tbuckley/cabot-search huggingface dataset:
Abstract 14801: The Ability of ECG Risk Variants to Predict Sudden Arrhythmic Death in Asymptomatic Middle-Aged Subjects Without a Known Cardiac Disease
Authors: Henri K Terho, Jani Tikkanen, Juhani Junttila, Olli Anttonen, Aapo Aro, Tuomas Kenttä, Tuomas Kerola, Harri Rissanen, Heikki Huikuri
Journal: Circulation (2013)

Background:  Numerous traditional and novel risk markers in standard 12-lead electrocardiogram (ECG) have been associated with increased risk of sudden arrhythmic death syndrome (SADS) in general population. However, in asymptomatic subjects without a known cardiac disease the actual clinical impact of these ECG risk markers is unknown. We investigated the predictive power of the ECG risk markers for SADS in asymptomatic middle-aged subjects.   Methods:  We evaluated 12-lead ECGs of 10009 asymptomatic Finnish middle-aged subjects without a known cardiac disease (51.6% men, mean age 43±8.3) with a follow-up of 30±11 years. The end point was SADS according to CAST criteria. ECG variables associated with an increased risk for SADS, such as prolonged intraventricular conduction delay (IVCD) >110 msec, left bundle branch block (LBBB), abnormal QRS angle, inverted T waves in leads other than V1-V3, prolonged QTc interval, inferior early repolarization (ER) ECG pattern and/or pathological Q waves were considered as abnormal ECGs. The risk of SCD was compared between the subjects with any ECG abnormality and those without abnormal ECG.   Results:  Prevalence of subjects with abnormal ECG was 8.7% (N=871). The strongest predictors of SADS were LBBB (relative risk [RR] 3.2, 95% CI 1.2-8.4), IVCD (RR 3.1, 95% CI 1.6-6.0), T-inversion (RR 3.0, 95% CI 1.5-6.0), abnormal QRST angle (RR 2.9, 95% CI 1.9-4.5), pathological Q-waves (RR 2.6, 95% CI 1.6-4.3), prolonged QTc (RR 2.6, 95% CI 1.9-3.5), and inferior ER (RR 2.2, 95% CI 1.6-3.2). IVCD, abnormal QRS angle, pathological Q-waves, prolonged QTc duration and inferior early repolarization remained as independent risk factors of SCD in Cox multiple regression analysis after adjusting for several other risk variables (p   Conclusions:  The prevalence of abnormal ECG increasing the risk of SADS is substantial in asymptomatic middle-aged subjects. Future studies using more rigorous statistics, such as c-statistics, reclassification and cost-effectiveness analyses, will reveal the impact of routine ECG screening of middle-aged subjects for SADS.
Phase I Study of Seviteronel, a Selective CYP17 Lyase and Androgen Receptor Inhibitor, in Men with Castration-Resistant Prostate Cancer
Authors: Shilpa Gupta, Luke T. Nordquist, Mark T. Fleming, William R. Berry, Jingsong Zhang, Sharon L. Ervin, Joel R. Eisner, Edwina S. Baskin-Bey, Neal D. Shore
Journal: Clinical Cancer Research (2018)

Purpose: Seviteronel (INO-464) is a selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) and androgen receptor (AR) inhibitor with antitumor activity in vitro and in vivo This open-label phase I clinical study evaluated the safety, tolerability, pharmacokinetics and activity of once-daily seviteronel in male chemotherapy-naïve subjects with castration-resistant prostate cancer (CRPC).Patients and Methods: Seviteronel was administered at 600 mg once daily with dose titration (DT) and in modified 3 + 3 dose escalation once-daily cohorts at 600, 750, and 900 mg without DT. The primary objectives of this study were to establish safety, tolerability, and the MTD of seviteronel in chemotherapy-naïve subjects with or without prior treatment with FDA-approved CRPC treatments, abiraterone acetate (AA), and enzalutamide. Secondary objectives were to assess pharmacokinetics, PSA, tumor response, and endocrine results.Results: Twenty-one subjects were enrolled. No dose-limiting toxicities (DLT) were observed through 750 mg once daily. Most treatment-emergent adverse events (AE) reported at grade 1-2. The most commonly reported AEs were fatigue (71%), dizziness (52%), blurred vision (38%), and dysgeusia (33%), with most AEs improving after dose reduction or dose interruption.Conclusions: Once-daily seviteronel was generally well tolerated in this phase I study of men with CRPC, a majority of which had progressed on prior AA or enzalutamide, or both. Of the doses evaluated, 600 mg once daily was chosen as the recommended phase II dose for future studies in subjects with CRPC. Clin Cancer Res; 24(21); 5225-32. ©2018 AACR.
Re: Gladell P. Paner, Walter M. Stadler, Donna E. Hansel, Rodolfo Montironi, Daniel W. Lin, Mahul B. Amin. Updates in the Eighth Edition of the Tumor-node-metastasis Staging Classification for Urologic Cancers. Eur Urol 2018;73:560–9
Authors: Vincenzo Di Nunno, Matteo Santoni, Alessia Cimadamore, Nicola Battelli, Francesco Massari
Journal: European Urology (2018)
Oxidative Stress-Induced Actin Reorganization Mediated by the p38 Mitogen-Activated Protein Kinase/Heat Shock Protein 27 Pathway in Vascular Endothelial Cells
Authors: JacquesHuot, FrancoisHoule, FrancoisMarceau, JacquesLandry
Journal: Circulation Research (1997)

Vascular endothelial cells are constantly in contact with oxyradicals and must be especially well equipped to resist their toxic effects and generate appropriate physiological responses. Despite the importance of oxyradicals in the physiopathology of the vascular endothelium, the mechanisms regulating the oxidative response of endothelial cells are poorly understood. In the present study, we observed that H sub 2 O2 in concentrations that induced severe fragmentation of F-actin in fibroblasts rather induced a reorganization of F-actin in primary cultures of human umbilical vein endothelial cells (HUVECs) that was characterized by the accumulation of stress fibers, the recruitment of vinculin to focal adhesions, and the loss of membrane ruffles. H2 O2 also induced in these cells a strong (10- to 14-fold) activation of the p38 mitogen-activated protein (MAP) kinase, which resulted in activation of MAP kinase-activated protein kinase-2/3 and phosphorylation of the F-actin polymerization modulator, heat shock...
Abstract 13107: Left Ventricular Diastolic Function Evaluated by the E/e’ Ratio is Impaired in Patients With Masked Uncontrolled Hypertension
Authors: Takahiro Komori, Kazuo Eguchi, Kabutoya Tomoyuki, Joji Ishikawa, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2013)

Background: Masked uncontrolled hypertension (MUH), defined as controlled office blood pressure (BP) but uncontrolled out-of-office BP in treated hypertensives, is a risk factor for cardiovascular ...
Regenerative Potential of Neonatal Porcine Hearts
Authors: Wuqiang Zhu, Eric Zhang, Meng Zhao, Zechen Chong, Chengming Fan, Yawen Tang, Jervaughn D. Hunter, Anton V. Borovjagin, Gregory P. Walcott, Jake Y. Chen, Gangjian Qin, Jianyi Zhang
Journal: Circulation (2018)

Rodent hearts can regenerate myocardium lost to apical resection or myocardial infarction for up to 7 days after birth, but whether a similar window for myocardial regeneration also exists in large mammals is unknown.Acute myocardial infarction (AMI) was surgically induced in neonatal pigs on postnatal days 1, 2, 3, 7, and 14 (ie, the P1, P2, P3, P7, and P14 groups, respectively). Cardiac systolic function was evaluated before AMI and at 30 days post-AMI via transthoracic echocardiography. Cardiomyocyte cell cycle activity was assessed via immunostaining for proliferation and mitosis markers, infarct size was evaluated histologically, and telomerase activity was measured by quantitative polymerase chain reaction.Systolic function at day 30 post-AMI was largely restored in P1 animals and partially restored in P2 animals, but significantly impaired when AMI was induced on postnatal day 3 or later. Hearts of P1 animals showed little evidence of scar formation or wall thinning on day 30 after AMI, with increased measures of cell-cycle activity seen 6 days after AMI (ie, postnatal day 7) compared with postnatal day 7 in noninfarcted hearts.The neonatal porcine heart is capable of regeneration after AMI during the first 2 days of life. This phenomenon is associated with induction of cardiomyocyte proliferation and is lost when cardiomyocytes exit the cell cycle shortly after birth.
Optimal Treatment for High-Risk Prostate Cancer—Reply
Authors: Amar U. Kishan, Ryan R. Cook, Christopher R. King
Journal: JAMA (2018)

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THU0544 Study of the effects of ozone versus steroid injection on patients with recalcitrant tennis elbow; a clinical trial
Authors: S.A. Raeissadat, M.H. Abdollahzadeh
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Tennis elbow is a prevalent musculoskeletal disorder. In recent years ozone injection has been proposed as a treatment for many musculoskeletal disorders. This study aims to compare the effect of ozone injection with steroid in patients with recalcitrant tennis elbow. <h3>Objectives</h3> The aim of this study is to compare the effect of ozone with the standard treatment of steroid injection in patients with tennis elbow, resistant to conservative treatments. This comparison is made according to VAS score, Pressure pain threshold (PPT) and modified Mayo clinic performance index for elbow. <h3>Methods</h3> In this study 64 patients with tennis elbow, which have had the symptoms for more than 3 months and were resistant to conservative treatments, were randomised to two groups. In steroid injection group 40 mg of methylprednisolone acetate and in zone injection group 4 ml of ozone with concentration of 15mcg/ml was injected. 32 patients in steroid and 29 patients in ozone injection group finished this study. Data were gathered before injection and 2 and 6 months after that by VAS score, modified Mayo clinic performance index for elbow and PPT (measured by the means of an algometer). Variables were compared between the two groups and also the changes in each group have been measured in reference to baseline data. <h3>Results</h3> In both groups VAS score, Mayo clinic performance index and PPT improved significantly in 2 and 6 month follow up. Steroid injection was significantly better than ozone injection in improving 2 and 6 months pressure pain threshold and 6 months Mayo clinic performance index. Other data didn't show significant difference between the two groups. <h3>Conclusions</h3> Both steroid and ozone injection improved pain and function in patients with recalcitrant tennis elbow for at least 6 months. Steroid injection was superior to ozone injection in improving PPT during the 2 and 6 month follow up and function improvement in steroid group was significantly more than ozone group after 6 month. <h3>References</h3> [1] Chourasia A, Buhr K, Rabago D, Kijowski R. Relationships between biomechanics, tendon pathology, and function in individuals with lateral epicondylosis. J Orthop2013; [2] Mawsouf M, El-Sawalhi M. Effect of ozone therapy on redox status in experimentally induced arthritis. Revista. 2012; <h3>Disclosure of Interest</h3> None declared
Relationship between symptoms and health-related quality of life benefits in patients with carcinoid syndrome: Post-hoc analyses from TELESTAR
Authors: M. Pavel, D. Cella, J.L. Beaumont, S. Hudgens, F. Marteau, M. Feuilly, S. Gabriel, A. Houchard, J. Ramage, D. Hörsch, M.H. Kulke
Journal: Annals of Oncology (2017)
Putting replication in its place
Authors: Evan Heit, Caren M. Rotello
Journal: Behavioral and Brain Sciences (2018)

Abstract Direct replication is valuable but should not be elevated over other worthwhile research practices, including conceptual replication and checking of statistical assumptions. As noted by Rotello et al. (2015), replicating studies without checking the statistical assumptions can lead to increased confidence in incorrect conclusions. Finally, successful replications should not be elevated over failed replications, given that both are informative.
Application of Multifunctional Nanomaterials in Radioprotection of Healthy Tissues
Authors: Jiani Xie, Chengyan Wang, Feng Zhao, Zhanjun Gu, Yuliang Zhao
Journal: Advanced Healthcare Materials (2018)

Abstract Radiotherapy has been extensively used in clinic for malignant tumors treatment. However, a severe challenge of it is that the ionizing radiation needed to kill tumors inevitably causes damage to surrounding normal tissues. Although some of the molecular radioprotective drugs, such as amifostine, have been used as clinical adjuvants to radio‐protect healthy tissues, their shortcomings such as short systemic circulation time and fast biological clearing from the body largely hinder the sustained bioactivity. Recently, with the rapid development of nanotechnology in the biological field, the multifunctional nanomaterials not only establish powerful drug delivery systems to improve the molecular radioprotective drugs' biological availability, but also open a new route to develop neozoic radioprotective agents because some nanoparticles possess intrinsic radioprotective abilities. Therefore, considering these overwhelming superiorities, this review systematically summarizes the advances in healthy tissue radioprotection applications of multifunctional nanomaterials. Furthermore, this review also points out a perspective of nanomaterial designs for radioprotection applications and discusses the challenges and future outlooks of the nanomaterial‐mediated radioprotection.
Role of the chemokine fractalkine (CX3CL1) and its receptor CX3CR1 in skeletal metastasis from prostate cancer
Authors: Whitney L. Jamieson, Julia A. Fox, Alessandro Fatatis
Journal: Cancer Research (2006)

2407  Approximately 90% of patients with advanced prostate cancer develop skeletal metastasis. Despite many efforts, the cellular and molecular mechanisms regulating the location of migrating cancer cells to secondary organs are still poorly defined. It is likely that, in addition to vascular patterns, unique characteristics of the endothelial cells lining the capillary beds of the colonized tissues play a role in cancer organ-tropism. In addition - similarly to hematopoietic stem cells - cancer cells may migrate from the luminal side of the endothelial cells into the surrounding tissue in response to chemotactic molecules released by bone marrow stromal cells. We have previously shown that: 1) prostate cancer cells express CX3CR1 in vitro and this receptor mediates their adhesion - under dynamic flow conditions - to bone marrow endothelial cells, which constitutively express the chemokine fractalkine/CX3CL1 on their surface; 2) human osteoblasts also express fractalkine and release it in a soluble form, which attracts prostate cancer cells in vitro. In the present study we show that epithelial cells in frozen sections of human prostate glands - either normal or affected by adenocarcinoma - stain positive for CX3CR1. This ex vivo evidence further support our previous in vitro observations and indicates that the expression of CX3CR1 by prostate epithelial cells does not require the necessary intervention of a positive selective pressure for its exclusive expression in the malignant phenotype. This is in contrast to what reported by others for CXCR4, the receptor for the chemokine SDF-1 (CXCL12), both also implicated in prostate bone secondary tumors. We also found that, in addition to osteoblasts, human bone mesenchymal and stromal cells express membrane-bound fractalkine and release its soluble, chemoattractant form. Consistently, high levels of soluble fractalkine were detected by ELISA in human bone marrow aspirates from normal donors. Further experiments were conducted to investigate the modulation of fractalkine cleavage and release in bone cells, with a particular focus on the role played by androgens in this process. Finally, silencing of CX3CR1, achieved using shRNA, was used to further define the role of this chemokine receptor in the adhesion of prostate cancer cells to bone marrow endothelial cells as well as their migration towards media conditioned by different types of bone cells. The long term goal of this study is to ascertain whether the chemokine fractalkine and its specific receptor CX3CR1 can be considered molecular targets for therapeutic strategies aiming to prevent or significantly impair the colonization of the skeleton in patients with prostate adenocarcinoma
Abstract 18060: Risk Stratification Following Mitral Valve Surgery for Chronic Ischemic Mitral Regurgitation: A Very Long-term Study
Authors: Carlo Fino, Diego Bellavia, Antonio Miceli, Joseph Malouf, Attilio Iacovoni, Diego Cugola, Alice Calabrese, Caterina Simon, Emilia Delia, Massimo Caputo, Maurizio Merlo, Lorenzo Galletti, Michele Senni, Marcello Traina, Julien Magne
Journal: Circulation (2015)

Background: Very few long-term data are available on patients undergoing mitral valve surgery for chronic ischemic mitral regurgitation (CIMR). Objective:to identify determinants of survival and adverse cardiovascular events, at very long-term outcome. Methods and Results: We reviewed complete left and right ventricular echocardiographic data, six-minute walking test (6-MWT) and BNP levels at pre, peri and follow-up, on 137 consecutive patients who underwent restrictive mitral annuloplasty (RMA) or mitral valve replacement (MVR) and CABG, for CIMR. Combined adverse cardiovascular events were defined as composite of death, heart failure, angina, myocardial infarction and re-hospitalization. Mean age was 67±0.7. Preoperative EF was 35±06%. Among 137 patients, 46% underwent RMA and 54% had MVR. Median follow- up was 7 years (range: 0.3-15.4). Early mortality was 7% (p=NS). In the RMA 42% of patients experienced MR recurrence. Overall survival at 5, 10 and 15 years were 84, 76 and 62% in RMA, and 87, 62 and 54% in MVR (p=0.65). At univariate analysis, preop B-blocker, 6-MWT, mean transmitral gradients and RV size were predictors of adverse events.The Cox Hazard multivariate analysis identified preoperative atrial fibrillation (p=0.005), preop BNP (p=0.025) as independent predictors of long-term mortality.Freedom from cardiovascular events at 5, 10 and 15 years were 90, 75 and 48% in RMA, and 90, 62 and 45% in MVR (p=0.57). . The Cox Hazard multivariate analysis identified preop B-blocker therapy (p=0.001), atrial fibrillation (p=0.01), postoperative mean transmitral gradients (p=0.047 ) and indexed effective orifice area (p=0.02) as independent predictors of adverse cardiovascular events. Conclusions: Our study confirms an high rate of true MR recurrence, at very long-term follow-up. Among collected variables, preoperative BNP and atrial fibrillation were independent predictors of survival, whereas B-blocker therapy, atrial fibrillation, postoperative mean transmitral gradients and indexed effective orifice area were independent predictors of adverse cardiovascular events. Type of surgery did not affect the very long-term outcome.
miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus
Authors: Qingjian Han, Di Liu, Marino Convertino, Zilong Wang, Changyu Jiang, Yong Ho Kim, Xin Luo, Xin Zhang, Andrea Nackley, Nikolay V. Dokholyan, Ru-Rong Ji
Journal: Neuron (2018)
Cancer-Specific and General Nutritional Scores and Cancer Risk: Results from the Prospective NutriNet-Santé Cohort
Authors: Céline Lavalette, Moufidath Adjibade, Bernard Srour, Laury Sellem, Thibault Fiolet, Serge Hercberg, Paule Latino-Martel, Philippine Fassier, Mélanie Deschasaux, Emmanuelle Kesse-Guyot, Mathilde Touvier
Journal: Cancer Research (2018)

Several national and international authorities have proposed nutritional and lifestyle recommendations with the aim of improving health of the general population. Scores of adherence to these recommendations can be calculated at the individual level. Here, we investigated the associations between four nutritional scores and overall, breast, prostate, and colorectal cancer risk in a large prospective population-based cohort: the cancer-specific World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) score, the Alternate Healthy Eating Index 2010 (AHEI-2010), a score based on adherence to the Mediterranean diet (MEDI-LITE), and the French National Nutrition Health Program-Guideline Score (PNNS-GS). This study included 41,543 participants aged ≥40 years from the NutriNet-Santé cohort (2009-2017). A total of 1,489 overall incident cancers were diagnosed. A one-point increment of the WCRF/AICR score was significantly associated with decreased overall [12%; 95% confidence interval (CI), 8%-16%; P < 0.0001], breast (14%; 95% CI, 6%-21%; P = 0.001), and prostate (12%; 95% CI, 0%-22%; P = 0.05) cancer risks. Hazard ratio for colorectal cancer risk was 0.86 (95% CI, 0.72-1.03; P = 0.09). The PNNS-GS score was associated with reduced colorectal cancer risk (P = 0.04) and AHEI-2010 was associated with reduced overall cancer risk (P = 0.03). The WCRF/AICR score performed best. Compared with other tested scores, it included a stronger penalty for alcohol, which is a major risk factor for several cancer sites. Better adherence to nutritional recommendations, especially those designed for cancer prevention, could substantially contribute to decreased cancer incidence.Significance: This large prospective population-based cohort study suggests that following dietary recommendations such as the ones proposed by the World Cancer Research Fund/American Institute for Cancer Research could significantly contribute to cancer prevention. Cancer Res; 78(15); 4427-35. ©2018 AACR.