tbuckley/cabot-search huggingface dataset:
Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials
Authors: Waleed Alhazzani, Fayez Alshamsi, Emilie Belley-Cote, Diane Heels-Ansdell, Romina Brignardello-Petersen, Mustafa Alquraini, Anders Perner, Morten Hylander Møller, Mette Krag, Saleh Almenawer, Bram Rochwerg, Joanna Dionne, Roman Jaeschke, Mohammed Alshahrani, Adam Deane, Dan Perri, Lehana Thebane, Awad Al-Omari, Simon Finfer, Deborah Cook, Gordon Guyatt
Journal: Intensive Care Medicine (2017)

Stress ulcer prophylaxis (SUP) is commonly prescribed in the intensive care unit. However, data from systematic reviews and conventional meta-analyses are limited by imprecision and restricted to direct comparisons. We conducted a network meta-analysis of randomized clinical trials (RCTs) to examine the safety and efficacy of drugs available for SUP in critically ill patients. We searched MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials through April 2017 for randomized controlled trials that examined the efficacy and safety of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), and sucralfate for SUP in critically ill patients. No date or language restrictions were applied. Data on study characteristics, methods, outcomes, and risk of bias were abstracted by two reviewers. Of 96 potentially eligible studies, we included 57 trials enrolling 7293 patients. The results showed that PPIs are probably more effective for preventing clinically important gastrointestinal bleeding (CIB) than H2RAs [odds ratio (OR) 0.38; 95% confidence interval (95% CI) 0.20, 0.73], sucralfate (OR 0.30; 95% CI 0.13, 0.69), and placebo (OR 0.24; 95% CI 0.10, 0.60) (all moderate quality evidence). There were no convincing differences among H2RA, sucralfate, and placebo. PPIs probably increase the risk of developing pneumonia compared with H2RAs (OR 1.27; 95% CI 0.96, 1.68), sucralfate (OR 1.65; 95% CI 1.20, 2.27), and placebo (OR 1.52; 95% CI 0.95, 2.42) (all moderate quality). Mortality is probably similar across interventions (moderate quality). Estimates of baseline risks of bleeding varied significantly across studies, and only one study reported on Clostridium difficile infection. Definitions of pneumonia varied considerably. Most studies on sucralfate predate pneumonia prevention strategies. Our results provide moderate quality evidence that PPIs are the most effective agents in preventing CIB, but they may increase the risk of pneumonia. The balance of benefits and harms leaves the routine use of SUP open to question.
Utilización de cianoacrilato en hda secundaria a varices esofágicas (VVEE). Experiencia en un hospital terciario
Authors: P Aranzabal Aguilar, C Urteaga Casares, J Aldai Larrinaga, A Sánchez Patón, L Urtasun Arlegui, I Ganchegui Aguirre, I Azagra De Miguel, E Merino Rodriguez, A Campos Ruiz, A Orive Calzada
Journal: Endoscopy (2017)

La esclerosis con cianocrilato es una técnica eficaz aprobada para la HDA por varices gástricas, no estando establecida su indicación para la hemorragia 2 ° a VVEE. El tratamiento endoscópico de elección en la HDA 2 ° a VVEE es la ligadura endoscópica con bandas (LEB), sin embargo, hasta un 20% de los episodios pueden ser refractarios a la terapia estándar pudiendo ser una alternativa el uso de cianocrilato.
Abstract 17715: Cardiovascular Risk in Pregnant Women With Hereditary Thrombophilia
Authors: Livia Trasca, Natalia Patrascu, Ramona Bruja, Octavian Munteanu, Oana Bodean, Monica Cirstoiu, Dragos Vinereanu
Journal: Circulation (2017)

Background: Hereditary thrombophilia (HT) increase the risk of thromboembolic events in pregnant women. Moreover, there are data supporting the association of HT with preeclampsia (PE), fetal growt...
Genomic features of bacterial adaptation to plants
Authors: Asaf Levy, Isai Salas Gonzalez, Maximilian Mittelviefhaus, Scott Clingenpeel, Sur Herrera Paredes, Jiamin Miao, Kunru Wang, Giulia Devescovi, Kyra Stillman, Freddy Monteiro, Bryan Rangel Alvarez, Derek S. Lundberg, Tse-Yuan Lu, Sarah Lebeis, Zhao Jin, Meredith McDonald, Andrew P. Klein, Meghan E. Feltcher, Tijana Glavina Rio, Sarah R. Grant, Sharon L. Doty, Ruth E. Ley, Bingyu Zhao, Vittorio Venturi, Dale A. Pelletier, Julia A. Vorholt, Susannah G. Tringe, Tanja Woyke, Jeffery L. Dangl
Journal: Nature Genetics (2017)
TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells
Authors: Nipun Verma, Heng Pan, Louis C. Doré, Abhijit Shukla, Qing V. Li, Bobbie Pelham-Webb, Virginia Teijeiro, Federico González, Andrei Krivtsov, Chan-Jung Chang, Eirini P. Papapetrou, Chuan He, Olivier Elemento, Danwei Huangfu
Journal: Nature Genetics (2017)
Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis
Authors: David Lagares, Alba Santos, Paula E. Grasberger, Fei Liu, Clemens K. Probst, Rod A. Rahimi, Norihiko Sakai, Tobias Kuehl, Jeremy Ryan, Patrick Bhola, Joan Montero, Mohit Kapoor, Murray Baron, Xaralabos Varelas, Daniel J. Tschumperlin, Anthony Letai, Andrew M. Tager
Journal: Science Translational Medicine (2017)

Persistent myofibroblast activation distinguishes pathological fibrosis from physiological wound healing, suggesting that therapies selectively inducing myofibroblast apoptosis could prevent progression and potentially reverse established fibrosis in diseases such as scleroderma, a heterogeneous autoimmune disease characterized by multiorgan fibrosis. We demonstrate that fibroblast-to-myofibroblast differentiation driven by matrix stiffness increases the mitochondrial priming (proximity to the apoptotic threshold) of these activated cells. Mitochondria in activated myofibroblasts, but not quiescent fibroblasts, are primed by death signals such as the proapoptotic BH3-only protein BIM, which creates a requirement for tonic expression of the antiapoptotic protein BCL-XL to sequester BIM and ensure myofibroblast survival. Myofibroblasts become particularly susceptible to apoptosis induced by "BH3 mimetic" drugs inhibiting BCL-XL such as ABT-263. ABT-263 displaces BCL-XL binding to BIM, allowing BIM to activate apoptosis on stiffness-primed myofibroblasts. Therapeutic blockade of BCL-XL with ABT-263 (navitoclax) effectively treats established fibrosis in a mouse model of scleroderma dermal fibrosis by inducing myofibroblast apoptosis. Using a BH3 profiling assay to assess mitochondrial priming in dermal fibroblasts derived from patients with scleroderma, we demonstrate that the extent of apoptosis induced by BH3 mimetic drugs correlates with the extent of their mitochondrial priming, indicating that BH3 profiling could predict apoptotic responses of fibroblasts to BH3 mimetic drugs in patients with scleroderma. Together, our findings elucidate the potential efficacy of targeting myofibroblast antiapoptotic proteins with BH3 mimetic drugs in scleroderma and other fibrotic diseases.
Cancer incidence in Danish phenoxy herbicide workers, 1947-1993.
Authors: E Lynge
Journal: Environmental Health Perspectives (1998)

A cohort study was undertaken of 2119 workers from Denmark who were potentially exposed to phenoxy herbicides. The workers were from two factories that produced phenoxy herbicides since 1947 and 1951, respectively. They had been employed either in the manufacture of phenoxy herbicide or in the manual service functions. The main product was 4-chloro-2-methylphenoxyacetic acid (MCPA). From 1947 to 1993 the 2119 workers had a slightly lower overall cancer incidence than the Danish population (observed = 204; expected [Exp] = 234.23; standardized incidence ratio [SIR] = 0.87; 95% confidence interval [CI] 0.8-1.0). Four soft-tissue sarcoma cases were observed (Exp = 2.47; SIR = 1.62; 95% CI = 0.4-4.1). All four cases occurred among men from Kemisk Vaerk Køge (Exp = 1.68; SIR = 2.38; 95% CI = 0.7-6.1). There were six cases of non-Hodgkin's lymphoma (Exp = 5.07; SIR = 1.10; 95% CI = 0.4-2.6) and no significantly elevated risk of other cancers. Based on small numbers, the study suggests an association between the exposure to MCPA and related phenoxy herbicides and the risk of soft-tissue sarcoma. The study does not indicate a risk of non-Hodgkin's lymphoma after exposure to these phenoxy herbicides or a risk of other cancer diseases.
Abstract IA27: A novel cancer-testis antigen protein microarray for autoimmune profiling in cancers: Diagnosis, stratification, and treatment monitoring
Authors: Jonathan Blackburn
Journal: Cancer Research (2017)

Abstract The cancer-testis antigens are a group of unrelated proteins aberrantly expressed in various cancers in adult somatic tissues. This aberrant expression can trigger spontaneous immune responses, a phenomenon exploited for the development of disease markers and therapeutic vaccines. However, expression levels often vary amongst patients presenting the same cancer type, and these antigens are therefore unlikely to be individually viable as diagnostic or prognostic markers. Nevertheless, patterns of antigen expression may provide correlates of specific cancer types and disease progression. This paper will describe the development and application of a novel, readily customizable cancer-testis antigen microarray platform, together with robust bioinformatics tools, which enable quantification of anti-cancer-testis antigen autoantibody profiles in patient sera. By exploiting the high affinity between autoantibodies and tumor antigens, our highly multiplexed protein microarray platform gives linearity of response over 4 orders of magnitude and an autoantibody quantitation limit in the pg/mL range. By using oriented attachment of folded, recombinant antigens and a polyethylene glycol microarray surface coating, our platform gives minimal non-specific antibody binding. Unlike other proteomics methods, which typically use lower affinity interactions between monoclonal antibodies and tumor antigens for detection, the high sensitivity and specificity realized using our autoantibody-based approach may facilitate the development of better cancer biomarkers, as well as potentially enabling pre-symptomatic diagnosis. We will illustrate the usage of our platform by monitoring the time-dependent response of melanoma patient cohorts to an experimental therapeutic NY-ESO-1-based cancer vaccine, to combination BRAF and MEK inhibitor treatment, and to anti-CTLA4/anti-PD1 vaccination. Citation Format: Jonathan Blackburn. A novel cancer-testis antigen protein microarray for autoimmune profiling in cancers: Diagnosis, stratification, and treatment monitoring [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA27.
Abstract P324: Cardiovascular Risk and Mortality Increase with Progression of Chronic Liver Disease
Authors: Kyungeh An, Cheongtag Kim, Jeanne Salyer, Shannon Bruffy, Richard Sterling
Journal: Circulation (2016)

Introduction: Patients with c hronic liver disease accounts for 30-45% of the adult population in North America; among them, more die from cardiovascular disease (CVD) than from liver cirrhosis. Reduction of CVD-mortality in this high risk population requires understanding of CVD-risk across the whole spectrum of liver disease progression ranging from mild forms (i.e. nonalcoholic fatty liver disease) to advanced forms (i.e. nonalcoholic- and alcoholic-liver cirrhosis) as well as understanding of the increase of CVD-risks by time. Hypothesis: We assessed two hypotheses that (1) CVD-risk and mortality are dependent on type of liver disease; and that (2) CVD-risk and mortality increase in five years in all three types of chronic liver disease. One exploratory hypothesis was (3) the increment of CVD-risk in five years is higher in advanced forms than in a mild form of chronic liver disease. Methods: A secondary data analysis was conducted using 2,765 records of patients with nonalcoholic fatty liver disease, nonalcoholic- and alcoholic-liver cirrhosis identified by the International Classification of Disease -9 codes. Framingham risk scores were calculated for each patient based on their sex, age, systolic blood pressure, total cholesterol and high density lipoprotein level or body mass index, smoking status, and the presence of diabetes with five year interval from 2009 to 2014. Results: Framingham CVD risk scores were significantly different among patients of nonalcoholic fatty liver disease (21.4%), nonalcoholic- (21.3%) and alcoholic-liver cirrhosis (28.1%) ( F =5.610, p= .004). The all-cause mortality rate was significantly different among nonalcoholic fatty liver disease (5.8%), nonalcoholic- (20.5%) and alcoholic-liver cirrhosis (23.4%) ( [[Unsupported Character - Symbol Font &amp;#61539;]] 2 =101.54, p =.000). In five years, CVD risk increased from 22.9 to 28.4% ( F =55.7, p =.000) with the greater extent in alcoholic- and nonalcoholic liver cirrhosis (increased by 7.2 and 6.0%, respectively) than in nonalcoholic fatty liver disease (increased by 3.4%) ( F =5.21, p =.023). Conclusions: We conclude that cardiovascular risks and mortality increase are dependent on type of liver disease. We also conclude that CVD risk increases in 5 years with the greater extent in advanced forms than in a mild form of chronic liver disease. To prevent CVD mortality, tailored risk reduction in earlier phases of chronic liver disease is crucial and may offer better outcomes.
Mommy or me? Who is the agent in a sense of agency in infant orofacial stereotypies?
Authors: Gerry Leisman
Journal: Behavioral and Brain Sciences (2017)

Abstract That neonates imitate is an assertion that lacks supporting evidence. Orofacial stereotypies are critical to optimizing food rejection. Matching of tongue-protrusion is not imitation, but a manifestation of the infant's arousal by the modeler's exhibition of the same behavior. The support for the nativist assertion that newborn infants imitate is not compelling, and we should proceed on the assumption that they do not.
Prevention and Control of Seasonal Influenza with Vaccines
Authors: Lisa A. Grohskopf, Leslie Z. Sokolow, Karen R. Broder, Sonja J. Olsen, Ruth A. Karron, Daniel B. Jernigan, Joseph S. Bresee
Journal: MMWR Recommendations and Reports (2016)

This report from CDC's Morbidity and Mortality Weekly Report (MMWR) updates the 2015–16 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines.
Ethical Challenges Confronted When Providing Nusinersen Treatment for Spinal Muscular Atrophy
Authors: Alyssa M. Burgart, David Magnus, Holly K. Tabor, Erin Daksha-Talati Paquette, Joel Frader, Jaqueline J. Glover, Brian M. Jackson, Charlotte H. Harrison, David K. Urion, Robert J. Graham, John F. Brandsema, Chris Feudtner
Journal: JAMA Pediatrics (2017)

The US Food and Drug Administration’s December 2016 approval of nusinersen for the treatment of patients with all subtypes of spinal muscular atrophy ushered in a new era for patients with spinal muscular atrophy, their families, and all those involved in their care. The extreme cost of the medication and the complicated logistical requirements for administering nusinersen via lumbar puncture have created practical challenges that raise important ethical considerations. We discuss 6 challenges faced at the institutional level in the United States: cost, limited evidence, informed consent, treatment allocation, fair distribution of responsibilities, and transparency with stakeholders. These challenges must be understood to ensure that patients with spinal muscular atrophy benefit from treatment, are protected from harm, and are treated fairly.
Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis
Authors: Suresh Vedantham, Samuel Z. Goldhaber, Jim A. Julian, Susan R. Kahn, Michael R. Jaff, David J. Cohen, Elizabeth Magnuson, Mahmood K. Razavi, Anthony J. Comerota, Heather L. Gornik, Timothy P. Murphy, Lawrence Lewis, James R. Duncan, Patricia Nieters, Mary C. Derfler, Marc Filion, Chu-Shu Gu, Stephen Kee, Joseph Schneider, Nael Saad, Morey Blinder, Stephan Moll, David Sacks, Judith Lin, John Rundback, Mark Garcia, Rahul Razdan, Eric VanderWoude, Vasco Marques, Clive Kearon
Journal: New England Journal of Medicine (2017)

The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome.
Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis
Authors: Siddharth Nath, Alex Koziarz, Jetan H Badhiwala, Waleed Alhazzani, Roman Jaeschke, Sunjay Sharma, Laura Banfield, Ashkan Shoamanesh, Sheila Singh, Farshad Nassiri, Wieslaw Oczkowski, Emilie Belley-Côté, Ray Truant, Kesava Reddy, Maureen O Meade, Forough Farrokhyar, Malgorzata M Bala, Fayez Alshamsi, Mette Krag, Itziar Etxeandia-Ikobaltzeta, Regina Kunz, Osamu Nishida, Charles Matouk, Magdy Selim, Andrew Rhodes, Gregory Hawryluk, Saleh A Almenawer
Journal: The Lancet (2017)
Abstract 15620: 20-HETE-mediated Neutrophil Adhesion Impairs Coronary Collateral Growth in Metabolic Syndrome
Authors: Gregory Joseph, Amanda Soler, Rebecca Hutcheson, Ian Hunter, Brenda Hutcheson, Chastity Bradford, Katherine H Gotlinger, John R Falck, Spencer Proctor, Michal L Schwartzman, Petra Rocic
Journal: Circulation (2016)

Transient, repetitive myocardial ischemia (RI)-induced coronary collateral growth (CCG) is impaired in metabolic syndrome patients and animal models. Endothelial cell (EC) dysfunction and chronic inflammation are hallmarks of metabolic syndrome. We showed that while in normal animals (SD), RI induces transient infiltration of monocytes, associated with successful CCG, in metabolic syndrome rats (JCR), RI induces sustained accumulation of neutrophils, which contributes to compromised CCG. 20-hydroxyeicosatetraeonic acid (20-HETE) is a pro-inflammatory metabolite of arachidonic acid. Its role in the regulation of CCG is unknown. We hypothesized that enhanced 20-HETE-mediated neutrophil adhesion to ECs and consequent EC dysfunction and apoptosis result in impaired CCG in metabolic syndrome. P-selectin and ICAM-1 expression was increased ~40% in JCR vs. SD rats. This increase was prevented by 20-HETE antagonists, 20-SOLA or 20-HEDGE. 20-HETE antagonists also prevented neutrophil accumulation observed in JCR rats. Coronary arteries from JCR rats exhibited reduced endothelium (Ach)-dependent vasodilation (20% JCR vs. 50% of max. SD). RI-induced eNOS activation and NO production were likewise decreased (~60% and~70%, respectively) in JCR vs. SD rats. EC apoptosis (TUNEL) was severely increased in response to RI in JCR rats (~75% vs. SD). Neutrophil adhesion-blocking antibodies partially attenuated EC apoptosis (~70%) and EC dysfunction (~75% eNOS activation and NO production, 75% Ach-dependent vasodilation). 20-HETE antagonists fully reversed impaired endothelium-dependent vasodilation, eNOS activation, NO production and prevented EC apoptosis. Finally, impaired CCG in JCR rats (collateral-dependent blood flow, microspheres) was completely restored by 20-HETE antagonists (CZ/NZ flow was 0.76±0.07 in JCR+20-SOLA, 0.84±0.05 in JCR+20-HEDGE vs. 0.11±0.02 in JCR vs. 0.84±0.03 ml/min/g in SD rats) and partially restored by neutrophil-blocking antibodies (0.49±0.05 ml/min/g). Taken together, these results indicate that 20-HETE-dependent neutrophil adhesion and accumulation compromises EC survival and function leading to impaired CCG. 20-HETE antagonists could provide therapy for restoration of CCG in metabolic syndrome.
Novel therapies for unresectable and metastatic melanoma
Authors: Chante Karimkhani, Bobby Y Reddy, Robert P Dellavalle, Srinath Sundararajan
Journal: BMJ (2017)

#### What you need to know A 60 year old white woman who had a melanoma excised a year ago now presents with multiple subcutaneous nodules along her left shin. Biopsy confirms the lesions as metastatic melanoma, with molecular analysis revealing a BRAF wild type genotype. Imaging also shows several small nodules throughout her lungs. The patient is recommended to start systemic treatment with immunotherapy. About 132 000 cases of melanoma are diagnosed globally every year.12 Surgical excision is the first line treatment for localised disease.3 A minority of patients present with increased tumour growth or ulceration, or with metastasis (see box 1). The prognosis varies by stage at diagnosis. Data from the United States show five year survival rates of 98% for local disease confined to site of origin, 63% for regional metastases with spread to surrounding lymph nodes or tissues, and 17% for distant metastases.6 Systemic chemotherapy with drugs such as dacarbazine has shown limited benefits in patients with metastatic melanoma, with median survival between six and 10 months.789 Over the past decade, understanding of molecular biology and immune regulation in melanoma has led to advancements in the treatment of unresectable and metastatic melanoma. #### Box 1: Definitions of terms45
Abstract IA15: Molecular navigation for cancer diagnosis and surgery: Imaging tumors and nerves
Authors: Quyen T. Nguyen
Journal: Clinical Cancer Research (2017)

Abstract Although treatment algorithms vary, surgery is the primary treatment modality for most solid cancers. The fundamental goal of a curative oncologic surgery is complete cancer removal but equally important from the patient's point of view is function preservation and pain control. Currently, there is an increasing trend to adopt minimally invasive technologies such as endoscopic and robotic surgery in order to decrease patient morbidity. However, the ability for surgeons to distinguish between normal and diseased tissue by texture or consistency is significantly reduced with these techniques (due to lack of ability to physically touch the tissue) and is limited to visual inspection alone. Using white light reflectance which is the current standard mode of illumination in operating rooms, the visual difference between normal and cancerous tissue can be imperceptible. The inability of surgeons to visually distinguish between tumor and normal tissue leads to residual cancer cells left behind at the edges of resection, i.e. positive surgical margins and can be as high as 20-40% in breast cancer lumpectomy, 21% for radical prostatectomy, and 13% for HNSCC. Molecular imaging with fluorescence provides enhanced visual definition between diseased and normal tissue and have been shown to decrease PSM in both animal models and patients. Molecular imaging with fluorescence can also provide enhanced visualization of important structures such as nerves to improve preservation and minimize inadvertent injury. Our laboratory has extensive experience in development of both nerve and tumor injectable markers for surgical visualization. In presentation we will discuss the development of nerve and tumor markers combinations to improve intraoperative visualization---aka color-coded surgery. Citation Format: Quyen T. Nguyen. Molecular navigation for cancer diagnosis and surgery: Imaging tumors and nerves [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA15.
Abstract 13771: Metformin Displays Cardioprotection in δ-sarcoglycan Deficiency Induced Cardiomyopathy Through Autophagic Activation via AMPK-mTOR Pathway
Authors: Hiromitsu Kanamori, Genki Naruse, Akihiro Yoshida, Shingo Minatoguchi, Hisaaki Komaki, Shinya Baba, Yoshihisa Yamada, Atsushi Mikami, Masanori Kawasaki, Kazuhiko NIshigaki, Genzou Takemura, Shinya MInatoguchi
Journal: Circulation (2017)

Although sarcoglycanopathy is characterized by incomplete dystrophin-glycoprotein complex causing both skeletal muscle dystrophy and cardiomyopathy, the role of autophagy in its pathogenesis is sti...