tbuckley/cabot-search huggingface dataset:
Comprehensive Characterization of Alternative Polyadenylation in Human Cancer
Authors: Yu Xiang, Youqiong Ye, Yanyan Lou, Yang Yang, Chunyan Cai, Zhao Zhang, Tingting Mills, Ning-Yuan Chen, Yoonjin Kim, Fatma Muge Ozguc, Lixia Diao, Harry Karmouty-Quintana, Yang Xia, Rodney E Kellems, Zheng Chen, Michael R Blackburn, Seung-Hee Yoo, Ann-Bin Shyu, Gordon B Mills, Leng Han
Journal: JNCI Journal of the National Cancer Institute (2017)

Alternative polyadenylation (APA) is emerging as a major post-transcriptional mechanism for gene regulation, and dysregulation of APA contributes to several human diseases. However, the functional consequences of APA in human cancer are not fully understood. Particularly, there is no large-scale analysis in cancer cell lines.We characterized the global APA profiles of 6398 patient samples across 17 cancer types from The Cancer Genome Atlas and 739 cancer cell lines from the Cancer Cell Line Encyclopedia. We built a linear regression model to explore the correlation between APA factors and APA events across different cancer types. We used Spearman correlation to assess the effects of APA events on drug sensitivity and the Wilcoxon rank-sum test or Cox proportional hazards model to identify clinically relevant APA events.We revealed a striking global 3'UTR shortening in cancer cell lines compared with tumor samples. Our analysis further suggested PABPN1 as the master regulator in regulating APA profile across different cancer types. Furthermore, we showed that APA events could affect drug sensitivity, especially of drugs targeting chromatin modifiers. Finally, we identified 1971 clinically relevant APA events, as well as alterations of APA in clinically actionable genes, suggesting that analysis of the complexity of APA profiles could have clinical utility.Our study highlights important roles for APA in human cancer, including reshaping cellular pathways and regulating specific gene expression, exemplifying the complex interplay between APA and other biological processes and yielding new insights into the action mechanism of cancer drugs.
TCT-416 Rationale and design of COMBINE (OCT–FFR) assessment of non-culprit lesions to better predict adverse event outcomes in diabetes mellitus patients.
Authors: Elvin Kedhi, Balazs Berta, Tomasz Roleder, Alexander Ijsselmuiden, Fernando Alfonso, Javier Escaned, Holger Nef, Wojtek Wojakowski
Journal: Journal of the American College of Cardiology (2017)
Tuberculosis screening in asylum seekers in Germany, 2015: characteristics of cases and yield
Authors: Lena Fiebig, Barbara Hauer, Marta Andrés, Walter Haas
Journal: European Respiratory Journal (2017)

In 2015, according to the International Organization for Migration (IOM), 244 million people worldwide were international migrants, representing the highest number ever recorded [1]. The level of forced displacement globally was the highest since World War II, with a dramatic increase in the number of refugees, asylum seekers and internally displaced people. Germany became one of the largest recipients of first asylum seeking claims [2]. TB screening among asylum seekers in Germany identified 1255 cases in 2015, and may have decreased TB exposure <http://ow.ly/2d4n30f9w9b> We thank everyone who contributed to the screening, case management and TB surveillance and control in Germany. We also thank Doris Altmann (Robert Koch Institute, Berlin, Germany) for data preparation, Bonita Brodhun (Robert Koch Institute) for the management of TB notification data, Nita Perumal (Robert Koch Institute) for helpful comments on the manuscript, and Harald Lederer (Bundesamt für Migration und Flüchtlinge) for providing the numbers of registered asylum seekers. Author contributions were as follows. Lena Fiebig, Barbara Hauer and Walter Haas conceptualised the study. Lena Fiebig drafted the manuscript and performed the data analysis. Barbara Hauer performed the literature review. Marta Andrés helped in the data analysis. Barbara Ha, Marta Andrés and Walter Haas collaborated in writing the manuscript. All authors reviewed and approved the final manuscript.
Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia
Authors: Alvin W. T. Ng, Song Ling Poon, Mi Ni Huang, Jing Quan Lim, Arnoud Boot, Willie Yu, Yuka Suzuki, Saranya Thangaraju, Cedric C. Y. Ng, Patrick Tan, See-Tong Pang, Hao-Yi Huang, Ming-Chin Yu, Po-Huang Lee, Sen-Yung Hsieh, Alex Y. Chang, Bin T. Teh, Steven G. Rozen
Journal: Science Translational Medicine (2017)

Many traditional pharmacopeias include Aristolochia and related plants, which contain nephrotoxins and mutagens in the form of aristolochic acids and similar compounds (collectively, AA). AA is implicated in multiple cancer types, sometimes with very high mutational burdens, especially in upper tract urothelial cancers (UTUCs). AA-associated kidney failure and UTUCs are prevalent in Taiwan, but AA's role in hepatocellular carcinomas (HCCs) there remains unexplored. Therefore, we sequenced the whole exomes of 98 HCCs from two hospitals in Taiwan and found that 78% showed the distinctive mutational signature of AA exposure, accounting for most of the nonsilent mutations in known cancer driver genes. We then searched for the AA signature in 1400 HCCs from diverse geographic regions. Consistent with exposure through known herbal medicines, 47% of Chinese HCCs showed the signature, albeit with lower mutation loads than in Taiwan. In addition, 29% of HCCs from Southeast Asia showed the signature. The AA signature was also detected in 13 and 2.7% of HCCs from Korea and Japan as well as in 4.8 and 1.7% of HCCs from North America and Europe, respectively, excluding one U.S. hospital where 22% of 87 "Asian" HCCs had the signature. Thus, AA exposure is geographically widespread. Asia, especially Taiwan, appears to be much more extensively affected, which is consistent with other evidence of patterns of AA exposure. We propose that additional measures aimed at primary prevention through avoidance of AA exposure and investigation of possible approaches to secondary prevention are warranted.
Abstract 15625: Insulin Receptor Substrates (IRS) Regulate the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training
Authors: Christian Riehle, Steven Valdez, Jack Bevins, Jung Noh, Bum J Kim, E. Dale Abel
Journal: Circulation (2013)

To test the hypothesis that insulin receptor substrate (IRS) isoforms mediate the cardiac growth and metabolic adaptations that follow exercise training, mice with cardiomyocyte-specific deletion of either IRS1 (CIRS1KO) or IRS2 (CIRS2KO) were subjected to swim training (Ex). At 12 weeks of age, heart weight-to-tibia length ratios (HW/TL) were reduced by 12.5% (p
Abstract 12183: SLCO1B1 Genotype-Guided Statin Therapy Lowers LDL Cholesterol in Patients With Statin-Intolerance- A Randomized Controlled Trial
Authors: Deepak Voora, Emily Perry, Kavisha Singh, Gloria Trujillo, Nicholas Milazzo, Dillon Savard, Susanne Haga, Michael D Musty, Yi-Ju Li, Bruce Peyser
Journal: Circulation (2016)

Introduction: Statin-intolerance is a barrier to reducing cardiovascular disease risk. A genetic variant (*5, rs4149056) in the SLCO1B1 statin hepatic transporter gene is well characterized and lin...
Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test
Authors: Manuel Zorzi, Cesare Hassan, Giulia Capodaglio, Chiara Fedato, Adriana Montaguti, Anna Turrin, Alberto Rosano, Daniele Monetti, Carmen Stocco, Susanna Baracco, Francesca Russo, Alessandro Repici, Massimo Rugge
Journal: Gut (2017)

The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear.In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (1) the FIT positivity rate, the CRC and advanced adenoma detection rate and the FIT's positive predictive value (PPV) for advanced neoplasia, at each round of screening and (2) the cumulative CRC and advanced adenoma detection rate after five rounds of FIT.Over 12 years (2002-2014), 123 347 individuals were administered the FIT up to six times, and 781 CRCs and 4713 advanced adenomas were diagnosed. The CRC and advanced adenoma detection rates declined substantially from the first to the third (rate ratio (RR) 0.25, 95% CI 0.20 to 0.32) and second (RR 0.51, 95% CI 0.47 to 0.56) rounds, respectively, and then remained stable. The PPV for advanced neoplasia dropped by 18% in the second round (RR 0.82, 95% CI 0.77 to 0.89), with no further reduction thereafter due to a concomitant decline in the FIT positivity rate (RR first to sixth rounds: 0.56, 95% CI 0.53 to 0.60).The cumulative CRC and advanced adenoma detection rates over five consecutive rounds were 8.5‰ (95% CI 7.8 to 9.2), and 58.9‰ (95% CI 56.9 to 61.0), respectively.Repeated FIT significantly reduces the burden of colorectal disease while facilitating an efficient use of colonoscopy resources. The cumulative detection rate after five rounds of FIT is similar to primary screening with colonoscopy, supporting the need to account for the cumulative sensitivity of repeated FITs when evaluating the test's efficacy.
TCT-95 Different Vascular Healing between Bioabsorbable Polymer-coated Everolimus-Eluting Stents versus Bioresorbable Vascular Scaffolds via Optical Coherence Tomography and Coronary Angioscopy (The ENHANCE study: ENdothelial Healing Assessment With Novel Coronary tEchnology)
Authors: Wan Azman Wan Ahmad, Takaharu Nakayoshi, Ahmad Syadi Mahmood Zuhdi, Yasushi Ino, Takashi Kubo, Takashi Akasaka, Takafumi Ueno
Journal: Journal of the American College of Cardiology (2017)
Will markets be master or servant to health at the World Bank?
Authors: Suerie Moon, Gorik Ooms
Journal: BMJ (2017)

In the 18 years since a six part series by Abbasi in The BMJ argued that the World Bank merits greater attention from the health community, the institution has received little scrutiny from global health scholars. 1This is despite its substantial and growing role in the health sector.][4][5][6] The authors paint a detailed picture of the bank's historical activities, growing investments, and considerable evolution in its approaches to health.They also critically analyse more recent developments.Whether considering the growth of health related trust funds at the bank, 3 its role in universal health coverage, 4 the recently launched global financing facility for women and children's health, 5 or the pandemic emergency financing facility, 6 the series persistently grapples with two key questions: firstly, can the bank's market oriented approach be consistent with health equity objectives such as the globally endorsed goal of universal health coverage?Secondly, how can the bank's immense economic and intellectual power be appropriately governed?
Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria
Authors: Anne Kessler, Selasi Dankwa, Maria Bernabeu, Visopo Harawa, Samuel A. Danziger, Fergal Duffy, Sam D. Kampondeni, Michael J. Potchen, Nicholas Dambrauskas, Vladimir Vigdorovich, Brian G. Oliver, Sarah E. Hochman, Wenzhu B. Mowrey, Ian J.C. MacCormick, Wilson L. Mandala, Stephen J. Rogerson, D. Noah Sather, John D. Aitchison, Terrie E. Taylor, Karl B. Seydel, Joseph D. Smith, Kami Kim
Journal: Cell Host & Microbe (2017)
Stage distribution of screen-detected colorectal cancers in the Netherlands
Authors: Esther Toes-Zoutendijk, Arthur I Kooyker, Marloes A Elferink, Manon C W Spaander, Evelien Dekker, Harry J de Koning, Valery E Lemmens, Monique E van Leerdam, Iris Lansdorp-Vogelaar
Journal: Gut (2017)

We read with interest the results of the pilot study in England, which was performed to establish the acceptability and diagnostic performance of screening with the faecal immunochemical test (FIT) over the guaiac faecal occult blood test (gFOBT).1 When comparing gFOBT to FIT, the uptake increased from 59.4% to 66.4%, positivity rate increased from 1.7% to 7.8% (at a cut-off level of 20 µg Hb/g faeces) and colorectal cancer (CRC) detection doubled. Moreover, this report showed that also with FIT cut-off levels above 20 µg Hb/g faeces, improved clinical outcomes can be achieved over gFOBT. However, for a screening programme to be effective, it is a prerequisite to detect cancers in an early stage. Thus far, information on stage distribution of screen-detected CRCs in a population-based FIT screening programme is lacking.

In our study, we collected data on all CRCs detected in patients aged 60–75 years in the Netherlands in 2015 through the Netherlands Cancer Registry. In total, 9437 CRCs were diagnosed in 9301 patients: 3579 (38.5%) patients were diagnosed after a positive FIT in the CRC screening programme (screen-detected), 4506 (48.4%) patients were diagnosed due …
TCT-39 Clinical Outcomes in SURTAVI Based on Revascularization Stratification
Authors: Lars Søndergaard, Jeffrey J. Popma, Michael J. Reardon, Thomas Engstroem, Nicolas Van Mieghem, G. Michael Deeb, Susheel Kodali, Isaac George, Mathew Williams, Steven Yakubov, A. Pieter Kappetein, Patrick Serruys
Journal: Journal of the American College of Cardiology (2017)
TCT-819 Prediabetes and its Impact on 1-Year Clinical Outcome After Treatment with Newer-Generation Drug-eluting Stents in 2,986 All-Comer Patients
Authors: Marlies Kok, Clemens Von Birgelen, Paolo Zocca, Marije Lowik, Peter Danse, Carl Schotborgh, Martijn Scholte, Marc Hartmann, Cees Doelman, Gert Kant, R. Melvyn Tjon Joe Gin, Martin Stoel, K. Gert van Houwelingen, Gerard C.M. Linssen, Carine J.M. Doggen, Liefke van der Heijden
Journal: Journal of the American College of Cardiology (2017)
Benefit‐risk assessment for sofosbuvir/velpatasvir/voxilaprevir based on patient population and hepatitis C virus genotype: U. S. Food and Drug Administration's evaluation
Authors: Kimberly Struble, Kirk Chan‐Tack, Karen Qi, Lisa K. Naeger, Debra Birnkrant
Journal: Hepatology (2017)

On July 18, 2017, the U.S. Food and Drug Administration (FDA) approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed-dose combination (FDC), an interferon-free, complete regimen for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have: • genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing a nonstructural protein 5A (NS5A) inhibitor; and • genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor. Approval was based on an acceptable safety profile and high sustained virological response rates 12 weeks after the end of treatment (SVR12) in two phase 3 clinical trials in subjects previously treated with a direct-acting antiviral (DAA) regimen. In POLARIS-1, 96% of SOF/VEL/VOX-treated subjects achieved SVR12. In POLARIS-4, 98% of SOF/VEL/VOX-treated subjects achieved SVR12. A key and challenging question in evaluating the data was determining the contribution of VOX to SOF/VEL and how this differed depending on the genotype and patient population. In this article, we provide our perspective on the issues considered in making these determinations, especially regarding the POLARIS-4 data in subjects who have previously been treated with a chronic HCV regimen containing sofosbuvir without an NS5A inhibitor. Conclusion: We seek to provide context as to why a broad indication was given for NS5A inhibitor-experienced patients (HCV genotypes 1-6) while the indication for NS5A inhibitor- naïve patients was limited to HCV genotypes 1a and 3 only. (Hepatology 2018;67:482-491).
Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection — United States, October 2017
Authors: Tolulope Adebanjo, Shana Godfred-Cato, Laura Viens, Marc Fischer, J. Erin Staples, Wendi Kuhnert-Tallman, Henry Walke, Titilope Oduyebo, Kara Polen, Georgina Peacock, Dana Meaney-Delman, Margaret A. Honein, Sonja A. Rasmussen, Cynthia A. Moore, E. Oscar Alleyne, Martina Badell, James F. Bale, Wanda D. Barfield, Richard Beigi, Audina M. Berrocal, Carina Blackmore, Eric C. Blank, Jennifer Bolden Pitre, Coleen Boyle, Erin Conners, Christine Curry, Richard N. Danila, Alberto De La Vega, Roberta L. DeBiasi, Gail J. Demmler-Harrison, Siobhan M. Dolan, Rita W. Driggers, Eric Dziuban, John Eichwald, Catherine Eppes, Nicole Fehrenbach, Meg Fisher, Kimberly B. Fortner, Elizabeth Garbarczyk, Francisco García, Stephanie Gaw, Valerie Godoshian, Ivan A. Gonzalez, Caitlin Green, Dixie D. Griffin, Manda Hall, Amy Houtrow, Mark Hudak, Lisa L. Hunter, David Kimberlin, Linda M. Lawrence, Ellen H. Lee, Rebecca Leeb, Deborah Levine, Claritsa Malave, Yvonne Maldonado, Lynne Mofenson, Sarah B. Mulkey, Flor M. Munoz, Scott Needle, Chloe Oram, Cassandra G. Pasley, Maria Paz Carlos, Alyssa Pensirikul, Emily E. Petersen, Lawrence Platt, S. Grace Prakalapakorn, Sarah Reagan-Steiner, Jeannie Rodriguez, Elizabeth Rosenblum, Pablo J. Sánchez, Magdalena Sanz Cortes, David J. Schonfeld, Carrie K. Shapiro-Mendoza, Dean E. Sidelinger, V. Fan Tait, Miguel Valencia-Prado, Lisa F. Waddell, Michael D. Warren, Susan Wiley, Eileen Yamada, Marshalyn Yeargin-Allsopp, Fernando Ysern, Christopher M. Zahn
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

CDC has updated its interim guidance for U.S. health care providers caring for infants with possible congenital Zika virus infection (1) in response to recently published updated guidance for health care providers caring for pregnant women with possible Zika virus exposure (2), unknown sensitivity and specificity of currently available diagnostic tests for congenital Zika virus infection, and recognition of additional clinical findings associated with congenital Zika virus infection. All infants born to mothers with possible Zika virus exposure* during pregnancy should receive a standard evaluation at birth and at each subsequent well-child visit including a comprehensive physical examination, age-appropriate vision screening and developmental monitoring and screening using validated tools (3-5), and newborn hearing screen at birth, preferably using auditory brainstem response (ABR) methodology (6). Specific guidance for laboratory testing and clinical evaluation are provided for three clinical scenarios in the setting of possible maternal Zika virus exposure: 1) infants with clinical findings consistent with congenital Zika syndrome regardless of maternal testing results, 2) infants without clinical findings consistent with congenital Zika syndrome who were born to mothers with laboratory evidence of possible Zika virus infection,
Visceral Adiposity in Psoriasis is Associated With Vascular Inflammation by 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Beyond Cardiometabolic Disease Risk Factors in an Observational Cohort Study
Authors: Joshua P Rivers, Tiffany M Powell-Wiley, Amit K Dey, Justin A Rodante, Jonathan H Chung, Aditya A Joshi, Balaji Natarajan, Aparna P Sajja, Abhishek Chaturvedi, Anshuma Rana, Charlotte L Harrington, Heather L Teague, Benjamin N Lockshin, Mark A Ahlman, Jianhua Yao, Martin P Playford, Joel M Gelfand, Nehal N Mehta
Journal: JACC. Cardiovascular imaging (2017)
TCT-683 Bivalirudin versus Heparin in Patients Undergoing Percutaneous Peripheral Interventions: A Systematic Review and Meta-analysis
Authors: Wilman Olmedo, Pedro Villablanca, Michael Weinreich, Tanush Gupta, Divyanshu Mohananey, Thomas Brevik, Cristina Sanina, Jeannine Brevik, Muhammad Farooq, Harish Ramakrishna, Robert Pyo, Mario Garcia, Jose Wiley
Journal: Journal of the American College of Cardiology (2017)
Private sector needs extensive reform to protect patients, says think tank
Authors: Jacqui Wise
Journal: BMJ (2017)

The private hospital sector in England needs radical reform following the Ian Paterson scandal which left hundreds of patients maimed and injured, a highly critical report by the Centre for Health and the Public Interest has said.1

The report, No Safety Without Liability , said that the private hospital business model makes it susceptible to exploitation by ill meaning or incompetent surgeons. The think tank’s report, based on a review of Care Quality Commission (CQC) inspection reports of 177 private hospitals, said that the refusal by private hospital companies to accept full responsibility for what happens in their facilities means that patients will always be at risk.

Breast surgeon Paterson was found guilty of wounding with intent and …
La rabia vulpina en Alemania
Authors: T Müller, T Selhorst, C Pötzsch
Journal: Eurosurveillance (2005)

En comparacion con los metodos tradicionales de control de la rabia salvaje, la vacunacion antirrabica oral de los zorros (oral rabies vaccination, ORV), es sin ninguna duda, el metodo mas adecuado en terminos de costo-eficacia. Como resultado del uso de la ORV, se ha erradicado la rabia en varios paises de Europa. Aunque haya sido eliminada la rabia de la mayor parte de Alemania, todavia existe un foco residual triangular cerca de la frontera, delimitado por los estados de Hesse, Baden-Wurttemberg y Rhineland Palatinate. Se han iniciado acciones correctivas para eliminar ese ultimo foco de rabia en Alemania.
How can we implement exercise therapy for patellofemoral pain if we don’t know what was prescribed? A systematic review
Authors: Sinead Holden, Michael Skovdal Rathleff, Martin Bach Jensen, Christian J Barton
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate the completeness of exercise prescription in randomised controlled trials (RCTs) for patellofemoral pain (PFP), identify which elements are most frequently missing and supplement recommendations based on additional data from authors. Design Systematic review. Data sources All studies included in the most recent Cochrane review were evaluated. Additionally, the Cochrane search was updated in June 2016 in Cochrane, MEDLINE, EMBASE, PEDro, CINAHL and AMED databases. Two raters independently assessed completeness of reporting using the Toigo and Boutellier mechanobiological exercise descriptors, and Template for Intervention Description and Replication (TIDieR) checklist. Authors were also contacted to provide additional information. Eligibility criteria for selecting studies RCTs of exercise interventions for PFP. Results We included 38 RCTs. The level of exercise prescription detail was low, with no study providing complete information. The most commonly reported exercise descriptors were the ’duration of the experimental period' (n=38/38) and ’number of exercise interventions' (n=35). From TIDieR, the most commonly reported items were the ’intervention name' (n=38) and ’rationale' (n=36). The least reported items from the exercise descriptors were ’volitional muscular failure', ’temporal distribution of contraction modes', ’time under tension' and ’recovery between exercise sessions' (all n=2/38). From TIDieR, the least reported item was ‘How well (fidelity and adherence)’ (n=3/38). 36 authors were contacted, with 22 replies and 13 providing additional exercise prescription details . Conclusion Exercise prescriptions in RCTs with proven efficacy for PFP are poorly reported, impairing their implementation in clinical practice. PROSPERO registration number CRD42016039138.
TCT-580 Outcome after percutaneous edge-to-edge mitral repair for functional and degenerative mitral regurgitation: a systematic review and meta-analysis
Authors: Mauro Chiarito, Matteo Pagnesi, Enrico Martino, Michele Pighi, Andrea Scotti, Giuseppe Biondi-Zoccai, Azeem Latib, Giovanni Landoni, Alberto Margonato, Francesco Maisano, Ted Feldman, Ottavio Alfieri, Antonio Colombo, Cosmo Godino
Journal: Journal of the American College of Cardiology (2017)