 ); GSLTPAQ 0.50 ( p&lt;0.001 ); SF12-Physical Component 0.73 ( p&lt;0.001 ); SF12-Mental Comp. 0.31 ( p&lt;0.001 ). Conclusions: The results confirmed the associations hypothesized. The total score of the MDI explained much more the variance of the quality of life and perceived physical capacity, than lung function explained the MDI score. It is aligned with the described impact of the symptom in the daily life of the patient and the complexity of the factors underlying its triggering and perception. The use of the MDI can be very helpful in the clinical follow-up, guiding the choice of the best therapeutic approach and evaluation the outcomes of the interventions implemented.
The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans
Authors: D.J. Wilkinson, M. Piasecki, P.J. Atherton
Journal: Ageing Research Reviews (2018)

Age-related loss of skeletal muscle mass and function, sarcopenia, is associated with physical frailty and increased risk of morbidity (chronic diseases), in addition to all-cause mortality. The loss of muscle mass occurs incipiently from middle-age (∼1%/year), and in severe instances can lead to a loss of ∼50% by the 8–9th decade of life. This review will focus on muscle deterioration with ageing and highlight the two underpinning mechanisms regulating declines in muscle mass and function: muscle fibre atrophy and muscle fibre loss (hypoplasia) – and their measurement. The mechanisms of muscle fibre atrophy in humans relate to imbalances in muscle protein synthesis (MPS) and breakdown (MPB); however, since there is limited evidence for basal alterations in muscle protein turnover, it would appear that "anabolic resistance" to fundamental environmental cues regulating diurnal muscle homeostasis (namely physical activity and nutrition), underlie age-related catabolic perturbations in muscle proteostasis. While the 'upstream' drivers of the desensitization of aged muscle to anabolic stimuli are poorly defined, they most likely relate to impaired efficiency of the conversion of nutritional/exercise stimuli into signalling impacting mRNA translation and proteolysis. Additionally, loss of muscle fibres has been shown in cadaveric studies using anatomical fibre counts, and from iEMG studies demonstrating motor unit loss, albeit with few molecular investigations of this in humans. We suggest that defining countermeasures against sarcopenia requires improved understandings of the co-ordinated regulation of muscle fibre atrophy and fibre loss, which are likely to be inextricably linked.
Diagnosis of Multiple Primary Intestinal-Type Adenocarcinoma in the Lung by 18F-FDG PET/CT
Authors: Yujing Hu, Dayong Wu, Congna Tian, Qiang Wei, Yanzhu Bian
Journal: Clinical Nuclear Medicine (2018)

Abstract A 74-year-old man with multiple soft tissue lesions in the lung, which were suspected to be metastatic neoplasms, underwent 18 F-FDG PET/CT scan to detect primary malignancy. The images demonstrated that the lung and 2 retroperitoneal lymph nodes were the only affected organ or tissues with suspected primary lung neoplasms. Multiple intestinal-type adenocarcinoma was eventually diagnosed by CT-guided transthoracic needle aspiration biopsy.
Effect of Quinidine and Pronethalol on Acetylstrophanthidin-Induced Ventricular Arrhythmia in Cats Treated with Reserpine
Authors: Barrielevitt, Jayroberts
Journal: Circulation Research (1966)

With pronethalol, quinidine, and reserpine it was necessary to increase the dose of acetylstrophanthidin which produced arrhythmia in combination with vagal stimulation. However, in reserpine-treated animals, quinidine and pronethalol were ineffective. The capability of large doses of acetylstrophanthidin to produce ventricular arrhythmia was not diminished by quinidine, pronethalol, or reserpine. While pronethalol decreased the S-A nodal rate in normal animals, it failed to produce an effect on rate after reserpine pretreatment. Since after catecholamine depletion by reserpine, pronethalol and quinidine did not affect acetylstrophanthidin-induced ventricular arrhythmia, it is suggested that the antidigitalis effect of these agents is related to their actions to diminish adrenergic nervous activity.
Abstract 12351: Dietary Antioxidant Deficiency is Associated With Increased Inflammatory Markers and Poorer Health-related Quality of Life in Patients With Heart Failure
Authors: Jia Rong Wu, Eun Kyeung Song, Debra K Moser, Terry Lennie
Journal: Circulation (2017)

Introduction: Dietary antioxidant deficiency is prevalent and associated with inflammatory markers and health-related quality-of-life (HRQOL) in healthy adults. However, the relationships among die...