tbuckley/cabot-search huggingface dataset:
Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells
Authors: Yumeng Guo, Cheng Xu, Andy W C Man, Bo Bai, Cuiting Luo, Yu Huang, Aimin Xu, Paul M Vanhoutte, Yu Wang
Journal: Cardiovascular Research (2018)

Aged arteries are characterized by attenuated vasodilator and enhanced vasoconstrictor responses, which contribute to the development of diseases such as arterial hypertension, atherosclerosis, and heart failure. SIRT1 is a longevity regulator exerting protective functions against vascular ageing, although the underlying mechanisms remain largely unknown. This study was designed to elucidate the signalling pathways involved in endothelial SIRT1-mediated vasodilator responses in the arteries of young and old mice. In particular, the contributions of nitric oxide (NO), endothelial NO synthase (eNOS), cyclooxygenase (COX), and/or soluble guanylyl cyclase (sGC) were examined.Wild type (WT) or eNOS knockout (eKO) mice were cross-bred with those overexpressing human SIRT1 selectively in the vascular endothelium (EC-SIRT1). Arteries were collected from the four groups of mice (WT, EC-SIRT1, eKO, and eKO-SIRT1) to measure isometric relaxations/contractions in response to various pharmacological agents. Reduction of NO bioavailability, hyper-activation of COX signalling, and down-regulation of sGC collectively contributed to the decreased vasodilator and increased vasoconstrictor responses in arteries of old WT mice. Overexpression of endothelial SIRT1 did not block the reduction in NO bioavailability but attenuated the hyper-activation of COX-2, thus protecting mice from age-induced vasoconstrictor responses in arteries of EC-SIRT1 mice. Deficiency of eNOS did not affect endothelial SIRT1-mediated anti-contractile activities in arteries of eKO-SIRT1 mice. Mechanistic studies revealed that overexpression of endothelial SIRT1 enhanced Notch signalling to up-regulate sGCβ1 in smooth muscle cells. Increased expression and activity of sGC prevented age-induced hyper-activation of COX-2 as well as the conversion of endothelium-dependent relaxations to contractions in arteries of EC-SIRT1 mice.Age-induced down-regulation of sGC and up-regulation of COX-2 in arteries are at least partly attributable to the loss-of-endothelial SIRT1 function. Enhancing the endothelial expression and function of SIRT1 prevents early vascular ageing and maintains vasodilator responses, thus representing promising drug targets for cardiovascular diseases.
Abstract 20739: Compared to C-Reactive Protein and Homocysteine, [18F]-FDG PET/CTA Uptake is Directly Related to Intraplaque Inflammatory Burden of High-Risk Carotid Plaque: A Sub-Study of the Canadian Atherosclerosis Imaging Network (CAIN-2)
Authors: Myra S Cocker, J. David Spence, Robert R Hammond, Robert A deKemp, Cheemun Lum, Andrew Hill, Sudhir Nagpal, Grant Stotts, Linda Garrard, Jean N DaSilva, Jean-Claude Tardif, Rob Beanlands
Journal: Circulation (2016)

Background: Inflammation may contribute to plaque instability. C-reactive protein (CRP) and total homocysteine (tHcy) are considered to be putative risk factors for cardiovascular disease. It is su...
Hospice Use and Palliative Care for Patients With Heart Failure
Authors: Shunichi Nakagawa, A. Reshad Garan
Journal: JAMA Cardiology (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 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
Surgical Decision Making in Elderly, Impaired Nursing Home Patients
Authors: Jessica Y. Liu, Karl Y. Bilimoria
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine
Authors: Federica Giannotti, Myriam Labopin, Roni Shouval, Jaime Sanz, William Arcese, Emanuele Angelucci, Jorge Sierra, Josep-Maria Ribera Santasusana, Stella Santarone, Bruno Benedetto, Alessandro Rambaldi, Riccardo Saccardi, Didier Blaise, Michele Angelo Carella, Vanderson Rocha, Frederic Baron, Mohamad Mohty, Annalisa Ruggeri, Arnon Nagler
Journal: Journal of Hematology & Oncology (2018)

Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established.This was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics.SUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002).Our results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.
HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy
Authors: Huai-yu Wang, Zhao Cui, Li-jun Xie, Li-jie Zhang, Zhi-Yong Pei, Fang-jin Chen, Zhen Qu, Jing Huang, Yi-miao Zhang, Xin Wang, Fang Wang, Li-qiang Meng, Xu-yang Cheng, Gang Liu, Xu-jie Zhou, Hong Zhang, Hanna Debiec, Pierre Ronco, Ming-hui Zhao
Journal: Kidney International (2018)
Increased Lactate Secretion by Cancer Cells Sustains Non-cell-autonomous Adaptive Resistance to MET and EGFR Targeted Therapies
Authors: Maria Apicella, Elisa Giannoni, Stephany Fiore, Karin Johanna Ferrari, Daniel Fernández-Pérez, Claudio Isella, Carlotta Granchi, Filippo Minutolo, Antonino Sottile, Paolo Maria Comoglio, Enzo Medico, Filippo Pietrantonio, Marco Volante, Diego Pasini, Paola Chiarugi, Silvia Giordano, Simona Corso
Journal: Cell Metabolism (2018)
Outstanding Challenges in the Transferability of Ecological Models
Authors: Katherine L. Yates, Phil J. Bouchet, M. Julian Caley, Kerrie Mengersen, Christophe F. Randin, Stephen Parnell, Alan H. Fielding, Andrew J. Bamford, Stephen Ban, A. Márcia Barbosa, Carsten F. Dormann, Jane Elith, Clare B. Embling, Gary N. Ervin, Rebecca Fisher, Susan Gould, Roland F. Graf, Edward J. Gregr, Patrick N. Halpin, Risto K. Heikkinen, Stefan Heinänen, Alice R. Jones, Periyadan K. Krishnakumar, Valentina Lauria, Hector Lozano-Montes, Laura Mannocci, Camille Mellin, Mohsen B. Mesgaran, Elena Moreno-Amat, Sophie Mormede, Emilie Novaczek, Steffen Oppel, Guillermo Ortuño Crespo, A. Townsend Peterson, Giovanni Rapacciuolo, Jason J. Roberts, Rebecca E. Ross, Kylie L. Scales, David Schoeman, Paul Snelgrove, Göran Sundblad, Wilfried Thuiller, Leigh G. Torres, Heroen Verbruggen, Lifei Wang, Seth Wenger, Mark J. Whittingham, Yuri Zharikov, Damaris Zurell, Ana M.M. Sequeira
Journal: Trends in Ecology & Evolution (2018)

Predictive models are central to many scientific disciplines and vital for informing management in a rapidly changing world. However, limited understanding of the accuracy and precision of models transferred to novel conditions (their 'transferability') undermines confidence in their predictions. Here, 50 experts identified priority knowledge gaps which, if filled, will most improve model transfers. These are summarized into six technical and six fundamental challenges, which underlie the combined need to intensify research on the determinants of ecological predictability, including species traits and data quality, and develop best practices for transferring models. Of high importance is the identification of a widely applicable set of transferability metrics, with appropriate tools to quantify the sources and impacts of prediction uncertainty under novel conditions.
Bile Acids, the Microbiome, Immunity, and Liver Tumors
Authors: Christoph Schramm
Journal: New England Journal of Medicine (2018)

Bile acids affect the expression of a chemokine ligand by liver sinusoidal endothelial cells, which in turn affects the extent to which a type of natural killer cell is present in and diminishes the burden of hepatocellular carcinomas in a mouse model of the disease.
Stabilizing Transthyretin to Treat ATTR Cardiomyopathy
Authors: C. Cristina Quarta, Scott D. Solomon
Journal: New England Journal of Medicine (2018)

Transthyretin amyloid cardiomyopathy is caused by intramyocardial deposition of transthyretin-derived amyloid fibrils, which leads to progressive ventricular wall thickening and stiffness of the heart. Once diagnosed, it is associated with a life expectancy of only 2 to 6 years. Transthyretin amyloid cardiomyopathy can be an inherited trait, caused by pathogenic mutations in the transthyretin gene TTR (ATTRm), or it can be acquired through the aggregation of wild-type transthyretin protein (ATTRwt). The condition is typically manifested as failure of the right side of the heart, cardiac conduction blocks, or supraventricular arrhythmias.1 Although ATTRwt mainly affects the hearts of patients 60 years . . .
Polyphenolic natural products and natural product–inspired steroidal mimics as aromatase inhibitors
Authors: Alexander J. Nielsen, James McNulty
Journal: Medicinal Research Reviews (2018)

Abstract The discovery of biologically active polyphenolic natural products, including chalcones, stilbenes, flavanones, and isoflavones as steroidal mimics has proven to be a subject of considerable importance in medicine. Some of these natural compounds have been shown to modulate key human metabolic processes via steroidal hormone receptors, or to inhibit crucial enzymes involved in the biosynthesis of steroidal hormones themselves. Isoflavone polyphenolics such as genistein are well known for this “phytoestrogenic” biological activity. This review focuses on the ability of select polyphenolics and their synthetic derivatives to function as steroidal mimics in the inhibition of the enzyme aromatase, thereby lowering production of endogenous estrogen growth hormones. The discovery of potent, natural product–based aromatase inhibitors (AIs) as hit compounds has led to the introduction of steroidal‐based irreversible inhibitors, such as exemestane and reversible AIs such as anastrozole and letrozole, now standard therapy in the treatment of estrogen receptor–positive breast cancer and other hormone related indications. Pursuit of this strategy over the last few decades has been largely successful although complications and challenges remain. This review highlights the aromatase activity of natural stilbenes, chalcones, and flavanones and synthetically inspired versions thereof and draws attention to new and under‐investigated areas within each class worthy of pursuit.
Corrigendum to “EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis” [J Hepatol 69 (2018) 406–460]
Authors: Paolo Angeli, Mauro Bernardi, Càndid Villanueva, Claire Francoz, Rajeshwar P. Mookerjee, Jonel Trebicka, Aleksander Krag, Wim Laleman, Pere Gines
Journal: Journal of Hepatology (2018)
Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types
Authors: L. Paré, T. Pascual, E. Seguí, C. Teixidó, M. Gonzalez-Cao, P. Galván, A. Rodríguez, B. González, M. Cuatrecasas, E. Pineda, A. Torné, G. Crespo, S. Martin-Algarra, E. Pérez-Ruiz, Ò Reig, M. Viladot, C. Font, B. Adamo, M. Vidal, L. Gaba, M. Muñoz, I. Victoria, G. Ruiz, N. Viñolas, B. Mellado, J. Maurel, J. Garcia-Corbacho, M Á Molina-Vila, M. Juan, J.M. Llovet, N. Reguart, A. Arance, A. Prat
Journal: Annals of Oncology (2018)

BackgroundWe hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer types.Patients and methodsRNASeqv2 data from 10078 tumor samples representing 34 different cancer types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated. To translate the in silico findings to the clinical setting, we analyzed the expression of PD1 mRNA using the nCounter platform in 773 formalin-fixed paraffin embedded (FFPE) tumor samples across 17 cancer types. To test the direct relationship between PD1 mRNA, PDL1 immunohistochemistry (IHC), stromal tumor-infiltrating lymphocytes (sTILs) and ORR, we evaluated an independent FFPE-based dataset of 117 patients with advanced disease treated with anti-PD1 monotherapy.ResultsIn pan-cancer TCGA, PD1 mRNA expression was found strongly correlated (r > 0.80) with CD8 T-cell genes and signatures and the proportion of PD1 mRNA-high tumors (80th percentile) within a given cancer type was variable (0%–84%). Strikingly, the PD1-high proportions across cancer types were found strongly correlated (r = 0.91) with the ORR following anti-PD1 monotherapy reported in the literature. Lower correlations were found with other immune-related genes/signatures, including PDL1. Using the same population-based cutoff (80th percentile), similar proportions of PD1-high disease in a given cancer type were identified in our in-house 773 tumor dataset as compared with TCGA. Finally, the pre-established PD1 mRNA FFPE-based cutoff was found significantly associated with anti-PD1 response in 117 patients with advanced disease (PD1-high 51.5%, PD1-intermediate 26.6% and PD1-low 15.0%; odds ratio between PD1-high and PD1-intermediate/low = 8.31; P < 0.001). In this same dataset, PDL1 tumor expression by IHC or percentage of sTILs was not found associated with response.ConclusionsOur study provides a clinically applicable assay that links PD1 mRNA abundance, activated CD8 T-cells and anti-PD1 efficacy.
Abstract 16133: Geographic Variation in Cardiac Rehabilitation Access
Authors: Justin M Bachmann, Meredith S Duncan, Robert S Greevy, Alexis L Beatty, Randal J Thomas, Mary A Whooley, Matthew S Freiberg
Journal: Circulation (2017)

Introduction: There is wide geographic variation in cardiac rehabilitation (CR) utilization, with the proportion of eligible patients participating in CR programs ranging from 10-40% at the state l...
Abstract 11134: Subclinical Coronary Plaque Burden in Asymptomatic Relatives of Patients With Documented Premature Coronary Artery Disease
Authors: Morten K Christiansen, Jesper M Jensen, Hans Erik Bøtker, Henrik K Jensen
Journal: Circulation (2015)

Introduction: A family history of premature coronary artery disease (CAD) is a well-known risk factor for adverse coronary events with age of onset being inversely related to the degree of heritability. Hypothesis: We hypothesized that asymptomatic first degree relatives, of patients with premature CAD, suffer a high burden of subclinical coronary atherosclerosis. Methods: First degree relatives, aged 30-65 years, of patients with a documented coronary revascularization procedure before the age of 40 years, were invited to participate in the study. Participants were matched by age, sex and absence of a family history, with patients referred for coronary CT angiography (CTA) because of atypical angina or non-anginal chest pain. A pooled blinded analysis was performed. The main outcome measure was the number of plaque-affected coronary segments. Results: 88 relatives and 88 symptomatic controls underwent CTA. Treatment of hypertension and dyslipidemia tended to be more common among controls (p=0.06). 4 relatives reported vague symptoms of which none had angiographic signs of obstructive CAD (any luminal stenosis above 50%). The calculated SCORE risk among relatives was generally low (85% having a 10-year risk of ≤1%). Relatives had significantly (p=0.006) more affected segments than controls (0 segments: 29,6% vs. 48,9%, 1-2 segments: 27,3% vs. 31,8%, 3-5 segments: 23,9% vs. 11,4% and ≥6 segments: 19,3% vs. 8,0%). In a multivariable logistic regression analysis, the presence of any CAD (OR 3.16 (1.50;6.70)) as well as non-calcified plaques (OR 2.2 (1.14;4.26)), mixed plaques (OR 6.77 (2.7;16.98)) and calcified plaques (OR 2.34 (1.01;5.43)) were more frequent. Although increased, the presence of obstructive plaques, however, did not differ statistically significantly between relatives and controls (OR 2.58 (0.85;7.83)). Conclusions: Asymptomatic relatives of patients with premature CAD suffer a high coronary plaque burden even when compared with symptomatic patients with an a priori higher risk of CAD. Our results indicate a strong genetic component in the genesis of coronary atherosclerosis and, moreover, underline the limitations of current guidelines on prevention of CAD.
Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation
Authors: Kyle T. Mincham, Naomi M. Scott, Jean-Francois Lauzon-Joset, Jonatan Leffler, Alexander N. Larcombe, Philip A. Stumbles, Sarah A. Robertson, Christian Pasquali, Patrick G. Holt, Deborah H. Strickland
Journal: Journal of Clinical Investigation (2018)

Chronic allergic inflammatory diseases are a major cause of morbidity, with allergic asthma alone affecting over 300 million people worldwide. Epidemiological studies demonstrate that environmental stimuli are associated with either the promotion or prevention of disease. Major reductions in asthma prevalence are documented in European and US farming communities. Protection is associated with exposure of mothers during pregnancy to microbial breakdown products present in farm dusts and unprocessed foods and enhancement of innate immune competence in the children. We sought to develop a scientific rationale for progressing these findings toward clinical application for primary disease prevention. Treatment of pregnant mice with a defined, clinically approved immune modulator was shown to markedly reduce susceptibility of their offspring to development of the hallmark clinical features of allergic airway inflammatory disease. Mechanistically, offspring displayed enhanced dendritic cell-dependent airway mucosal immune surveillance function, which resulted in more efficient generation of mucosal-homing regulatory T cells in response to local inflammatory challenge. We provide evidence that the principal target for maternal treatment effects was the fetal dendritic cell progenitor compartment, equipping the offspring for accelerated functional maturation of the airway mucosal dendritic cell network following birth. These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention.
Assessment of ultra-sensitive malaria diagnosis versus standard molecular diagnostics for malaria elimination: an in-depth molecular community cross-sectional study
Authors: Natalie E Hofmann, Maria Gruenberg, Elma Nate, Alice Ura, Daniela Rodriguez-Rodriguez, Mary Salib, Ivo Mueller, Thomas A Smith, Moses Laman, Leanne J Robinson, Ingrid Felger
Journal: The Lancet Infectious Diseases (2018)
Oropharyngeal Squamous Cell Carcinoma Metastasis to Distal Skeletal Muscle on FDG PET/CT
Authors: Zachary James Drew
Journal: Clinical Nuclear Medicine (2018)

We present a case of a tongue squamous cell carcinoma (SCC) metastasizing to distal skeletal muscle detected on FDG PET/CT imaging. A 48-year-old man with locally recurrent tongue SCC underwent a restaging FDG PET/CT to investigate neck and unilateral leg pain. The PET scan showed large, intensely FDG-avid lesions in the right scalene and left hamstring muscles, which were biopsy proven as metastatic SCC. Skeletal muscle metastases from oropharyngeal SCCs are rare; however, PET/CT has allowed increased detection of atypical metastatic sites. Such cases support the consideration of metastasis for muscular lesions in head and neck cancer patients.