tbuckley/cabot-search huggingface dataset:
Prognostic value of genomic signatures in metastatic Clear Cell Renal Cell Carcinoma (mRCC) using The Cancer Genome Atlas (TCGA) data.
Authors: Guillermo de Velasco, Andre Poisl Fay, Aedin Culhane, A. Ari Hakimi, Martin Henner Voss, Nizar M. Tannir, Pheroze Tamboli, Leonard Joseph Appleman, Joaquim Bellmunt, Kimryn Rathmell, Laurence K. Albiges, James Hsieh, Daniel Yick Chin Heng, Sabina Signoretti, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

4560 Background: Gene-expression signatures for prognosis have been reported in localized RCC. The aim of this study was to validate two different signatures; ClearCode34, a 34-gene signature model (Brooks et al. Eur Urol., 2014) and an 8-gene signature model (Choudhury et al. Eur Urol., 2015) in a population of mRCC. Methods: mRCC patients from five institutions who were part of TCGA KIRC were identified and clinical data were retrieved. Normalized RNAseq gene expression data were downloaded from the public TCGA portal. mRCC patients were dichotomized to good and poor prognostic risk groups using the 2 models. Cox proportional hazard regression was used to investigate an association between molecular subtype and overall survival (OS) from first-line therapy. Results: Overall, 56 patients were included in the analysis. Median age was 62 years. The proportions of patients in IMDC prognostic risk groups were 14%, 66%, and 20% for good, intermediate, and poor risk respectively. Fifty two (92.8%) patients received VEGF-targeted therapy. Median follow-up from initiation of first-line therapy was 25.2 months. Applying the ClearCode34, median survival for the ccA (n = 18) and ccB (n = 38) subtypes were 27.6 and 22.3 months (HR: 2.33; 95% CI, 1.02 to 5.31; P = 0.03), respectively. On multivariable analyses and adjusting for IMDC groups, ccB remained independly associated with a worse OS (p = 0.044). On the other hand, the 8-gene signature molecular subtypes did not predict survival in this cohort (HR 1.76; 95% CI, 0.8 to 3.85, P = 0.15). Conclusions: ClearCode34, but not the 8-gene molecular signature model, is prognostic in patients with mRCC. These data need to be externally and prospectively validated.
Abstract 17157: Chronic Troponin I Leak After Heart Transplantation: What is its Meaning?
Authors: Jignesh Patel, Michelle Kittleson, Dael Geft, Tamar Aintablian, Yanqing Li, David H Chang, Lawrence Czer, Fardad Esmailian, Jon Kobashigawa
Journal: Circulation (2016)

Introduction:  Elevations in serum troponin I (cTnI) have been noted to reflect myocardial injury in non-transplant patients. Chronic cTnI leaks are also known to occur at various times in certain heart transplant patients; it is suggested that these patients have poor outcome. We sought to assess outcomes of patients with increased serum concentrations in cTnI within the first year post-heart transplantation.   Methods:  Between 2010 and 2014 we assessed 449 heart transplant patients, 15 of which had cTnl leak. Chronic cTnl leak was defined as elevated serum cTnl ≥ 0.05 ng/ml for a duration ≥2 months. For these patients, subsequent 1-year survival, rejection, cardiac allograft vasculopathy (CAV) as defined by stenosis ≥ 30% by angiography and Non-Fatal Major Adverse Cardiac Events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke) were assessed. There were 38 patients who had no cTnl leak that were used as a control. These patients were also followed for the subsequent year post-transplant for the same outcome parameters as noted above.   Results:  The chronic cTnl leak group compared to the no cTnl leak group had significantly reduced subsequent 1-year survival and NF-MACE. No significant difference was observed for subsequent 1-year freedom from CAV, acute cellular, antibody-mediated and biopsy negative rejection.   Conclusions:  cTnl leak in heart transplant patients appears to predict poor outcome for survival and prospect of NF-MACE events. A longer follow-up period is needed to confirm these early observations.
Abstract 11867: Effects of the Use of Preoperative Aspirin Among Patient Undergoing Cardiac Surgery
Authors: Zugui Zhang, Qian Ding, Hong Liu, Eric Yuen, Zhongmin Li, Linong Yao, J Goldhammer, R R. Morris, William S Weintraub, Jianzhong Sun
Journal: Circulation (2016)

Background: Continuing or stopping aspirin prior to coronary artery bypass graft (CABG) surgery remains controversial with a major concern of risk of bleeding, but some studies have shown that aspirin did not increase the risk of bleeding and may be beneficial to be continued until the time of surgery or after surgery. Hypothesis: The preoperative aspirin could have short- and long-term effects on patients with CABG or valve surgery. Methods: Consecutive patients (9584) with cardiac surgery from Thomas Jefferson University hospital, Abington Memorial hospital and UC Davis Medical Center during 2001 to 2015 were included in this study. The preoperative use of aspirin was defined as within 5 days preceding surgery. Patients excluded were those with preoperative anticoagulants (except unfractionated heparin), adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, anti-platelets, unknown preoperative aspirin use. Outcomes were analyzed with the use of propensity scores and inverse-probability-weighting adjustment to reduce treatment selection bias. Results: Among 6219 patients met inclusion criteria, 4033 (64.8%) had preoperative aspirin (PreASA) and 2186 (35.0%) didn’t (No-PreASA). The median follow-up period was 3.6 years. At 30 days after surgery, there was significant difference in adjusted mortality between the groups (3.69% in the PreASA group vs. 5.31% in the No-PreASA group; risk ratio, 0.69; 95% confidence interval [CI], 0.59 to 0.84). At 4 years, there was still lower mortality with PreASA than with No-PreASA (15.79% in the PreASA vs. 17.78% in the No-PreASA group; risk ratio, 0.89; 95% CI, 0.86 to 0.92). With the use of different analytic methods and sensitivity analysis to assess residual confounding, similar results were noted in postoperative renal failure (4.02% in the PreASA group vs. 5.81% in the No-PreASA group; odds ratio: 0.74; 95%CI: 0.63-0.88 ) and major adverse cardiocerebral events (10.76% in the PreASA group vs. 14.46% in the No-PreASA group; odds ratio: 0.77; 95%CI: 0.69-0.85). Conclusions: In this observational study, we found that among patients with cardiac surgery, there was a short- and long-term survival advantage among patients who used preoperative aspirin as compared with patients who didn’t.
Allergic profiles of mothers and fathers in the Japan Environment and Children’s Study (JECS): a nationwide birth cohort study
Authors: Kiwako Yamamoto-Hanada, Limin Yang, Kazue Ishitsuka, Tadayuki Ayabe, Hidetoshi Mezawa, Mizuho Konishi, Tetsuo Shoda, Kenji Matsumoto, Hirohisa Saito, Yukihiro Ohya
Journal: Journal of Allergy and Clinical Immunology (2018)
LSD1 Stimulates Cancer-Associated Fibroblasts to Drive Notch3-Dependent Self-Renewal of Liver Cancer Stem–like Cells
Authors: Chungang Liu, Limei Liu, Xuejiao Chen, Jiamin Cheng, Heng Zhang, Chengcheng Zhang, Juanjuan Shan, Junjie Shen, Cheng Qian
Journal: Cancer Research (2017)

Abstract Cancer stem-like cells (CSC) in hepatocellular carcinoma (HCC) are thought to mediate therapeutic resistance and poor survival outcomes, but their intrinsic and extrinsic control is not well understood. In this study, we found that the chromatin modification factor LSD1 is highly expressed in HCC CSC where it decreases during differentiation. LSD1 was responsible for maintaining CSC self-renewal and tumorigenicity in HCC, and its overexpression was sufficient to drive self-renewal of non-CSC. Levels of acetylated LSD1 were low in CSC with high LSD1 activity, and these CSC were capable of self-renewal. Notch signaling activated LSD1 through induction of the sirtuin SIRT1, leading to deacetylation and activation of LSD1 and CSC self-renewal. Notably, we found that LSD1 expression was increased in cancer-associated fibroblasts (CAF) as an upstream driver of Notch3-mediated CSC self-renewal. In clinical specimens of HCC, the presence of CAF, LSD1, and Notch3 strongly associated with poor patient survival. Overall, our results reveal that CAF-induced expression of Notch3 is responsible for LSD1 activation in CSC, driving their self-renewal in HCC. Significance: These seminal findings illuminate a complex pathway in the tissue microenvironment of liver cancer, which is responsible for orchestrating the self-renewal of stem-like cancer cells, with potential implications to improve therapy and limit relapses. Cancer Res; 78(4); 938–49. ©2017 AACR.
Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial
Authors: Claire N Harrison, Alessandro M Vannucchi, Uwe Platzbecker, Francisco Cervantes, Vikas Gupta, David Lavie, Francesco Passamonti, Elliott F Winton, Hua Dong, Jun Kawashima, Julia D Maltzman, Jean-Jacques Kiladjian, Srdan Verstovsek
Journal: The Lancet Haematology (2017)
In Vitro JAK1/2 Inhibition, in Association with Bortezomib and Lenalidomide, Is Comparable with Bortezomib, Lenalidomide and Dexametasone: An Alternative for Multiple Myeloma Patients with JAK2 overexpression?
Authors: Mariana Bleker de Oliveira, Veruska Lia Fook Alves, Angela Isabel Eugenio, Rodrigo Carlini Fernando, Mihoko Yamamoto, Gisele W. B. Colleoni
Journal: Blood (2016)
A mindfulness-based intervention to increase resilience to stress in university students (the Mindful Student Study): a pragmatic randomised controlled trial
Authors: Julieta Galante, Géraldine Dufour, Maris Vainre, Adam P Wagner, Jan Stochl, Alice Benton, Neal Lathia, Emma Howarth, Peter B Jones
Journal: The Lancet Public Health (2017)

The rising number of young people going to university has led to concerns about an increasing demand for student mental health services. We aimed to assess whether provision of mindfulness courses to university students would improve their resilience to stress.We did this pragmatic randomised controlled trial at the University of Cambridge, UK. Students aged 18 years or older with no severe mental illness or crisis (self-assessed) were randomly assigned (1:1), via remote survey software using computer-generated random numbers, to receive either an 8 week mindfulness course adapted for university students (Mindfulness Skills for Students [MSS]) plus mental health support as usual, or mental health support as usual alone. Participants and the study management team were aware of group allocation, but allocation was concealed from the researchers, outcome assessors, and study statistician. The primary outcome was self-reported psychological distress during the examination period, as measured with the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), with higher scores indicating more distress. The primary analysis was by intention to treat. This trial is registered with the Australia and New Zealand Clinical Trials Registry, number ACTRN12615001160527.Between Sept 28, 2015, and Jan 15, 2016, we randomly assigned 616 students to the MSS group (n=309) or the support as usual group (n=307). 453 (74%) participants completed the CORE-OM during the examination period and 182 (59%) MSS participants completed at least half of the course. MSS reduced distress scores during the examination period compared with support as usual, with mean CORE-OM scores of 0·87 (SD 0·50) in 237 MSS participants versus 1·11 (0·57) in 216 support as usual participants (adjusted mean difference -0·14, 95% CI -0·22 to -0·06; p=0·001), showing a moderate effect size (β -0·44, 95% CI -0·60 to -0·29; p<0·0001). 123 (57%) of 214 participants in the support as usual group had distress scores above an accepted clinical threshold compared with 88 (37%) of 235 participants in the MSS group. On average, six students (95% CI four to ten) needed to be offered the MSS course to prevent one from experiencing clinical levels of distress. No participants had adverse reactions related to self-harm, suicidality, or harm to others.Our findings show that provision of mindfulness training could be an effective component of a wider student mental health strategy. Further comparative effectiveness research with inclusion of controls for non-specific effects is needed to define a range of additional, effective interventions to increase resilience to stress in university students.University of Cambridge and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East of England.
Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia
Authors: Mary Butler, Victoria A. Nelson, Heather Davila, Edward Ratner, Howard A. Fink, Laura S. Hemmy, J. Riley McCarten, Terry R. Barclay, Michelle Brasure, Robert L. Kane
Journal: Annals of Internal Medicine (2017)

Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain.To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis.Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews.English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls.Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence.Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, β-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported.Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures.Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI.Agency for Healthcare Research and Quality.
The FDA NIH Biomarkers, EndpointS, and other Tools (BEST) resource in neuro-oncology
Authors: Daniel N Cagney, Joohee Sul, Raymond Y Huang, Keith L Ligon, Patrick Y Wen, Brian M Alexander
Journal: Neuro-Oncology (2017)

In early 2016, the FDA and the National Institutes of Health (NIH) published the first version of the glossary included in the Biomarkers, EndpointS, and other Tools (BEST) resource.1 The BEST glossary was constructed to harmonize and clarify terms used in translational science and medical product development and to provide a common language used for communication by those agencies. It is considered a "living" document that will be updated in the future. This review will discuss the main biomarker and clinical outcome categories contained in the BEST glossary as they apply to neuro-oncology, as well as the overlapping and hierarchical relationships among them.
A real-world, community-based cohort study comparing the effectiveness of topical fluorouracil versus topical imiquimod for the treatment of actinic keratosis
Authors: Romain Neugebauer, Katherine A. Levandoski, Zheng Zhu, Monica Sokil, Mary-Margaret Chren, Gary D. Friedman, Maryam M. Asgari
Journal: Journal of the American Academy of Dermatology (2017)
Correspondence regarding the article “The asbestos fibre burden in human lungs: new insights into the chrysotile debate”
Authors: Pietro Sartorelli
Journal: European Respiratory Journal (2017)

We read with interest the generally excellent article by Feder et al. [1] published in the European Respiratory Journal and we would like to add just a comment. Authors screened the German Mesothelioma Register for patients with asbestos body (AB) counts ≥500 per gramme of wet lung (corresponding to approximately ≥5000 AB per gramme of dry lung tissue) which had been analysed twice from different tissue excisions at minimum interval of 4 years. In the 12 patients with longitudinal data the asbestos fibre burden in the lung tissue was stable in particular for chrysotile. Authors stated that the study was the first to present intra-individual longitudinal data about the asbestos fibre burden in living human lungs. Longitudinal intra-individual data demonstrate the high biopersistence of both amphiboles and chrysotile in the lung <http://ow.ly/ksnk30guepj>
La rabia, una enfermedad descuidada
Authors: A. R. Fooks
Journal: Eurosurveillance (2005)

Europa debe constantemente enfrentarse a la amenaza que representan las enfermedades zoonoticas, incluyendo bacterias antiguas como Mycobacterium tuberculosis, virus RNA como el SRAS-CoV, los virus Heninipah, los virus de la gripe aviar y los lyssavirus emergentes.
Bronchiectasis as a Cause of Elevated CA-19-9 Demonstrated on 18F-FDG PET/CT
Authors: Paul Mikhail, Ken Le, Chuong Bui, Robert Mansberg
Journal: Clinical Nuclear Medicine (2017)

A 64-year-old woman with a history of weight loss and a markedly elevated serum carbohydrate antigen 19-9 level of 560 U/mL was referred for an F-FDG PET study to evaluate for occult malignancy. In addition to the weight loss, she had suffered from a chronic cough secondary to bronchiectasis and had been investigated for a suspected gastrointestinal malignancy. Multiple FDG-avid foci were detected throughout both lungs on FDG PET, corresponding to areas of bronchiectasis on CT with no obvious suspicious FDG-avid foci elsewhere. This supported an inflammatory process causing her elevated carbohydrate antigen 19-9 rather than malignancy.
大動脈弁直下起源の心室性期外収縮(PVC)アブレーションにカルトマッピングが有用であった1例
Authors: 渡辺敦之, 橋本克史, 河合勇介, 川合晴朗, 杉山弘恭, 中濱一, 山田信行
Journal: Circulation (2008)
Natural Killer Cell Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide: Elimination of Donor-Derived Mature Alloreactive NK Cells, but Favorable Conditions for Adoptive Immunotherapy
Authors: Antonio Russo, Giacomo Oliveira, Sofia Berglund, Raffaella Greco, Valentina Gambacorta, Nicoletta Cieri, Cristina Toffalori, Laura Zito, Simona Piemontese, Mara Morelli, Fabio Giglio, Andrea Angelo Assanelli, Maria Teresa Lupo Stanghellini, Chiara Bonini, Jacopo Peccatori, Leo Luznik, Fabio Ciceri, Luca Vago
Journal: Blood (2016)
Prevalence of Obesity Among Adults, by Household Income and Education — United States, 2011–2014
Authors: Cynthia L. Ogden, Tala H. Fakhouri, Margaret D. Carroll, Craig M. Hales, Cheryl D. Fryar, Xianfen Li, David S. Freedman
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Studies have suggested that obesity prevalence varies by income and educational level, although patterns might differ between high-income and low-income countries (1-3). Previous analyses of U.S. data have shown that the prevalence of obesity varied by income and education, but results were not consistent by sex and race/Hispanic origin (4). Using data from the National Health and Nutrition Examination Survey (NHANES), CDC analyzed obesity prevalence among adults (aged ≥20 years) by three levels of household income, based on percentage (≤130%, >130% to ≤350%, and >350%) of the federal poverty level (FPL) and individual education level (high school graduate or less, some college, and college graduate). During 2011-2014, the age-adjusted prevalence of obesity among adults was lower in the highest income group (31.2%) than the other groups (40.8% [>130% to ≤350%] and 39.0% [≤130%]). The age-adjusted prevalence of obesity among college graduates was lower (27.8%) than among those with some college (40.6%) and those who were high school graduates or less (40.0%). The patterns were not consistent across all sex and racial/Hispanic origin subgroups. Continued progress is needed to achieve the Healthy People 2020 targets of reducing age-adjusted obesity prevalence to <30.5% and reducing disparities (5).
Deficiency of Natriuretic Peptide Receptor 2 Promotes Bicuspid Aortic Valves, Aortic Valve Disease, Left Ventricular Dysfunction, and Ascending Aortic Dilatations in Mice
Authors: Mark C. Blaser, Kuiru Wei, Rachel L.E. Adams, Yu-Qing Zhou, Laura-lee Caruso, Zahra Mirzaei, Alan Y.-L. Lam, Richard K.K. Tam, Hangjun Zhang, Scott P. Heximer, R. Mark Henkelman, Craig A. Simmons
Journal: Circulation Research (2017)

Aortic valve disease is a cell-mediated process without effective pharmacotherapy. CNP (C-type natriuretic peptide) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve health in vivo.The aim of this study is to determine whether a deficient CNP signaling axis in mice causes accelerated progression of aortic valve disease.In cultured porcine valve interstitial cells, CNP inhibited pathological differentiation via the guanylate cyclase NPR2 (natriuretic peptide receptor 2) and not the G-protein-coupled clearance receptor NPR3 (natriuretic peptide receptor 3). We used Npr2+/- and Npr2+/-;Ldlr-/- mice and wild-type littermate controls to examine the valvular effects of deficient CNP/NPR2 signaling in vivo, in the context of both moderate and advanced aortic valve disease. Myofibrogenesis in cultured Npr2+/- fibroblasts was insensitive to CNP treatment, whereas aged Npr2+/- and Npr2+/-;Ldlr-/- mice developed cardiac dysfunction and ventricular fibrosis. Aortic valve function was significantly impaired in Npr2+/- and Npr2+/-;Ldlr-/- mice versus wild-type littermates, with increased valve thickening, myofibrogenesis, osteogenesis, proteoglycan synthesis, collagen accumulation, and calcification. 9.4% of mice heterozygous for Npr2 had congenital bicuspid aortic valves, with worse aortic valve function, fibrosis, and calcification than those Npr2+/- with typical tricuspid aortic valves or all wild-type littermate controls. Moreover, cGK (cGMP-dependent protein kinase) activity was downregulated in Npr2+/- valves, and CNP triggered synthesis of cGMP and activation of cGK1 (cGMP-dependent protein kinase 1) in cultured porcine valve interstitial cells. Finally, aged Npr2+/-;Ldlr-/- mice developed dilatation of the ascending aortic, with greater aneurysmal progression in Npr2+/- mice with bicuspid aortic valves than those with tricuspid valves.Our data establish CNP/NPR2 signaling as a novel regulator of aortic valve development and disease and elucidate the therapeutic potential of targeting this pathway to arrest disease progression.
What Parents Need to Know About the Risks of Lead Exposure for Children
Authors: Megan A. Moreno
Journal: JAMA Pediatrics (2017)

Amber L. Beckley, PhD; Avshalom Caspi, PhD; Jonathan Broadbent, PhD; Honalee Harrington, BA; Renate M. Houts, PhD; Richie Poulton, PhD; Sandhya Ramrakha, PhD; Aaron Reuben, MEM; Terrie E. Moffitt, PhD