tbuckley/cabot-search huggingface dataset:
Abstract 14074: Oral ApoA-I Mimetic Tg6F Enhances Ezetimibe Amelioration of Dyslipidemia
Authors: Pallavi Mukherjee, Greg Hough, Arnab Chattopadhyay, Srinivasa T Reddy, Mohamad Navab, Alan M Fogelman
Journal: Circulation (2016)

Introduction:  Recent reports indicate that as a single agent, ezetimibe or an apoA-I mimetic peptide can modulate trans-intestinal cholesterol efflux (TICE).   Hypothesis:  We hypothesized that if ezetimibe and an apoA-I mimetic peptide were acting on the same target, and if the two agents were given together at near maximal doses of each, the resulting readouts would be significantly less than additive.   Methods:  Female LDLR null mice (n = 20 per group) were fed a chow or Western diet (WD) without or with Ezetimibe (EZE) at 10 mg/kg/day or with a concentrate of transgenic tomatoes at 0.06% by weight expressing a control marker protein (EV) or the apoA-I mimetic peptide 6F (Tg6F), or the mice were fed WD + EZE + EV or WD + EZE + Tg6F added together at the same doses as for the single agents. After 2 weeks levels of plasma total cholesterol, triglycerides, HDL-cholesterol and paraoxonase-1 (PON) activity were determined.   Results:  Plasma total cholesterol levels (mg/dL) on chow were 53.4 ± 19; on WD the levels were 635 ± 79; on WD + EV the levels were 606 ± 107; on WD + EZE the levels were 535 ± 82; on WD + EZE + EV the levels were 543 ± 125; on WD + Tg6F the levels were 502 ± 113; on WD + EZE + Tg6F the levels were 285 ± 36. The addition of EV did not significantly change results; WD + EZE and WD + Tg6F were significantly different from WD alone (p    Conclusions:  The apoA-I mimetic Tg6F significantly enhanced ezetimibe amelioration of dyslipidemia in this mouse model.
Nicorandil potentiates sodium butyrate induced preconditioning of neurons and enhances their survival upon subsequent treatment with H2O2
Authors: Parisa Tabeshmehr, Haider Kh Husnain, Mahin Salmannejad, Mahsa Sani, Seyed Mojtaba Hosseini, Mohammad Hossein Khorraminejad Shirazi
Journal: Translational Neurodegeneration (2017)

Extensive loss of donor neural stem cell (NSCs) due to ischemic stress and low rate of differentiation at the site of cell graft are two of the major issues that hamper optimal outcome in NSCs transplantation studies. Given that histone deacetylases (HDACs) modulate various cellular processes by deacetylating histones and non-histone proteins, we hypothesized that combined treatment with small molecules, sodium butyrate (NaB; a known HDAC inhibitor) and nicorandil, will enhance the rate neuronal differentiation of NSCs besides their preconditioning to resist oxidative stress.NSCs derived from 14-day old Sprague Dawley rat ganglion eminence were characterized for tri-lineage differentiation. Treatment with 1 mM NaB significantly changed their culture characteristics while continuous treatment for 10 days enhanced their neural differentiation. NaB treatment also preconditioned the cells for their resistance to oxidative stress.The highest rate of neural differentiation and preconditioning effect was achieved when the NSCs were treated concomitantly with NaB and nicorandil. Cell proliferation assay showed that concomitant treatment with NaB and nicorandil retarded their rate of proliferation.These data conclude that preconditioning of NSCs with NaB and nicorandil effectively enhances their differentiation capacity besides preconditioning the cells to support their survival under ischemic conditions.
TCT-415 The influence of sex on fractional flow reserve is different by lesion location
Authors: Chee Hae Kim, Jonghanne Park, Ki Hong Choi, Joo Myung Lee, Jung-Kyu Han, Han-Mo Yang, Kyung Woo (KW) Park, Hyun-Jae Kang, Hyo-Soo Kim, Bon-Kwon Koo
Journal: Journal of the American College of Cardiology (2017)
Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids
Authors: Jun Won Park, Jeffrey R Curtis, Jinyoung Moon, Yeong Wook Song, Suhnggwon Kim, Eun Bong Lee
Journal: Annals of the Rheumatic Diseases (2017)

To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.The study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).During a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8-29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33-124)) was lower than the number needed to harm for serious ADR (131 (55-∞)).TMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.
Foveal Development in Infants Treated with Bevacizumab or Laser Photocoagulation for Retinopathy of Prematurity
Authors: Ryan N. Vogel, Margaret Strampe, Oladipo E. Fagbemi, Alexis Visotcky, Sergey Tarima, Joseph Carroll, Deborah M. Costakos
Journal: Ophthalmology (2017)
Safety and efficacy of gemcitabine plus nab-paclitaxel therapy in elderly patients with advanced pancreatic cancer
Authors: Yu Aoki, Yasutaka Sukawa, Kenta Kawasaki, Takeshi Suzuki, Kenro Hirata, Akiyoshi Kasuga, Eisuke Iwasaki, Yasuo Hamamoto, Hiromasa Takaishi, Takanori Kanai
Journal: Annals of Oncology (2017)
Inteligencia Epidémica: un nuevo marco para reforzar la vigilancia de las enfermedades en Europa
Authors: C Paquet, D Coulombier, R Kaiser, M Ciotti
Journal: Eurosurveillance (2006)

En un ambiente de rapida evolucion, las instituciones nacionales encargadas de la seguridad sanitaria no pueden basarse unicamente en los sistemas tradicionales de vigilancia de enfermedades, que no fueron concebidos para identificar la emergencia de nuevos riesgos. La Inteligencia Epidemica (epidemic intelligence, EI), proporciona un marco conceptual en el cual los paises podran adaptar sus sistemas de vigilancia de salud publica para responder a nuevos desafios.
La EI incluye todas actividades asociadas a la identificacion precoz de los riesgos potenciales para la salud, su verificacion y evaluacion, y la investigacion que permite hacer recomendaciones de medidas de control en salud publica. La EI tiene dos tipos de componentes, el primero basado en indicadores y el segundo en eventos. El primero utiliza datos estructurados recogidos por los sistemas de vigilancia rutinarios. El componente basado en eventos utiliza datos no estructurados recogidos mediante fuentes de informacion de todo tipo. 
Todos los Estados miembros de la UE disponen desde hace mucho tiempo de sistemas de vigilancia que proporcionan una vigilancia adecuada basada en indicadores. Para la mayoria de los paises el desafio consiste ahora en desarrollar y estructurar el componente de la EI basado en eventos, dentro de las instituciones nacionales encargadas de la vigilancia de salud publica. 
En mayo de 2006, los Estados miembros de la Union Europea se comprometieron a cumplir con las disposiciones del Reglamento sanitario internacional revisado (RSI 2005) consideradas como necesarias frente a los riesgos potenciales de pandemia de gripe aviar y humana. Esto proporciona una oportunidad al Centro europeo de prevencion y control de enfermedades (ECDC) de guiar a los Estados miembros en el desarrollo y/o el refuerzo de su capacidad nacional de EI, ademas de su papel en el desarrollo de un sistema de EI para la Union Europea.
TCT-509 Fractional flow reserve-guided complete revascularization in STEMI patients with multivessel disease compared to culprit-only revascularization: A meta-analysis
Authors: Alexandre Hideo-Kajita, Hector Garcia-Garcia, Kayode Kuku, Solomon Beyene, Viana Azizi, Yael Meirovich, Gebremedhin Melaku, Ahn Bui, Aaphtaab Dheendsa, Echo Brathwaite, Sameer Desale, Michael Lipinski, Ron Waksman
Journal: Journal of the American College of Cardiology (2017)
Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors
Authors: Dafna Gladman, William Rigby, Valderilio F. Azevedo, Frank Behrens, Ricardo Blanco, Andrzej Kaszuba, Elizabeth Kudlacz, Cunshan Wang, Sujatha Menon, Thijs Hendrikx, Keith S. Kanik
Journal: New England Journal of Medicine (2017)

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors.In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis.At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib.In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).
Understanding the Antibody Repertoire in Neuropsychiatric Systemic Lupus Erythematosus and Neuromyelitis Optica Spectrum Disorder
Authors: Simone Mader, Venkatesh Jeganathan, Yoshiyuki Arinuma, Yuichiro Fujieda, Irena Dujmovic, Jelena Drulovic, Yuka Shimizu, Yuko Sakuma, Joel N. H. Stern, Cynthia Aranow, Meggan Mackay, Shinsuke Yasuda, Tatsuya Atsumi, Shunsei Hirohata, Betty Diamond
Journal: Arthritis & Rheumatology (2017)

Objective IgG anti‐ DWEYS antibodies cross‐reactive with DNA and the N ‐methyl‐ d ‐aspartate receptor subunits GluN2A and GluN2B are known to be associated with neuropsychiatric systemic lupus erythematosus ( NPSLE ). IgG anti‐ DWEYS have not been investigated in demyelinating NPSLE or in another demyelinating disorder, neuromyelitis optica spectrum disorder ( NMOSD ), which is a disease also found mainly in young women and associated with aquaporin 4 ( AQP ‐4) or myelin oligodendrocyte glycoprotein ( MOG ) antibodies. This study was undertaken to investigate the frequency of all of these brain‐reactive antibodies in patients with NPSLE , those with demyelinating NPSLE , and those with NMOSD . Methods Serum samples from patients with NPSLE (n = 108), patients with SLE without neuropsychiatric manifestations (n = 38), patients with NMOSD (n = 33), and healthy controls (n = 106) were assessed for the frequency of IgG anti‐brain antibodies as well as IgG antibodies to AQP ‐4, MOG , GluN2A/GluN2B, and double‐stranded DNA (ds DNA ). Results Sera were positive for IgG anti– AQP ‐4 antibodies in 27 (82%) of 33 patients with NMOSD and 3 (27%) of 11 patients with demyelinating NPSLE , whereas all sera from patients with non‐demyelinating NPSLE , patients with SLE , and healthy controls were negative for IgG anti– AQP ‐4. IgG anti‐ MOG were detected at high titers in 3 (50%) of 6 patients with NMOSD who were negative for IgG anti– AQP ‐4, and at low titers in 2 (18%) of 11 patients with demyelinating NPSLE and 1 (1%) of 97 patients with non‐demyelinating NPSLE . IgG antibodies to ds DNA were present in 11 (33%) of 33 patients with NMOSD . Only 4 (12%) of 33 patients with NMOSD were positive for IgG anti‐ DWEYS , compared to 11 (29%) of 38 patients with SLE and 59 (55%) of 108 patients with NPSLE . IgG anti‐ DWEYS antibodies were present in 56 (58%) of 97 patients with non‐demyelinating NPSLE and 3 (27%) of 11 patients with demyelinating NPSLE . Serum IgG brain‐reactive antibodies were present at a similar frequency in patients with non‐demyelinating NPSLE (72 [75%] of 96), those with demyelinating NPSLE (9 [82%] of 11), and those with SLE (32 [84%] of 38), but were less frequent in patients with NMOSD (20 [61%] of 33). Conclusion Patients with demyelinating NPSLE should be tested for IgG antibodies to AQP ‐4, MOG , and DWEYS . IgG anti– AQP ‐4 can be considered diagnostic for NMOSD , whereas none of these antibodies appear to be diagnostic for demyelinating NPSLE . Moreover, IgG anti‐ds DNA are present in patients with NMOSD but are not cross‐reactive with IgG anti‐ DWEYS , indicating that the antigenic stimulus and mechanisms of tissue damage are potentially different between demyelinating NPSLE and NMOSD .
La rabia vulpina en Francia
Authors: B Toma
Journal: Eurosurveillance (2005)

La rabia vulpina o del zorro se detecto por primera vez en Francia en Marzo de 1968, y fue un problema de salud publica hasta 1998. Durante las dos primeras decadas, y a pesar de las medidas tomadas, se extendio tanto en superficie como en numero de casos. 
Las medidas aplicadas incluian acciones para reducir la densidad de poblacion de los zorros, la vacunacion obligatoria de los carnivoros domesticos en las areas infectadas y el uso de profilaxis en humanos. 
Tras la implementacion a gran escala de la vacunacion oral de los zorros, que comenzo en 1989-1990, el frente de la rabia retrocedio y la incidencia anual decrecio hasta ser eliminada a finales de 1998. La comparacion de los resultados obtenidos durante esos dos periodos de aplicacion de varias estrategias es espectacular. 
Francia sigue expuesta por un lado al riesgo de la rabia de los murcielagos y, por otro, al de casos accidentales de rabia canina importada de paises enzooticos.
Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer
Authors: Wan-xin Peng, Jian-guo Huang, Liu Yang, Ai-hua Gong, Yin-Yuan Mo
Journal: Molecular Cancer (2017)

The conversion from estrogen-dependent to estrogen-independent state of ER+ breast cancer cells is the key step to promote resistance to endocrine therapies. Although the crucial role of MAPK/ERK signaling pathway in estrogen-independent breast cancer cell growth is well established, the underlying mechanism is not fully understood. In this study, we profiled lncRNA expression against a focused group of lncRNAs selected from lncRNA database. CRISPR/Cas9 was employed to knockout (KO) linc-RoR in MCF-7 cells, while rescue experiments were carried out to re-express linc-RoR in KO cells. Colony formation and MTT assays were used to examine the role of linc-RoR in estrogen-independent growth and tamoxifen resistance. Western blot and qRT-PCR were used to determine the change of protein and lncRNA levels, respectively. The expression of DUSP7 in clinical specimens was downloaded from Oncomine ( www.oncomine.org ) and the dataset from Kaplan-Meier Plotter ( http://kmplot.com ) was used to analyze the clinical outcomes in relation to DUSP7. We identified that linc-RoR functions as an onco-lncRNA to promote estrogen-independent growth of ER+ breast cancer. Under estrogen deprivation, linc-RoR causes the upregulation of phosphorylated MAPK/ERK pathway which in turn activates ER signaling. Knockout of linc-RoR abrogates estrogen deprivation-induced ERK activation as well as ER phosphorylation, whereas re-expression of linc-RoR restores all above phenotypes. Moreover, we show that the ERK-specific phosphatase Dual Specificity Phosphatase 7 (DUSP7), also known as MKP-X, is involved in linc-RoR KO-induced repression of MAPK/ERK signaling. Interestingly, linc-RoR KO increases the protein stability of DUSP7, resulting in repression of ERK phosphorylation. Clinical data analysis reveal that DUSP7 expression is lower in ER+ breast cancer samples than that in ER- breast cancer. Moreover, downregulation of DUSP7 expression is associated with poor patient survival. Taken together, these results suggest that linc-RoR promotes estrogen-independent growth and activation of MAPK/ERK pathway of breast cancer cells by regulating the ERK-specific phosphatase DUSP7. Thus, this study might help not only in establishing a role for linc-RoR in estrogen-independent and tamoxifen resistance of ER+ breast cancer, but also suggesting a link between linc-RoR and MAPK/ERK pathway.
Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy
Authors: Pascale Paul, Christophe Picard, Emmanuelle Sampol, Luc Lyonnet, Julie Di Cristofaro, Louise Paul-Delvaux, Guillaume Lano, Corinne Nicolino-Brunet, Eleonore Ravis, Frederic Collart, Francoise Dignat-George, Bertrand Dussol, Florence Sabatier, Annick Mouly-Bandini
Journal: Circulation (2017)

Cardiac transplantation is an effective therapy for end-stage heart failure. Because cardiac allograft vasculopathy (CAV) is the major cause of late mortality after heart transplant (HT), there is a need to identify markers that reflect inflammatory or cytotoxic immune mechanisms contributing to its onset. Noninvasive and early stratification of patients at risk remains a challenge for adapting individualized therapy. The CD16 (Fc-gamma receptor 3A [FCGR3A]) receptor was recently identified as a major determinant of antibody-mediated natural killer (NK) cell activation in HT biopsies; however, little is known about the role of CD16 in promoting allograft vasculopathy. This study aimed to investigate whether markers that reflect CD16-dependent circulating NK cell activation may identify patients at higher risk of developing CAV after HT.Blood samples were collected from 103 patients undergoing routine coronarography angiography for CAV diagnosis (median 5 years since HT). Genomic and phenotypic analyses of FCGR3A/CD16 Fc-receptor profiles were compared in CAV-positive (n=52) and CAV-free patients (n=51). The levels of CD16 expression and rituximab-dependent cell cytotoxic activity of peripheral NK cells in HT recipients were evaluated using a noninvasive NK-cellular humoral activation test.Enhanced levels of CD16 expression and antibody-dependent NK cell cytotoxic function of HT recipients were associated with the FCGR3A-VV genotype. The frequency of the FCGR3A-VV genotype was significantly higher in the CAV+ group (odds ratio, 3.9; P=0.0317) than in the CAV- group. The FCGR3A-VV genotype was identified as an independent marker correlated with the presence of CAV at the time of coronary angiography by using multivariate logistic regression models. The FCGR3A-VV genotype was also identified as a baseline-independent predictor of CAV risk (odds ratio, 4.7; P=0.023).This study unravels a prominent role for the CD16-dependent NK cell activation pathway in the complex array of factors that favor the progression of transplant arteriosclerosis. It highlights the clinical potential of a noninvasive evaluation of FCGR3A/CD16 in the early stratification of CAV risk. The recognition of CD16 as a major checkpoint that controls immune surveillance may promote the design of individualized NK cell-targeted therapies to limit vascular damage in highly responsive sensitized patients.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01569334.
Building a house of sentiment on sand: Epistemological issues with contempt
Authors: Heather C. Lench, Shane W. Bench, Kenneth A. Perez
Journal: Behavioral and Brain Sciences (2017)

Abstract Contempt shares its features with other emotions, indicating that there is no justification for creating “sentiment” as a new category of feelings. Scientific categories must be created or updated on the basis of evidence. Building a new category on the currently limited contempt literature would be akin to building a house on sand – likely to fall at any moment.
Prevalence, awareness, treatment, and control of hypertension in China: data from 1·7 million adults in a population-based screening study (China PEACE Million Persons Project)
Authors: Jiapeng Lu, Yuan Lu, Xiaochen Wang, Xinyue Li, George C Linderman, Chaoqun Wu, Xiuyuan Cheng, Lin Mu, Haibo Zhang, Jiamin Liu, Meng Su, Hongyu Zhao, Erica S Spatz, John A Spertus, Frederick A Masoudi, Harlan M Krumholz, Lixin Jiang
Journal: The Lancet (2017)
AGA White Paper: Optimizing Endoscopic Ultrasound–Guided Tissue Acquisition and Future Directions
Authors: Sachin Wani, V. Raman Muthusamy, Cindy M. McGrath, Antonia R. Sepulveda, Ananya Das, Wells Messersmith, Michael L. Kochman, Janak Shah
Journal: Clinical Gastroenterology and Hepatology (2017)
Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial
Authors: Sandra van Brunschot, Janneke van Grinsven, Hjalmar C van Santvoort, Olaf J Bakker, Marc G Besselink, Marja A Boermeester, Thomas L Bollen, Koop Bosscha, Stefan A Bouwense, Marco J Bruno, Vincent C Cappendijk, Esther C Consten, Cornelis H Dejong, Casper H van Eijck, Willemien G Erkelens, Harry van Goor, Wilhelmina M U van Grevenstein, Jan-Willem Haveman, Sijbrand H Hofker, Jeroen M Jansen, Johan S Laméris, Krijn P van Lienden, Maarten A Meijssen, Chris J Mulder, Vincent B Nieuwenhuijs, Jan-Werner Poley, Rutger Quispel, Rogier J de Ridder, Tessa E Römkens, Joris J Scheepers, Nicolien J Schepers, Matthijs P Schwartz, Tom Seerden, B W Marcel Spanier, Jan Willem A Straathof, Marin Strijker, Robin Timmer, Niels G Venneman, Frank P Vleggaar, Rogier P Voermans, Ben J Witteman, Hein G Gooszen, Marcel G Dijkgraaf, Paul Fockens, Eric R Manusama, Mohammed Hadithi, Camiel Rosman, Alexander F Schaapherder, Erik J Schoon
Journal: The Lancet (2017)