tbuckley/cabot-search huggingface dataset:
Dual Inhibition of EZH2 and EZH1 Sensitizes PRC2-Dependent Tumors to Proteasome Inhibition
Authors: Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
Journal: Clinical Cancer Research (2017)

Abstract Purpose: EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on multiple myeloma and prostate cancer. Experimental Design: In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in multiple myeloma cell lines, primary patient cells, and in a xenograft model. RNA-seq and ChIP-seq were performed to uncover the targets of UNC1999 in multiple myeloma. The efficacy of the combination therapy was validated in prostate cancer cell lines. Results: Proteasome inhibitors repressed EZH2 transcription via abrogation of the RB-E2F pathway, thereby sensitizing EZH2-dependent multiple myeloma cells to EZH1 inhibition by UNC1999. Correspondingly, combination of proteasome inhibitors with UNC1999, but not with an EZH2-specific inhibitor, induced synergistic antimyeloma activity in vitro. Bortezomib combined with UNC1999 remarkably inhibited the growth of myeloma cells in vivo. Comprehensive analyses revealed several direct targets of UNC1999 including the tumor suppressor gene NR4A1. Derepression of NR4A1 by UNC1999 resulted in suppression of MYC, which was enhanced by the combination with bortezomib, suggesting the cooperative blockade of PRC2 function. Notably, this combination also exhibited strong synergy in prostate cancer cells. Conclusions: Our results identify dual inhibition of EZH2 and EZH1 together with proteasome inhibition as a promising epigenetics-based therapy for PRC2-dependent cancers. Clin Cancer Res; 23(16); 4817–30. ©2017 AACR.
Peripheral and intrahepatic virological phenotyping in eAg negative chronic hepatitis B to evaluate risk of disease progression and hepatocellular carcinoma in the “grey-zone” viral load cohort
Authors: V. Svicher, R. Salpini, L. Colagrossi, A. Battisti, L. Piermatteo, N. Hansi, C.F. Perno, U.S. Gill, P.T.F. Kennedy
Journal: Journal of Hepatology (2017)
Osteoprotegerin is more than a serum marker in liver fibrosis
Authors: A. Adhyatmika, L. Beljaars, K.S.S. Putri, C. Reker-Smit, C.E. Boorsma, B. Guney, A. Haak, E. Post, K. Poelstra, B.N. Melgert
Journal: Journal of Hepatology (2017)
WORKLOAD SPIKES COMBINED WITH HIGH CUMULATIVE LOAD IS ASSOCIATED WITH INCREASED INJURY RISK IN ELITE RUGBY SEVENS PLAYERS
Authors: Stephen West, Sean Williams, Matthew Cross, Dan Howells, Remi Mobed, Simon Kemp, Keith Stokes
Journal: British Journal of Sports Medicine (2017)

Background Match and training demands differ between seven and fifteen-a-side rugby. The association between training load and injury risk has not been examined in elite Rugby Sevens. Objective To explore the association between training load measures and injury risk in elite Rugby Sevens players. Design Two-season (2014/15 and 2015/16) prospective cohort study. Setting The England men's Rugby Sevens squad. Participants 42 players (31 players followed over one-season, 11 players over two-seasons). Assessment of Risk Factors Training loads were recorded for all sessions using the session-Rating of Perceived Exertion method. A generalised linear mixed effects model examined the association between training load measures and injury risk in the subsequent week. The acute:chronic workload variable (one-week load divided by four-week average load) was parsed into tertiles: low=&lt;1.15; medium=1.15–1.45; high=&gt;1.45. Main Outcome Measurements Injury and the relative risk (RR) associated with increases in training load measures. Results 152 training and 30 match injuries were recorded. The incidence rate was 91/1000 player-match-hours (90% CI: 68–123) and 14/1000 player-training-hours (90% CI: 12–16). Mean severity (day's absence) of injuries was 31 days during matches and 21 days during training. There was a substantial interaction between four-week cumulative load and acute:chronic workloads, such that typically high versus typically low four-week cumulative loads (i.e., a 7140 AU difference) coupled with high acute:chronic workloads were clearly associated with injury risk (RR: 2.08, 90% CI 1.17–3.68). This effect was unclear in the low (RR: 1.02, 90% CI: 0.62–1.68) and medium (RR: 1.44, 90% CI: 0.81–2.55) acute:chronic workload ranges. Conclusions The injury incidence rate in elite Rugby Sevens training is substantially higher than in the 15-a-side game. The coupling of high cumulative loads with high acute:chronic workloads was associated with an increased injury risk, therefore practitioners should avoid high acute:chronic workloads during periods of high cumulative load.
Hepatitis E virus infection and acute non-traumatic neurological injury: an international prospective pilot study
Authors: G.W. Webb, J.J.J. van Eijk, P. Cintas, B. Norton, R.G. Madden, C. Jones, J.G. Hunter, N. Devooght-Johnson, J. Pique, K. Woolson, M. Saunders, B.N. Mclean, E. Househam, J. Griffiths, R.P. Bendall, J. Izopet, N. Kamar, B.C. Jacobs, H.R. Dalton
Journal: Journal of Hepatology (2017)
Effect of age on risk for atrial fibrillation following robotic-assisted video-thoracoscopic pulmonary lobectomy
Authors: J. Glover, S. Reynolds, E. Ng, M. Echavarria, F. Velez-Cubian, C. Moodie, J. Garrett, J. Fontaine, E. Toloza
Journal: Annals of Oncology (2017)
Mohs Micrographic Surgery Use in the United States Based on Medicare Data
Authors: Jonathan Kantor
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Prognostic delineation of papillary cholangiocarcinoma based on the invasive proportion.
Authors: Shunsuke Onoe, Yoshie Shimoyama, Tomoki Ebata, Yukihiro Yokoyama, Tsuyoshi Igami, Gen Sugawara, Shigeo Nakamura, Masato Nagino
Journal: Journal of Clinical Oncology (2013)

4119 Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a presumed precursor lesion in biliary carcinogenesis, clinicopathologically overlapping with papillary cholangiocarcinoma (PCC); however, as IPNB has no standardized definition, this relationship remains equivocal. Here, we aimed to develop a new PCC prognostic model, focusing on the invasive proportion. Methods: Among 605 patients with surgically resected cholangiocarcinoma in Nagoya University Hospital between 2000 and 2011, 173 (29%) had intraductal exophytic papillary lesions. These were divided into four subsets based on the invasive component: non-invasive (PCC-1, n = 13), ≤10% (PCC-2, n = 30), 11-50% (PCC-3, n = 55), and &gt;50% (PCC-4, n = 75). Results: Invasion beyond the ductal wall was observed in 83% of PCCs and 99% of non-papillary cholangiocarcinomas (NPCC, n = 432; P &lt; 0.001). Regional lymph node metastases were more frequent in NPCC (48%) than PCC (32%; P &lt; 0.001). Five-year survival was better for PCC (52%) than NPCC (37%; P &lt; 0.001), indicating the papillary component to be a significant independent prognosticator. PCC-4 and NPCC had similar clinicopathological features and overlapping survival curves: 32% and 37% at 5 years (P = 0.877), both lower than those of PCC-1, PCC-2, and PCC-3 (respectively, 91%, 71%, and 60% at 5 years; P &lt; 0.01 in all combinations). Multivariate analysis in PCC showed &gt;50% invasive component, nodal metastasis, and positive surgical margin as independent predictors. Conclusions: The presence of an intraductal papillary component was an important determinant of better survival in cholangiocarcinoma. PCC exhibited a more aggressive histologic character and worse survival with progression of the invasive component. PCC with &gt;50% invasive component was morphologically and prognostically similar to NPCC. Therefore, we propose that IPNB should be nosologically applied only for PCC cases with ≤50% invasive component.
Tai Chi Chih Compared With Cognitive Behavioral Therapy for the Treatment of Insomnia in Survivors of Breast Cancer: A Randomized, Partially Blinded, Noninferiority Trial
Authors: Michael R. Irwin, Richard Olmstead, Carmen Carrillo, Nina Sadeghi, Perry Nicassio, Patricia A. Ganz, Julienne E. Bower
Journal: Journal of Clinical Oncology (2017)

Purpose Cognitive behavioral therapy for insomnia (CBT-I) and Tai Chi Chih (TCC), a movement meditation, improve insomnia symptoms. Here, we evaluated whether TCC is noninferior to CBT-I for the treatment of insomnia in survivors of breast cancer. Patients and Methods This was a randomized, partially blinded, noninferiority trial that involved survivors of breast cancer with insomnia who were recruited from the Los Angeles community from April 2008 to July 2012. After a 2-month phase-in period with repeated baseline assessment, participants were randomly assigned to 3 months of CBT-I or TCC and evaluated at months 2, 3 (post-treatment), 6, and 15 (follow-up). Primary outcome was insomnia treatment response-that is, marked clinical improvement of symptoms by the Pittsburgh Sleep Quality Index-at 15 months. Secondary outcomes were clinician-assessed remission of insomnia; sleep quality; total sleep time, sleep onset latency, sleep efficiency, and awake after sleep onset, derived from sleep diaries; polysomnography; and symptoms of fatigue, sleepiness, and depression. Results Of 145 participants who were screened, 90 were randomly assigned (CBT-I: n = 45; TCC: n = 45). The proportion of participants who showed insomnia treatment response at 15 months was 43.7% and 46.7% in CBT-I and TCC, respectively. Tests of noninferiority showed that TCC was noninferior to CBT-I at 15 months ( P = .02) and at months 3 ( P = .02) and 6 ( P < .01). For secondary outcomes, insomnia remission was 46.2% and 37.9% in CBT-I and TCC, respectively. CBT-I and TCC groups showed robust improvements in sleep quality, sleep diary measures, and related symptoms (all P < .01), but not polysomnography, with similar improvements in both groups. Conclusion CBT-I and TCC produce clinically meaningful improvements in insomnia. TCC, a mindful movement meditation, was found to be statistically noninferior to CBT-I, the gold standard for behavioral treatment of insomnia.
2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease
Authors: Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Donald E. Casey, Kim A. Eagle, Luke K. Hermann, Eric M. Isselbacher, Ella A. Kazerooni, Nicholas T. Kouchoukos, Bruce W. Lytle, Dianna M. Milewicz, David L. Reich, Souvik Sen, Julie A. Shinn, Lars G. Svensson, David M. Williams
Journal: Circulation (2010)
A Large Right Shoulder Mass
Authors: Minerva A. Romero Arenas, Sarah B. Fisher, Reza J. Mehran
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Altered Dopamine Responses to Monetary Rewards in Female Fibromyalgia Patients with and without Depression: A [&lt;sup&gt;11&lt;/sup&gt;C]Raclopride Bolus-plus-Infusion PET Study
Authors: Katharina Ledermann, Josef Jenewein, Haiko Sprott, Gregor Hasler, Ulrich Schnyder, Geoffrey Warnock, Anass Johayem, Spyridon Kollias, Alfred Buck, Chantal Martin-Soelch
Journal: Psychotherapy and Psychosomatics (2017)

We herein report results of our pilot study using bolus-plus-infusion [11C]raclopride positron emission tomography (PET) scanning to assess endogenous dopamine (DA) release associated with unpredictable monetary rewards in patients with fibromyalgia syndrome (FMS) and healthy controls. The aim of this project was to investigate whether FMS was associated with a dysfunction of the central reward system.
Twenty-four women with FMS, based on the American College of Rheumatology classification criteria for FMS, and 17 age-matched healthy women were included in the study. Eleven of the patients with FMS met the DSM-V criteria for major depressive disorder (MDD) [1] (current and past depressive episode). A slot machine task validated by Martin-Soelch et al. [2], which has been shown to reliably induce equilibrium and task-related changes in raclopride binding, was used to measure endogenous DA release in response to unpredictable rewards. PET examinations were performed on a full ring PET/computerized tomography (CT) scanner with a 15.3-cm axial field of view in 3-dimensional mode (Discovery DSTX, GE Healthcare, Waukesha, WI, USA), at the Department of Nuclear Medicine, University Hospital Zurich, Switzerland. The emission data were corrected for attenuation, scatter, random, and dead time using the corresponding CT (120 kV/80 mA), and reconstructed using filtered back projection.
Comparison of modified (m)RECISTand RECIST 1.1 assessments in the phase 3 RESORCE trial comparing regorafenib and placebo in patients with hepatocellular carcinoma who progressed during sorafenib treatment
Authors: J. Bruix, P. Merle, A. Granito, Y.-H. Huang, G. Bodoky, M. Pracht, . Yokosuka, O. Rosmorduc, V. Breder, R. Gerolami, G. Masi, P.J. Ross, S. Qin, T. Song, J.-P. Bronowicki, I. Ollivier-Hourmand, M. Kudo, A. Baumhauer, M.-A. LeBerre, G. Meinhardt, G. Han
Journal: Journal of Hepatology (2017)
Effect of statins and metformin on survival in epithelial ovarian cancer.
Authors: Christina Tierney, Craig Miller, Kevin Holcomb, Yue Wu, Sandeep Raj, Astrid Marshall, Thomas A. Caputo, Divya Gupta
Journal: Journal of Clinical Oncology (2015)

e16561 Background: Prior studies have shown that metformin and statin medications may have anti-cancer properties in solid tumors. The study’s objective is to analyze if their use is associated with progression-free survival (PFS) or overall survival (OS) in epithelial ovarian cancer. Methods: This single-institution retrospective cohort study included patients treated for epithelial ovarian (Ov), fallopian tube (Fp) or primary peritoneal (Pp) cancers from 2000-2013. Patients with complete medical records were included. Exclusion criteria were no adjuvant chemotherapy, no primary or interval cytoreductive surgery, borderline pathology, or other active cancers within 5 years of current diagnosis. Clinical data was extracted from electronic medical records, including demographics, FIGO stage, co-morbidities, concominant medications and cancer treatment. Cox regression analysis and Fisher’s exact test were used to evaluate the associations between the variables and PFS and OS. Results: Of the 950 patients identified, 178 met inclusion criteria (8% Pp, 12% Fp, and 80% Ov). Most patients had primary cytoreductive surgery (79%). FIGO stage distribution was 35% I-II, 53% III, 12% IV. A total of 67% had serous only cancers (67%), and 87% received platinum-taxane adjuvant therapy; 48% were overweight/obese (BMI > 25), 7% had diabetes, and 23% had hyperlipidemia. On multivariate analysis, non-serous pathology and primary Fp cancer were associated with improved PFS (p < 0.0001, p = 0.004, respectively). BMI, diabetes, hyperlipidemia, statin or metformin use were not associated with PFS or OS in all patients. Stage III/IV patient with serous cancer who did not take statins or metformin had an improved PFS (HR 1.8, p = 0.045). Conclusions: Statin or metformin therapies do not benefit patients with epithelial ovarian cancers. More research is indicated on the anti-cancer properties of these agents and the association between metabolic diseases and ovarian cancer.
Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls
Authors: Christoph U. Correll, Marco Solmi, Nicola Veronese, Beatrice Bortolato, Stella Rosson, Paolo Santonastaso, Nita Thapa‐Chhetri, Michele Fornaro, Davide Gallicchio, Enrico Collantoni, Giorgio Pigato, Angela Favaro, Francesco Monaco, Cristiano Kohler, Davy Vancampfort, Philip B. Ward, Fiona Gaughran, André F. Carvalho, Brendon Stubbs
Journal: World Psychiatry (2017)

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta‐analysis is lacking. We conducted a large‐scale meta‐analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD‐related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4‐13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross‐sectional studies (odds ratio, OR=1.53, 95% CI: 1.27‐1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47‐1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21‐1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7‐5.3) during a median follow‐up of 8.4 years (range 1.8‐30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60‐1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30‐1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26‐2.14), congestive heart failure (HR=2.10, 95% CI: 1.64‐2.70), and CVD‐related death (HR=1.85, 95% CI: 1.53‐2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD‐related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large‐scale meta‐analysis confirms that SMI patients have significantly increased risk of CVD and CVD‐related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention.
High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block
Authors: Anna R Lisney, Franziska Szelinski, Karin Reiter, Gerd R Burmester, Thomas Rose, Thomas Dörner
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB. Methods Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied. SIGLEC1 expression was measured by flow cytometry and was correlated to plasma IFN-α levels measured by ELISA, and IFN-γ-induced protein 10 (IP-10) levels measured by Bio-Plex technique. Results Mothers of affected children had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children. SIGLEC1 and IFN-α expression were reduced by hydroxychloroquine and oral glucocorticoids. Conclusions High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development, and these women may benefit especially from IFN-α directed therapy, for example with hydroxychloroquine.
A two gene-based risk score predicts alcoholic cirrhosis development in males with at-risk alcohol consumption
Authors: F. Ferri, R. Mancina, M. Mischitelli, A. Farcomeni, E. Poli, L. Parlati, M.A. Burza, A. De Santis, C. Codazzo, F. Attilia, M. Rando, M.L. Attilia, S. Romeo, S.G. Corradini
Journal: Journal of Hepatology (2017)
Effects of Exercise on Liver Fat and Metabolism in Alcohol Drinkers
Authors: David Houghton, Kate Hallsworth, Christian Thoma, Sophie Cassidy, Timothy Hardy, Sarah Heaps, Kieren G. Hollingsworth, Roy Taylor, Christopher P. Day, Steven Masson, Stuart McPherson, Quentin M. Anstee, Michael I. Trenell
Journal: Clinical Gastroenterology and Hepatology (2017)