tbuckley/cabot-search huggingface dataset:
BRD4 and Cancer: going beyond transcriptional regulation
Authors: Benedetta Donati, Eugenia Lorenzini, Alessia Ciarrocchi
Journal: Molecular Cancer (2018)

BRD4, member of the Bromodomain and Extraterminal (BET) protein family, is largely acknowledged in cancer for its role in super-enhancers (SEs) organization and oncogenes expression regulation. Inhibition of BRD4 shortcuts the communication between SEs and target promoters with a subsequent cell-specific repression of oncogenes to which cancer cells are addicted and cell death. To date, this is the most credited mechanism of action of BET inhibitors, a class of small molecules targeting BET proteins which are currently in clinical trials in several cancer settings. However, recent evidence indicates that BRD4 relevance in cancer goes beyond its role in transcription regulation and identifies this protein as a keeper of genome stability. Indeed, a non-transcriptional role of BRD4 in controlling DNA damage checkpoint activation and repair as well as telomere maintenance has been proposed, throwing new lights into the multiple functions of this protein and opening new perspectives on the use of BETi in cancer. Here we discuss the current available information on non-canonical, non-transcriptional functions of BRD4 and on their implications in cancer biology. Integrating this information with the already known BRD4 role in gene expression regulation, we propose a "common" model to explain BRD4 genomic function. Furthermore, in light of the transversal function of BRD4, we provide new interpretation for the cytotoxic activity of BETi and we discuss new possibilities for a wide and focused employment of these drugs in clinical settings.
The bacterial siderophore enterobactin confers survival advantage to <i>Salmonella</i> in macrophages
Authors: Piu Saha, Xia Xiao, Beng San Yeoh, Qiuyan Chen, Bhuvana Katkere, Girish Soorappa Kirimanjeswara, Matam Vijay-Kumar
Journal: Gut Microbes (2018)

Enterobactin (Ent), a prototypical bacterial siderophore known for its unparalleled affinity for iron, is widely conserved among members of the
Abstract 006: Role of Providers in Implementation of Blood Pressure Control Strategies in Patients with Hypertension
Authors: Katherine T Mills, Katherine M Obst, Wei Shen, Sandra Molina, Hui-Jie Zhang, Hua He, Jiang He
Journal: Circulation (2018)

Introduction: Globally, only 13.8% of hypertensive patients have their blood pressure (BP) controlled. Trials testing implementation strategies to overcome barriers to BP control have produced mixed results. Providers who deliver the intervention may play an important role in implementation strategy success. This meta-analysis aimed to determine which provider-led interventions are most effective for BP reduction. Methods: We searched Medline and Embase (through September 2017) for randomized controlled trials of various provider-led implementation strategies targeting barriers to hypertension control in hypertensive patients. Seventy-four trials with 22,180 hypertensive participants met our eligibility criteria and were included in this analysis. These trials were grouped by intervention provider, and the effects of the intervention on BP change were combined using random effects models. Results: Pharmacist-led health coaching and team-based care had the greatest reduction in systolic and diastolic BP. Nurse- and community health worker-led interventions also resulted in significant reductions in BP. Interventions led by multiple providers were less effective for BP reduction. Research staff-led interventions were also effective at reducing BP but questions of sustainability persist. Conclusions: Pharmacists are most effective for the delivery of implementation strategies for BP control among patients with hypertension. Nurse- and community health worker-led interventions were also effective for BP reduction. Pharmacist-, nurse- and community health worker-led interventions should be prioritized in future BP control efforts.
Association of Prenatal Exposures of Polybrominated Diphenyl Ethers With Hypospadias
Authors: Shanxi A. Jen, Nicole Quah Qin Xian, Wan Wei Ang
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Bladder Preservation With Twice-a-Day Radiation Plus Fluorouracil/Cisplatin or Once Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer: NRG/RTOG 0712—A Randomized Phase II Trial
Authors: John J. Coen, Peixin Zhang, Philip J. Saylor, Cheryl T. Lee, Chin-Lee Wu, William Parker, Timothy Lautenschlaeger, Anthony L. Zietman, Jason A. Efstathiou, Ashesh B. Jani, Omer Kucuk, Luis Souhami, Joseph P. Rodgers, Howard M. Sandler, William U. Shipley
Journal: Journal of Clinical Oncology (2018)

Purpose Fluorouracil plus cisplatin and radiation twice a day (FCT) is an established chemoradiation (CRT) regimen for selective bladder-sparing treatment of muscle-invasive bladder cancer. Gemcitabine and once daily radiation (GD) is a well-supported alternative. The current trial evaluates these regimens. Methods Patients with cT2-4a muscle-invasive bladder cancer were randomly assigned to FCT or GD. Patients underwent transurethral resection and induction CRT to 40 Gy. Patients who achieved a complete response (CR) received consolidation CRT to 64 Gy and others underwent cystectomy. We administered adjuvant gemcitabine/cisplatin chemotherapy. The primary end point was the rate of freedom from distant metastasis at 3 years (DMF3). The trial was not statistically powered to compare regimens, but to assess whether either regimen exceeded a DMF3 benchmark of 75%. Toxicity and efficacy end points, including CR and bladder-intact distant metastasis free survival at 3 years (BI-DMFS3), were assessed. Results From December 2008 to April 2014, 70 patients were enrolled, of which 66 were eligible for analysis, 33 per arm. Median follow-up was 5.1 years (range, 0.4 to 7.8 years) for eligible living patients. DMF3 was 78% and 84% for FCT and GD, respectively. BI-DMFS3 was 67% and 72%, respectively. Postinduction CR rates were 88% and 78%, respectively. Of 33 patients in the FCT arm, 21 (64%) experienced treatment-related grade 3 and 4 toxicities during protocol treatment, with 18 (55%), two (6%), and two patients (6%) experiencing grade 3 and 4 hematologic, GI, and genitourinary toxicity, respectively. For the 33 patients in the GD arm, these figures were 18 (55%) overall and 14 (42%), three (9%) and two patients (6%), respectively. Conclusion Both regimens demonstrated DMF3 greater than 75%. There were fewer toxicities observed in the GD arm. Either gemcitabine and once daily radiation or a cisplatin-based regimen could serve as a base for future trials of systemic therapy.
Association Between Obesity and Cardiovascular Outcomes
Authors: Haris Riaz, Muhammad Shahzeb Khan, Tariq Jamal Siddiqi, Muhammad Shariq Usman, Nishant Shah, Amit Goyal, Sadiya S. Khan, Farouk Mookadam, Richard A. Krasuski, Haitham Ahmed
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Although dyslipidemia has been consistently shown to be associated with atherogenesis, an association between obesity and cardiovascular disease outcomes remains controversial. Mendelian randomization can minimize confounding if variables are randomly and equally distributed in the population of interest. <h3>Objective</h3> To assess evidence from mendelian randomization studies to provide a less biased estimate of any association between obesity and cardiovascular outcomes. <h3>Data Sources</h3> Systematic searches of MEDLINE and Scopus from database inception until January 2018, supplemented with manual searches of the included reference lists. <h3>Study Selection</h3> Studies that used mendelian randomization methods to assess the association between any measure of obesity and the incidence of cardiovascular events and those that reported odds ratios (ORs) with 95% CIs estimated using an instrumental variable method were included. The 5 studies included in the final analysis were based on a consensus among 3 authors. <h3>Data Extraction and Synthesis</h3> Two investigators independently extracted study characteristics using a standard form and pooled data using a random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. <h3>Main Outcomes and Measures</h3> Obesity associated with type 2 diabetes, coronary artery disease, or stroke. The hypothesis was formulated prior to data collection. <h3>Results</h3> Of 4660 potentially relevant articles, 2511 titles were screened. Seven studies were included in the systematic review, and 5 studies with 881 692 participants were eligible to be included in the meta-analysis. Pooled estimates revealed that obesity was significantly associated with an increased risk of type 2 diabetes (OR, 1.67; 95% CI, 1.30-2.14;<i>P</i> &lt; .001;<i>I</i><sup>2</sup> = 93%) and coronary artery disease (OR, 1.20; 95% CI, 1.02-1.41;<i>P</i> = .03;<i>I</i><sup>2</sup> = 87%). No association between obesity and stroke was found (OR, 1.02; 95% CI, 0.95-1.09;<i>P</i> = .65;<i>I</i><sup>2</sup> = 0%). <h3>Conclusions and Relevance</h3> The present meta-analysis suggests that obesity is associated with type 2 diabetes and coronary artery disease. Although this analysis of mendelian randomization studies does not prove causality, it is supportive of a causal association. Hence, health care practitioners should continue to emphasize weight reduction to combat coronary artery disease.
Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide
Authors: Angela L. Nocera, Sarina K. Mueller, Jules R. Stephan, Loretta Hing, Philip Seifert, Xue Han, Derrick T. Lin, Mansoor M. Amiji, Towia Libermann, Benjamin S. Bleier
Journal: Journal of Allergy and Clinical Immunology (2018)
Renal Denervation Prevents Heart Failure Progression Via Inhibition of the Renin-Angiotensin System
Authors: Thomas E. Sharp, David J. Polhemus, Zhen Li, Pablo Spaletra, J. Stephen Jenkins, John P. Reilly, Christopher J. White, Daniel R. Kapusta, David J. Lefer, Traci T. Goodchild
Journal: Journal of the American College of Cardiology (2018)
Government must guarantee EU doctors’ rights after Brexit, says BMA
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The BMA has urged the government to formally guarantee the rights of European citizens in the event of the UK leaving the EU without an agreement next March, after a poll of doctors from other European countries working in the UK showed that more than a third were considering leaving the UK.

A BMA survey of more than 1500 UK based doctors from other European Economic Area countries showed that only 22% were convinced by the prime minister’s verbal commitment to protect the rights of European citizens if a no-deal Brexit occurred. More than a third (35%) said that they were considering moving abroad, although 66% said that they were committed to working in the UK. …
EP2 prostanoid receptor promotes A431 cell growth and invasion by iNOS and ERK1-2 pathways
Authors: Sandra Donnini, Federica Finetti, Raffaella Solito, Lucia Morbidelli, Erika Terzuoli, Marina Ziche
Journal: Cancer Research (2006)

3484  The levels of nitric oxide (NO) derived from inducible NO synthase (iNOS) and prostaglandin E2 (PGE2) derived from cyclooxygenase-2 (COX-2) correlate with tumor growth, metastasis and angiogenesis. The present study examined the role of iNOS signalling pathway in PGE2-mediated tumor invasiveness and proliferation in A431 cells. Cell invasion and proliferation promoted by PGE2 were completely blocked by iNOS specific silencing RNA (siiNOS) or iNOS-guanylate cyclase (GC) pharmacological inhibition. Consistently, iNOS-GC pathway inhibition also blocked mitogen activated protein kinase-extracellular receptor kinase1-2 (MAPK-ERK1-2) phosphorylation, which was required to mediate PGE2 functions. PGE2 effects were confined to the selective activation of the EP2 receptor subtype. Indeed, EP2-mediated MAPK ERK1-2 activation and cell invasion and proliferation were abolished by the PKA inhibitor H89, as well as by silencing iNOS or by pharmacological inhibiting iNOS-GC pathway. Together, these results indicate that in A431 tumor cell line, PGE2 mediates ERK1-2 phosphorylation, cell growth and invasion through EGFR transactivation via PKA activity and activation of iNOS/GC pathway. Funded by the Italian Ministry for Research (FIRB project n. RBNE01A882_002; MIUR, FIRB project n. RBNE01M9HS_002 and PRIN project n. 2004065317_001), EU project EICOSANOX, NuGO (FOOD-CT-2004-506360) and Fondazione Callerio (Trieste, Italy).
Over-gap PCR amplification to identify presence of replication-competent HBV DNA from integrated HBV DNA: An updated occult HBV infection definition
Authors: Yongzhen Liu, Wanjia Zeng, Jingyuan Xi, Hui Liu, Hao Liao, Guangxin Yu, Xiangmei Chen, Fengmin Lu
Journal: Journal of Hepatology (2018)
OP0075 Ultrasound-detected shoulder pathologies cluster into groups with different clinical associations: data from a prospective study of 500 community referrals for shoulder pain
Authors: G. Tran, E. Hensor, P. O’Connor, S. Kingsbury, P. Conaghan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Shoulder pain is common and its management remains challenging, often resulting in poor outcomes: 50% of people continue to have shoulder pain at 18 months. This may be in part due to inaccurate clinical diagnosis. Ultrasound offers accurate detection of pathology and its use is increasing. However, the relationship between ultrasound findings and clinical phenotype is unclear. <h3>Objectives</h3> A prospective study was undertaken to explore latent class groupings and explore the association between patient reported outcome measures and the different groups. <h3>Methods</h3> 500 primary care patients attending for shoulder ultrasound were prospectively recruited. Radiologists and sonographers underwent training to ensure standardised reporting. Baseline data was collected via self-reported questionnaires. Outcome measures collected included pain, function, quality of life, treatments received, activity, self-efficacy and levels of acceptable symptom states. These measures underwent Rasch analysis. Latent class analysis was undertaken to identify groups. <h3>Results</h3> Mean age was 53.6% and 52% were female. Latent class analysis confirmed the existence of 4 groups: limited bursitis; extensive inflammation; RC tears; limited pathology. The oldest age group were those with RC tears, and the youngest was those with limited bursitis. The rotator cuff tear group had the highest levels of pain and disability, and the lowest levels of acceptable symptom states. Those with limited pathology had the highest levels of acceptable symptom states. The extensive inflammation group had the lowest activity scores. Summary statistics for classes obtained prior to covariate adjustment (complete data only) <h3>Conclusions</h3> This study confirms that ultrasound pathologies cluster into groups. These groups appear to differ in symptom associations at baseline; expanding the LCA to include covariates will allow us to formally explore these associations. A longitudinal study will provide understanding of the relevance of these groups to long-term patient outcomes. <h3>Disclosure of Interest</h3> None declared
Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases
Authors: Valerio De Stefano, Elena Rossi, Alessandra Carobbio, Arianna Ghirardi, Silvia Betti, Guido Finazzi, Alessandro M. Vannucchi, Tiziano Barbui
Journal: Blood Cancer Journal (2018)

We collected 1500 patients with myeloproliferative neoplasms (MPN) and arterial or venous thrombosis (935/565), pooling three independent cohorts previously reported. Long-term treatment with antiplatelet drugs or vitamin K-antagonists (VKA) was given to 1391 (92.7%) patients; 975 (65%) patients received hydroxyurea (HU). We recorded 348 recurrences (venous in 142 cases) over 6075 patient-years, with an incidence rate of 5.7 per 100 pt-years (95% CI 5.1-6.4). The site of the first thrombosis predicted the site of recurrence. Independent factors influencing the rate of novel arterial thrombosis were HU (HR 0.67, 95% CI 0.46-0.98), antiplatelet treatment (HR 0.54, 95% CI 0.35-0.82), and VKA (HR 0.58, 95% CI 0.35-0.96). On the contrary, the recurrence of venous thromboses was significantly diminished only by VKA (HR 0.60, 95% CI 0.37-0.95), while HU prevented late but not early recurrences after venous thrombosis at common sites. Of note, we failed to demonstrate a positive effect of HU in the prevention of recurrent splanchnic vein thrombosis. In conclusion, in MPN patients, HU plays a role in the prevention of arterial thrombosis, together with aspirin and VKA, whereas its action in the prevention of recurrent venous thrombosis is uncertain. Such findings call for future studies to optimize and personalize secondary prophylaxis after MPN-related thrombosis.
Abstract 14857: Infarcted Hearts Respond Better to Cardiac Stem Cell Therapy After Pre-treatment With a Collagen Hydrogel
Authors: Kay Maeda, Ghazaleh Rafatian, Richard Seymour, Marc Ruel, Darryl R Davis, Erik J Suuronen
Journal: Circulation (2015)

Background: Cell therapy is a promising approach for repairing the injured myocardium. However, cells delivered too soon after myocardial infarction (MI) suffer from low retention and survival due to the harsh inflammatory post-MI milieu. In addition, autologous cells such as cardiac stem cells (CSCs) require time for isolation and culture prior to use, which precludes their delivery soon after MI. However, biomaterial therapy is not limited by these factors and can be applied in acute MI to limit myocardial damage. In this study, we treated the myocardium at the time of MI with a collagen matrix in order to prime the healing post-infarct environment and improve the efficacy of CSC therapy delivered late after MI. Methods/Results: C57BL/6J mice underwent LAD ligation to induce MI. Mice were then randomized to receive intramyocardial injection of PBS or matrix treatment at 3h post-MI, followed by PBS or 5х105 eGFP-CSCs at 7d post-MI. In total, 4 groups were evaluated: 1) 3h PBS/7d PBS (n=7), 2) 3h PBS/7d CSC (n=11), 3) 3h matrix/7d PBS (n=6) and 4) 3h matrix/7d CSC (n=12). Treatment with the matrix at 3h (groups 3 and 4) improved cardiac LVEF at 1wk post-MI (42.4±2.7%) compared to PBS-treated mice (groups 1 and 2; 37.9±3.7%; p=0.0004). After 4wk, the matrix/CSC treated mice (group 4) had superior LVEF (45.3±3.9%) compared to all other groups (29.4±3.9%, 35.9±2.5% and 40.1±4.0% for groups 1, 2 and 3, respectively; p≤0.02). Immunostaining for GFP+ cells revealed 1.5-fold greater CSC retention in the myocardium of matrix pre-treated mice (p=0.04). Vascular density (# of CD31+ capillaries/FOV) in the infarct area was 2.5-fold greater in PBS/CSC mice than in PBS-treated mice (group 1; p=0.001), and increased further in the matrix/CSC group (1.4-fold vs. group 2; p=0.03). The matrix/CSC treated mice (group 4) had significantly reduced scar size (% scar/total myocardial area) (by ≥40%; p≤0.002) and better preserved ventricular wall thickness (by ≥15%; p≤0.02) compared to all other treatment groups. Conclusion: Collagen matrix treatment in acute MI primes the injured heart to be more responsive to CSC therapy. This may constitute a plausible synergistic strategy to protect the myocardium and improve the benefits that can be achieved with cell therapy.
Response to: ‘Inflammation in SLE-PAH: good news or not?’ by Junyan Qian <i>et al</i>
Authors: Fangfang Sun, Yunxia Lei, Xiao Zhang, Shuang Ye
Journal: Annals of the Rheumatic Diseases (2018)

Thank you very much for your interest in our article ‘Two distinct clinical phenotypes of pulmonary arterial hypertension secondary to systemic lupus erythematosus’, and we are glad to answer the question ‘Inflammation in SLE-PAH: good news or not?’ as below.

First, referral bias may exist and contribute to the different outcome. As an example, the Peking Union Medical College Hospital (PUMCH) cohort has more patients with pulmonary arterial hypertension secondary to systemic lupus erythematosus …
Abstract 18398: Time Course of Cardiac Markers During Acute Myocarditis
Authors: Jan Kottwitz, Mawahib Elhassan, Jan Berg, Nora Baltensperger, Christine K Kissel, Marina Lovrinovic, Dimitri Patriki, Frank Scherff, Christian Schmied, Christian Templin, Thomas F Lüscher, Robert Manka, Bettina Heidecker
Journal: Circulation (2017)

Introduction: Acute myocarditis is an inflammatory process that leads to leak of intracellular components into the blood including cardiac markers. The time course of cardiac markers has been well ...
Ibrutinib + Obinutuzumab Versus Chlorambucil + Obinutuzumab As First-Line Treatment in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL): Results from Phase 3 iLLUMINATE
Authors: Carol Moreno, Richard Greil, Fatih Demirkan, Alessandra Tedeschi, Bertrand Anz, Loree Larratt, Martin Simkovic, Olga Samoilova, Jan Novak, Dina Ben-Yehuda, Vladimir Strugov, Devinder Gill, John G. Gribben, Emily Hsu, Cathy Zhou, Fong Clow, Danelle F. James, Lori Styles, Ian W. Flinn
Journal: Blood (2018)