tbuckley/cabot-search huggingface dataset:
Sirtuin 1 activation attenuates cardiac fibrosis in a rodent pressure overload model by modifying Smad2/3 transactivation
Authors: Antoinette Bugyei-Twum, Christopher Ford, Robert Civitarese, Jessica Seegobin, Suzanne L Advani, Jean-Francois Desjardins, Golam Kabir, Yanling Zhang, Melissa Mitchell, Jennifer Switzer, Kerri Thai, Vanessa Shen, Armin Abadeh, Krishna K Singh, Filio Billia, Andrew Advani, Richard E Gilbert, Kim A Connelly
Journal: Cardiovascular Research (2018)

Transforming growth factor β1 (TGF-β1) is a prosclerotic cytokine involved in cardiac remodelling leading to heart failure (HF). Acetylation/de-acetylation of specific lysine residues in Smad2/3 has been shown to regulate TGF-β signalling by altering its transcriptional activity. Recently, the lysine de-acetylase sirtuin 1 (SIRT1) has been shown to have a cardioprotective effect; however, SIRT1 expression and activity are paradoxically reduced in HF. Herein, we investigate whether pharmacological activation of SIRT1 would induce cardioprotection in a pressure overload model and assess the impact of SIRT1 activation on TGF-β signalling and the fibrotic response.Eight weeks old male C57BL/6 mice were randomized to undergo sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Post-surgery, animals were further randomized to receive SRT1720 or vehicle treatment. Echocardiography, pressure-volume loops, and histological analysis revealed an impairment in cardiac function and deleterious left ventricular remodelling in TAC-operated animals that was improved with SRT1720 treatment. Genetic ablation and cell culture studies using a Smad-binding response element revealed SIRT1 to be a specific target of SRT1720 and identified Smad2/3 as a SIRT1 specific substrate.Overall, our data demonstrate that Smad2/3 is a specific SIRT1 target and suggests that pharmacological activation of SIRT1 may be a novel therapeutic strategy to prevent/reverse HF via modifying Smad activity.
Mindfulness-Based Attention Training Improves Cognitive and Affective Processes in Daily Life in Remitted Patients with Recurrent Depression: A Randomized Controlled Trial
Authors: Christina Timm, Bettina Rachota-Ubl, Theresa Beddig, Vera E. Zamoscik, Ulrich Ebner-Priemer, Iris Reinhard, Peter Kirsch, Christine Kuehner
Journal: Psychotherapy and Psychosomatics (2018)
Glycosylated superparamagnetic nanoparticle gradients for osteochondral tissue engineering
Authors: Chunching Li, James PK. Armstrong, Isaac J. Pence, Worrapong Kit-Anan, Jennifer L. Puetzer, Sara Correia Carreira, Axel C. Moore, Molly M. Stevens
Journal: Biomaterials (2018)

In developmental biology, gradients of bioactive signals direct the formation of structural transitions in tissue that are key to physiological function. Failure to reproduce these native features in an in vitro setting can severely limit the success of bioengineered tissue constructs. In this report, we introduce a facile and rapid platform that uses magnetic field alignment of glycosylated superparamagnetic iron oxide nanoparticles, pre-loaded with growth factors, to pattern biochemical gradients into a range of biomaterial systems. Gradients of bone morphogenetic protein 2 in agarose hydrogels were used to spatially direct the osteogenesis of human mesenchymal stem cells and generate robust osteochondral tissue constructs exhibiting a clear mineral transition from bone to cartilage. Interestingly, the smooth gradients in growth factor concentration gave rise to biologically-relevant, emergent structural features, including a tidemark transition demarcating mineralized and non-mineralized tissue and an osteochondral interface rich in hypertrophic chondrocytes. This platform technology offers great versatility and provides an exciting new opportunity for overcoming a range of interfacial tissue engineering challenges.
Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non–Small Cell Lung Cancer
Authors: Louis Fehrenbacher, Joachim von Pawel, Keunchil Park, Achim Rittmeyer, David R. Gandara, Santiago Ponce Aix, Ji-Youn Han, Shirish M. Gadgeel, Toyoaki Hida, Diego L. Cortinovis, Manuel Cobo, Dariusz M. Kowalski, Filippo De Marinis, Mayank Gandhi, Bradford Danner, Christina Matheny, Marcin Kowanetz, Pei He, Federico Felizzi, Hina Patel, Alan Sandler, Marcus Ballinger, Fabrice Barlesi
Journal: Journal of Thoracic Oncology (2018)
Abstract 12448: Is a Novel Aortic Stiffness Parameter Cardio-ankle Vascular Index Useful Predictor for Exercise Tolerance?
Authors: Toshihiko Goto, Nobuyuki Ohte, Hidekatsu Fukuta, Noriyuki Ikehara, Shyouhei Kikuchi, Kazuaki Wakami, Takafumi Kato, Nobukatsu Akita, Hiroo Sonoda, Genjiro Kimura
Journal: Circulation (2012)

Exercise intolerance is generally considered to be associated with left ventricular (LV) diastolic dysfunction. In addition, increased aortic stiffness has also been known as a restricting factor of exercise capacity. Recently, the cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive parameter of aortic stiffness which is independent of blood pressure. CAVI = a[ρ/ΔP×[ln Ps/Pd] PWV 2 ]+b (a, b, constant; ρ, blood density; ΔP, difference in systolic and diastolic pressure; Ps, systolic pressure; Pd, diastolic pressure; PWV, heart-ankle pulse wave velocity). Accordingly, we examined whether CAVI could detect exercise intolerance in patients with preserved left ventricular ejection fraction (LVEF).   Methods:  Sixty one patients who referred to exercise stress testing for clinical reasons and had preserved LVEF were enrolled (age 68.3±10.4 years; male 67.2%). All patients were evaluated with standardized cardio-pulmonary exercise testing (CPX) including the analysis for oxygen uptake at peak exercise (peak VO 2 ). Before testing, B-type natriuretic peptide (BNP) level was measured and comprehensive Doppler echocardiography was carried out. Early diastolic mitral annular velocity (Ea) was also measured. Aortic stiffness was evaluated using the heart-ankle PWV and CAVI.   Results:  Peak VO 2  significantly and inversely correlated with the PWV (r=-0.41, p=0.001), the CAVI (r=-0.36, p=0.004), and Ea(r=-0.47, p  2  also had significant inverse correlation with age (r=-0.43, p 2 , the PWV (β =-0.40, p 2 . The PWV and CAVI were significantly correlated each other (r=0.78, p   Conclusion:  Increased arterial stiffness was inversely correlated with exercise capacity. Both the PWV and CAVI have significant power to estimate peak VO 2 . Elevated aortic stiffness as well as deteriorated LV relaxation is important to explain exercise intolerance in patients with preserved LVEF.
Association of Statin Use With Overall and Cancer Survival
Authors: Thomas P. Ahern, Signe Borgquist, Deirdre P. Cronin-Fenton
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Over 1500 visa applications from doctors blocked in four months
Authors: Abi Rimmer
Journal: BMJ (2018)

Over 1500 visa applications from doctors wanting to work in the UK were refused over a four month period, figures gathered by the Campaign for Science and Engineering show.1

The results of a freedom of information request sent to the Home Office show that between December 2017 and March 2018 the government refused 1518 applications for certificates of sponsorship for doctors.

Doctors from outside the European Economic Area who apply for …
Abstract 15726: Reduced Lung Function in Adults with Cardiovascular Disease: The Strong Heart Study
Authors: Fawn Yeh, Strong Heart Study
Journal: Circulation (2012)

Objective:  The aim of this study was to test whether reduced lung function is independently associated with cardiovascular disease (CVD) and whether it independently predicts subsequent incident CVD in American Indians (AI), the US population with highest prevalence of obesity.   Methods:  The Strong Heart Study (SHS), a multicenter, population-based study of CVD and its risk factors among AI adults, enrolled 4549 men and women 45-74 years old at the 1 st  examination (SHS1) in 1989 to 1992. The present analysis utilized lung function assessment by standard spirometry at the SHS 2 nd  examination (SHS2,1993-95) in 352 CVD and 2873 non-CVD adults free of overt lung disease (mean age 60 years).   Results:  AI with CVD had significantly lower pulmonary function than non-CVD AI. Differences remained significant after adjustment for age, gender, abdominal obesity, smoking, physical activity index, SHS field center, hypertension, insulin resistance, non-HDL cholesterol, and albuminuria. Significant negative associations were observed between CV abnormalities, insulin resistance, markers of inflammation, renal function, and FVC and FEV1 (P trend     Conclusions:  In this AI population, lower lung function was independently associated with prevalent CVD, and its impairment predicted CVD mortality many years later. Additional research is needed to identify pathophysiologic mechanisms and to determine the clinical significance of this finding.
Management of Bleeding in Patients Taking Oral Anticoagulants
Authors: Irsk Anderson, Adam S. Cifu
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
Association Between Reappearance of Myeloperoxidase–Antineutrophil Cytoplasmic Antibody and Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Haruki Watanabe, Ken‐Ei Sada, Yoshinori Matsumoto, Masayoshi Harigai, Koichi Amano, Hiroaki Dobashi, Shouichi Fujimoto, Joichi Usui, Kunihiro Yamagata, Tatsuya Atsumi, Shogo Banno, Takahiko Sugihara, Yoshihiro Arimura, Seiichi Matsuo, Hirofumi Makino
Journal: Arthritis & Rheumatology (2018)

To evaluate clinical links between levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and relapse in patients with ANCA-associated vasculitis (AAV) using a data set from 2 nationwide prospective cohort studies.From the cohort studies, MPO-ANCA-positive patients who achieved remission during the 6 months after remission induction therapy were enrolled. We measured MPO-ANCA levels at months 0, 3, 6, 12, 18, 24, and at the time of relapse. The primary outcome measure was relapse. A nested case-control analysis and multivariable analysis were performed to investigate the relationship between ANCA reappearance and relapse.Of 271 patients, 183 were classified as having microscopic polyangiitis, 34 as having granulomatosis with polyangiitis, 15 as having eosinophilic granulomatosis with polyangiitis, and 39 were unclassifiable. The median age was 73 years, and 165 (61%) were female. In 195 patients (72%), MPO-ANCA levels decreased to normal levels within 6 months after commencement of treatment, and MPO-ANCA reappeared in 73 of 181 patients (40%) with complete follow-up data. Reappearance of MPO-ANCA was more frequent in patients with relapse than in 75 age- and sex-matched control patients without relapse (odds ratio 26.2 [95% confidence interval 8.2-101], P < 0.0001) after adjustment for confounding factors.Reappearance of MPO-ANCA could be a clinically useful biomarker for predicting relapse in patients with MPO-ANCA-positive AAV in remission. This suggests that routine MPO-ANCA monitoring should be implemented in this patient population.
A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells
Authors: Yoichiro Fujioka, Shinya Nishide, Toyoyuki Ose, Tadaki Suzuki, Izumi Kato, Hideo Fukuhara, Mari Fujioka, Kosui Horiuchi, Aya O. Satoh, Prabha Nepal, Sayaka Kashiwagi, Jing Wang, Mika Horiguchi, Yuko Sato, Sarad Paudel, Asuka Nanbo, Tadaaki Miyazaki, Hideki Hasegawa, Katsumi Maenaka, Yusuke Ohba
Journal: Cell Host & Microbe (2018)
MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding
Authors: Matteo Perino, Guido van Mierlo, Ino D. Karemaker, Siebe van Genesen, Michiel Vermeulen, Hendrik Marks, Simon J. van Heeringen, Gert Jan C. Veenstra
Journal: Nature Genetics (2018)
Incidence of Cellulitis among Children with Primary Lymphedema
Authors: Isabelle Quéré, Nicolas Nagot, Miikka Vikkula
Journal: New England Journal of Medicine (2018)

Cellulitis in Children with Lymphedema The incidence of cellulitis among 128 patients with lymphedema was 4.2 episodes per 100 patient-years. In 29% of the cases, patients had a second episode, and...
Abstract P068: Use of Plastic Food Wrappers High in Phthalates is Associated with Metabolic Syndrome Among Mexican Women
Authors: Jordan Rodriguez, Humberto Gomez, Eduardo Ortiz-Panozo, Elsa Yunes, Martin Lajous, Ruy Lopez-Ridaura
Journal: Circulation (2016)

Introduction: Exposure to phthalates has been associated to metabolic abnormalities and cardiovascular risk. Commonly used plastic food wrappers may contain up to 40% of phthalates and could be an important source of exposure to these chemicals especially when heated. Hypothesis: Use of plastic food wrappers high in phthalates affects metabolic homeostasis. Methods: We assessed the cross-sectional relation of plastic food wrappers use and metabolic syndrome in 188 women from the Mexican Teachers’ Cohort. We evaluated self-reported frequency of use of food wrappers based on 3 questions and categorized participants in tertiles. Fasting blood samples and anthropometry were obtained in a clinical visit to determine metabolic syndrome status. Continuous variables were log-transformed. We used multivariable logistic and linear regression models to estimate odds ratios, mean % change and 95% confidence intervals (CI) for metabolic syndrome and its components using the lowest tertile of exposure as the reference. Results: Mean (±SD) frequency use of total plastic food wrapper was 1.52± 3 times/week and the prevalence of metabolic syndrome was 34%. Use of total plastic food wrappers was associated with metabolic syndrome even after adjusting for diet and other important confounders. The multivariable-adjusted odds ratio (OR) comparing extreme tertiles was 2.61 (95% CI: 1.03, 6.61; ptrend = 0.10). The association appeared to be driven by use of plastic food wrappers that were heated in a microwave oven. We did not observe an independent association with metabolic syndrome components. Conclusions: In this cross-sectional study use of plastic food wrappers, especially when heated in the microwave oven, was associated with the presence of metabolic syndrome. These associations did not appear to be driven by a particular metabolic syndrome component. Longitudinal studies are warranted to confirm this association, ideally with measures of urinary phthalate metabolites to confirm its mediation in the association.
Adjuvant carboplatin, docetaxel, bevacizumab, and erlotinib versus chemotherapy alone in patients with resected non-small cell lung cancer: A randomized phase II study of the Sarah Cannon Research Institute (SCRI).
Authors: David Michael Waterhouse, John D. Hainsworth, Frank A. Greco, Edward K. Barnes, Christopher F. Lobo, Victor Gian, Mathew John Joseph, James D. Peyton, Sang Y. Huh, Davey B. Daniel, Raven Quinn, Howard A. Burris, David R. Spigel
Journal: Journal of Clinical Oncology (2012)

7035 Background: Adjuvant chemotherapy improves overall survival (OS) in patients (pts) with resected non small cell lung cancer (NSCLC). Bevacizumab and erlotinib improve survival in pts with advanced unresectable NSCLC. This randomized phase II multicenter pilot study examined the safety and efficacy of chemotherapy and bevacizumab followed by bevacizumab and erlotinib vs. chemotherapy alone in pts with resected NSCLC. Methods: Eligible pts had completely resected (R0) stage IB, II, or IIIA NSCLC (TNM 6 th Ed.), any NSCLC histology, and an ECOG PS 0-1. Pts were excluded for preoperatively confirmed N2 disease; N2 disease found at surgery was allowed. Pts were randomized 1:1 to carboplatin AUC=5, docetaxel 60 mg/m 2 , and bevacizumab 15 mg/kg IV d1 q 21 days x 4, followed by maintenance bevacizumab 15 mg/kg d1 and erlotinib 150 mg PO daily x 8 cycles (Arm A) or carboplatin AUC=6 and docetaxel 75 mg/m 2 IV d1 q 21 days x 4 (Arm B). The primary endpoint was 1-year disease-free survival (DFS); safety, 2-year DFS, and OS were secondary endpoints. Results: 106 pts were enrolled from 2/2008 to trial closure 1/2012 (A=54; B=52). Baseline features were balanced: age 63 yrs (42–87); 54% male; IB (46%), IIA (8%), IIB (27%), IIIA (18%); adenocarcinoma (61%), squamous (31%). Arm A received a median of 7 cycles (1-12); Arm B 4 cycles (1-4). 1- and 2-year DFS by stage are shown in the table. The 1-year DFS for all stages were 78% (A) and 88% (B) (p=.66). The 3-year OS for all stages were 81% (A) and 63% (B). Neutropenia was the most common grade 3/4 hematologic toxicity (A 18%; B 29%). Severe non-hematologic toxicity was rare: fatigue (A 6%), diarrhea (B 6%). Bronchopleural fistulae occurred in 2 pts (1 per arm), and grade 3 gastrointestinal hemorrhage was seen in 1 pt (A). Conclusions: This pilot study demonstrated that bevacizumab and erlotinib could be safely added to platinum-doublet chemotherapy in the adjuvant setting in all histologies. Larger randomized studies will best define the roles of these agents in pts with resectable NSCLC. [Table: see text]
Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor Guadecitabine (SGI‐110) in Hepatocellular Carcinoma
Authors: Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El‐Khoueiry, John Daniels, Casey O'Connell, Tanya B. Dorff, Qianjin Lu, Daniel J. Weisenberger, Gangning Liang
Journal: Hepatology (2018)

There is an urgent need to develop more effective therapies for hepatocellular carcinoma (HCC) because of its aggressiveness. Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi), which is currently in clinical trials for HCC and shows greater stability and performance over first-generation DNMTis. In order to identify potential therapeutic targets of SGI-110 for clinical trials, HCC cell lines (SNU398, HepG2, and SNU475) were used to evaluate the effects of transient SGI-110 treatment by an integrative analysis of DNA methylation, nucleosome accessibility, gene expression profiles, and its clinical relevance by comparison to The Cancer Genome Atlas (TCGA) HCC clinical data. Each HCC cell line represents a different DNA methylation subtype of primary HCC tumors based on TCGA data. After SGI-110 treatment, all cell lines were sensitive to SGI-110 with prolonged antiproliferation effects. Expression of up-regulated genes, including tumor suppressors, was positively correlated with nucleosome accessibility and negatively correlated with gene promoter DNA methylation. Alternatively, expression of down-regulated genes, such as oncogenes, was negatively correlated with nucleosome accessibility and positively correlated with gene body DNA methylation. SGI-110 can also act as a dual inhibitor to down-regulate polycomb repressive complex 2 (PRC2) genes by demethylating their gene bodies, resulting in reactivation of PRC2 repressed genes without involvement of DNA methylation. Furthermore, it can up-regulate endogenous retroviruses to reactivate immune pathways. Finally, about 48% of frequently altered genes in primary HCC tumors can be reversed by SGI-110 treatment.Our integrative analysis has successfully linked the antitumor effects of SGI-110 to detailed epigenetic alterations in HCC cells, identified potential therapeutic targets, and provided a rationale for combination treatments of SGI-110 with immune checkpoint therapies.
Chinese expert consensus on programming deep brain stimulation for patients with Parkinson’s disease
Authors: Shengdi Chen, Guodong Gao, Tao Feng, Jianguo Zhang
Journal: Translational Neurodegeneration (2018)

Deep Brain Stimulation (DBS) therapy for the treatment of Parkinson's Disease (PD) is now a well-established option for some patients. Postoperative standardized programming processes can improve the level of postoperative management and programming, relieve symptoms and improve quality of life.In order to improve the quality of the programming, the experts on DBS and PD in neurology and neurosurgery in China reviewed the relevant literatures and combined their own experiences and developed this expert consensus on the programming of deep brain stimulation in patients with PD in China.This Chinese expert consensus on postoperative programming can standardize and improve postoperative management and programming of DBS for PD.