tbuckley/cabot-search huggingface dataset:
Angiocrine Wnt signaling controls liver growth and metabolic maturation in mice
Authors: Thomas Leibing, Cyrill Géraud, Iris Augustin, Michael Boutros, Hellmut G. Augustin, Jürgen G. Okun, Claus‐Dieter Langhans, Johanna Zierow, Sebastian A. Wohlfeil, Victor Olsavszky, Kai Schledzewski, Sergij Goerdt, Philipp‐Sebastian Koch
Journal: Hepatology (2017)

Postnatal liver development is characterized by hepatocyte growth, proliferation, and functional maturation. Notably, canonical Wnt signaling in hepatocytes has been identified as an important regulator of final adult liver size and metabolic liver zonation. The cellular origin of Wnt ligands responsible for homeostatic liver/body weight ratio (LW/BW) remained unclear, which was also attributable to a lack of suitable endothelial Cre driver mice. To comprehensively analyze the effects of hepatic angiocrine Wnt signaling on liver development and metabolic functions, we used endothelial subtype-specific Stab2-Cre driver mice to delete Wls from hepatic endothelial cells (HECs). The resultant Stab2-Cretg/wt ;Wlsfl/fl (Wls-HECKO) mice were viable, but showed a significantly reduced LW/BW. Specifically, ablation of angiocrine Wnt signaling impaired metabolic zonation in the liver, as shown by loss of pericentral, β-catenin-dependent target genes such as glutamine synthase (Glul), RhBg, Axin2, and cytochrome P450 2E1, as well as by extended expression of periportal genes such as arginase 1. Furthermore, endothelial subtype-specific expression of a c-terminally YFP-tagged Wls fusion protein in Wls-HECKO mice (Stab2-Cretg/wt ;Wlsfl/fl ;Rosa26:Wls-YFPfl/wt [Wls-rescue]) restored metabolic liver zonation. Interestingly, lipid metabolism was altered in Wls-HECKO mice exhibiting significantly reduced plasma cholesterol levels, while maintaining normal plasma triglyceride and blood glucose concentrations. On the contrary, zonal expression of Endomucin, LYVE1, and other markers of HEC heterogeneity were not altered in Wls-HECKO livers.Angiocrine Wnt signaling controls liver growth as well as development of metabolic liver zonation in mice, whereas intrahepatic HEC zonation is not affected. (Hepatology 2017).
TCT-488 Determinants of stent healing in optical coherence tomography. Validation study with histopathology in the porcine coronary restenosis model
Authors: Maciej Pruski, Aleksandra Blachut, Mateusz Kachel, Magdalena Michalak, Adam Janas, Carlos Fernandez, Paweł Buszman, Krzysztof Milewski, Piotr Buszman
Journal: Journal of the American College of Cardiology (2017)
Targeting CDH17 in Cancer: When Blocking the Ligand Beats Blocking the Receptor?
Authors: John F. Marshall
Journal: Clinical Cancer Research (2017)

Cadherin-17 (CDH17) has been implicated as protumorigenic for many years, but mechanisms have been unclear. A Spanish team has generated antibodies to an RGD motif in CDH17 that inhibits integrin α2β1 binding to CDH17 and thereby inhibits integrin activation, tumorigenesis, and metastasis. These reagents may have therapeutic potential. Clin Cancer Res; 24(2); 253-5. ©2017 AACRSee related article by Bartolomé et al., p. 433.
TCT-179 Outcomes After Left Main PCI Versus CABG According to Ostial/Shaft Versus Distal Bifurcation Involvement: Insights From the EXCEL Trial
Authors: Anthony Gershlick, David Kandzari, Amerjeet Banning, Marie-Claude Morice, Nicholas Lembo, William Brown, Adrian Banning, Ad Van Boven, Piet Willem Boonstra, Ovidiu Dressler, Joseph Sabik, Patrick Serruys, A. Pieter Kappetein, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
TCT-373 Diagnostic accuracy of combined pressure and flow-derived indices versus pressure only indices for myocardial ischemia
Authors: Gilbert Wijntjens, Tim van de Hoef, Valérie Stegehuis, Martijn Meuwissen, Mauro Echavarria Pinto, Steven Chamuleau, Michiel Voskuil, Karel Koch, Robbert de Winter, Jan Piek
Journal: Journal of the American College of Cardiology (2017)
FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity
Authors: Xiaoxin X. Wang, Dong Wang, Yuhuan Luo, Komuraiah Myakala, Evgenia Dobrinskikh, Avi Z. Rosenberg, Jonathan Levi, Jeffrey B. Kopp, Amanda Field, Ashley Hill, Scott Lucia, Liru Qiu, Tao Jiang, Yingqiong Peng, David Orlicky, Gabriel Garcia, Michal Herman-Edelstein, Vivette D’Agati, Kammi Henriksen, Luciano Adorini, Mark Pruzanski, Cen Xie, Kristopher W. Krausz, Frank J. Gonzalez, Suman Ranjit, Alexander Dvornikov, Enrico Gratton, Moshe Levi
Journal: Journal of the American Society of Nephrology (2017)

Bile acids are ligands for the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5. We have shown that FXR and TGR5 have renoprotective roles in diabetes- and obesity-related kidney disease. Here, we determined whether these effects are mediated through differential or synergistic signaling pathways. We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db mice with type 2 diabetes, and C57BL/6J mice with high-fat diet-induced obesity. We also examined the individual effects of the selective FXR agonist obeticholic acid (OCA) and the TGR5 agonist INT-777 in diabetic mice. The FXR agonist OCA and the TGR5 agonist INT-777 modulated distinct renal signaling pathways involved in the pathogenesis and treatment of diabetic nephropathy. Treatment of diabetic DBA/2J and db/db mice with the dual FXR/TGR5 agonist INT-767 improved proteinuria and prevented podocyte injury, mesangial expansion, and tubulointerstitial fibrosis. INT-767 exerted coordinated effects on multiple pathways, including stimulation of a signaling cascade involving AMP-activated protein kinase, sirtuin 1, PGC-1
Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study
Authors: Hisashi Yamanaka, Shigenori Tamaki, Yumiko Ide, Hyeteko Kim, Kouichi Inoue, Masayuki Sugimoto, Yuji Hidaka, Atsuo Taniguchi, Shin Fujimori, Tetsuya Yamamoto
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To determine whether febuxostat with stepwise dose increase is as useful as colchicine prophylaxis in reducing gout flares during the initial introduction of urate-lowering therapy in patients with gout in comparison with febuxostat with no dose titration. Methods In this prospective, multicentre, randomised open-label comparative study, patients were randomised to group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (fixed-dose febuxostat 40 mg/day plus colchicine 0.5 mg/day) or group C (fixed-dose febuxostat 40 mg/day) and observed for 12 weeks. Gout flare was defined as non-steroidal anti-inflammatory drug use for gout symptoms. Results A total of 255 patients were randomised, and 241 patients were treated. Among the treated patients, gout flares were experienced by 20/96 (20.8%) in group A, 18/95 (18.9%) in group B and 18/50 (36.0%) in group C. The incidence of flare was significantly lower in groups A and B than that in group C (P=0.047 and P=0.024, respectively), although the differences were not significant after correction for multiple comparisons. No significant difference was noted between the incidence of gout flare in groups A and B. Conclusions Our data suggested that stepwise dose increase of febuxostat and low-dose colchicine prophylaxis effectively reduced gout flares in comparison with fixed-dose febuxostat alone. Stepwise dose increase of febuxostat may be an effective alternative to low-dose colchicine prophylaxis during the introduction of urate-lowering therapy. Trial registration number UMIN 000008414 .
TCT-266 Complications of Indwelling Urinary Catheters In Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Joshua Lampert, Matthew Finn, Alex Kantor, Deniz Akkoc, Ming Liao, Kathryn Fidlow, Pablo Codner, Amisha Patel, Omar Khalique, Rebecca Hahn, Torsten Vahl, Isaac George, Martin Leon, Susheel Kodali, Tamim Nazif
Journal: Journal of the American College of Cardiology (2017)
Impact of clinical pharmacists collaborating with oncologists in outpatient cancer chemotherapy on cost of chemotherapy
Authors: Hayato Kamata, Hidetaka Suzuki, Yuka Sugama, Ken Demachi, Kiwako Ikegawa, Takashi Igarashi, Shinya Suzuki, Makoto Tahara, Masakazu Yamaguchi
Journal: Annals of Oncology (2017)
Efficacy and Safety of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis of Phase III Trials
Authors: Alessandro Cucchetti, Fabio Piscaglia, Antonio Daniele Pinna, Benjamin Djulbegovic, Federico Mazzotti, Luigi Bolondi
Journal: Liver Cancer (2017)

After the introduction of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC), different studies tried to evaluate whether other systemic therapies can improve survival. To provide a comprehensive indirect treatment comparison of efficacy and safety of novel drugs, a network meta-analysis (NMA) of phase III randomized controlled trials was performed.After pertinent literature search up to November 1, 2016, 6 studies were eligible for the analysis including 4,812 individual patients with advanced HCC: 2,454 received sorafenib, 577 received brivanib, 530 received sunitinib, 514 received linifanib, 358 received sorafenib + erlotinib and 379 received placebo. Frequentist NMA was used to compare treatments within a single analytical framework.NMA showed that sorafenib alone, regardless of combination with erlotinib, and linifanib provide a significant survival advantage over placebo (p < 0.05) but without any significant difference between each other. Conversely, all regimens significantly ameliorate progression-free survival versus placebo (p < 0.05). The rank order of efficacy was: sorafenib ± erlotinib, linifanib, brivanib, sunitinib, and placebo. Sorafenib ± erlotinib was the regimen with the fewest number of adverse events that required discontinuation of treatment, whereas linifanib and brivanib resulted in the most adverse events. The risk-benefit summary identified one cluster of therapies with a similar balance between efficacy and safety which included sorafenib alone or in combination with erlotinib, having, at the same time, the highest efficacy and safety.Sorafenib remains the best systemic treatment for advanced HCC; linifanib also resulted in survival advantages over placebo but with a lower safety profile.
Clinicopathological features of PD-L1 expression with MMR, EBV status and cancer genome alterations in MGC
Authors: Akihito Kawazoe, Kohei Shitara, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Takayuki Yoshino, Atsushi Ohtsu, Atsushi Ochiai, Toshihiko Doi, Takeshi Kuwata
Journal: Annals of Oncology (2017)
Legionelosis asociada a viajes en Europa : 2004
Authors: K D Ricketts, B McNaught, C A Joseph
Journal: Eurosurveillance (2006)

En 2004, 25 paises notificaron 655 casos de legionelosis asociada a viajes al sistema de vigilancia EWGLINET. El 84,9% de los casos fueron diagnosticados por el test de antigeno en orina y se obtuvieron 37 cultivos positivos. El numero de fallecimientos notificado fue de 37, lo que equivale a una tasa de mortalidad de 5,6%. 
En las 86 agrupaciones de casos detectadas, 45% no hubieran sido identificadas sin el programa EWGLINET. Se investigaron 94 lugares de alojamiento y se publicaron los nombres de cuatro sitios turisticos en la pagina web de EWGLI. Quince lugares fueron asociados con casos suplementarios despues de recibir un informe diciendo que la investigacion se habia llevado a cabo, y las medidas de control aplicadas correctamente. 
En cuanto a posibles mejoras en el sistema, se deberia mejorar la informacion sobre defunciones por legionelosis asociadas a viajes, asi como aumentar el numero de muestras para cultivos en toda Europa.
Cystic fibrosis liver disease in adults: Limits of noninvasive tests of fibrosis
Authors: Sophie Hillaire, Dominique Cazals‐Hatem, Serge Erlinger, Valerie Paradis
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. TO THE EDITOR: The article by Koh et al. suggests that cystic fibrosis liver disease (CFLD) in adults is more prevalent than previously described. The researchers propose new diagnostic criteria and tools for this entity.1 We agree with most of their conclusions, but we would like to add several comments that the researchers and readers may wish to consider. First, they propose noninvasive tests of liver fibrosis. Although such tests may be useful, it should be kept in mind that the extent of fibrosis is not correlated with the degree of portal hypertension, as we recently reported in a series of 10 patients with CFLD who had whole‐liver histological examination after liver transplantation.2 In our series, 8 patients had idiopathic noncirrhotic portal hypertension (INCPH), as the only patient with a liver biopsy in the Koh et al. study. The high frequency of INCPH in patients with CFLD also explains why liver biopsy has been described as inconsistent for the accurate diagnosis of liver disease in cystic fibrosis, unless a dual pass is performed.3 Second, the researchers suggest that focal nodular hyperplasia observed in their patient with liver biopsy may be related to long‐standing antibiotic use. In our study, we have proposed the alternative hypothesis that, in these patients, INCPH (including focal nodular hyperplasia) could be attributed to portal obliterative venopathy. In all patients, we have observed histological signs of portal venopathy, such as thickening of the portal wall or even absence of portal branches in small portal tracts. Several mechanisms could be involved in the pathogenesis of this lesion, such as a prothrombic state, septic embolization of portal venules, platelet activation, inflammation secondary to repeated pulmonary, or intestinal infections. Finally, we would like to emphasize that, in addition to diagnostic tests of liver disease in cystic fibrosis patients, as described by Koh et al., we urgently need markers of the severity of portal hypertension and of the risk of hepatic decompensation. Around 20% of the adult patients with cystic fibrosis are candidates for lung transplantation, and portal hypertension can decompensate after lung transplantation. This is why hepatic transplantation was performed in our patients who underwent lung transplantation.2 It would be extremely useful to have predictive markers of liver decompensation to better select the patients to whom liver transplantation should be proposed.
The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates fibroblast activation in systemic sclerosis
Authors: Christina Bergmann, Amelie Brandt, Benita Merlevede, Ludwig Hallenberger, Clara Dees, Thomas Wohlfahrt, Sebastian Pötter, Yun Zhang, Chih-Wei Chen, Tatiana Mallano, Ruifang Liang, Rosebeth Kagwiria, Alexander Kreuter, Ioanna Pantelaki, Aline Bozec, David Abraham, Ralf Rieker, Andreas Ramming, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2017)

Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis.JMJD3 was inactivated by small interfering RNA-mediated knockdown and by pharmacological inhibition with GSKJ4. The effects of targeted inactivation of JMJD3 were analysed in cultured fibroblasts and in the murine models of bleomycin-induced and topoisomerase-I (topoI)-induced fibrosis. H3K27me3 at the FRA2 promoter was analysed by ChIP.The expression of JMJD3, but not of UTX, was increased in fibroblasts in SSc skin and in experimental fibrosis in a transforming growth factor beta (TGFβ)-dependent manner. Inactivation of JMJD3 reversed the activated fibroblast phenotype in SSc fibroblasts and prevented the activation of healthy dermal fibroblasts by TGFβ. Pharmacological inhibition of JMJD3 ameliorated bleomycin-induced and topoI-induced fibrosis in well-tolerated doses. JMJD3 regulated fibroblast activation in a FRA2-dependent manner: Inactivation of JMJD3 reduced the expression of FRA2 by inducing accumulation of H3K27me3 at the FRA2 promoter. Moreover, the antifibrotic effects of JMJD3 inhibition were reduced on knockdown of FRA2.We present first evidence for a deregulation of JMJD3 in SSc. JMJD3 modulates fibroblast activation by regulating the levels of H3K27me3 at the promoter of FRA2. Targeted inhibition of JMJD3 limits the aberrant activation of SSc fibroblasts and exerts antifibrotic effects in two murine models.
TCT-183 Clinical Outcomes and Prognosis Markers of Patients With Liver Disease Undergoing Transcatheter Aortic Valve Replacement: A Propensity Score-matched Analysis
Authors: Luis Nombela-Franco, Gabriela Tirado-Conte, Josep Rodés-Cabau, Ramon Rodríguez-Olivares, Marco Barbanti, Thibault Lhermusier, Ignacio Amat-Santos, Stefan Toggweiler, Asim Cheema, Antonio Munoz-Garcia, Vicente Serra, Francesca Giordana, Gabriela Veiga, Pilar Jimenez Quevedo, Francisco Campelo-Parada, Lucca Loretz, Maria Del Trigo, Jose Maria Hernandez, Pieter Stella, Corrado Tamburino, Carlos Macaya
Journal: Journal of the American College of Cardiology (2017)
Oxidation, glycation and glycoxidation—The vicious cycle and lung cancer
Authors: Saheem Ahmad, Mohd Yasir Khan, Zeeshan Rafi, Hamda Khan, Zeba Siddiqui, Shahnawaz Rehman, Uzma Shahab, Mohd Sajid Khan, Mohd Saeed, Sultan Alouffi, Mohd Shahnawaz Khan
Journal: Seminars in Cancer Biology (2017)
Enhanced AMPA Receptor Trafficking Mediates the Anorexigenic Effect of Endogenous Glucagon-like Peptide-1 in the Paraventricular Hypothalamus
Authors: Ji Liu, Kristie Conde, Peng Zhang, Varoth Lilascharoen, Zihui Xu, Byung Kook Lim, Randy J. Seeley, J. Julius Zhu, Michael M. Scott, Zhiping P. Pang
Journal: Neuron (2017)
Triquinosis relacionada con el consumo de carne de caballo: Normativa europea y control del riesgo
Authors: E Maillot
Journal: Eurosurveillance (1998)

Varios brotes de triquinosis en Italia y Francia a finales de 1975 implicaron como origen al caballo, un animal al que previamente no se habia considerado como en riesgo para esta enfermedad. En ese momento, la normativa europea solo se ocupaba del control del cerdo.
Epidémie de fièvre typhoïde autochtone à Leipzig, Allemagne, juin 2004
Authors: M Muehlen, C Frank, W Rabsch, A Fruth, M Suckau, I Moeller, B Gronemann, R Prager, B R Ruf, T Grünewald, A Ammon, K Stark, K Alpers
Journal: Eurosurveillance (2007)

En juin 2004, trois cas confirmes de fievre typhoide ont ete notifies aux autorites sanitaires de Leipzig, Allemagne. Les patients avaient ete hospitalises pour une fievre inexpliquee et d’autres symptomes moderes. Tous faisaient partie du meme club equestre, et aucun n’avait effectue de voyage a l’etranger. Une etude de cohorte retrospective a ete realisee parmi les membres du club equestre afin d’identifier la source de l’infection. Un cas etait defini comme suspect s’il presentait une fievre inexpliquee superieure ou egale a 38,5°C durant au moins trois jours depuis le 1er mai 2004. Un cas probable etait defini par une serologie positive et un cas confirme par l’isolement de S. Typhi par culture de sang ou de selles. Les hopitaux, les pediatres et les medecins generalistes de Leipzig et des environs ont ete contactes pour identifier les cas supplementaires.
Les six cas identifies etaient tous membres du club equestre : quatre cas confirmes, comprenant les trois cas notifies, plus un cas probable et un cas suspect. La seule exposition commune a ces cas pendant la periode probable de contamination etait la consommation de sandwiches avec une sauce aux herbes provenant d’un snack-bar, les 25 ou 26 mai (25 mai : RR=5,7; 95%IC 0,9-37,9; les deux jours : RR=, p=0.007). Les analyses des aliments du snack-bar et celles realisees chez le personnel se sont toutes revelees negatives. Cependant, un employe qui n’avait pas ete enregistre par les autorites sanitaires a ete identifie lors d’une visite de l’etablissement. On ne peut exclure que d’autres personnes non enregistrees aient travaille dans ce snack-bar entre mai et juin 2004. En depit d’une recherche intensive de cas, aucun autre cas n’a pu etre identifie dans la population. 
Les sandwichs a la sauce aux herbes restent le vehicule de contamination le plus probable dans cette epidemie, bien que la source elle-meme soit inconnue. Meme en l’absence d’antecedents de voyages dans des pays endemiques, les medecins devraient penser a la fievre typhoide quand ils recoivent des patients avec une fievre inexpliquee.
Understanding Mitochondrial Polymorphisms in Cancer
Authors: Karen M. Bussard, Linda D. Siracusa
Journal: Cancer Research (2017)

Alterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms. In this issue of Cancer Research, Vivian and colleagues utilize a unique mouse model, called Mitochondrial Nuclear eXchange mice, that contain the nuclear DNA from one inbred mouse strain, and the mtDNA from a different inbred mouse strain to examine the genome-wide nuclear DNA methylation and gene expression patterns of brain tissue. Results demonstrated there were alterations in nuclear DNA expression and DNA methylation driven by mtDNA. These alterations may impact disease pathogenesis. In light of these results, in this review, we highlight alterations in mtDNA, with a specific focus on polymorphisms associated with cancer susceptibility and/or prognosis, mtDNA as cancer biomarkers, and considerations for investigating the role of mtDNA in cancer progression for future studies. Cancer Res; 77(22); 6051-9. ©2017 AACR.
PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group
Authors: Peter Borchmann, Helen Goergen, Carsten Kobe, Andreas Lohri, Richard Greil, Dennis A Eichenauer, Josée M Zijlstra, Jana Markova, Julia Meissner, Michaela Feuring-Buske, Andreas Hüttmann, Judith Dierlamm, Martin Soekler, Hans-Joachim Beck, Wolfgang Willenbacher, Wolf-Dieter Ludwig, Thomas Pabst, Max S Topp, Felicitas Hitz, Martin Bentz, Ulrich Bernd Keller, Dagmar Kühnhardt, Helmut Ostermann, Norbert Schmitz, Bernd Hertenstein, Walter Aulitzky, Georg Maschmeyer, Tom Vieler, Hans Eich, Christian Baues, Harald Stein, Michael Fuchs, Georg Kuhnert, Volker Diehl, Markus Dietlein, Andreas Engert
Journal: The Lancet (2017)
Prévalence de l'infection à VIH-2 en Europe
Authors: F Cazein, F F Hamers, J Alix, J B Brunet
Journal: Eurosurveillance (1996)

La pandemie d'infection a VIH et de SIDA est essentiellement liee au VIH-1. Il existe un autre type de virus, le VIH-2, que l'on trouve principalement dans certains pays d'Afrique occidentale (1-5). En Europe, (6) le VIH-2 est le plus souvent decrit chez des personnes originaires d'Afrique. L'objectif de ce travail est d'etudier la prevalence du VIH-2 dans differents pays d'Europe, et de comparer la prevalence du VIH-2 et du VIH-1 dans les populations testees.