tbuckley/cabot-search huggingface dataset:
SIRT6 as a key event linking P53 and NRF2 counteracts APAP-induced hepatotoxicity through inhibiting oxidative stress and promoting hepatocyte proliferation
Authors: Yanying Zhou, Xiaomei Fan, Tingying Jiao, Wenzhou Li, Panpan Chen, Yiming Jiang, Jiahong Sun, Yixin Chen, Pan Chen, Lihuan Guan, Yajie Wen, Min Huang, Huichang Bi
Journal: Acta Pharmaceutica Sinica B (2020)

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively. Sirt6 knockdown in AML12 cells aggravated APAP-induced hepatocyte death and oxidative stress, inhibited cell viability and proliferation, and downregulated CCNA1, CCND1 and CKD4 protein levels. Sirt6 knockdown significantly prevented APAP-induced NRF2 activation, reduced the transcriptional activities of GSTμ and NQO1 and the mRNA levels of Nrf2, Ho-1, Gstα and Gstμ. Furthermore, SIRT6 showed potential protein interaction with NRF2 as evidenced by co-immunoprecipitation (Co-IP) assay. Additionally, the protective effect of P53 against APAP-induced hepatocytes injury was Sirt6-dependent. The Sirt6 mRNA was significantly down-regulated in P53−/− mice. P53 activated the transcriptional activity of SIRT6 and exerted interaction with SIRT6. Our results demonstrate that SIRT6 protects against APAP hepatotoxicity through alleviating oxidative stress and promoting hepatocyte proliferation, and provide new insights in the function of SIRT6 as a crucial docking molecule linking P53 and NRF2.
Quantitative analysis of pulmonary vasculature in systemic sclerosis at spirometry-gated chest CT
Authors: Mariaelena Occhipinti, Cosimo Bruni, Gianna Camiciottoli, Maurizio Bartolucci, Silvia Bellando-Randone, Anna Bassetto, Giovanna Cuomo, Dilia Giuggioli, Giulia Ciardi, Alessio Fabbrizzi, Sara Tomassetti, Federico Lavorini, Massimo Pistolesi, Stefano Colagrande, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2020)

Objective To prospectively investigate whether differences in pulmonary vasculature exist in systemic sclerosis (SSc) and how they are distributed in patients with different pulmonary function. Methods Seventy-four patients with SSc undergoing chest CT scan for interstitial lung disease (ILD) screening or follow-up were prospectively enrolled. A thorough clinical, laboratory and functional evaluation was performed the same day. Chest CT was spirometry gated at total lung capacity and images were analysed by two automated software programs to quantify emphysema, ILD patterns (ground-glass, reticular, honeycombing), and pulmonary vascular volume (PVV). Patients were divided in restricted (FVC% &lt;80, DLco%&lt;80), isolated DLco% reduction (iDLco- FVC%≥80, DLco%&lt;80) and normals (FVC%≥80, DLco%≥80). Spearman ρ, Mann-Whitney tests and logistic regressions were used to assess for correlations, differences among groups and relationships between continuous variables. Results Absolute and lung volume normalised PVV (PVV/LV) correlated inversely with functional parameters and positively with all ILD patterns (ρ=0.75 with ground glass, ρ=0.68 with reticular). PVV/LV was the only predictor of DLco at multivariate analysis (p=0.007). Meanwhile, the reticular pattern prevailed in peripheral regions and lower lung thirds, PVV/LV prevailed in central regions and middle lung thirds. iDLco group had a significantly higher PVV/LV (2.2%) than normal (1.6%), but lower than restricted ones (3.8%). Conclusions Chest CT in SSc detects a progressive increase in PVV/LV as DLco decreases. Redistribution of perfusion to less affected lung regions rather than angiogenesis nearby fibrotic lung may explain the results. Further studies to ascertain whether the increase in PVV/LV reflects a real increase in blood volume are needed.
Statins for Primary Prevention in the Elderly
Authors: Stephen J. Nicholls, Adam J. Nelson
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Chest Pain With ST-Segment Elevation
Authors: Dinkar Bhasin, Praveen Gupta, Anunay Gupta
Journal: Circulation (2020)

ECG CHALLENGEA 52-year-old man presented to our emergency department with precordial chest discomfort of 4 hours' duration.The patient had been evaluated in another hospital and was presumed to have an acute coronary syndrome.He was referred to our center for primary percutaneous coronary intervention.The patient had no cardiovascular risk factors but complained of episodic palpitations in the past.The patient's vitals were stable, and the cardiovascular examination was unremarkable.The 12-lead ECG at presentation is shown in Figure 1.What is the diagnosis?How will you manage this patient?Should this patient undergo a coronary angiogram?Please turn the page to read the diagnosis.
Abstract IA23: Therapeutic approaches for ARID1A-mutated ovarian cancer
Authors: Rugang Zhang
Journal: Clinical Cancer Research (2020)

Abstract Ovarian cancer remains the most lethal gynecologic malignancy in the developed world. Despite the unprecedented progress in understanding the genetics of ovarian cancer, cures remain elusive due to a lack of insight into the mechanisms that can be targeted to develop new therapies. SWI/SNF chromatin remodeling complexes are genetically altered in ~20% of all human cancers. SWI/SNF alterations vary in different histologic subtypes of ovarian cancer, with ARID1A mutation occurring in ~50% of ovarian clear-cell carcinomas. Given the prevalence of ARID1A mutation, ovarian cancer represents a paradigm for investigating the molecular basis and exploring therapeutic strategies for SWI/SNF alterations. The presentation will discuss our recent efforts in understanding SWI/SNF alterations in ovarian cancer and specifically focuses on ARID1A mutation in endometriosis-associated clear cell and endometrioid histologic subtypes of ovarian cancer. Understanding the molecular underpinning of ARID1A mutation in ovarian cancer will provide mechanistic insights into how ARID1A inactivation contributes to ovarian cancer. In addition, how these newly gained insights can be leveraged to develop urgently needed therapeutic strategies in a personalized manner for ovarian cancer will be discussed. Citation Format: Rugang Zhang. Therapeutic approaches for ARID1A-mutated ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA23.
Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta
Authors: Dominique Roulot, Ségolène Brichler, Richard Layese, Zahia BenAbdesselam, Fabien Zoulim, Vincent Thibault, Caroline Scholtes, Bruno Roche, Corinne Castelnau, Thierry Poynard, Olivier Chazouillères, Nathalie Ganne, Hélène Fontaine, Jerome Gournay, Dominique Guyader, Frédéric Le Gal, Pierre Nahon, Françoise Roudot-Thoraval, Emmanuel Gordien, Jean-Didier Grangé, Roland Landman, Christophe Hezode, Ghassan Riachi, Caroline Lascoux-Combe, Véronique Loustaud-Ratti, Isabelle Rosa, Philippe Mathurin, Eric Nguyen-Khac, Xavier Causse, Sylvie Naveau, François Habersetzer, Sophie Metivier, Hélène Labadie, Pierre Sellier, Julie Bottero, Victor de Ledinghen, Laurent Alric, Paul Calès, Cecile Goujard, Jean-François Cadranel, Dominique Salmon, Sophie Hillaire
Journal: Journal of Hepatology (2020)
Discovery of hemocompatible bacterial biofilm-resistant copolymers
Authors: Taranjit Singh, Andrew L. Hook, Jeni Luckett, Manfred F. Maitz, Claudia Sperling, Carsten Werner, Martyn C. Davies, Derek J. Irvine, Paul Williams, Morgan R. Alexander
Journal: Biomaterials (2020)

Blood-contacting medical devices play an important role within healthcare and are required to be biocompatible, hemocompatible and resistant to microbial colonization. Here we describe a high throughput screen for copolymers with these specific properties. A series of weakly amphiphilic monomers are combinatorially polymerized with acrylate glycol monomers of varying chain lengths to create a library of 645 multi-functional candidate materials containing multiple chemical moieties that impart anti-biofilm, hemo- and immuno-compatible properties. These materials are screened in over 15,000 individual biological assays, targeting two bacterial species, one Gram negative (Pseudomonas aeruginosa) and one Gram positive (Staphylococcus aureus) commonly associated with central venous catheter infections, using 5 different measures of hemocompatibility and 6 measures of immunocompatibililty. Selected copolymers reduce platelet activation, platelet loss and leukocyte activation compared with the standard comparator PTFE as well as reducing bacterial biofilm formation in vitro by more than 82% compared with silicone. Poly(isobornyl acrylate-co-triethylene glycol methacrylate) (75:25) is identified as the optimal material across all these measures reducing P. aeruginosa biofilm formation by up to 86% in vivo in a murine foreign body infection model compared with uncoated silicone.
The effect of food taxes and subsidies on population health and health costs: a modelling study
Authors: Tony Blakely, Christine Cleghorn, Anja Mizdrak, Wilma Waterlander, Nhung Nghiem, Boyd Swinburn, Nick Wilson, Cliona Ni Mhurchu
Journal: The Lancet Public Health (2020)

BackgroundOne possible policy response to the burden of diet-related disease is food taxes and subsidies, but the net health gains of these approaches are uncertain because of substitution effects between foods. We estimated the health and cost impacts of various food taxes and subsidies in one high-income country, New Zealand.MethodsIn this modelling study, we compared the effects in New Zealand of a 20% fruit and vegetable subsidy, of saturated fat, sugar and salt taxes (each set at a level that increased the total food price by the same magnitude of decrease from the fruit and vegetable subsidy), and of an 8% so-called junk food tax (on non-essential, energy-dense food). We modelled the effect of price changes on food purchases, the consequent changes in fruit and vegetable and sugar-sweetened beverage purchasing, nutrient risk factors, and body-mass index, and how these changes affect health status and health expenditure. The pre-intervention intake for 340 food groups was taken from the New Zealand National Nutrition Survey and the post-intervention intake was estimated using price and expenditure elasticities. The resultant changes in dietary risk factors were then propagated through a proportional multistate lifetable (with 17 diet-related diseases) to estimate the changes in health-adjusted life years (HALYs) and health system expenditure over the 2011 New Zealand population's remaining lifespan.FindingsHealth gains (expressed in HALYs per 1000 people) ranged from 127 (95% uncertainty interval 96–167; undiscounted) for the 8% junk food tax and 212 (102–297) for the fruit and vegetable subsidy, up to 361 (275–474) for the saturated fat tax, 375 (272–508) for the salt tax, and 581 (429–792) for the sugar tax. Health expenditure savings across the remaining lifespan per capita (at a 3% discount rate) ranged from US$492 (334–694) for the junk food tax to $2164 (1472–3122) for the sugar tax.InterpretationThe large magnitude of the health gains and cost savings of these modelled taxes and subsidies suggests that their use warrants serious policy consideration.FundingHealth Research Council of New Zealand.
Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure
Authors: Jean-Philippe Brandel, M Bustuchina Vlaicu, Audrey Culeux, Maxime Belondrade, Daisy Bougard, Katarina Grznarova, Angeline Denouel, Isabelle Plu, Elodie Bouaziz-Amar, Danielle Seilhean, Michèle Levasseur, Stéphane Haïk
Journal: New England Journal of Medicine (2020)

Variant CJD in a Laboratory Technician Variant Creutzfeldt–Jakob disease was identified in a technician who had cut her thumb while handling brain sections of mice infected with adapted BSE 7.5 yea...
68Ga-DOTATOC PET for Treatment Efficacy Evaluation of Cardiac Sarcoidosis
Authors: Alessio Imperiale, Vincent Poindron, Matias Martinez, Patrick Ohlmann, Thomas H. Schindler, Soraya El Ghannudi
Journal: Clinical Nuclear Medicine (2020)

Abstract Cardiac sarcoidosis (CS) has a poor prognosis related to life-threating arrhythmias and heart failure. Treatment includes anti-inflammatory therapies and implantable pacemaker and/or cardioverter defibrillator. The presence of cardiac devices and physiologic myocardial glucose uptake are major limitations of both cardiac magnetic resonance and 18 F-FDG PET/CT, reducing their diagnostic value. Somatostatin-based PET/CT has been proposed to detect active CS. Contrarily to 18 F-FDG uptake, which reflects nonspecific leukocyte infiltration, 68 Ga-DOTATOC may identify active granulomatosis. Herein, we underline the specificity of 68 Ga-DOTATOC PET in challeging clinical situations including refractory CS, and chronic CS in patients with cardiac device, or false-positive 18 F-FDG PET/CT results.
Characterization of the Cancer Spectrum in Men With Germline<i>BRCA1</i>and<i>BRCA2</i>Pathogenic Variants
Authors: Valentina Silvestri, Goska Leslie, Daniel R. Barnes, Bjarni A. Agnarsson, Kristiina Aittomäki, Elisa Alducci, Irene L. Andrulis, Rosa B. Barkardottir, Alicia Barroso, Daniel Barrowdale, Javier Benitez, Bernardo Bonanni, Ake Borg, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Carlo Capalbo, Ian Campbell, Wendy K. Chung, Kathleen B.M. Claes, Sarah V. Colonna, Laura Cortesi, Fergus J. Couch, Miguel de la Hoya, Orland Diez, Yuan Chun Ding, Susan Domchek, Douglas F. Easton, Bent Ejlertsen, Christoph Engel, D. Gareth Evans, Lidia Feliubadalò, Lenka Foretova, Florentia Fostira, Lajos Géczi, Anne-Marie Gerdes, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Eric Hahnen, Frans B.L. Hogervorst, John L. Hopper, Peter J. Hulick, Claudine Isaacs, Angel Izquierdo, Paul A. James, Ramunas Janavicius, Uffe Birk Jensen, Esther M. John, Vijai Joseph, Irene Konstantopoulou, Allison W. Kurian, Ava Kwong, Elisabetta Landucci, Fabienne Lesueur, Jennifer T. Loud, Eva Machackova, Phuong L. Mai, Keivan Majidzadeh-A, Siranoush Manoukian, Marco Montagna, Lidia Moserle, Anna Marie Mulligan, Katherine L. Nathanson, Heli Nevanlinna, Joanne Ngeow Yuen Ye, Liene Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Laura Papi, Sue K. Park, Inge Sokilde Pedersen, Pedro Perez-Segura, Annabeth H. Petersen, Pedro Pinto, Berardino Porfirio, Miquel Angel Pujana, Paolo Radice, Johanna Rantala, Muhammad U. Rashid, Barak Rosenzweig, Maria Rossing, Marta Santamariña, Rita K. Schmutzler, Leigha Senter, Jacques Simard, Christian F. Singer, Angela R. Solano, Melissa C. Southey, Linda Steele, Zoe Steinsnyder, Dominique Stoppa-Lyonnet, Yen Yen Tan, Manuel R. Teixeira, Soo H. Teo, Mary Beth Terry, Mads Thomassen, Amanda E. Toland, Sara Torres-Esquius, Nadine Tung, Christi J. van Asperen, Ana Vega, Alessandra Viel, Jeroen Vierstraete, Barbara Wappenschmidt, Jeffrey N. Weitzel, Greet Wieme, Sook-Yee Yoon, Kristin K. Zorn, Lesley McGuffog, Michael T. Parsons, Ute Hamann, Mark H. Greene, Judy A. Kirk, Susan L. Neuhausen, Timothy R. Rebbeck, Marc Tischkowitz, Georgia Chenevix-Trench, Antonis C. Antoniou, Eitan Friedman, Laura Ottini
Journal: JAMA Oncology (2020)

The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population.
Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline
Authors: Charles L. Daley, Jonathan M. Iaccarino, Christoph Lange, Emmanuelle Cambau, Richard J. Wallace, Claire Andrejak, Erik C. Böttger, Jan Brozek, David E. Griffith, Lorenzo Guglielmetti, Gwen A. Huitt, Shandra L. Knight, Philip Leitman, Theodore K. Marras, Kenneth N. Olivier, Miguel Santin, Jason E. Stout, Enrico Tortoli, Jakko van Ingen, Dirk Wagner, Kevin L. Winthrop
Journal: European Respiratory Journal (2020)

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii , and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
Mesenchymal stromal cells and their secreted extracellular vesicles as therapeutic tools for COVID-19 pneumonia?
Authors: Maurizio Muraca, Augusto Pessina, Michela Pozzobon, Massimo Dominici, Umberto Galderisi, Lorenza Lazzari, Ornella Parolini, Enrico Lucarelli, Giorgio Perilongo, Eugenio Baraldi
Journal: Journal of Controlled Release (2020)
From Rare Copy Number Variants to Biological Processes in ADHD
Authors: Benjamin Harich, Monique van der Voet, Marieke Klein, Pavel Čížek, Michaela Fenckova, Annette Schenck, Barbara Franke
Journal: American Journal of Psychiatry (2020)

Objective: Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric disorder. The objective of this study was to define ADHD-associated candidate genes and their associated molecular modules and biological themes, based on the analysis of rare genetic variants. Methods: The authors combined data from 11 published copy number variation studies in 6,176 individuals with ADHD and 25,026 control subjects and prioritized genes by applying an integrative strategy based on criteria including recurrence in individuals with ADHD, absence in control subjects, complete coverage in copy number gains, and presence in the minimal region common to overlapping copy number variants (CNVs), as well as on protein-protein interactions and information from cross-species genotype-phenotype annotation. Results: The authors localized 2,241 eligible genes in the 1,532 reported CNVs, of which they classified 432 as high-priority ADHD candidate genes. The high-priority ADHD candidate genes were significantly coexpressed in the brain. A network of 66 genes was supported by ADHD-relevant phenotypes in the cross-species database. Four significantly interconnected protein modules were found among the high-priority ADHD genes. A total of 26 genes were observed across all applied bioinformatic methods. Lookup in the latest genome-wide association study for ADHD showed that among those 26 genes, POLR3C and RBFOX1 were also supported by common genetic variants. Conclusions: Integration of a stringent filtering procedure in CNV studies with suitable bioinformatics approaches can identify ADHD candidate genes at increased levels of credibility. The authors’ analytic pipeline provides additional insight into the molecular mechanisms underlying ADHD and allows prioritization of genes for functional validation in validated model organisms.
Head Circumference as a Measure of In Utero Zika Virus Exposure and Outcomes
Authors: Sarah B. Mulkey
Journal: JAMA Network Open (2020)

Jessica S. Cranston, BS; Sophia Finn Tiene, BS; Karin Nielsen-Saines, MD, MPH; Zilton Vasconcelos, PhD; Marcos V. Pone, MD; Sheila Pone, MD; Andrea Zin, MD, PhD; Tania Saad Salles, MD; Jose Paulo Pereira Jr, MD, PhD; Dulce Orofino, MD, PhD; Patricia Brasil, MD, PhD; Tara Kerin, PhD; Kristina Adachi, MD; Fernanda Mendes Soares, PhD; Andrea Dunshee de Abranches, PhD; Ana Carolina C. da Costa, PhD; Maria Elisabeth Lopes Moreira, MD, PhD