tbuckley/cabot-search huggingface dataset:
8 weeks of ledipasvir-sofosbuvir for non-cirrhotic patients with HCV genotype 4: A single-arm multicenter phase 3b study (HepNed-001)
Authors: A. Boerekamps, T. Vanwolleghem, M. van der Valk, E. Van den Berk Guido, D. Posthouwe, D. Anton, B.V. Hoek, S. Ramsoekh, M.V. Kasteren, J. Schinkel, E. Florence, J.E. Arends, B. Rijnders
Journal: Journal of Hepatology (2018)
Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial
Authors: Stephan Stilgenbauer, Barbara Eichhorst, Johannes Schetelig, Peter Hillmen, John F. Seymour, Steven Coutre, Wojciech Jurczak, Stephen P. Mulligan, Anna Schuh, Sarit Assouline, Clemens-Martin Wendtner, Andrew W. Roberts, Matthew S. Davids, Johannes Bloehdorn, Talha Munir, Sebastian Böttcher, Lang Zhou, Ahmed Hamed Salem, Monali Desai, Brenda Chyla, Jennifer Arzt, Su Young Kim, Maria Verdugo, Gary Gordon, Michael Hallek, William G. Wierda
Journal: Journal of Clinical Oncology (2018)

Purpose Venetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration and European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 patients were enrolled in a safety expansion cohort. Extended analysis of all enrolled patients, including the effect of minimal residual disease (MRD) negativity on outcome, is now reported. Patients and Methods Overall, 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL received venetoclax 400 mg per day after an initial dose ramp up. Responses were based on 2008 International Workshop on Chronic Lymphocytic Leukemia criteria, with monthly physical exams and blood counts. Computed tomography scan was mandatory at week 36, after which assessment made was by clinical evaluation. Marrow biopsy was performed when complete remission was suspected. MRD was assessed by flow cytometry. Results Patients had a median of two prior therapies (range, zero to 10 therapies), 71% had TP53 mutation, and 48% had nodes that were ≥ 5 cm. Median time on venetoclax was 23.1 months (range, 0 to 44.2 months) and median time on study was 26.6 months (range, 0 to 44.2 months). For all patients, investigator-assessed objective response rate was 77% (122 of 158 patients; 20% complete remission) and estimated progression-free survival at 24 months was 54% (95% CI, 45% to 62%). For 16 patients who received prior kinase inhibitors, objective response rate was 63% (10 of 16 patients) and 24-month progression-free survival estimate was 50% (95% CI, 25% to 71%). By intent-to-treat analysis, 48 (30%) of 158 patients achieved MRD below the cutoff of 10
Stratification of hepatocellular carcinoma risk using the GLOBE score in patients with primary biliary cholangitis– the Global PBC Study Group
Authors: W.J. Lammers, P. Trivedi, G. Hirschfield, C. Corpechot, A. Floreani, F. Nevens, D. Thorburn, A. Pares, K.V. Kowdley, N. Larusso, P.M. Battezzati, C. Ponsioen, A.L. Mason, M.J. Mayo, P. Invernizzi, T. Bruns, G. Dalekos, V. Xavier, M. Harms, J. Goet, K. Lindor, H. Janssen, B. Hansen, H. Van Buuren
Journal: Journal of Hepatology (2018)
Metabolomic patterns associated with known genetic variants for hepatic steatosis and non-alcoholic steatohepatitisidentify biomarkers that may be of utility in predicting adverse liver outcomes
Authors: J. Mann, M. Allison, L. Wittemans, E.D.L. Rolfe, F. Imamura, N. Forouhi, L.A. Lotta, J.L. Griffin, A. Koulman, C. Langenberg, N.J. Wareham
Journal: Journal of Hepatology (2018)
Bursectomy versus omentectomy alone for resectable gastric cancer (JCOG1001): a phase 3, open-label, randomised controlled trial
Authors: Yukinori Kurokawa, Yuichiro Doki, Junki Mizusawa, Masanori Terashima, Hitoshi Katai, Takaki Yoshikawa, Yutaka Kimura, Shuji Takiguchi, Yasunori Nishida, Norimasa Fukushima, Yoshiaki Iwasaki, Masahide Kaji, Motohiro Hirao, Hiroshi Katayama, Mitsuru Sasako
Journal: The Lancet. Gastroenterology & hepatology (2018)
Prevalence of alcoholic steatosis in the general adult Portuguese population
Authors: J.A.M.C.P. Leitao, S. Carvalhana, J. Cochicho, A.P. Silva, F. Velasco, I.S. Medeiros, A.C. Alves, M. Bourbon, B. Oliveiros, V. Rodrigues, A. Carvalho, H. Cortez-Pinto
Journal: Journal of Hepatology (2018)
HCV screening in the adult general population of a basic health area in the Valencian Region (Spain)
Authors: L.G.-E. Viejo, A.G. Herola, I.S. Lloret, I. Clemente, F. Sanchez-Ruano, C.Q. Ivorra, I.A. Saavedra, J. Valverde
Journal: Journal of Hepatology (2018)
First-in-human phaseⅠstudy of JPH203 in patients with advanced solid tumors.
Authors: Naohiro Okano, Kirio Kawai, Yoshiya Yamauchi, Takaaki Kobayashi, Daisuke Naruge, Fumio Nagashima, Hitoshi Endou, Junji Furuse
Journal: Journal of Clinical Oncology (2018)

419 Background: Uptake of amino acids is essential for cancer growth. L-type amino acid transporter-1 (LAT-1) is overexpressed in various cancers, and uptake of LAT-1 substrate amino acids is known to have a critical role in cancer growth. JPH203 is a novel, selective, LAT-1 inhibitor. A first-in-human phase I study of JPH203 was designed to determine the safety, maximum-tolerated dose (MTD) and recommended dose. This study included evaluation of the anti-tumor effect, pharmacokinetics, and pharmacodynamics of JPH203 and analyzed plasma free amino acids. Methods: JPH203 was administered intravenously for 7 days followed by 21 days’ rest at planned doses ranging from 12 to 110 mg/m 2 in patients with advanced solid tumors refractory to standard therapy. Before starting this schedule, we confirmed safety of a single dose of JPH203. Dose-limiting toxicity was evaluated during the first cycle, using a 3+3 design. Results: 17 patients were enrolled from January 2015 to August 2016. One patient was discontinued after a single dose of JPH203 because of tumor progression. Dosage was escalated up to 85 mg/m 2 . Grade 3 liver dysfunction occurred in 1 of 6 patients at 60 mg/m 2 and in the first patient at 85 mg/m 2 . Therefore, it was determined that MTD was 60 mg/m 2 . Common treatment-related adverse events were increased ALT/AST, malaise, nausea, hypertension and fever of Grade 1 or 2. Partial response was achieved in a patient with biliary tract cancer (BTC) who continued JPH203 for two years without progression. Disease control (PR+SD) was observed in 3 of 5 patients with BTC and 2 of 6 with colorectal cancer. LAT-1 substrate amino acids and branched chain amino acids including LAT-1 substrate amino acids were higher in patients with BTC than in those with other cancers. All patients with disease control had a body mass index more than the median of 20.5 kg/m 2 . In exploratory analysis, longer survival was achieved in patients with high inhibition of uptake of LAT-1 substrate amino acids, compared with patients with low inhibition of uptake. Conclusions: JPH203 was well tolerated, resulting in promise against BTC. This phase I study suggested that LAT-1 could be targeted in treatment for advanced BTC, because LAT-1 substrate amino acids in plasma tended to remain high. Clinical trial information: UMIN000016546.
Do laboratory challenge tests for occupational asthma represent what happens in the workplace?
Authors: P. Sherwood Burge, Vicky C. Moore, Alastair S. Robertson, Gareth I. Walters
Journal: European Respiratory Journal (2018)

Specific inhalation challenge (SIC) is the diagnostic reference standard for occupational asthma; however, a positive test cannot be considered truly significant unless it can be reproduced by usual work exposures. We have compared the timing and responses during SIC in hospital to Oasys analysis of serial peak expiratory flow (PEF) during usual work exposures.All workers with a positive SIC to occupational agents between 2006 and 2015 were asked to measure PEF every 2 h from waking to sleeping for 4 weeks during usual occupational exposures. Responses were compared between the laboratory challenge and the real-world exposures at work.All 53 workers with positive SIC were included. 49 out of 53 had records suitable for Oasys analysis, 14 required more than one attempt and all confirmed occupational work-related changes in PEF. Immediate SIC reactors and deterioration within the first 2 h of starting work were significantly correlated with early recovery, and late SIC reactors and a delayed start to workplace deterioration were significantly correlated with delayed recovery. Dual SIC reactions had features of immediate or late SIC reactions at work rather than dual reactions.The concordance of timings of reactions during SIC and at work provides further validation for the clinical significance of each test.
The vaginal microbiota and its association with human papillomavirus, Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections: a systematic review and meta-analysis
Authors: J. Tamarelle, A.C.M. Thiébaut, B. de Barbeyrac, C. Bébéar, J. Ravel, E. Delarocque-Astagneau
Journal: Clinical Microbiology and Infection (2018)
TCTAP C-032 The Stentless Strategy with Direct Coronary Atherectomy and Drug-coated Balloon Was Useful for Young and Bleeding Risk Case
Authors: Takamasa Tanaka, Atsunori Okamura, Hiroyuki Nagai, Tomohiro Yamasaki, Akinori Sumiyoshi, Kota Tanaka, Kenshi Fujii
Journal: Journal of the American College of Cardiology (2018)
P515Phosphorylcholine antibodies preserve cardiac function and reduce infarct size by attenuation of the inflammatory response following myocardial ischemia-reperfusion injury
Authors: N J Pluijmert, RCM De Jong, M R De Vries, K Pettersson, J W Jukema, P H A Quax
Journal: Cardiovascular Research (2018)

On behalf of: Cardiovascular and metabolic research group Introduction: Metabolic diseases including hypercholesterolemia are risk factors for ischemic heart disease.We have previously shown that endogenous cardioprotective mechanisms are largely impaired in in vivo and ex vivo hypercholesterolemic models.In vitro hypercholesterolemic cell culture models would be suitable for exploration of intracellular signaling pathways or cardioprotective drug testing in hypercholesterolemia and ischemia/reperfusion comorbidity conditions.Aim: Our aim was to set up an in vitro comorbidity model of ischemia/reperfusion and hypercholesterolemia in cardiac myocytes.Methods: Cardiomyocytes were isolated from neonatal rats and cultured for 3 days in control or cholesterol-containing supplement (SP) with increasing concentrations of components (group SP1, SP2, SP3).Filippin staining was performed to quantify the membrane cholesterol content changes.We applied a 4-hour simulated ischemia followed by 2-hour of simulated reperfusion (SI/R).Normoxic groups served as controls.After the SI/R the cell viability was measured.For the assessment of oxidative stress, 2',7'-dichlorodihydrofluorescein-diacetate staining (for reactive oxygen species -ROS) and dihydroethidium (for superoxide level) were applied.Results: The membrane cholesterol concentration was increased in the treated groups (SP1: 135.8613%,SP2: 170620%, SP3: 190626%).The viability of neonatal cardiomyocytes decreased significantly at the highest cholesterol concentration after SI/R (SP1: 135635%, SP2: 132640%, SP3: 58628%).In normoxic condition, superoxide level elevated significantly (SP1: 137611%, SP2: 134619%, SP3: 183614%) and ROS level in neonatal cardiomyocytes elevated only after SI/R (SP3: 2526157% -all data are expressed in percentage compared to the vehicle control groups). Conclusion:We have found that SI/R injury in the presence of hypercholesterolemia aggravated cell death and increased oxidative stress in vitro, which mimics the effect of hypercholesterolemia in vivo.Therefore, the present in vitro comorbidity model may be suitable for testing SI/R injury in the presence of hypercholesterolemia.P513 methodological approaches to detection autophagy in muscle cell line C2C12 and influence of destine gene mutations an the formation dynamics of autophagosome
Benefit of Bet v 1 contiguous overlapping peptide immunotherapy persists during first follow-up season
Authors: Alexander Kettner, Gilles DellaCorte, Fréderic de Blay, Lars Jacobsen, Marek Jutel, Margitta Worm, Vincent Charlon, Kim Simonsen, Christophe Reymond, François Spertini
Journal: Journal of Allergy and Clinical Immunology (2018)
Using hepatitis C viral load distribution data from a global database to derive the optimal limit of detection for a point-of-care diagnostic test
Authors: J. Morgan Freiman, J. Wang, P. Easterbrook, G. Kamkamidze, M. Krajden, A. Loarec, F. Marinucci, N.V. Kinh, R. Njouom, S.S. Solomon, T. Tsertsvadze, L.F. White, C. Denkinger, B. Linas
Journal: Journal of Hepatology (2018)
TCTAP A-085 A Clinical Study of Risk Factor Profile Especially with Reference to Diabetes in Patients Presenting with Angina and Showing Normal Coronaries
Authors: Raghu Kishore Galla, Maddury Jyotsna, Lalita Nemani, Rama Krishna Janapati, Indrani Garre, Janaswamy Vibhav Sri Narayana
Journal: Journal of the American College of Cardiology (2018)
Pregnancy and autoimmune hepatitis: presentation and outcomes
Authors: L.P. Llovet, D. Horta, M.G. Eliz, M. Berenguer, E. Fábrega, F. Sáez-Royuela, M. García-Retortillo, Y.S. Torrijos, M.R. Gomez, C. Fernández-Rodríguez, E.G. Domínguez, A. Parés, M.C. Londoño
Journal: Journal of Hepatology (2018)
Treating Blood Pressure Correctly by Measuring It Correctly
Authors: Robert B. Baron
Journal: JAMA Internal Medicine (2018)

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Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab
Authors: Fanny Zulay Acero Brand, Nicolas Suter, Jean-Philippe Adam, Bernard Faulques, Antonio Maietta, Denis Soulières, Normand Blais
Journal: Journal for ImmunoTherapy of Cancer (2018)

Pembrolizumab is an anti-programmed death 1 (PD-1) receptor monoclonal antibody that has shown activity as second line treatment for metastatic head and neck squamous cell carcinoma (HNSCC). Immune-related adverse events are now well described complications of PD-1 inhibitors and most organ sites have been shown to be potentially affected.We describe a 69-year old patient with a relapsed squamous cell carcinoma of the supraglottic larynx with lung metastasis after receiving adjuvant concurrent cisplatin and radiotherapy. This patient was treated with pembrolizumab and benefitted from therapy with major radiological improvement of disease. After 14 cycles of pembrolizumab 200 mg IV each 3 weeks, he experienced dysphagia that evolved to a grade 4 oral cavity and pharynx mucositis and esophagitis. Histologic analysis showed ulcerative esophagitis associated with granulation tissue. Pembrolizumab was discontinued and IV methylprednisolone 2 mg/kg/day was initiated. Two days later, the patient reported a 50% recovery in his symptoms which were completely resolved after 2 weeks. Methylprednisolone was switched to oral prednisone and a taper was planned over 8 weeks. During the fourth week of taper, the patient presented recurrence of grade 1 oral mucositis. Prednisone was increased 2 mg/kg/day for 2 weeks followed by slower tapering over a period of 5 months. Pembrolizumab was not reinitiated.This is the first described case of grade 4 immune mucositis and esophagitis associated with pembrolizumab. Because the use of pembrolizumab is increasing in oncology, pharmacists and physicians should be aware of this rare manifestation.
Anxiety, Depression, and Decision Making: A Computational Perspective
Authors: Sonia J. Bishop, Christopher Gagne
Journal: Annual Review of Neuroscience (2018)

In everyday life, the outcomes of our actions are rarely certain. Further, we often lack the information needed to precisely estimate the probability and value of potential outcomes as well as how much effort will be required by the courses of action under consideration. Under such conditions of uncertainty, individual differences in the estimation and weighting of these variables, and in reliance on model-free versus model-based decision making, have the potential to strongly influence our behavior. Both anxiety and depression are associated with difficulties in decision making. Further, anxiety is linked to increased engagement in threat-avoidance behaviors and depression is linked to reduced engagement in reward-seeking behaviors. The precise deficits, or biases, in decision making associated with these common forms of psychopathology remain to be fully specified. In this article, we review evidence for which of the computations supporting decision making are altered in anxiety and depression and consider the potential consequences for action selection. In addition, we provide a schematic framework that integrates the findings reviewed and will hopefully be of value to future studies.
Switched Memory B Cells Are Increased in Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis and Their Change Over Time Is Related to Response to Tumor Necrosis Factor Inhibitors
Authors: Emiliano Marasco, Angela Aquilani, Simona Cascioli, Gian Marco Moneta, Ivan Caiello, Chiara Farroni, Ezio Giorda, Valentina D'Oria, Denise Pires Marafon, Silvia Magni‐Manzoni, Rita Carsetti, Fabrizio De Benedetti
Journal: Arthritis & Rheumatology (2018)

Objective To investigate whether abnormalities in B cell subsets in patients with juvenile idiopathic arthritis ( JIA ) correlate with clinical features and response to treatment. Methods A total of 109 patients diagnosed as having oligoarticular JIA or polyarticular JIA were enrolled in the study. B cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry. Results Switched memory B cells were significantly increased in patients compared to age‐matched healthy controls ( P &lt; 0.0001). When patients were divided according to age at onset of JIA , in patients with early‐onset disease (presenting before age 6 years) the expansion in switched memory B cells was more pronounced than that in patients with late‐onset disease and persisted throughout the disease course. In longitudinal studies, during methotrexate ( MTX ) treatment, regardless of the presence or absence of active disease, the number of switched memory B cells increased significantly (median change from baseline 36% [interquartile range {IQR} 15, 66]). During treatment with MTX plus tumor necrosis factor inhibitors ( TNF i), in patients maintaining disease remission, the increase in switched memory B cells was significantly lower than that in patients who experienced active disease (median change from baseline 4% [IQR −6, 32] versus 41% [IQR 11, 73]; P = 0.004). The yearly rate of increases in switched memory B cells was 1.5% in healthy controls, 1.2% in patients who maintained remission during treatment with MTX plus TNF i, 4.7% in patients who experienced active disease during treatment with MTX plus TNF i, and ~4% in patients treated with MTX alone. Conclusion Switched memory B cells expand during the disease course at a faster rate in JIA patients than in healthy children. This increase is more evident in patients with early‐onset JIA . TNF i treatment inhibits this increase in patients who achieve and maintain remission, but not in those with active disease.
Adherence to AASLD treatment guidelines on treatment initiation among treatment-eligible patients with chronic hepatitis B: Experiences from primary care and referral practices
Authors: V.H. Nguyen, A. Le, M. Chung, T. Johnson, B. Levitt, H. Nguyen, K. Nguyen, H. Trinh, C. Wong, C. Wong, J. Zhang, J. Li, G. Garcia, M. Nguyen
Journal: Journal of Hepatology (2018)
Nocturnal cerebral hypoxia in obstructive sleep apnoea: a randomised controlled trial
Authors: Esther I. Schwarz, Michael Furian, Christian Schlatzer, John R. Stradling, Malcolm Kohler, Konrad E. Bloch
Journal: European Respiratory Journal (2018)

Cerebral hypoxia may promote cerebral damage in patients with obstructive sleep apnoea (OSA). We investigated whether OSA patients experience nocturnal cerebral hypoxia that is prevented by continuous positive airway pressure (CPAP).OSA patients using CPAP underwent sleep studies including pulse oximetry (arterial oxygen saturation (SpO2 )) and near-infrared spectroscopy to monitor cerebral tissue oxygenation (CTO) at baseline and after 2 weeks on either subtherapeutic or therapeutic CPAP according to randomised allocation. Changes in oxygenation at end of the 2-week intervention were compared between groups.Among 21 patients (mean apnoea/hypopnoea index 50.3 events·h-1), OSA recurred in all nine patients using subtherapeutic CPAP and in none of the patients using therapeutic CPAP: mean (95% CI) between-group differences in changes of oxygen desaturation index from baseline to 2 weeks +40.7 (31.1-50.4) events·h-1 for SpO2 and +37.0 (25.3-48.7) events·h-1 for CTO (both p<0.001). Mean nocturnal SpO2 and CTO decreased more in patients using subtherapeutic versus therapeutic CPAP: -2.4 (-3.4--1.1)% and -3.8 (-7.4--0.1)%, respectively; both p<0.03. Severe CTO drops ≥13% associated with cerebral dysfunction in previous studies occurred in four out of nine patients using subtherapeutic CPAP, but in none out of 12 patients using therapeutic CPAP (p=0.01).In patients with OSA, CPAP withdrawal resulted in nocturnal cerebral deoxygenation, suggesting a role of cerebral hypoxia in predisposing untreated OSA patients to cerebral damage.
Changes in hepatic steatosis measured by CAP-fibroscan in patients with chronic hepatitis C treated with direct action antivirals
Authors: P. Linares, R. Quinones, B. Álvarez-Cuenllas, F. Jorquera, N. Reyes, C. Villar, G. Molina, R.P. Fernandez, L. Vaquero
Journal: Journal of Hepatology (2018)
P565Vascular endothelial cells exposed to oxidized HDL increases LOX-1 destination at the plasma membrane through a mechanism involving ROS/NOX/NF-kB/LOX-1 pathway
Authors: F Simon, L Perez
Journal: Cardiovascular Research (2018)

phosphorylation on the inhibitory Ser377 in response to inflammatory stimuli.Endothelial cell-specific CSE deletion reduced H2S bioavailability by 70%, increased 5-fold L-cystathionine circulating levels and resulted in endothelial cell dysfunction in murine aortas, elevated monocyte adhesion and accelerated atherosclerosis.Overall, reduced H2S bioavailability in the murine and human vascular wall resulted in the loss of sulfhydration of the RNA binding protein HuR, which potentiated the homodimerization of HuR and its capacity to bind to the 3' UTR of its targets CD62E and CTSS.Conclusion: H2S produced by CSE, constitutively S-sulfhydrates HuR to inhibit its activity and limit the expression of its pro-atherogenic protein targets.L-cystathionine may serve as a biomarker of endothelial cell dysfunction and a prognostic marker of CSE activity and atherosclerosis development. P565Vascular endothelial cells exposed to oxidized HDL increases LOX-1 destination at the plasma membrane through a mechanism involving ROS/NOX/NF-kB/LOX-1 pathway