tbuckley/cabot-search huggingface dataset:
Pilot evaluation of sulforaphane in melanoma patients with multiple atypical nevi: Tissue STAT1 and STAT3 as risk markers.
Authors: David Lobur, Diwakar Davar, Shivendra Singh, Jan Hendrik Beumer, Howard Edington, Ahmad A. Tarhini, Hussein Tawbi, Hassane M. Zarour, Paul Talalay, John M. Kirkwood
Journal: Journal of Clinical Oncology (2012)

TPS8606 Background: Increasing incidence and the poor prognosis of advanced melanoma argue for prevention efforts. Primary prevention and ultraviolet radiation (UVR) reduction have failed to gain traction in the population, making chemoprevention increasingly attractive. Sulforaphanes (SFN) are bioactive cruciferous compounds rich in the Brassica family, especially broccoli sprouts. Topical broccoli sprout extracts (BSE) decrease UVR erythema response in human skin, and may protect against UVR DNA damage. We have shown SFN inhibition of STAT3, which is constitutively activated in melanoma. We have therefore initiated a pilot study to evaluate BSE SFN in relation to melanoma progression biomarkers, and expression of STAT proteins of atypical melanocytic nevi. Methods: Melanoma patients with &gt;2 atypical nevi are eligible for this trial, which aims to define the safety and clinico-pathological response to oral BSE-SFN. Secondary objectives are documentation of pharmacokinetics and pharmacodynamics of BSE-SFN, and the modulation of STAT 1/3 expression in atypical nevi and normal skin. Baseline photo-documentation and atypical nevus biopsy is performed to assess histopathological atypia and STAT 1/3 expression. Adjacent normal skin biopsies will establish baseline skin SFN levels. Six subjects per group will be accrued at daily dosages of 50, 100, and 200 μM. Subjects must abstain from dietary glucosinolates and isothiocyanates for the study duration and maintain food diaries. Following 27 days of BSE-SFN, blood samples, photography of index atypical nevi, and biopsies of selected atypical nevi and normal skin will be obtained. The three dosage groups will be analyzed for changes in atypia, SFN localization histopathology, and STAT 1/3 expression in the nevi and skin harvested at baseline and at study completion. This trial, UPCI 10-114, has received an IND and is IRB-approved. Accrual is planned to be completed during 2012-13.
ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension
Authors: Ekkehard Grünig, Christina Eichstaedt, Joan-Albert Barberà, Nicola Benjamin, Isabel Blanco, Eduardo Bossone, Antonio Cittadini, Gerry Coghlan, Paul Corris, Michele D'Alto, Antonello D'Andrea, Marion Delcroix, Frances de Man, Sean Gaine, Stefano Ghio, Simon Gibbs, Lina Gumbiene, Luke S. Howard, Martin Johnson, Elena Jurevičienė, David G. Kiely, Gabor Kovacs, Alison MacKenzie, Alberto M. Marra, Noel McCaffrey, Paul McCaughey, Robert Naeije, Horst Olschewski, Joanna Pepke-Zaba, Abílio Reis, Mário Santos, Stéphanie Saxer, Robert M. Tulloh, Silvia Ulrich, Anton Vonk Noordegraaf, Andrew J. Peacock
Journal: European Respiratory Journal (2018)

Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training for pulmonary hypertension (PH) patients. An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms. In studies (784 PH patients in total, including six randomised controlled trials, three controlled trials, 10 prospective cohort studies and four meta-analyses), exercise training has been shown to improve exercise capacity, muscular function, quality of life and possibly right ventricular function and pulmonary haemodynamics. Nevertheless, further studies are needed to confirm these data, to investigate the impact on risk profiles and to identify the most advantageous training methodology and underlying pathophysiological mechanisms. As exercise training appears to be effective, cost-efficient and safe, but is scarcely reimbursed, support from healthcare institutions, commissioners of healthcare and research funding institutions is greatly needed. There is a strong need to establish specialised rehabilitation programmes for PH patients to enhance patient access to this treatment intervention.
Abstract 17264: Impaired Exercise Chronotropic Efficiency and Left Atrial Enlargement as Typical Feature of Exercise Gas Exchange Impairment in Subjects at Cardiovascular Risk: Data From the Euro-Ex Trial
Authors: Pietro L Laforgia, Francesco Bandera, Marco Guazzi
Journal: Circulation (2017)

Background: Chronotropic incompetence (CI) is defined as the inability of the heart to increase its rate commensurate with increased activity or demand. CI is an independent predictor of major adve...
Results of SWOG 1318: A Phase 2 Trial of Blinatumomab Followed By Pomp (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) Maintenance in Elderly Patients with Newly Diagnosed Philadelphia Chromosome Negative B-Cell Acute Lymphoblastic Leukemia
Authors: Anjali S. Advani, Anna Moseley, Kristen Marie O'Dwyer, Brent Wood, Min Fang, Matthew J. Wieduwilt, Ibrahim Aldoss, Jae H. Park, Rebecca Klisovic, Maria R. Baer, Wendy Stock, Rupali Bhave, Megan Othus, Mark R. Litzow, Richard M. Stone, Harry P. Erba
Journal: Blood (2018)
Abstract 19139: Asthma is Associated With Carotid Arterial Injury in Children: The Childhood Origins of Asthma (COAST) Cohort
Authors: Matthew C Tattersall, Michael D Evans, Claudia E Korcarz, Robert F Lemanske, Carol Mitchell, James E Gern, James H Stein
Journal: Circulation (2017)

Background: Asthma is associated with an increased cardiovascular disease (CVD) risk in adults, but this risk in children has not been evaluated. We hypothesized that children with asthma and atopy...
Development and validation of a simplified method to generate human microglia from pluripotent stem cells
Authors: Amanda McQuade, Morgan Coburn, Christina H. Tu, Jonathan Hasselmann, Hayk Davtyan, Mathew Blurton-Jones
Journal: Molecular Neurodegeneration (2018)

Microglia, the principle immune cells of the brain, play important roles in neuronal development, homeostatic function and neurodegenerative disease. Recent genetic studies have further highlighted the importance of microglia in neurodegeneration with the identification of disease risk polymorphisms in many microglial genes. To better understand the role of these genes in microglial biology and disease, we, and others, have developed methods to differentiate microglia from human induced pluripotent stem cells (iPSCs). While the development of these methods has begun to enable important new studies of microglial biology, labs with little prior stem cell experience have sometimes found it challenging to adopt these complex protocols. Therefore, we have now developed a greatly simplified approach to generate large numbers of highly pure human microglia. iPSCs are first differentiated toward a mesodermal, hematopoietic lineage using commercially available media. Highly pure populations of non-adherent CD43+ hematopoietic progenitors are then simply transferred to media that includes three key cytokines (M-CSF, IL-34, and TGFβ-1) that promote differentiation of homeostatic microglia. This updated approach avoids the prior requirement for hypoxic incubation, complex media formulation, FACS sorting, or co-culture, thereby significantly simplifying human microglial generation. To confirm that the resulting cells are equivalent to previously developed iPSC-microglia, we performed RNA-sequencing, functional testing, and transplantation studies. Our findings reveal that microglia generated via this simplified method are virtually identical to iPS-microglia produced via our previously published approach. To also determine whether a small molecule activator of TGFβ signaling (IDE1) can be used to replace recombinant TGFβ1, further reducing costs, we examined growth kinetics and the transcriptome of cells differentiated with IDE1. These data demonstrate that a microglial cell can indeed be produced using this alternative approach, although transcriptional differences do occur that should be considered. We anticipate that this new and greatly simplified protocol will enable many interested labs, including those with little prior stem cell or flow cytometry experience, to generate and study human iPS-microglia. By combining this method with other advances such as CRISPR-gene editing and xenotransplantation, the field will continue to improve our understanding of microglial biology and their important roles in human development, homeostasis, and disease.
Toward a better understanding of folate metabolism in health and disease
Authors: Yuxiang Zheng, Lewis C. Cantley
Journal: The Journal of Experimental Medicine (2018)

Folate metabolism is crucial for many biochemical processes, including purine and thymidine monophosphate (dTMP) biosynthesis, mitochondrial protein translation, and methionine regeneration. These biochemical processes in turn support critical cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. Not surprisingly, abnormal folate metabolism has been causally linked with a myriad of diseases. In this review, we provide a historical perspective, delve into folate chemistry that is often overlooked, and point out various missing links and underdeveloped areas in folate metabolism for future exploration.
Feasibility of Reidentifying Individuals in Large National Physical Activity Data Sets From Which Protected Health Information Has Been Removed With Use of Machine Learning
Authors: Liangyuan Na, Cong Yang, Chi-Cheng Lo, Fangyuan Zhao, Yoshimi Fukuoka, Anil Aswani
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Despite data aggregation and removal of protected health information, there is concern that deidentified physical activity (PA) data collected from wearable devices can be reidentified. Organizations collecting or distributing such data suggest that the aforementioned measures are sufficient to ensure privacy. However, no studies, to our knowledge, have been published that demonstrate the possibility or impossibility of reidentifying such activity data. <h3>Objective</h3> To evaluate the feasibility of reidentifying accelerometer-measured PA data, which have had geographic and protected health information removed, using support vector machines (SVMs) and random forest methods from machine learning. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2005-2006 data sets were analyzed in 2018. The accelerometer-measured PA data were collected in a free-living setting for 7 continuous days. NHANES uses a multistage probability sampling design to select a sample that is representative of the civilian noninstitutionalized household (both adult and children) population of the United States. <h3>Exposures</h3> The NHANES data sets contain objectively measured movement intensity as recorded by accelerometers worn during all walking for 1 week. <h3>Main Outcomes and Measures</h3> The primary outcome was the ability of the random forest and linear SVM algorithms to match demographic and 20-minute aggregated PA data to individual-specific record numbers, and the percentage of correct matches by each machine learning algorithm was the measure. <h3>Results</h3> A total of 4720 adults (mean [SD] age, 40.0 [20.6] years) and 2427 children (mean [SD] age, 12.3 [3.4] years) in NHANES 2003-2004 and 4765 adults (mean [SD] age, 45.2 [19.9] years) and 2539 children (mean [SD] age, 12.1 [3.4] years) in NHANES 2005-2006 were included in the study. The random forest algorithm successfully reidentified the demographic and 20-minute aggregated PA data of 4478 adults (94.9%) and 2120 children (87.4%) in NHANES 2003-2004 and 4470 adults (93.8%) and 2172 children (85.5%) in NHANES 2005-2006 (<i>P</i> &lt; .001 for all). The linear SVM algorithm successfully reidentified the demographic and 20-minute aggregated PA data of 4043 adults (85.6%) and 1695 children (69.8%) in NHANES 2003-2004 and 4041 adults (84.8%) and 1705 children (67.2%) in NHANES 2005-2006 (<i>P</i> &lt; .001 for all). <h3>Conclusions and Relevance</h3> This study suggests that current practices for deidentification of accelerometer-measured PA data might be insufficient to ensure privacy. This finding has important policy implications because it appears to show the need for deidentification that aggregates the PA data of multiple individuals to ensure privacy for single individuals.
Innate immunity as a target for acute cardioprotection
Authors: Coert J Zuurbier, Antonio Abbate, Hector A Cabrera-Fuentes, Michael V Cohen, Massimo Collino, Dominique P V De Kleijn, James M Downey, Pasquale Pagliaro, Klaus T Preissner, Masafumi Takahashi, Sean M Davidson
Journal: Cardiovascular Research (2018)

Acute obstruction of a coronary artery causes myocardial ischaemia and if prolonged, may result in an ST-segment elevation myocardial infarction (STEMI). First-line treatment involves rapid reperfusion. However, a highly dynamic and co-ordinated inflammatory response is rapidly mounted to repair and remove the injured cells which, paradoxically, can further exacerbate myocardial injury. Furthermore, although cardiac remodelling may initially preserve some function to the heart, it can lead over time to adverse remodelling and eventually heart failure. Since the size of the infarct corresponds to the subsequent risk of developing heart failure, it is important to find ways to limit initial infarct development. In this review, we focus on the role of the innate immune system in the acute response to ischaemia–reperfusion (IR) and specifically its contribution to cell death and myocardial infarction. Numerous danger-associated molecular patterns are released from dying cells in the myocardium, which can stimulate pattern recognition receptors including toll like receptors and NOD-like receptors (NLRs) in resident cardiac and immune cells. Activation of the NLRP3 inflammasome, caspase 1, and pyroptosis may ensue, particularly when the myocardium has been previously aggravated by the presence of comorbidities. Evidence will be discussed that suggests agents targeting innate immunity may be a promising means of protecting the hearts of STEMI patients against acute IR injury. However, the dosing and timing of such agents should be carefully determined because innate immunity pathways may also be involved in cardioprotection. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.
Abstract 17015: When is a Pathological Q Wave Truly Pathological?
Authors: Keerthi Prakash, Aneil Malhotra, Harshil Dhutia, Philippe Siegenthaler, Grant Nolan, Henry Roth, Michael Papadakis, Sanjay Sharma
Journal: Circulation (2015)

Introduction: Pathological Q waves are considered harbingers of cardiac pathology and should instigate comprehensive evaluation of athletes. Several definitions of the depth or duration of a Q wave exist, with disagreement between scientific bodies as to the most useful. Objectives: 1. Determine the prevalence of pathological Q waves in large cohorts of the general population, athletes and patients with hypertrophic cardiomyopathy (HCM). 2. Identify the most accurate Q wave criterion. Methods: ECGs were retrospectively analysed in consecutive cohorts of 10,008 healthy young athletes (14-35 years old), 2,994 healthy young non-athletes and 468 HCM patients. Results: Pathological Q waves that fulfilled at least one of the 4 individual definitions (Table 1) were identified in 0.7% athletes (n = 75), 1.2% non-athletes (n = 36) and 22.6% patients with HCM (n = 106). In the healthy athletic and non-athletic population, all pathological Q waves (n = 111) met the &gt;3mm depth definition. In contrast, the majority of pathological Q waves in HCM patients met the ≥40msec duration definition (n = 75; 70.75%). We tested the ability of all 4 criteria to distinguish between health and disease in the entire cohort. Seattle and Refined had the best sensitivity for detecting HCM. Refined criteria however, had a significantly higher positive predictive value and 7 times lower false positive rate compared to Seattle. (Table 2) Conclusion: Pathological Q waves are present in up to 1.2% of healthy young individuals and do not correlate with physical activity. Of the proposed criteria, the Refined criteria has the lowest false positive rate and should be utilised in the context of cardiac evaluation in young athletes.
Clinical and immunological features of pemphigus relapse
Authors: I. Ujiie, H. Ujiie, H. Iwata, H. Shimizu
Journal: British Journal of Dermatology (2018)

More than half of patients with pemphigus experience relapse during the disease course. The risk factors and clinical and immunological characteristics of relapse remain largely unclear.To elucidate the risk factors and clinical features of pemphigus relapse.We carried out a retrospective review of the clinical records of 42 cases of pemphigus at a single centre.Sixty-two per cent of patients experienced relapse, usually when oral prednisolone was tapered to around 0·1 mg kg-1 . In mucocutaneous pemphigus vulgaris (mcPV), the initial doses (mean ± SD) of prednisolone were significantly lower in patients with relapse (0·78 ± 0·24 mg kg-1 ) than in those without relapse (1·01 ± 0·01 mg kg-1 ). At relapse, mcPV shifted to mucosal dominant PV (mPV; 40%), pemphigus foliaceus (PF) (20%) or 'other' (20%). In contrast, relapsing mPV and PF had the same clinical phenotypes as the initial phenotypes. Patients with both anti-desmoglein (Dsg)1 and anti-Dsg3 antibodies at onset had recurrence with anti-Dsg3 antibodies alone (40%), with both anti-Dsg1 and anti-Dsg3 antibodies (30%), with anti-Dsg1 antibody alone (20%) or were subthreshold (10%).mcPV shows transitions in clinical phenotype and autoantibody profile at relapse. At least 1 mg kg-1 daily of prednisolone, especially for patients with mcPV, and prudent tapering around 0·1 mg kg-1 may lead to better outcomes.
Association Between Antithrombotic Medication Use After Bioprosthetic Aortic Valve Replacement and Outcomes in the Veterans Health Administration System
Authors: Dawn M. Bravata, Jessica M. Coffing, Devan Kansagara, Jennifer Myers, Lauren Murphy, Barbara J. Homoya, Anthony J. Perkins, Kathryn Snow, Jacquelyn A. Quin, Ying Zhang, Laura J. Myers
Journal: JAMA Surgery (2018)

The recommendations about antithrombotic medication use after bioprosthetic aortic valve replacement (bAVR) vary.To describe the post-bAVR antithrombotic medication practice across the Veterans Health Administration (VHA) and to assess the association between antithrombotic strategies and post-bAVR outcomes.Retrospective cohort study. Multivariable modeling with propensity scores was conducted to adjust for differences in patient characteristics across the 3 most common antithrombotic medication strategies (aspirin plus warfarin sodium, aspirin only, and dual antiplatelets). Text mining of notes was used to identify the patients with bAVR (fiscal years 2005-2015).This study used VHA and non-VHA outpatient pharmacy data and text notes to classify the following antithrombotic medications prescribed within 1 week after discharge from the bAVR hospitalization: aspirin plus warfarin, aspirin only, dual antiplatelets, no antithrombotics, other only, and warfarin only. The 90-day outcomes included all-cause mortality, thromboembolism risk, and bleeding events. Outcomes were identified using primary diagnosis codes from emergency department visits or hospital admissions.The cohort included 9060 veterans with bAVR at 47 facilities (mean [SD] age, 69.3 [8.8] years; 98.6% male). The number of bAVR procedures per year increased from 610 in fiscal year 2005 to 1072 in fiscal year 2015. The most commonly prescribed antithrombotic strategy was aspirin only (4240 [46.8%]), followed by aspirin plus warfarin (1638 [18.1%]), no antithrombotics (1451 [16.0%]), dual antiplatelets (1010 [11.1%]), warfarin only (439 [4.8%]), and other only (282 [3.1%]). Facility variation in antithrombotic prescription patterns was observed. During the 90-day post-bAVR period, adverse events were uncommon, including all-cause mortality in 127 (1.4%), thromboembolism risk in 142 (1.6%), and bleeding events in 149 (1.6%). No differences in 90-day mortality or thromboembolism were identified across the 3 antithrombotic medication groups in either the unadjusted or adjusted models. Patients receiving the combination of aspirin plus warfarin had higher odds of bleeding than patients receiving aspirin only in the unadjusted analysis (odds ratio, 2.58; 95% CI, 1.71-3.89) and after full risk adjustment (adjusted odds ratio, 1.92; 95% CI, 1.17-3.14).These data demonstrate that bAVR procedures are increasingly being performed in VHA facilities and that aspirin only was the most commonly used antithrombotic medication strategy after bAVR. The risk-adjusted results suggest that the combination of aspirin plus warfarin does not improve either all-cause mortality or thromboembolism risk but increases the risk of bleeding events compared with aspirin only.
Abstract 15790: Fetal Outcomes in Pregnant Women With Heart Failure - A Population-Based Study
Authors: Angie T Ng, Theresa Win, Lewei Duan, Albert Y Shen, Ming-Sum Lee
Journal: Circulation (2017)

Introduction: The goal of this study is to characterize maternal and fetal outcomes in pregnant women diagnosed with heart failure in a large-sample, community-based cohort. Methods: This is a retr...
Abstract 15633: A Biophysical Lens into the Development of Anti Atherosclerotic HSP27 Immunotherapy
Authors: Michael H Chiu, Chunhua Shi, Mathew F Clarkson, Edward R O'Brien
Journal: Circulation (2017)

Introduction: Heat Shock Protein 27 (HSP27) attenuates atherogenesis by reducing inflammation and lowering both plasma and plaque cholesterol levels. Atherosclerosis-prone ApoE-null mice that over-...
Abstract 13091: The Prefereble Anatomical Location of the Functional Conduction Block Line Preceded by the Onset of Random Meandering Reentrant Wave Propagation in Patients with Atrial Fibrillation: Analysis by the Non-Contact Mapping
Authors: Tadashi Hoshiyama, Hiroshige Yamabe, Junjiroh Koyama, Hisanori Kanazawa, Hisao Ogawa
Journal: Circulation (2012)

Background: It has been shown that the random reentrant wave propagation is induced following the formation of the functional line of block in the left atrium (LA). However precise anatomical locat...