tbuckley/cabot-search huggingface dataset:
Long-term albumin administration improves survival in patients with decompensated cirrhosis: final results of the “ANSWER” study
Authors: P. Caraceni, O. Riggio, P. Angeli, C. Alessandria, S. Neri, F.G. Foschi, F. Levantesi, A. Airoldi, S. Boccia, G.S. Baroni, S. Fagiuoli, G. Laffi, R. Cozzolongo, V. Di Marco, V. Sangiovanni, F. Morisco, P. Toniutto, A. Gasbarrini, R. De Marco, F. De Leonardis, I. Cacciola, G. Elia, A. Federico, S. Massironi, R. Guarisco, G. Marin, G. Ballardini, M. Rendina, S. Nardelli, S. Piano, C. Elia, L. Prestianni, E. Neri, A. Mastroianni, L. Cesarini, L. Simone, M. Marzioni, G. Magini, R.G. Romanelli, M. Zappimbulso, V. Calvaruso, G. Parrella, N. Caporaso, F. Pugliese, A. Tortora, C. Pasquale, M. Cavallin, A. Andrealli, F. Fidone, A. Lanzi, M. Vangeli, F. Salerno, A. Roncadori, M. Tufoni, G. Zaccherini, M. Bernardi
Journal: Journal of Hepatology (2017)
Integrating voluntary hepatitis B, C and HIV screening in the compulsory tuberculosis entry screening for immigrants, The Netherlands: a pilot project
Authors: J. Bil, P. Schrooders, M. Prins, P. Kouw, J. Klomp, M. Scholing, L. Huijbregts, G. Sonder, T. Waegemaekers, H. de Vries, W. Meijer, F. Zuure, A. Tostmann
Journal: Journal of Hepatology (2017)
Immune Checkpoint Blockade in Metastatic Urothelial Cancer
Authors: Arjun Vasant Balar
Journal: Journal of Clinical Oncology (2017)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 62-year-old man with a 45 pack per year tobacco-smoking history presented with painless gross hematuria in the fall of 2015 and was ultimately diagnosed with muscle-invasive urothelial bladder cancer. He received four cycles of cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy with pelvic lymph node dissection, which disclosed residual high-grade muscle-invasive urothelial cancer extending to the perivesical fat and involving two of 20 pelvic lymph nodes (pT3N2). Six months later, surveillance imaging identified new retroperitoneal lymphadenopathy and a large right pelvic mass with possible rectal wall invasion consistent with locally recurrent and metastatic urothelial cancer. Although feeling generally well, he reported having had progressive constipation, pelvic pressure, and narrow-caliber stools for 2 months. He was seen in consultation for management of recurrent bladder cancer.
Elevated serum levels of sonic hedgehog are associated with fibrotic and vascular manifestations in systemic sclerosis
Authors: Christian Beyer, Dörte Huscher, Andreas Ramming, Christina Bergmann, Jerome Avouac, Serena Guiducci, Florian Meier, Serena Vettori, Elise Siegert, Veronika K Jaeger, Britta Maurer, Gabriela Riemekasten, Ulrich Walker, Ulf Müller-Ladner, Gabriele Valentini, Marco Matucci-Cerinic, Yannick Allanore, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2017)

Fibrotic tissue remodelling and vascular alterations cause high morbidity and mortality in patients with systemic sclerosis (SSc).1 2 While the pathogenesis of SSc is only partially understood, recent evidence demonstrates a fundamental role of hedgehog signalling in fibrotic disease manifestations. Hedgehog signalling is activated in fibrotic SSc skin, and it induces an SSc-like phenotype in resting fibroblasts.3 Overexpression of sonic hedgehog (SHH) induces skin fibrosis, whereas inhibition of hedgehog signalling ameliorates experimental fibrosis.4 

Based on these experimental findings, this European Scleroderma Trials and Research group (EUSTAR) multicentre cooperative study investigates whether circulating SHH may serve as a surrogate marker for a more severe disease phenotype in patients with SSc. We decided to evaluate SHH serum levels rather than total circulating SHH. Measurements of SHH serum levels are easy and robust but may not assess particulated SHH in various different extracellular vesicles. …
Effect of resistance-associated substitutions on retreatment of direct acting antiviral-exposed patients in the real-world setting (ANRS CO22 HEPATHER)
Authors: S. Chevaliez, P. Trimoulet, C. Dorival, S. Larrat, C. Scholtes, J.-F. Meritet, E. Tuaillon, L. Bocket, F. Carrat, S. Pol, J.-M. Pawlotsky
Journal: Journal of Hepatology (2017)
The Genetics of Pain: Implications for Therapeutics
Authors: Jane E. Sexton, James J. Cox, Jing Zhao, John N. Wood
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Pain is an increasing clinical challenge affecting about half the population, with a substantial number of people suffering daily intense pain. Such suffering can be linked to the dramatic rise in opioid use and associated deaths in the United States. There is a pressing need for new analgesics with limited side effects. Here, we summarize what we know about the genetics of pain and implications for drug development. We make the case that chronic pain is not one but a set of disease states, with peripheral drive a key element in most. We argue that understanding redundancy and plasticity, hallmarks of the nervous system, is critical in developing analgesic drug strategies. We describe the exploitation of monogenic pain syndromes and genetic association studies to define analgesic targets, as well as issues associated with animal models of pain. We appraise present-day screening technologies and describe recent approaches to pain treatment that hold promise.
The changing prevalence and incidence of dementia over time — current evidence
Authors: Yu-Tzu Wu, Alexa S. Beiser, Monique M. B. Breteler, Laura Fratiglioni, Catherine Helmer, Hugh C. Hendrie, Hiroyuki Honda, M. Arfan Ikram, Kenneth M. Langa, Antonio Lobo, Fiona E. Matthews, Tomoyuki Ohara, Karine Pérès, Chengxuan Qiu, Sudha Seshadri, Britt-Marie Sjölund, Ingmar Skoog, Carol Brayne
Journal: Nature Reviews Neurology (2017)
Severe histological liver phenotype of lean subjects with non-alcoholic fatty liver disease
Authors: L. Denkmayr, A. Feldman, L. Stechemesser, M. Strasser, S. Ruhaltinger, S. Zandanell, M. Schranz, S. Buch, U. Huber-Schönauer, J. Hampe, C. Datz, E. Aigner
Journal: Journal of Hepatology (2017)
Early treatment of HCV-recurrent infection post liver transplantation in the era of the new direct acting antivirals, what we learned till now?
Authors: M.A. Sakr, H.M. Dabbous, I.F. Montasser, H.E. Ebada, K.A. Abdelhafeez, Y.M. Massoud, M.M. Bahaa, M.S. Elmeteini
Journal: Journal of Hepatology (2017)
Development and validation of diagnostic and prognostic criteria for chronic hepatitis B-related acute-on-chronic liver failure
Authors: J. Li, T. Wu, J. Li, L. Shao, Q. Zhou, J. Xin, L. Jiang, D. Shi, J. Jiang, S. Sun, L. Jin, T. Li, J. Huang, X. Xu, J. Chen, S. Hao, Y. Chen, S. Xin, Z. Gao, Z. Duan, T. Han, Y. Wang, J. Gan, T. Feng, C. Pan, Y. Chen, H. Li, Y. Huang, Q. Xie, S. Lin, L. Li
Journal: Journal of Hepatology (2017)
Functional Characterization of the <i>GUCY1A3</i> Coronary Artery Disease Risk Locus
Authors: Thorsten Kessler, Jana Wobst, Bernhard Wolf, Juliane Eckhold, Baiba Vilne, Ronja Hollstein, Simon von Ameln, Tan An Dang, Hendrik B. Sager, Philipp Moritz Rumpf, Redouane Aherrahrou, Adnan Kastrati, Johan L.M. Björkegren, Jeanette Erdmann, Aldons J. Lusis, Mete Civelek, Frank J. Kaiser, Heribert Schunkert
Journal: Circulation (2017)

Background: A chromosomal locus at 4q32.1 has been genome-wide significantly associated with coronary artery disease risk. The locus encompasses GUCY1A3 , which encodes the α 1 subunit of the soluble guanylyl cyclase (sGC), a key enzyme in the nitric oxide/cGMP signaling pathway. The mechanism linking common variants in this region with coronary risk is not known. Methods: Gene expression and protein expression were analyzed with quantitative polymerase chain reaction and immunoblotting, respectively. Putative allele-specific transcription factors were identified with in silico analyses and validated via allele-specific quantification of antibody-precipitated chromatin fractions. Regulatory properties of the lead risk variant region were analyzed with reporter gene assays. To assess the effect of zinc finger E box-binding homeobox 1 transcription factor (ZEB1), siRNA-mediated knockdown and overexpression experiments were performed. Association of GUCY1A3 genotype and cellular phenotypes was analyzed with vascular smooth muscle cell migration assays and platelet aggregation analyses. Results: Whole-blood GUCY1A3 mRNA levels were significantly lower in individuals homozygous for the lead (rs7692387) risk variant. Likewise, reporter gene assays demonstrated significantly lower GUCY1A3 promoter activity for constructs carrying this allele. In silico analyses located a DNase I hypersensitivity site to rs7692387 and predicted binding of the transcription factor ZEB1 rather to the nonrisk allele, which was confirmed experimentally. Knockdown of ZEB1 resulted in more profound reduction of nonrisk allele promoter activity and a significant reduction of endogenous GUCY1A3 expression. Ex vivo–studied platelets from homozygous nonrisk allele carriers displayed enhanced inhibition of ADP-induced platelet aggregation by the nitric oxide donor sodium nitroprusside and the phosphodiesterase 5 inhibitor sildenafil compared with homozygous risk allele carriers. Moreover, pharmacological stimulation of sGC led to reduced migration only in vascular smooth muscle cells homozygous for the nonrisk allele. In the Hybrid Mouse Diversity Panel, higher levels of GUCY1A3 expression correlated with less atherosclerosis in the aorta. Conclusions: Rs7692387 is located in an intronic site that modulates GUCY1A3 promoter activity. The transcription factor ZEB1 binds preferentially to the nonrisk allele, leading to an increase in GUCY1A3 expression, higher sGC levels, and higher sGC activity after stimulation. Finally, human and mouse data link augmented sGC expression to lower risk of atherosclerosis.
Abstract B47: A novel combination of Biochanin-A/ 5-Fluorouracil against colon cancer: Impact on Wnt/beta-catenin signaling
Authors: Mohamed Mahmoud, Mohamed El-Sesy, Mai F. Tolba, Dalal A. Abou El Ella
Journal: Cancer Research (2017)

Abstract Giza, Egypt. Colon cancer is one of the most common types of cancer worldwide. It is considered the second leading cause of cancer deaths in both women and men combined. Although 5-fluorouracil (5FU) is the first line of therapy for colon cancer, its use is significantly hampered by drug toxicity and development of tumor resistance. Therefore, it is important to investigate strategies to overcome such stumbling block. Biochanin-A (Bio-A) is a promising natural isoflavone that has selective cytotoxicity against cancer cells. This study aimed at investigating the modulatory impact of Bio-A on 5FU cytotoxicity in colon cancer cells and exploring the possible underlying mechanisms with emphasis on Wnt/beta catenin signals. Cytotoxicity and Calcusyn synergy analyses were conducted to assess IC50 and synergism between Bio-A and 5FU in both Caco-2 and HCT-116 cell lines. The effect of the different treatments on Wnt/ β-catenin signals was assessed using phospho-tracer enzyme linked immunoassays. Bio-A alone showed cytotoxic activity against Caco-2 and HCT-116 colon cancer cells with IC50 values of 34.34 and 34.41 μM respectively using sulforhodamine-B cytotoxicity assay. Combined treatment of 5FU/ Bio-A at 1:2 and 1:4 ratios reduced the IC50 of 5FU significantly by 26.7 and 57% in Caco-2 cell line. The same treatments produced reduction of 5FU IC50 by 13.2 and 39.6% in HCT-116. Calcusyn® analysis indicated that the combinations were synergistic in both cell lines with combination index CI&amp;lt;1. Since Wnt/ β-catenin signaling plays an important role in the pathogenesis of colon cancer, the study was substantiated to investigate the effects of Bio-A and Bio-A/5FU combination on some key signals in addition to cell cycle analysis and assessment of cyclin D1 expression. Bio-A significantly suppressed Akt-phosphorylation and hence reduced GSK3β phosphorylation and preserved it in the active form. Hence, treatment with Bio-A boosted the ratio of phosphorylated β-catenin(p-S45)/total β-catenin indicating an increased degradation of β-catenin and reduced signaling. In conclusion, these results underscore the potential merit of Bio-A as an adjuvant to 5FU for the management of colon cancer. Further tumor xenograft studies are encouraged in order to verify this effect in vivo. Citation Format: Mohamed Mahmoud, Mohamed El-Sesy, Mai F. Tolba, Dalal A. Abou El Ella. A novel combination of Biochanin-A/ 5-Fluorouracil against colon cancer: Impact on Wnt/beta-catenin signaling. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B47.
Point shear wave elastography method for assessing liver stiffness in different etiologies of liver diseases – a prospective study
Authors: T. Saadi, J. Khoury, W. Toukan, H. Sholy, R. Krimasky, V. Ben-Hakoon, E. Veitzman, Y. Baruch, D. Gaitini
Journal: Journal of Hepatology (2017)
Circulating serum exosomal microRNA-203 as a non-invasive biomarker for predicting prognosis in hepatocellular carcinoma
Authors: S.Y. Jang, G. Kim, K. Hur, S.Y. Park, W.Y. Tak, Y.O. Kweon, Y.R. Lee, J.S. Yoon, S.H. Kwon, H.S. Kim, J.S. Lee, J.G. Park
Journal: Journal of Hepatology (2017)
P3.02b-082 Gefitinib in First-Line Treatment of Caucasian Patients with NSCLC and EGFR Mutations in Exons 19 or 21
Authors: Jana Skrickova, Karel Hejduk, Zbynek Bortlicek, Milos Pesek, Vitezslav Kolek, Leona Koubkova, Ivona Grygarkova, Marketa Cernovska, Libor Havel, Marcela Tomiskova, Milada Zemanová, Jaromir Roubec, Dimka Sixtova, Helena Coupkova, Monika Satankova, Andrea Benejova, Michal Hrnčiarik, Miloslav Marel
Journal: Journal of Thoracic Oncology (2017)
Virus-specific coexpression of T-bet and Eomes defines highly functional CD8 and CD4 T cells in hepatitis B virus infection
Authors: H. Karimzadeh, P. Kurktschiev, D. Scharafin, W. Schraut, N.H. Grüner, M.-C. Jung, M. Wächtler, R. Zachoval, M. Spannagl, T. Böttler, B. Raziorrouh
Journal: Journal of Hepatology (2017)
Hepatitis C Virus Infection Among Reproductive-Aged Women and Children in the United States, 2006 to 2014
Authors: Kathleen N. Ly, Ruth B. Jiles, Eyasu H. Teshale, Monique A. Foster, Rick L. Pesano, Scott D. Holmberg
Journal: Annals of Internal Medicine (2017)

In the United States, hepatitis C virus (HCV) infection has increased among young persons who inject drugs, but the extent of this epidemic among reproductive-aged women and their children is unknown.To estimate numbers and describe characteristics of reproductive-aged women with HCV infection and of their offspring.Analysis of the National Notifiable Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014.United States.171 801 women (aged 15 to 44 years) and 1859 children (aged 2 to 13 years) with HCV infection reported to the NNDSS; 2.1 million reproductive-aged women and 56 684 children who had HCV testing by Quest Diagnostics.NNDSS HCV case reports and Quest laboratory data regarding unique reproductive-aged women and children who were tested for HCV infection.The number of reproductive-aged women with acute and past or present HCV infection in the NNDSS doubled, from 15 550 in 2006 to 31 039 in 2014. Of 581 255 pregnant women tested by Quest from 2011 to 2014, 4232 (0.73% [95% CI, 0.71% to 0.75%]) had HCV infection. Of children tested by Quest, 0.76% (CI, 0.69% to 0.83%) had HCV infection, but the percentage was 3.2-fold higher among children aged 2 to 3 years (1.62% [CI, 1.34% to 1.96%]) than those aged 12 to 13 years (0.50% [CI, 0.41% to 0.62%]). Applying the Quest HCV infection rate to annual live births from 2011 to 2014 resulted in an estimated average of 29 000 women (CI, 27 400 to 30 900 women) with HCV infection, who gave birth to 1700 infants (CI, 1200 to 2200 infants) with the infection each year.Only a fraction of HCV infections is detected and reported to the NNDSS. Quest data are potentially biased, because women who are asymptomatic, do not access health care, or have unreported risks may be less likely to be tested for HCV infection.These data suggest a recent increase in HCV infection among reproductive-aged women and may inform deliberations regarding a role for routine HCV screening during pregnancy.Centers for Disease Control and Prevention.
Abstract IA06: Genomic approaches to drug discovery
Authors: Todd R. Golub
Journal: Clinical Cancer Research (2017)

Abstract The principles of genomics (systematic, high throughput approaches to biology) can increasingly be brought to bear on drug discovery. Our group is developing two new approaches: Connectivity Map and PRISM. The concept of the Connectivity Map (CMap) is that disease states, cellular states and the action of pharmacologic or genetic perturbation can be captured by gene expression profiling. In order to make large-scale perturbational profiling feasible, we developed a high-throughput, ultra-low cost profiling method (named L1000) whereby the abundance of 1000 transcripts are quantified by hybridization to Luminex microspheres. As part of the NIH LINCS program, we have now generated over 2 million such L1000 profiles representing knock-down and over-expression of over 3000 genes and perturbation with over 4000 small molecules in more than 15 cell types. Examples of discoveries emanating from this next generation Connectivity Map will be presented. The PRISM method takes inspiration from recent large-scale drug sensitivity profiling studies demonstrating the value of determining the pattern of compound killing across a large panel of genetically characterized cancer cell lines. In order to increase the scale at which such studies can be performed, we inserted unique molecular barcodes (24-mer oligonucleotides) into the genomes of cancer cell lines, such that the lines could then be pooled and the pooled lines exposed to a compound of interest. Drug sensitivity is then quantified by changes in abundance of the molecular barcodes. We have demonstrated feasibility of pooling more than 500 cancer cell lines in a single pool, and have demonstrated feasibility of high throughput screening using the PRISM method. These experiments suggest that PRISM can be used as a starting point for oncology drug discovery and for the characterization of lead compounds for the genotype-specific patterns of cancer cell killing. Examples of recent PRISM discoveries will be presented. Citation Format: Todd R. Golub. Genomic approaches to drug discovery. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA06.
Erratum: Primary care managemenr of chronic stable angina and asymptomatic suspected or known coronary artery disease: A clinical practice guideline from the American College of Physicians (Annals of Internal Medicine (2004) 141 (562-567))
Authors: V. Snow, P. Barry, S. D. Fihn, R. J. Gibbons, D. K. Owens, S. V. Williams
Journal: Annals of Internal Medicine (2005)
Prognostic and Predictive Value of a Breast Cancer Expression Signature in Localized Prostate Cancer
Authors: Wassim Abida, Howard I. Scher
Journal: JAMA Oncology (2017)

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MAGELLAN-1, Part 2: glecaprevir and pibrentasvir for 12 or 16 weeks in patients with chronic hepatitis C virus genotype 1 or 4 and prior direct-acting antiviral treatment failure
Authors: F. Poordad, S. Pol, A. Asatryan, M. Buti, D. Shaw, C. Hézode, J. Lalezari, F. Felizarta, R.W. Reindollar, S.C. Gordon, S. Pianko, M.W. Fried, D.E. Bernstein, J. Gallant, C.-W. Lin, Y. Lei, T.I. Ng, T. Pilot-Matias, J. Kort, F. Mensa
Journal: Journal of Hepatology (2017)
Concurrent Treatment with Prolonged Exposure for Co-Occurring Full or Subthreshold Posttraumatic Stress Disorder and Substance Use Disorders: A Randomized Clinical Trial
Authors: Lesia M. Ruglass, Teresa Lopez-Castro, Santiago Papini, Therese Killeen, Sudie E. Back, Denise A. Hien
Journal: Psychotherapy and Psychosomatics (2017)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; To test whether an integrated prolonged exposure (PE) approach could address posttraumatic stress disorder (PTSD) symptoms effectively in individuals with co-occurring substance use disorders (SUD), we compared concurrent treatment of PTSD and SUD using PE (COPE) to relapse prevention therapy (RPT) for SUD and an active monitoring control group (AMCG). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We conducted a randomized 12-week trial with participants (&lt;i&gt;n&lt;/i&gt; = 110; 64% males; 59% African Americans) who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for full or subthreshold PTSD and SUD. Participants were randomly assigned to COPE (&lt;i&gt;n&lt;/i&gt; = 39), RPT (&lt;i&gt;n&lt;/i&gt; = 43), or AMCG (&lt;i&gt;n&lt;/i&gt; = 28). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; At the end-of-treatment, COPE and RPT demonstrated greater reduction in PTSD symptom severity relative to AMCG (COPE-AMCG = -34.06, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; RPT-AMCG = -22.58, &lt;i&gt;p&lt;/i&gt; = 0.002). Although the difference between COPE and RPT was not significant in the complete sample, the subset of participants with full (vs. subthreshold) PTSD demonstrated significantly greater reduction of PTSD severity in COPE relative to RPT. Both treatments were superior to AMCG in reducing the days of primary substance use (COPE-AMCG = -0.97, &lt;i&gt;p&lt;/i&gt; = 0.01; RPT-AMCG = -2.07, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Relative to COPE, RPT showed significantly more improvement in SUD outcome at end-of-treatment (RPT-COPE = -1.10, &lt;i&gt;p&lt;/i&gt; = 0.047). At 3-month follow-up, COPE and RPT maintained their treatment gains and were not significantly different in PTSD severity or days of primary substance use. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; COPE and RPT reduced PTSD and SUD severity in participants with PTSD + SUD. Findings suggest that among those with full PTSD, COPE improves PTSD symptoms more than a SUD-only treatment. The use of PE for PTSD was associated with significant decreases in PTSD symptoms without worsening of substance use.
Evolution of platelets in chronic hepatitis C infected patients and advanced liver fibrosis after direct-acting antiviral treatment
Authors: F. Sáez-Royuela, P. Linares, S. Calvo, I. Martín, C. Almohalla, F. Jorquera, H. Ramos, M. De Benito, B. Bernad, B. Alvarez, E.B. Aranda
Journal: Journal of Hepatology (2017)