tbuckley/cabot-search huggingface dataset:
The management of menopause in women with a history of endometriosis: a systematic review
Authors: L.C. Gemmell, K.E. Webster, S. Kirtley, K. Vincent, K.T. Zondervan, C.M. Becker
Journal: Human Reproduction Update (2017)

Endometriosis is typically regarded as a premenopausal disease, resolving after natural or iatrogenic menopause due to declining oestrogen levels. Nonetheless, case reports over the years have highlighted the incidence of recurrent postmenopausal endometriosis. It is now clear that both recurrence and malignant transformation of endometriotic foci can occur in the postmenopausal period. Postmenopausal women are commonly treated with hormone replacement therapy (HRT) to treat climacteric symptoms and prevent bone loss; however, HRT may reactivate endometriosis and stimulate malignant transformation in women with a history of endometriosis. Given the uncertain risks of initiating HRT, it is difficult to determine the best menopausal management for this group of women.
A behavioral Intervention improves the rate of hepatitis C treatment initiation among HIV/HCV coinfected patients: results of a randomized controlled trial
Authors: J.J. Weiss, C. Aaronson, L. Cervantes, M. Georgi, K. Prochno, T.R. Miller, T. Kang, S. Prieto, G. Mhango, S. Heffron, L.A. Lugo, J. Fishberger, M. Zewde, A. Stivala, O. Douglas, D. Ferris, D.T. Dieterich, J. Wisnivesky
Journal: Journal of Hepatology (2017)
Development of human liver extracellular matrix hydrogel for three dimensional cell culture and cell transplantation
Authors: L. Frenguelli, W. Al-Akkad, C. Crowley, M. Tiwari, A. Mani, A. Telese, P.D. Coppi, K. Moore, K. Rombouts, M. Pinzani, G. Mazza
Journal: Journal of Hepatology (2017)
Use of the 6 million viral load cut-off to guide treatment duration with ledipasvir/sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection: results from the German Hepatitis C-Registry (DHC-R)
Authors: J. Vermehren, C. Athmann, R. Günther, E. Schott, A. Pathil, K.H. Boeker, M. Cornberg, C. Niederau, K.-G. Simon, B. Maasoumy, C. Sarrazin, H. Wedemeyer, P. Buggisch, G.H. C-Registry
Journal: Journal of Hepatology (2017)
Plasma miR-122 levels in chronic hepatitis C patients achieving sustained virological response following DAA treatment with and without previous anti-miR-122 (RG-101) dosing
Authors: M.H. van der Ree, F. Stelma, S.B. Willemse, M. van der Valk, J.M.L. de Vree, N.A. Kootstra, H.W. Reesink
Journal: Journal of Hepatology (2017)
Perioperative COX-2 and β-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial
Authors: Lee Shaashua, Maytal Shabat-Simon, Rita Haldar, Pini Matzner, Oded Zmora, Moshe Shabtai, Eran Sharon, Tanir Allweis, Iris Barshack, Lucile Hayman, Jesusa Arevalo, Jeffrey Ma, Maya Horowitz, Steven Cole, Shamgar Ben-Eliyahu
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients. Experimental Design: In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a β-adrenergic antagonist (propranolol) and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors and sequential blood samples were assessed for prometastatic biomarkers. Results: Drugs were well tolerated with adverse event rates comparable with placebo. Transcriptome profiling of the primary tumor tested a priori hypotheses and indicated that drug treatment significantly (i) decreased epithelial-to-mesenchymal transition, (ii) reduced activity of prometastatic/proinflammatory transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor-infiltrating monocytes while increasing tumor-infiltrating B cells. Drug treatment also significantly abrogated presurgical increases in serum IL6 and C-reactive protein levels, abrogated perioperative declines in stimulated IL12 and IFNγ production, abrogated postoperative mobilization of CD16− “classical” monocytes, and enhanced expression of CD11a on circulating natural killer cells. Conclusions: Perioperative inhibition of COX-2 and β-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer. Clin Cancer Res; 23(16); 4651–61. ©2017 AACR.
Association Between Hospital Volume and 30-Day Readmissions Following Transcatheter Aortic Valve Replacement
Authors: Sahil Khera, Dhaval Kolte, Tanush Gupta, Andrew Goldsweig, Poonam Velagapudi, Ankur Kalra, Gilbert H. L. Tang, Wilbert S. Aronow, Gregg C. Fonarow, Deepak L. Bhatt, Herbert D. Aronow, Neal S. Kleiman, Michael Reardon, Paul C. Gordon, Barry Sharaf, J. Dawn Abbott
Journal: JAMA Cardiology (2017)

With the approval of transcatheter aortic valve replacement (TAVR) for patients with severe symptomatic aortic stenosis at intermediate surgical risk, TAVR volume is projected to increase exponentially in the United States. The 30-day readmission rate for TAVR was recently reported at 17.9%. The association between institutional TAVR volume and the 30-day readmission metric has not been examined. To assess the association between hospital TAVR volume and 30-day readmission. In this observational study, we used the 2014 Nationwide Readmissions Database to identify hospitals with established TAVR programs (performing at least 5 TAVRs in the first quarter of 2014). Based on annual TAVR volume, hospitals were classified as low (<50), medium (≥50 to <100), and high (≥100) volume. Rates, causes, and costs of 30-day readmissions were compared between low-, medium-, and high-volume hospitals. Data were analyzed from November to December 2016. Transcatheter aortic valve replacement. Thirty-day readmissions. Of 129 hospitals included in this study, 20 (15.5%) were categorized as low volume, 47 (36.4%) as medium volume, and 62 (48.1%) as high volume. Of 16 252 index TAVR procedures, 663 (4.1%), 3067 (18.9%), and 12 522 (77.0%) were performed at low-, medium-, and high-volume hospitals, respectively. Thirty-day readmission rates were significantly lower in high-volume compared with medium-volume (adjusted odds ratio, 0.76; 95% CI, 0.68-0.85; P < .001) and low-volume (adjusted odds ratio, 0.75; 95% CI, 0.60-0.92; P = .007) hospitals. Noncardiac readmissions were more common in low-volume hospitals (65.6% vs 60.6% in high-volume hospitals), whereas cardiac readmissions were more common in high-volume hospitals (39.4% vs 34.4% in low-volume hospitals). There were no significant differences in length of stay and costs per readmission among the 3 groups (mean [SD], 5.5 [5.0] days vs 5.9 [7.5] days vs 6.0 [5.8] days; P = .74, and $13 886 [18 333] vs $14 135 [17 939] vs $13 432 [15 725]; P = .63, respectively). We report for the first time, to our knowledge, an inverse association between hospital TAVR volume and 30-day readmissions. Lower readmission at higher-volume hospitals was associated with significantly lower cost to the health care system.
Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine
Authors: Karen K. Wong, Erin Burdette, Barbara E. Mahon, Eric D. Mintz, Edward T. Ryan, Arthur L. Reingold
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can be severe and rapidly fatal without prompt rehydration. Cholera is endemic in approximately 60 countries and causes epidemics as well. Globally, cholera results in an estimated 2.9 million cases of disease and 95,000 deaths annually (1). Cholera is rare in the United States, and most U.S. cases occur among travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases were reported in 2011 after a cholera epidemic began in Haiti (2); however, <25 cases per year have been reported in the United States since 2012.
Safety and efficacy of the fixed-dose combination regimen of MK-3682/grazoprevir/ruzasvir in cirrhotic or non-cirrhotic patients with chronic HCV GT1 infection who previously failed a direct-acting antiviral regimen (C-SURGE)
Authors: H. Wedemeyer, D. Wyles, R. Reddy, A. Luetkemeyer, I. Jacobson, J.M. Vierling, S. Gordon, R. Nahass, S. Zeuzem, J. Wahl, E. Barr, B.-Y.T. Nguyen, M. Robertson, H.-K. Joeng, H. Liu, P. Jumes, F. Dutko, E. Martin
Journal: Journal of Hepatology (2017)
Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery
Authors: Lorna Ewart, Eva-Maria Dehne, Kristin Fabre, Susan Gibbs, James Hickman, Ellinor Hornberg, Magnus Ingelman-Sundberg, Kyung-Jin Jang, David R. Jones, Volker M. Lauschke, Uwe Marx, Jerome T. Mettetal, Amy Pointon, Dominic Williams, Wolfram-Hubertus Zimmermann, Peter Newham
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug safety and metabolism. By focusing on MPS models that have been developed for these organs, alongside other relevant in vitro models, we review the current state of the art and the challenges that still need to be overcome to ensure application of this technology in enhancing drug discovery.
Abstract IA25: Targeting cancers with deletion of the p16/p14 tumor suppressor locus
Authors: Kevin Marks
Journal: Clinical Cancer Research (2017)

Abstract Mutations in tumor suppressor genes are a hallmark of cancer and contribute substantially to the molecular pathogenesis of the disease. Particularly prevalent are homozygous deletions of the CDKN2A tumor suppressor locus on chromosome 9p21, which occur in at least 15% of all cancer and lead to loss of the dual tumor suppressors p16(INK4A) and p14(ARF). Targeted therapies selective for loss of CDKN2A have proven elusive, and it may be necessary to identify alternate approaches to target tumors with this deletion. Notably, Chr9p21 deletions frequently involve co-deletion of genes proximal to CDKN2A. Foremost among these is the methylthioadenosine phosphorylase (MTAP) gene, which resides within 100 kb of CDKN2A, and is co-deleted in 80-90% of tumors with CDKN2A deletion. We sought therefore to evaluate whether the frequent co-deletion of the adjacent metabolic gene methylthioadenosine phosphorylase (MTAP) creates targetable vulnerabilities. We conducted an shRNA screen in isogenic cells that varied only in their MTAP-deletion status, and identified the metabolic enzyme, methionine adenosyltransferase II, alpha (MAT2A), and the arginine methyltransferase, PRMT5, as vulnerable enzymes in cells with MTAP deletion. Metabolomic and biochemical studies revealed a mechanistic basis for this synthetic lethality. MTAP substrate methylthioadenosine (MTA) accumulates upon MTAP loss, and biochemical profiling of a methyltransferase enzyme panel revealed that MTA is a potent and selective inhibitor of PRMT5. MTAP-deletion leads to reduced basal PRMT5 methylation activity and increased sensitivity to PRMT5 targeting. MAT2A produces PRMT5 substrate S-adenosylmethionine (SAM), and targeting of MAT2A reduces growth and PRMT5 methylation activity selectively in MTAP-deleted cells. Further, this vulnerability extends to PRMT5 co-complex proteins such as the atypical kinase Rio Kinase 1 (RIOK1). Thus, MAT2A, PRMT5, and RIOK1 comprise an unappreciated axis of targets that is selectively vulnerable in CDKN2A/MTAP-deleted tumors. Unique biochemical features of PRMT5 create this vulnerability, which presents a promising new avenue for targeted therapy. Citation Format: Kevin Marks. Targeting cancers with deletion of the p16/p14 tumor suppressor locus. [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 IA25.
NLST screening criteria performance in Asian-American lung cancer patients.
Authors: Huo Xiang Zheng, Yiqing Xu, Yiwu Huang, Michael Bergman, Kevin Douglas Becker
Journal: Journal of Clinical Oncology (2014)

e12525 Background: In the National Lung Screening Trial (NLST), CT screening in high-risk patients improved survival. Entry criteria included 1) age 55-74, 2) 30 pack year smoking history and 3) current smokers or quit within 15 years. The US Preventative Services Task Force (USPSTF) recommends screening for patients aged 55-80 with the same smoking exposure. Lung cancer in Asian populations is associated with additional non-tobacco risk factors and a high prevalence of driver mutations. Asian patients represent only 2% of NLST; therefore, the ability of the NLST criteria to identify Asian patients at risk of lung cancer is unknown. It is estimated that 26.7% of US lung cancers could be detected using NLST criteria. We aim to evaluate the percentage of Asian patients with lung cancer that would have met screening criteria and examine the characteristics of those not meeting criteria. Methods: We conducted a retrospective chart review of Asian lung cancer patients diagnosed or treated at Maimonides Cancer Center between 1/2008 and 6/2013 identified from the tumor registry. We analyzed data on demographics, cancer stage, histology, EGFR/ALK status, and imaging findings. Results: 151 patients were identified; 116 with documented smoking history were included in the analysis. The age range was 33-92 years and 77 were male. 63% had adenocarcinoma, 20% carried EGFR mutations and 56% were stage 4. Using NLST criteria, 27.6% patients would have been eligible for screening. The remaining patients would not meet the NLST screening criteria: 56% due to age (21% younger than 55, 35% older than 74), 48.8% nonsmokers, 10.7% quit more than 15 years ago, 22.6% < 30 pack year smoking history. No female patients met screening criteria. Using USPSTF, 35.3% of our patients would have met criteria for screening. Conclusions: The percentage of Asian patients with lung cancer who would have met screening criteria was not different from the general US population. A minority of patients with lung cancer in both groups will be eligible for screening based on current guidelines. In particular, lung cancer in Asian women is unlikely to be affected by screening. Further studies are needed to identify additional risk factors to select patients at risk of lung cancer within this population.
Safety of glecaprevir/pibrentasvir in adults with chronic genotype 1–6 hepatitis C virus infection: an integrated analysis
Authors: J.-F. Dufour, E. Zuckerman, N. Zadeikis, C. Hezode, S.W. Paik, P. Andreone, O. Weiland, J. Slim, S.L. Flamm, T. Morgan, H. Vargas, S. Strasser, A. Brown, Y. Yu, A. Porcalla, F. Mensa
Journal: Journal of Hepatology (2017)
Prognostic factors and treatment-related outcomes in patients with uterine serous cancer (USC).
Authors: Maria deLeon, Lingeng Lu, Pei Hui, Alessandro Santin, Thomas J. Rutherford, Dan Arin-Silasi, Masoud Azodi, Elena Ratner, Peter E. Schwartz
Journal: Journal of Clinical Oncology (2012)

5099 Background: USC an uncommon (10%) but aggressive form of uterine cancer, causes 50% of uterine cancer deaths. The purpose of this study is to report a large single-institution experience with USC investigating the effects of clinicopathological parameters and treatment on overall (OS) and disease-free survival (DFS). Methods: Records from our institution were reviewed from 1987-2009. All 334 USC patients (pts) identified were surgically staged. Postoperative treatments used were: (1) observation (OBS, n=33); (2) platinum-based chemotherapy (PCH, n=78); (3) whole pelvis radiation therapy (WPRT, n=16); (4) PCH and vaginal apex brachytherapy (PCHR, n=165); (5) vaginal apex brachytherapy (VAB, n=35). The cancer stages were 121 pts IA (36.2%), 36 IB (10.8%), 27 II (8.1%), 39 IIIA (11.7%), 2 IIIB (0.6%), 32 IIIC1 (9.6%), 9 IIIC2 (2.7%), 28 IVA (8.4%) and 40 IVB (12%). Results: The 5-year OS for stage IA/IB, II, IIIA/IIIB, IIIC1/IIIC2, IVA/IVB were 82%, 70%, 64%, 36%, and 9%, respectively. The 5-year DFS for stage IA/IB, II, IIIA/IIIB, IIIC1/IIIC2, IVA/IVB were 82%, 68%, 56%, 24%, 6%, respectively. Advanced stage was associated with significantly shorter OS and DFS (p &lt;0.01). The 5-year OS for stage IA/IB disease was 94% for pts who received PCHR, 90% for OBS, 75% for PCH, 65% for VAB and 0% for WPRT. The 5-year DFS for PCHR, OBS, PCH, VAB and WPRT for Stage IA/IB were 89%, 82%, 86%, 72% and 0% respectively. For stage II-IVB pts, the 5-year OS was 51% for PCHR, 0% for OBS, 23% for PCH and 20% for WPRT. The 5-year DFS for stage II-IVB with PCHR, OBS, PCH and WPRT were 42%, 0%, 17% and 13% respectively. Older age pts had worse survival, (p&lt;0.01). Race and BMI did not impact survival. Incomplete surgical debulking (p&lt;0.01), depth of myometrial invasion &gt;50% (p&lt;0.01) and lymph node metastasis (p&lt;0.01) were all associated with worse prognosis. Conclusions: PCHR overall exhibited better OS and DFS regardless of disease stage. Age, incomplete surgical debulking, depth of myometrial invasion and lymph node involvement were independent prognostic factors in USC patients in this study.
Kupffer cell pool is maintained by local proliferation and the differentiation of bone marrow monocytes into short-lived monocyte-derived Kupffer cells during non-alcoholic steatohepatitis and recovery
Authors: L. Devisscher, C.L. Scott, S. Lefere, S. Raevens, E. Bogaerts, A. Paridaens, X. Verhelst, A. Geerts, M. Guilliams, H. Van Vlierberghe
Journal: Journal of Hepatology (2017)
Interferon-free therapy of chronic hepatitis C does not change the short-term risk for de novo hepatocellular carcinomas in patients with liver cirrhosis
Authors: F. Mettke, B. Schlevogt, K. Deterding, A. Wranke, K. Port, M.P. Manns, A. Vogel, M. Cornberg, H. Wedemeyer
Journal: Journal of Hepatology (2017)
Effectiveness of DAA-based treatment of HCV in active people who inject drugs living in middle income countries (MIC): the results of a prospective cohort study in Tbilisi, Georgia
Authors: J. Bouscaillou, T. Kikvidze, M. Butsashvili, K. Labartkava, I. Inaridze, A. Etienne, G. Kamkamidze, A. Gamezardashvili, E. Avril, N. Luhmann
Journal: Journal of Hepatology (2017)
Home Dialysis in the Prospective Payment System Era
Authors: Eugene Lin, Xingxing S. Cheng, Kuo-Kai Chin, Talhah Zubair, Glenn M. Chertow, Eran Bendavid, Jayanta Bhattacharya
Journal: Journal of the American Society of Nephrology (2017)

The ESRD Prospective Payment System introduced two incentives to increase home dialysis use: bundling injectable medications into a single payment for treatment and paying for home dialysis training. We evaluated the effects of the ESRD Prospective Payment System on home dialysis use by patients starting dialysis in the United States from January 1, 2006 to August 31, 2013. We analyzed data on dialysis modality, insurance type, and comorbidities from the United States Renal Data System. We estimated the effect of the policy on home dialysis use with multivariable logistic regression and compared the effect on Medicare Parts A/B beneficiaries with the effect on patients with other types of insurance. The ESRD Prospective Payment System associated with a 5.0% (95% confidence interval [95% CI], 4.0% to 6.0%) increase in home dialysis use by the end of the study period. Home dialysis use increased by 5.8% (95% CI, 4.3% to 6.9%) among Medicare beneficiaries and 4.1% (95% CI, 2.3% to 5.4%) among patients covered by other forms of health insurance. The difference between these groups was not statistically significant (1.8%; 95% CI, −0.2% to 3.8%). Conversely, in both populations, the training add-on did not associate with increases in home dialysis use beyond the effect of the policy. The ESRD Prospective Payment System bundling, but not the training add-on, associated with substantial increases in home dialysis, which were identical for both Medicare and non-Medicare patients. These spill-over effects suggest that major payment changes in Medicare can affect all patients with ESRD.
Prevalence of hepatitis C in the spanish population. The prevhep study (ethon cohort)
Authors: A.C. Lavin, C. Perello, S. Llerena, M. Gomez, M.D. Escudero, L. Rodriguez, A. Estebanez, B. Gamez, L. Puchades, J. Cabezas, M.A. Serra, J.L. Calleja, J. Crespo
Journal: Journal of Hepatology (2017)
Clinical Psychology Training: Accreditation and Beyond
Authors: Robert W. Levenson
Journal: Annual Review of Clinical Psychology (2017)

Beginning with efforts in the late 1940s to ensure that clinical psychologists were adequately trained to meet the mental health needs of the veterans of World War II, the accreditation of clinical psychologists has largely been the province of the Commission on Accreditation of the American Psychological Association. However, in 2008 the Psychological Clinical Science Accreditation System began accrediting doctoral programs that adhere to the clinical science training model. This review discusses the goals of accreditation and the history of the accreditation of graduate programs in clinical psychology, and provides an overview of the evaluation procedures used by these two systems. Accreditation is viewed against the backdrop of the slow rate of progress in reducing the burden of mental illness and the changes in clinical psychology training that might help improve this situation. The review concludes with a set of five recommendations for improving accreditation.
Arthur Courtenay Saunders
Authors: Maggie Saunders
Journal: BMJ (2017)

Arthur Courtenay Saunders (“Sandy”) was born in Liverpool. In 1941 he won a scholarship to Liverpool University, where he started a BSc in electrical engineering, but in 1943 he volunteered and became a radar officer with the Royal Electrical and Mechanical Engineers (REME). After Arnhem and the crossing of the Rhine, he decided that what he was doing was rather boring and so volunteered to become a glider pilot. He did his training with the Royal Air Force then transferred to the Army Air Corps to train as a glider pilot. During this training he …
Farewell to a Cancer That Never Was
Authors: Jeff Lyon
Journal: JAMA (2017)

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