tbuckley/cabot-search huggingface dataset:
Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease
Authors: Antonio Riva, Vishal Patel, Ayako Kurioka, Hannah C Jeffery, Gavin Wright, Sarah Tarff, Debbie Shawcross, Jennifer M Ryan, Alexander Evans, Sarah Azarian, Jasmohan S Bajaj, Andrew Fagan, Vinood Patel, Kosha Mehta, Carlos Lopez, Marieta Simonova, Krum Katzarov, Tanya Hadzhiolova, Slava Pavlova, Julia A Wendon, Ye Htun Oo, Paul Klenerman, Roger Williams, Shilpa Chokshi
Journal: Gut (2017)

Background/aims Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown. Methods/design We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively. Results In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments. Conclusions In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the ‘leaky’ gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients.
La mortalidad en España durante la ola de calor del verano de 2003
Authors: F Simon, G Lopez-Abente, E Ballester, F Martinez
Journal: Eurosurveillance (2005)

Las altas temperaturas experimentadas en Europa el verano 2003 tuvieron un efecto en la mortalidad en varios paises incluyendo Espana. Este capitulo describe la mortalidad del 1 de junio al 31 de agosto, y valora el impacto de las olas de calor sobre esta en Espana.
El numero de defunciones se obtuvo de los Registros Civiles de las 50 capitales de provincia. La mortalidad observada se comparo con la mortalidad esperada estimada mediante un modelo de regresion de Poisson sobre series historicas de defunciones, corregido por la tendencia ascendente y la estacionalidad de la mortalidad. La informacion meteorologica la proporciono el Instituto Nacional de Meteorologia.
Espana experimento tres periodos de temperaturas elevadas. El exceso de defunciones asociado fue del 8% (43.212 observadas por 40.046 esperadas). El exceso de mortalidad afecto exclusivamente a mayores de 75 anos (15% mas defunciones de las esperadas para el grupo de edad 75 a 84 y 29% para los mayores de 84). 
Este fenomeno (exceso de mortalidad asociado a altas temperaturas ambientales) es un problema de salud publica emergente por su riesgo atribuible creciente, el envejecimiento de la poblacion espanola y el incremento previsto en la frecuencia de olas de calor debido al calentamiento global. Frente a ello se pueden plantear sistemas de alerta y respuesta basados en la monitorizacion de riesgos naturales, demanda medica de urgencia y defunciones y en el fortalecimiento de la capacidad de respuesta de los servicios sociales y sanitarios.
TCT-723 Clinical and Angiographic Predictors of No-Reflow Phenomenon in ST Segment Elevation Myocardial Infarction Treated with Successful Primary Percutaneous Intervention
Authors: Luis Arcay, Joao Braghiroli, Maria Silva-Chuecos, Vanessa Blumer, Robert Chait, Gustavo Cardenas
Journal: Journal of the American College of Cardiology (2017)
TCT-176 Diagnostic Accuracy of Coronary Computed Tomography Angiography for the Evaluation of Bioresorbable Vascular Scaffolds
Authors: Carlos Collet, Patrick Serruys, Bernard Chevalier, Angel Cequier, Jean Fajadet, Ad Van Boven, Dougal Mcclean, Jan Piek, Antonio Bartorelli, Stephan Windecker, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2017)
TCT-427 Three Year Clinical Performance of the Dual-therapy COMBO stent: Insights from the REMEDEE Registry
Authors: Deborah Kalkman, Pier Woudstra, M. Beijk, Ian Brian Alexander Menown, Peter Den Heijer, Harry Suryapranata, Arnoud van't Hof, Andrejs Erglis, Karin Arkenbout, Andres Iñiguez, Philippe Muller, Jan Tijssen, Robbert de Winter
Journal: Journal of the American College of Cardiology (2017)
Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients With Nonalcoholic Liver Disease
Authors: Cyrielle Caussy, Jun Chen, Mosab H. Alquiraish, Sandra Cepin, Phirum Nguyen, Carolyn Hernandez, Meng Yin, Ricki Bettencourt, Edward R. Cachay, Saumya Jayakumar, Lynda Fortney, Jonathan Hooker, Ethan Sy, Mark A. Valasek, Emily Rizo, Lisa Richards, David A. Brenner, Claude B. Sirlin, Richard L. Ehman, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2018)
Morphine to relieve exertional dyspnoea in COPD: myth, dream or reality?
Authors: Louis Laviolette, Pierantonio Laveneziana
Journal: European Respiratory Journal (2017)

Dyspnoea, "the subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity" [1], is ever present in patients with chronic obstructive pulmonary disease (COPD) and affects almost all aspects of their daily lives [2]: up 60% of patients have limitations in normal physical activity and more than a third are restricted in family activities [2]. Dyspnoea is usually the earliest and most troublesome complaint for which these patients seek medical attention. As the underlying disease advances, dyspnoea progresses relentlessly, invariably leading to a gradual decrease in activity levels and associated skeletal muscle deconditioning and impoverished quality of life [2]. Dyspnoea also has strong prognostic value for mortality: stronger than the forced expiratory volume in 1 s in patients with COPD or angina in patients with heart disease [3, 4]. Opioids show promise in managing exertional dyspnoea; safety of widespread use in COPD patients remains unproven <http://ow.ly/A9bX30fr7FR>
Abstract 261: Liver-specific Pcsk9 Knockout And Transgenic Mice
Authors: Ahmed Zaid, Anna Roubtsova, Jean Davignon, Nabil G. Seidah, Annik Prat
Journal: Circulation (2007)

Background: PCSK9 is primarily expressed in liver and intestine and was recently identified as the third locus implicated in autosomal dominant hypercholesterolemia, after LDLR and APOB. PCSK9 tran...
Epidemiologia della rosolia in Finlandia
Authors: I Davidkin, H Peltola, P Leinikki
Journal: Eurosurveillance (2004)

Prima dell'avvio dei programmi di vaccinazione, la rosolia era prevalente tra i bambini finlandesi. Dei focolai epidemici apparivano in maniera ricorrente a qualche anno di intervallo. I bambini dai 2 ai 12 anni erano quelli che piu frequentemente contraevano la rosolia. Verso la meta degli anni 1970 sono state introdotte le vaccinazioni con un vaccino monovalente con lo scopo specifico di eradicare la rosolia. Quanto al programma di vaccinazione in due iniezioni contro morbillo, parotite e rosolia (MPR), questo e stato introdotto nel 1982. Una netta diminuzione dei casi di rosolia si e cominciata a vedere qualche anno dopo il lancio del programma di vaccinazione MPR. Grazie a una copertura vaccinale sufficientemente elevata (g95% dopo il 1987) la circolazione del virus autoctono della rosolia nella popolazione finlandese e stata fermata alla fine degli anni 1990. Dopo l'eliminazione, qualche caso di rosolia e stato importato in Finlandia, senza provocare tuttavia casi secondari. Questo prova inequivocabilmente che la protezione contro la rosolia resta efficace, nonostante i nostri studi di coorte dimostrino che i livelli di anticorpi indotti dal vaccino effettivamente decrescono con il tempo. Il programma di vaccinazione MPR ha ugualmente permesso di eliminare dal paese la sindrome da rosolia congenita (SRC). L'ultimo caso di MPR dichiarato rimonta al 1986. Grazie alla forte copertura vaccinale dovuta al programma di vaccinazione MPR in due dosi, in Finlandia la rosolia e stata eradicata con successo. Da ora in avanti resta da vedere quanto durera la protezione acquisita.
A Galaxy Implementation of Next-Generation Clustered Heatmaps for Interactive Exploration of Molecular Profiling Data
Authors: Bradley M. Broom, Michael C. Ryan, Robert E. Brown, Futa Ikeda, Mark Stucky, David W. Kane, James Melott, Chris Wakefield, Tod D. Casasent, Rehan Akbani, John N. Weinstein
Journal: Cancer Research (2017)

Clustered heatmaps are the most frequently used graphics for visualization of molecular profiling data in biology. However, they are generally rendered as static, or only modestly interactive, images. We have now used recent advances in web technologies to produce interactive "next-generation" clustered heatmaps (NG-CHM) that enable extreme zooming and navigation without loss of resolution. NG-CHMs also provide link-outs to additional information sources and include other features that facilitate deep exploration of the biology behind the image. Here, we describe an implementation of the NG-CHM system in the Galaxy bioinformatics platform. We illustrate the algorithm and available computational tool using RNA-seq data from The Cancer Genome Atlas program's Kidney Clear Cell Carcinoma project. Cancer Res; 77(21); e23-26. ©2017 AACR.
Triquiníase associada ao consumo de carne de cavalo: regulamentos europeus e gestão de risco
Authors: E Maillot
Journal: Eurosurveillance (1998)

Os surtos de triquiniase em Italia e em Franca, nos finais de 1975, foram causados por carne de cavalo, um animal que, ate entao, nao era considerado como um risco para esta patologia. Os regulamentos europeus daquela epoca apenas consideravam o controlo da carne de porco.
TCT-72 Computational fractional flow reserve derived from three-dimensional intravascular ultrasound: a new algorithm of fusion between anatomy and physiology
Authors: Cristiano Bezerra, Fábio A. Pinton, Breno Falcão, José Mariani, Carlos A. Bulant, Gonzalo Talou, Antonio Esteves Filh Esteves, Pablo Blanco, Pedro A. Lemos
Journal: Journal of the American College of Cardiology (2017)
Conversion of PRPS Hexamer to Monomer by AMPK-Mediated Phosphorylation Inhibits Nucleotide Synthesis in Response to Energy Stress
Authors: Xu Qian, Xinjian Li, Lin Tan, Jong-Ho Lee, Yan Xia, Qingsong Cai, Yanhua Zheng, Hongxia Wang, Philip L. Lorenzi, Zhimin Lu
Journal: Cancer Discovery (2017)

Abstract Tumors override energy stress to grow. However, how nucleotide synthesis is regulated under energy stress is unclear. We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. Knock-in of nonphosphorylatable PRPS1/2 mutants, which have uninhibited activity, in brain tumor cells under energy stress exhausts cellular ATP and NADPH and increases reactive oxygen species levels, thereby promoting cell apoptosis. The expression of those mutants inhibits brain tumor formation and enhances the inhibitory effect of the glycolysis inhibitor 2-deoxy-d-glucose on tumor growth. Our findings highlight the significance of recalibrating tumor cell metabolism by fine-tuning nucleotide and NAD synthesis in tumor growth. Significance: Our findings elucidate an instrumental function of AMPK in direct regulation of nucleic acid and NAD synthesis in tumor cells in response to energy stress. AMPK phosphorylates PRPS1/2, converts PRPS1/2 hexamers to monomers, and inhibits PRPS1/2 activity and subsequent nucleotide and NAD synthesis to maintain tumor cell growth and survival. Cancer Discov; 8(1); 94–107. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1
Détection tardive d’une épidémie de shigellose dans une école de Madrid
Authors: J Jonsson, M C del Álvarez-Castillo, J C Sanz, R Ramiro, E Ballester, M Fernánez, A Echeíta, J. F. Martinez Navarro
Journal: Eurosurveillance (2005)

Bien que la shigellose soit rare en Espagne, il arrive occasionnellement qu’une epidemie soit detectee. Cet article decrit une epidemie dans une ecole de Madrid, due a une transmission de Shigella sonnei de personne a personne.
Suite a la detection de Shigella sonnei dans les selles d’une fillette de trois ans, une investigation a debute dans l’etablissement scolaire qu’elle frequentait. Des questionnaires ont ete distribues aux parents de 520 eleves. Un cas etait defini comme un cas scolaire lorsqu’il s’agissait du premier cas dans la famille d’un enfant, et comme un cas familial si d’autres membres de la famille du cas avaient presente les symptomes avant le cas. 
Quatre vingt huit cas (60 eleves et 28 membres de leurs familles) ont ainsi ete identifies. Le taux d’attaque (TA) etait de 12% dans l’etablissement scolaire et de 32% dans les familles. Il existait une association significative entre un taux d’attaque eleve et le bas âge des enfants. L’epidemie a dure deux mois. La longueur et la forme de la courbe epidemique des 60 cas chez les eleves suggerent une transmission de personne a personne. Le typage de Shigella sonnei par electrophorese en champ pulse (PFGE) realise a partir des prelevements chez cinq cas a permis de montrer que la souche etait identique. La detection tardive de l’epidemie etait probablement a l’origine de sa duree prolongee. L’epidemie a ete controlee des l’introduction des premieres mesures de controle.
Picogram detection of doxorubicin in breast cancer cells using accelerator mass spectrometry
Authors: Karen H. Dingley, Esther A. Ubick, Gregory T. Wurz, Michael W. Degregorio
Journal: Cancer Research (2004)

525  Doxorubicin (Dox) is a widely used cancer chemotherapeutic drug. Unfortunately, treatment success can be compromised by the development of multidrug resistance (MDR), an accumulation defect which reduces the drug concentration in tumor cells. Our goal is to develop a highly sensitive assay for quantifying Dox at the tumor level which will have applications in the early detection of drug resist-ance in cancer patients, as well as monitoring the effects of resistance modifiers in vivo. Towards this goal, we used accelerator mass spectrometry (AMS) to com-pare the accumulation of [14C]Dox in MDR+ and wildtype MDA-MB-231 human breast cancer cells in vitro. In an experiment to establish that AMS analysis could reproduce drug kinetic profiles obtained by HPLC with fluorescence detection (the current “gold standard” method of analysis), we quantified the cellular drug content using AMS following exposure to 2 μg/ml [14C]Dox for up to 4 hours. The AMS data successfully reproduced the kinetic profiles obtained by HPLC in which the wildtype cells had 5-fold higher levels of Dox than the resistant cells at 4 hours. A study conducted in cells using [14C]Dox at concentrations ranging from 0.2 pg/ml to 2 μg/ml with analysis at 4 hours demonstrated that AMS has approximately a 1 million-fold sensitivity improvement over fluorescence-based HPLC. The extreme sensitivity of AMS should facilitate similar studies in vivo to establish target site drug delivery and to potentially determine the optimal treatment dose and regimen in humans. Conducted under auspices of US DOE (LLNL W-7405-ENG-48) and supported by UCDRD and NIH grant 1 P30 CA93373-01.
TCT-191 Incidence, mortality and predictors of stroke risk in patients with ST-elevation myocardial infarction undergoing the pharmaco-invasive therapy
Authors: Marco Tulio Souza, Adriano Barbosa, Rodrigo Souza, Beatriz Paiva, Ana Faccinetto, Suzi Kawakami, Manuel Pereira Marques Gomes Junior, Ricardo Faraco, Pedro Ivo de Marqui Morais, Geovana Joao, Adriano Caixeta, Iran Gonçalves, Jose Marconi Almeida Sousa, Antonio Moreno, Jose Souza, Flavius Augustus Magliano, Gabriel Dotta, Leonardo Guimaraes, Eduardo Moreira, Claudia Alves, Antonio Carvalho
Journal: Journal of the American College of Cardiology (2017)
DETECT III/IV: Two combined clinical trials based on the phenotype of circulating tumor cells (CTCs).
Authors: Susanne Albrecht, Fabienne Schochter, Carola Anna Melcher, Carsten Hagenbeck, Thomas W. P. Friedl, Bernadette Jaeger, Brigitte Kathrin Rack, Volkmar Mueller, Peter A. Fasching, Wolfgang Janni, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2014)

TPS11132 Background: Although the prognostic value of CTC enumeration in metastatic breast cancer (MBC) is well understood, the value of taking into account the molecular characteristics of CTCs in treatment decision requires further investigation. Trial Design: The DETECT studies are prospective, multicenter, open-label clinical trials designed for patients with HER2-negative MBC and CTCs in the peripheral blood. DETECT III is a two-arm, phase III study for patients with HER2-positive CTCs, randomized to physician's choice chemotherapy with or without additional HER2-targeted treatment with lapatinib. DETECT IV is a single-arm phase-II study including postmenopausal women with hormone-receptor-positive, HER2-negative MBC and HER2-negative CTCs that will be treated with the mTOR-inhibitor everolimus in combination with an endocrine therapy of physician's choice. Specific aims: The primary objective of both trials is to estimate the clinical efficacy of treatments, assessed by the CTC clearance rate for DETECT III and progression-free survival (PFS) for DETECT IV. Present and target accrual: Overall, about 2000 MBC patients with a HER2-negative primary tumor will have to be screened to be able to include 120 patients with HER2-positive CTCs for DETECT III (started in February 2012) and 400 patients with HER2-negative CTCs for DETECT IV (started in December 2013). So far, 751 patients have been screened for CTCs. Methods: Prevalence of CTCs at various time points as well as the HER2 status of CTCs will be determined using the FDA-approved CellSearch System (Veridex, USA). Survival endpoints will be estimated using the Kaplan-Meier method. Perspectives: The DETECT III trial is the first study in which treatment is based on phenotypic characteristics of CTCs. If this trial succeeds in proving efficacy of lapatinib in patients with HER2-negative primary tumor but HER2-positive CTCs, it may lead to new treatment strategies for MBC. DETECT IV complements DETECT III with regard to additional therapy indications. The innovative study concept of these clinical trials with therapy decisions being based on prevalence and molecular phenotypes of CTCs is an important step towards a more personalized cancer treatment for MBC. Clinical trial information: NCT01619111/ NCT02035813.
Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles
Authors: Tian Zhou, Hang Su, Prasanta Dash, Zhiyi Lin, Bhagya Laxmi Dyavar Shetty, Ted Kocher, Adam Szlachetka, Benjamin Lamberty, Howard S Fox, Larisa Poluektova, Santhi Gorantla, JoEllyn McMillan, Nagsen Gautam, R Lee Mosley, Yazen Alnouti, Benson Edagwa, Howard E Gendelman
Journal: Biomaterials (2017)

Long-acting parenteral (LAP) antiretroviral drugs have generated considerable interest for treatment and prevention of HIV-1 infection. One new LAP is cabotegravir (CAB), a highly potent integrase inhibitor, with a half-life of up to 54 days, allowing for every other month parenteral administrations. Despite this excellent profile, high volume dosing, injection site reactions and low body fluid drug concentrations affect broad use for virus infected and susceptible people. To improve the drug delivery profile, we created a myristoylated CAB prodrug (MCAB). MCAB formed crystals that were formulated into nanoparticles (NMCAB) of stable size and shape facilitating avid monocyte-macrophage entry, retention and reticuloendothelial system depot formulation. Drug release kinetics paralleled sustained protection against HIV-1 challenge. After a single 45 mg/kg intramuscular injection to BALB/cJ mice, the NMCAB pharmacokinetic profiles was 4-times greater than that recorded for CAB LAP. These observations paralleled replicate measurements in rhesus macaques. The results coupled with improved viral restriction in human adult lymphocyte reconstituted NOD/SCID/IL2Rγc-/- mice led us to conclude that NMCAB can improve biodistribution and viral clearance profiles upon current CAB LAP formulations.
Examining Lead Exposures in California through State-Issued Health Alerts for Food Contamination and an Exposure-Based Candy Testing Program
Authors: Margaret A. Handley, Kali Nelson, Eric Sanford, Cassidy Clarity, Sophia Emmons-Bell, Anuhandra Gorukanti, Patrick Kennelly
Journal: Environmental Health Perspectives (2017)

In California, the annual number of children under age 6 y of age with blood lead levels (BLL) ≥10 lg=dL is estimated at over 1,000 cases, and up to 10,000 cases when BLL between 4:5 and 9:5 lg=dL are included.State-issued health alerts for food contamination provide one strategy for tracking sources of food-related lead exposures.As well, California passed legislation in 2006 for the Food and Drug Branch (FDB) of the state health department to test and identify lead in candy.This report presents health alert data from California over a 14-y period, compares data before and after the candy testing program began, and examines country of origin, ZIP code data, and time from candy testing to release of health alerts for lead-contaminated candies for 2011-2012.After 2007, health alerts issued for lead in candy and food increased significantly.Analysis of candy-testing data indicated that multiple counties and ZIP codes were affected.Seventeen candies with high lead concentrations were identified, resulting in rapid dissemination (<2 wk) of health alerts to local health departments and community clinicians and to the public.Surveillance of lead exposures from state-based food and candy testing programs provides an opportunity to identify and immediately act to remove nonpaint sources of lead affecting children.
TCT-54 First-in-Human Compassionate Use Results of the Novel PASCAL Transcatheter Mitral Valve Repair System for the Treatment of Severe Mitral Regurgitation
Authors: Fabien Praz, Konstantinos Spargias, Michael Chrissoheris, Lutz Buellesfeld, Georg Nickenig, Florian Deuschl, Robert Schueler, Neil Fam, Robert Moss, Moody Makar, Robert Boone, Jeremy Edwards, Aris Moschovitis, Saibal Kar, John Webb, Ulrich Schäfer, Ted Feldman, Stephan Windecker
Journal: Journal of the American College of Cardiology (2017)