tbuckley/cabot-search huggingface dataset:
Abstract P370: Cardiovascular Health Metrics, Lifetime Risks of Cardiovascular Disease and Chronic Disease Mortality, and Life Expectancy in Men and Women
Authors: ChongLee
Journal: Circulation (2015)

Whether cardiovascular health metrics relates to lifetime risks of cardiovascular disease (CVD) and chronic disease mortality and life expectancy in U.S. population remains less explored. PURPOSE: We investigated the combined impact of 7 ideal cardiovascular health metrics on lifetime risks of CVD and chronic disease mortality and life expectancy in US men and women at 30 years of age. METHODS: Lifetime risks of CVD and chronic disease mortality to 80 years of age were estimated for men and women, with death free of chronic diseases as a competing event. We followed 11,341 men and women, aged 30 to 80 years, who participated in the Third National Health and Nutrition Examination Survey. All participants completed baseline lifestyle factors and lifestyle behavior questionnaires. The 7 ideal cardiovascular health metrics was defined as physically active, never smoking, a healthy diet, waist girth (<102/88 cm), untreated blood pressure (<120/80 mmHg), untreated total cholesterol (<200 mg/dL), and untreated f...
Abstract 5309: Determining EGFR and STK11 mutational status in lung adenocarcinoma histopathology images using deep learning
Authors: Nicolas Coudray, Andre L. Moreira, Theodore Sakellaropoulos, David Fenyö, Narges Razavian, Aristotelis Tsirigos
Journal: Cancer Research (2018)

Abstract To characterize a tumor and suggest appropriate treatments, pathologists rely on the visual assessment of histopathology slides as well as molecular profiling of the tumors. This is especially true in lung adenocarcinoma cases where targeted therapies exist for tumors with EGFR mutations. In this work, we studied the use of deep learning approaches to classify lung cancer histopathology images and predict the mutational status of frequently mutated genes. To achieve these tasks, more than 1600 scanned histopathology slides, obtained from TCGA, were separated into independent training, validation and test sets. They were then tiled into 512x512 pixel windows, and the training set was used to feed the inception v3 convolutional neural network developed by Google. The resulting model was evaluated on the test set, and the generated per-tile probabilities were aggregated to generate a per-slide classification score. We based our study on whole-slide images of adenocarcinoma, squamous cells carcinoma and normal lung tissues and the neural network was trained on several tasks: first, the goal was to identify normal from tumor regions, and then, once the tumor regions were identified, it was trained to identify adenocarcinoma versus squamous cell carcinoma. Finally, the neural network was trained predict the mutational status of the most frequently mutated genes in lung adenocarcinoma. After verifying that the trained network properly identifies tumor slides compared to normal tissue (AUC=0.99) and distinguishes adenocarcinomas from squamous cell carcinomas (AUC=0.95), the network was trained to simultaneously identify different mutations. It achieved AUC scores of 0.82 and 0.86 for STK11 and EGFR respectively, showing that mutations in these two genes may confer specific macroscopic features, visible in histopathology images, and that a deep convolutional neural network can be trained to recognize those features. Our results demonstrate that, given the availability of sufficient data, convolutional neural networks learn to perform complex diagnoses and thus assist pathologists in their work. Citation Format: Nicolas Coudray, Andre L. Moreira, Theodore Sakellaropoulos, David Fenyö, Narges Razavian, Aristotelis Tsirigos. Determining EGFR and STK11 mutational status in lung adenocarcinoma histopathology images using deep learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5309.
Abstract 4172: Radiation-induced blood-tumor barrier permeability in a preclinical model of lung cancer brain metastasis
Authors: Samuel A. Sprowls, Neal Shah, Afroz S. Mohammad, Marc Pinti, Rachel M. Tallman, Devin U. John, Paul R. Lockman
Journal: Cancer Research (2018)

Abstract BACKGROUND: Lung cancer has the highest mortality rate among all cancers and accounts for over half of newly diagnosed brain metastases each year. Standard therapeutic advancements are prolonging lives of lung cancer patients with each new approved formulation, however patients with brain metastases have limited options and no curative measures currently exist. Current treatment modalities for brain metastases from primary lung cancer include differing methodologies of radiotherapy (whole brain radiotherapy and/or stereotactic radiosurgery), systemic chemotherapies, and neurosurgery. Radiation in many cases is not ablative, but palliative. Herein we demonstrate the ability of radiotherapy to influence blood-tumor barrier permeability in a novel preclinical model of lung cancer brain metastasis. METHODS: Athymic female nude mice were intracardially injected with our novel PC-9-BR brain specific lung cancer cell line. Tumors were allowed to develop and monitored using bioluminescent imaging. Using the Xstrahl XenX small animal irradiator, we were able to deliver 26 Gy to the right hemisphere of the immobilized mouse. 4 hours post radiotherapy, mice were perfused with the passive permeability marker Oregon Green, followed by an indocyanine green (bound to albumin) washout to infer vascular space. Brains were then extracted, snap frozen in isopentane (-50°C), and sliced to 20μm. Florescence was quantified using a MVX microscope and cellsense software. RESULTS: Analysis of irradiated brain regions demonstrated statistically significant more accumulation of the passive permeability marker, Oregon Green, compared to the contralateral hemisphere. CONCLUSIONS: Radiation induced permeability was witness in mice after a single dose of 26 Gy when compared to non-irradiated tumor tissue 4 hours post treatment. FURTURE DIRECTIVES: Experiments utilizing ionizing radiation to simulate treatment of CNS metastases could reveal better adjunctive chemotherapeutic regimens and or provide insight to the mechanism underlying this enhanced permeability. Citation Format: Samuel A. Sprowls, Neal Shah, Afroz S. Mohammad, Marc Pinti, Rachel M. Tallman, Devin U. John, Paul R. Lockman. Radiation-induced blood-tumor barrier permeability in a preclinical model of lung cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4172.
Studies of Cat Heart Muscle during Recovery after Prolonged Hypothermia
Authors: Tadasitamai, Shunsukekagiyama
Journal: Circulation Research (1968)

Cat heart muscles preserved in normal Tyrode's solution at 4°C for prolonged periods were investigated by recording the transmembrane potentials after rewarming to 37°C. The cell membranes were gradually hyperpolarized during rewarming, the maximum hyperpolarization being reached within a few hours. The amplitude of resting potentials obtained at a maximally hyperpolarized stage was largest for ventricular muscle that had been preserved for 20 hours at 4°C and for atrial muscle that had been preserved for about 50 hours at 4°C. The maximum potentials averaged 267.7 mv for the ventricles and 184.4 mv for the atria. KC1 at 10 x normal and epinephrine and norepinephrine in final concentrations of 2.5 x 10-7 g/ml brought about a marked hyperpolarization of the cell membrane when the membrane potential of the muscles was declining. The cells of muscles loaded with Li had a greater than normal membrane potential for an hour during gradual equilibration over a range of 4 to 22°C before rewarming. When muscles we...
Abstract 2078: Analysis of DNA structural variations in context of the gene regulatory landscape of pediatric ALL
Authors: Laura Oksa, Miikka Vouttilainen, Tapio Vuorenmaa, Saara Laukkanen, Mari Lahnalampi, Olli Lohi, Merja Heinäniemi
Journal: Cancer Research (2018)

Abstract Acute lymphoblastic leukemia (ALL) is the most common pediatric leukemia. It comprises of multiple subtypes with combinations of chromosomal rearrangements, indels and copy number variations. Furthermore, there is a significant number of somatic mutations located outside of protein coding regions of the genome. These DNA alterations can be classified based on whether they 1) introduce novel transcription factor binding sites, 2) create aberrant (super-)enhancers, or 3) lead to the loss of regulatory boundaries at oncogene loci upon disruption of CTCF binding sites. We performed whole genome sequencing (WGS) on two T-ALL and 16 pre-B ALL patients from diagnostic and remission samples, and measured transcriptional activity using Global Nuclear Run-on sequencing (GRO-seq). These results were integrated with chromatin topology information and transcript annotations to yield comprehensive characterization of the gene regulatory landscape. The effect on gene expression was further analyzed based on monoallelic expression. Altogether, we found 49 translocations, 153 deletions, 9 duplications and 22 inversions across the pre-B ALL samples. Majority of the changes were located within the annotated gene regions. At 25 of these 233 sites, we found evidence that active enhancers resulted in transcription-coupled genetic instability at DNA breakpoints. In a pre-B ALL case, our analysis successfully captured complex translocation event involving ETV6 (ETV6-MUTYH, ETV6-chr7, ETV6-chr21, ETV6-TXNRD2), and deletion at chr22 that hit to active promoters of PATZ1 and DRG1 genes leading to monoallelic expression of these genes. In T-ALLs, we found 13 translocations (8 intergenic) and 9 deletions. In a T-ALL case, we found that translocation between TCR-beta locus and chr9 brought an active promoter to the proximity of TMEM38B resulting in increased gene expression. We also found a deletion in active promoter at chr9 leading to decreased expression of MTAP and CDKN2A genes. Moreover, a large deletion in chr11 brought oncogenic transcription factor LMO2 and RAG1 close to each other. In summary, we present a genome-wide approach to link structural variation events with gene regulatory features in ALL cells. This extends previous approaches that have mainly focused on genetic changes at coding regions. Citation Format: Laura Oksa, Miikka Vouttilainen, Tapio Vuorenmaa, Saara Laukkanen, Mari Lahnalampi, Olli Lohi, Merja Heinäniemi. Analysis of DNA structural variations in context of the gene regulatory landscape of pediatric ALL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2078.
Prognostic Value of the Modified American College of Cardiology/American Heart Association Stenosis Morphology Classification for Long-Term Angiographic and Clinical Outcome After Coronary Stent Placement
Authors: AdnanKastrati, AlbertSchömig, ShpendElezi, JosefDirschinger, JulindaMehilli, HelmutSchühlen, RudolfBlasini, Franz-JosefNeumann
Journal: Circulation (1999)

Background—The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology criteria are predictive of early outcome after various coronary catheter interventions. Their potential prognostic value after stent implantation and, in particular, for restenosis and long-term clinical outcome has not been studied. We assessed the prognostic value of the modified ACC/AHA criteria for the long-term angiographic and clinical outcome of patients after coronary stenting. Methods and Results—This study includes 2944 consecutive patients with symptomatic coronary artery disease treated with coronary stent placement. Modified ACC/AHA lesion morphology criteria were used to qualitatively assess the angiograms; type A and B1 lesions were categorized as simple, and type B2 and C lesions were designated complex. Primary end points were angiographic restenosis and 1-year event-free survival. Restenosis rate was 33.2% in complex lesions and 24.9% in simple lesions (P<0.001). It was 21.7% for...
Adding body load modifies the vibratory sensation of the foot sole and affects the postural control
Authors: Yves Jammes, Eva Ferrand, Corentin Fraud, Alain Boussuges, Jean Paul Weber
Journal: Military Medical Research (2018)

Heavy backpacks are often used by soldiers and firefighters. Weight carrying could reduce the speed and efficiency in task completion by altering the foot sole sensitivity and postural control.In fifteen healthy subjects, we measured the changes in sensitivity to vibrations applied to the foot sole when standing upright or walking after load carrying (30% body weight). The participants were asked to judge different vibration amplitudes applied on the 2nd or 5th metatarsal head and the heel at two frequencies (25 and 150 Hz) to determine the vibration threshold and the global perceptual representation (Ѱ)of the vibration amplitude (Ф) given by the Stevens power function (Ѱ = k × Фn). Any increase in negative k value indicated a reduction in sensitivity to the lowest loads. Pedobarographic measurements, with computation of the center of pressure (COP) and its deviations, were performed during weight carrying.The 25-Hz vibration threshold significantly increased after weight carrying when standing upright or walking. After standing with the added loads, the absolute negative k value increased for the 25 Hz frequency. After walking with the added loads, the k coefficient increased for the two vibration frequencies. Weight carrying significantly increased both the CoP surface and CoP lateral deviation.Our data show that weight carrying reduces the sensory pathways from the foot sole and accentuates the center of pressure deviations.
Usefulness of Electron-Beam Computed Tomography in Arrhythmogenic Right Ventricular Dysplasia
Authors: HiroshiTada, WataruShimizu, TohruOhe, SeikiHamada, TakashiKurita, NaohikoAihara, ShirKamakura, MakotoTakamiya, KatsuroShimomura
Journal: Circulation (1996)

Background Electron-beam computed tomography (CT) may be useful for detecting myocardial fat infiltration and diagnosing arrhythmogenic right ventricular dysplasia (ARVD). There are several characteristic electron-beam CT findings of ARVD. However, the incidence, their relation to electrophysiological abnormalities, and the usefulness of electron-beam CT for evaluating left ventricular involvement are unknown. This study aimed to clarify these issues. Methods and Results Electron-beam CT was performed in 14 patients with ARVD (ARVD group), 16 age- and sex-matched patients with right ventricular enlargement and/or dysfunction without ARVD (RV enlargement group), and 13 control subjects (control group). The incidences of abnormal electron-beam CT findings in the three groups were examined. Furthermore, we examined the endocardial fat–infiltrated areas detected by electron-beam CT (CT-A) and electrophysiologically abnormal areas detected in the mapping study (EPS-A) and compared the relationship between them...
Selective Rac-1 Inhibition Protects From Diabetes-Induced Vascular Injury
Authors: CarmineVecchione, AlessandraAretini, GennaroMarino, UmbertoBettarini, RobertaPoulet, AngeloMaffei, MauroSbroggiò, LucioPastore, Maria TeresaGentile, AntonellaNotte, LucaIorio, EmilioHirsch, GuidoTarone, GiuseppeLembo
Journal: Circulation Research (2006)

Diabetes mellitus is a main risk factor for vascular diseases. Vascular injury induced by diabetes mellitus is characterized by endothelial dysfunction attributable to an increased oxidative stress. So far, the molecular mechanisms involved in the vasculotoxic effects of diabetes are only partially known. We examined the effect of diabetes mellitus on oxidative stress and Rac-1 activation, a small G-protein involved in the activation of NADPH oxidase. Our results show that oxidative stress in vessels of different murine models of diabetes mellitus and in endothelial cells treated with high glucose is associated with an increased Rac-1/PAK binding and Rac-1 translocation from cytosol to plasma membrane, thus demonstrating an enhanced Rac-1 activity. More important, selective Rac-1 inhibition by an adenoviral vector carrying a dominant negative mutant of Rac-1 protected from oxidative stress and vascular dysfunction induced by diabetes mellitus. Our study demonstrates that Rac-1 plays a crucial role in diab...
Abstract 13558: Which Cutoff Value of Clinic BP Better Stratify Cardiovascular Risk in Patinets with Type 2 Diabetes ? - the J-HOP Study -
Authors: KazuoEguchi, SatoshiHoshide, ShoichiroNagasaka, KazuomiKario
Journal: Circulation (2014)

Introduction: In the JNC-8 guideline, target clinic BP in type 2 diabetes (T2DM) was raised to 140/90mmHg based on recent clinical trials. However, there are still some opinions that the cutoff value of clinic BP 130/80mmHg might be better than 140/90. Hypothesis: We sought to clarify the hypothesis that different clinic BP cutoff values, 130/80mmHg or 140/90mmHg, could have different impact on cardiovascular risk stratification in patients with T2DM. Methods: We enrolled 4326 patients who have at least one cardiovascular risk factor, and performed clinic BP monitoring and measured urinary albumin creatinine ratio (UACR) as a surrogate marker of cardiovascular risk. Patients were stratified by 4 groups using SBP 140mmHg and DBP 90 mmHg: Group1, SBP>140,DBP>90; Group2, >140,≤90; Group3; ≤140,>90; Group4; ≤140≤90. Alternatively, SBP 130mmHg and DBP 80mmHg were also used as a cutoff value. Multivariable logistic regression analyses adjusting for age, sex, BMI, history of hypertension, and renal dysfunction w...
Expression Pattern of Connexin Gene Products at the Early Developmental Stages of the Mouse Cardiovascular System
Authors: BrunoDelorme, EdgarDahl, ThérèseJarry-Guichard, Jean-PaulBriand, KlausWillecke, DanielGros, MagaliThéveniau-Ruissy
Journal: Circulation Research (1997)

Abstract The synchronized contraction of myocytes in cardiac muscle requires the structural and functional integrity of the gap junctions present between these cells. Gap junctions are clusters of intercellular channels formed by transmembrane proteins of the connexin (Cx) family. Products of several Cx genes have been identified in the mammalian heart (eg, Cx45, Cx43, Cx40, and Cx37), and their expression was shown to be regulated during the development of the myocardium. Cx43, Cx40, and Cx45 are components of myocyte gap junctions, and it has also been demonstrated that Cx40 was expressed in the endothelial cells of the blood vessels. The aim of the present work was to investigate the expression and regulation of Cx40, Cx43, and Cx37 during the early stages of mouse heart maturation, between 8.5 days post coitum (dpc), when the first rhythmic contractions appear, and 14.5 dpc, when the four-chambered heart is almost completed. At 8.5 dpc, only the reverse-transcriptase polymerase chain reaction techniqu...
Long-Term (29 Years) Results of Reconstructive Surgery in Rheumatic Mitral Valve Insufficiency
Authors: Sylvain Chauvaud, Jean-François Fuzellier, Alain Berrebi, Alain Deloche, Jean-Noël Fabiani, Alain Carpentier
Journal: Circulation (2001)

Background Results of conservative surgery are well established in degenerative mitral valve (MV) insufficiency. However, there are controversies in rheumatic disease. This study is the evaluation of one center for rheumatic MV insufficiency based on a functional approach. Methods and Results From 1970 to 1994, 951 patients with rheumatic MV insufficiency were operated on with the reconstructive techniques elaborated by Alain Carpentier. Aortic valve diseases were excluded. Mean age was 25.8 years (4 to 75), and sinus rhythm was present in 63%. The functional classification used was type I, normal leaflet motion, 71 patients (7%); type II, prolapsed leaflet, 311 patients (33%); and type III, restricted leaflet motion, 345 patients (36%). The combined lesion of prolapse of the anterior leaflet and restriction of the posterior was present in 224 patients (24%). Surgical techniques used were implantation of a prosthetic ring in 95%, shortening of the chords and leaflet enlargement with autologous pericardium, and commissurotomy. Hospital mortality rate was 2%. The mean follow-up was 12 years (maximum, 29 years): 8618 patients per year. Actuarial survival was 89±19% at 10 years and 82±18% at 20 years. The rate of thromboembolic events was 0.4% patients per year (33 events), with 3 deaths. Freedom from reoperation was 82±19% at 10 years and 55±25% at 20 years. The main cause (83%) of reoperation was progressive fibrosis of the MV. The actuarial rate of reoperation was 2% patients per year and was correlated to the degree of preoperative fibrosis. Conclusions Conservative surgery of rheumatic MV insufficiency has a low hospital mortality rate and an acceptable rate of reoperation. The results are excellent regarding the minimal risk of thromboembolic events.
Insulin Induces Upregulation of Vascular AT1 Receptor Gene Expression by Posttranscriptional Mechanisms
Authors: GeorgNickenig, JörgRöling, KerstinStrehlow, PetraSchnabel, MichaelBöhm
Journal: Circulation (1998)

Background—An interaction of insulin with angiotensin II effects could be pathophysiologically important for the pathogenesis of atherosclerosis and hypertension. Methods and Results—We examined the effect of insulin on AT1 receptor gene expression in cultured vascular smooth muscle cells (VSMCs). A 24-hour incubation with insulin (100 nmol/L) produced a 2-fold increase in AT1 receptor density on VSMCs, as assessed by radioligand binding assays. This enhanced AT1 receptor expression was caused by a time- and concentration-dependent upregulation of the AT1 receptor mRNA levels, as assessed by Northern analysis. The maximal effect was detected after a 24-hour incubation of cells with 100 nmol/L insulin (270±20%). AT1 receptor upregulation was caused by a stabilization of the AT1 receptor mRNA, because the AT1 receptor mRNA half-life was prolonged from 5 hours under basal conditions to 10 hours after insulin stimulation. In contrast, insulin had no influence on AT1 receptor gene transcription, as assessed by...
Abstract 4687: Double positive (DP) CD4+CD8+ T cells with an exhausted phenotype in renal cell carcinoma (RCC) patients
Authors: Laurence Menard, Paul Fischer, Bijal Kakrecha, Deborah Lee, Becky Penhallow, Nataly Manjarrez Orduno, Steven Nadler
Journal: Cancer Research (2018)

Abstract Checkpoint inhibitors target the inhibitory receptors expressed by tumor infiltrating T cells in order to reinvigorate an anti-tumor immune response. Therefore, understanding T cell composition and phenotype in human tumors is crucial. We analyzed by flow cytometry tumor infiltrating lymphocytes from two independent cohorts of patients with different cancer types, including RCC, lung and colon cancer. T cells are usually either CD4+ or CD8+ with a small percentage of CD4+ CD8+ DP cells (&amp;lt;5%). Compared to several other cancer types, including lung and colorectal cancers, about a third of RCC patients showed an increased proportion of DP CD4+CD8+ T cells (&amp;gt;5%, reaching 30-50% of T cells in some patients). These DP T cells express high level of PD1 and TIM-3 that tend to correlate with higher expression of PD1 and TIM-3 in conventional CD8 T cells. DP T cells also express markers of antigen-experienced T cells such as CD38 and HLA-DR. These results suggest that double positive T cells might be exhausted tumor specific T cells with the potential to be reactivated by checkpoint inhibitors. Citation Format: Laurence Menard, Paul Fischer, Bijal Kakrecha, Deborah Lee, Becky Penhallow, Nataly Manjarrez Orduno, Steven Nadler. Double positive (DP) CD4+CD8+ T cells with an exhausted phenotype in renal cell carcinoma (RCC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4687.