tbuckley/cabot-search huggingface dataset:
Abstract P303: High Birth Weight Modifies Estimated Effects of Physical Activity on Cardiometabolic Health in Females
Authors: Thomas L Jeanne, Rebecca Sacks, Thuan Nguyen, Lynne Messer, Janne Boone-Heinonen
Journal: Circulation (2017)

Background: Birth weight and physical activity are independently associated with cardiometabolic health outcomes. Low or high birth weight are indicators of adverse prenatal development, which may alter physiological response to physical activity later in life. However, few studies have explored the potential interaction between birth weight and physical activity as determinants of cardiometabolic health. Objective: We evaluated the hypothesis that high or low birth weight modifies the association of early life physical activity with cardiovascular disease or diabetes later in life. Methods: We analyzed data from the National Longitudinal Study of Adolescent and Adult Health (Add Health), a nationally representative cohort of US adolescents followed into adulthood ( n =20,745) with four data collection waves between 1994 and 2008. Outcomes were assessed in early adulthood: (1) predicted 30-year cardiovascular disease (CVD) risk, computed by a validated algorithm based on objective measures, and (2) prevalent pre-diabetes and diabetes. Using gender-stratified multivariable regression on multiply imputed data, we modeled (1) log-transformed 30-year CVD risk (linear regression) and (2) prevalent pre-diabetes and diabetes (PDM/DM; ordinal regression) each as a function of birth weight (low, normal, high; LBW, NBW, HBW) and self-reported moderate-to-vigorous physical activity frequency (MVPA) in adolescence and young adulthood, adjusting for age, smoking, and sociodemographic factors. Results: A greater proportion of women born at LBW had diabetes than NBW and HBW women (10.8% versus 5.9% and 5.4%, respectively). In adjusted analyses, MVPA in adolescence (MVPA1) and early adulthood (MVPA3) were not significantly associated with predicted CVD risk and prevalent pre-diabetes diabetes in men or women overall. However, greater MVPA1 was associated with lower predicted 30-year CVD risk in HBW females (estimated effect coefficient -0.02 [95% CI: -0.03, -0.005, p =0.02], p =0.05 for HBWхMVPA1 interaction), and the HBWхMVPA1 interaction on PDM/DM approached significance in females ( p =0.12). In females and males of LBW or NBW, MVPA1 was not significantly associated with predicted 30-year CVD risk or PDM/DM and LBWхMVPA1 interactions were not significant. Conclusions: Greater adolescent physical activity was most strongly associated with lower 30-year CVD risk in young women born at HBW. A similar association with prevalent DM/PDM approached significance, with greater adolescent physical activity most strongly associated in HBW women. Females born at HBW may be especially sensitive to the effects of physical activity on reducing risk of cardiometabolic disease later in life, with important implications for disease prevention and health policy.
DNA Demethylating Agents Generate a Brcaness Effect in Multiple Sporadic Tumor Types: Prediction for Sensitivity to PARP Inhibitors in AML
Authors: Aksinija A Kogan, Lena J Mclaughlin, Michael Topper, Nidal Muvarak, Lora Stojanovic, T Michael Creed, Soren Bentzen, Curt I. Civin, Maria R. Baer, Tami J Kingsbury, Stephen Baylin, Feyruz V. Rassool
Journal: Blood (2017)
Corrigendum to “Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV” [J Hepatol 68 (2018) 33–41]
Authors: Aimilia Karampatou, Xue Han, Loreta A. Kondili, Gloria Taliani, Alessia Ciancio, Filomena Morisco, Rosina Maria Critelli, Enrica Baraldi, Veronica Bernabucci, Giulia Troshina, Maria Guarino, Simonetta Tagliavini, Federica D'Ambrosio, Laura Bristot, Laura Turco, Stefano Rosato, Stefano Vella, Tommaso Trenti, Isabella Neri, Antonio La Marca, Shivaji Manthena, Andrea S. Goldstein, Savino Bruno, Yanjun Bao, Yuri Sanchez Gonzalez, Erica Villa
Journal: Journal of Hepatology (2018)
Excess Risk of Dying From Infectious Causes in Those With Type 1 and Type 2 Diabetes
Authors: Dianna Josephine Magliano, Jessica L. Harding, Kerryn Cohen, Rachel R. Huxley, Wendy A. Davis, Jonathan E. Shaw
Journal: Diabetes Care (2015)

OBJECTIVE To investigate infection-related mortality in individuals with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 1,108,982 individuals with diabetes who were registered with the Australian Diabetes register between 2000 and 2010 were linked to the National Death Index. Mortality outcomes were defined as infection-relatedA-B death (ICD codes A99–B99), pneumonia (J12–J189), septicemia (A40 and A41), and osteomyelitis (M86). RESULTS During a median follow-up of 6.7 years, there were 2,891, 2,158, 1,248, and 147 deaths from infection-relatedA-B causes, pneumonia, septicemia, or osteomyelitis, respectively. Crude mortality rates from infectionsA-B were 0.147 and 0.431 per 1,000 person-years in type 1 and type 2 diabetes, respectively. Standardized mortality ratios (SMRs) were higher in type 1 and type 2 diabetes for all outcomes after adjustment for age and sex. For infection-relatedA-B mortality, SMRs were 4.42 (95% CI 3.68–5.34) and 1.47 (1.42–1.53) for type 1 and type 2 diabetes (P &amp;lt; 0.001), respectively. For pneumonia in type 1 diabetes, SMRs were approximately 5 and 6 in males and females, respectively, while the excess risk was ∼20% for type 2 (both sexes). For septicemia, SMRs were approximately 10 and 2 for type 1 and type 2 diabetes, respectively, and similar by sex. For osteomyelitis in type 1 diabetes, SMRs were 16 and 58 in males and females, respectively, and ∼3 for type 2 diabetes (both sexes). CONCLUSIONS Although death owing to infection is rare, we confirm that patients with diabetes have an increased mortality from a range of infections, compared with the general population, and that the increased risk appears to be greater for type 1 than type 2 diabetes.
Coronary Adventitial and Perivascular Adipose Tissue Inflammation in Patients With Vasospastic Angina
Authors: Kazuma Ohyama, Yasuharu Matsumoto, Kentaro Takanami, Hideki Ota, Kensuke Nishimiya, Jun Sugisawa, Satoshi Tsuchiya, Hirokazu Amamizu, Hironori Uzuka, Akira Suda, Tomohiko Shindo, Yoku Kikuchi, Kiyotaka Hao, Ryuji Tsuburaya, Jun Takahashi, Satoshi Miyata, Yasuhiko Sakata, Kei Takase, Hiroaki Shimokawa
Journal: Journal of the American College of Cardiology (2018)
Abstract 18062: Long Term Mortality is Significantly Higher in Patients With Type II Compared With Type I Myocardial Infarction: A Propensity Matched Analysis
Authors: Amjad Abualsuod, Anusha Shanbhag, Jawahar L Mehta, Srikanth Vallurupalli
Journal: Circulation (2017)

Background: Type 2 myocardial infarction (MI) is broadly defined as myocardial injury secondary to oxygen supply-demand mismatch while type I MI occurs due to reduction primarily in oxygen supply. ...
Abstract 16400: The Diagnostic Value of Abnormal Heart Rate Recovery During Exercise Stress Testing in Predicting the Presence of Endothelial and Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease
Authors: Vedant S Pargaonkar, Yuhei Kobayashi, Takumi Kimura, David P Lee, Marcia L Stefanick, William F Fearon, Alan C Yeung, Jennifer A Tremmel
Journal: Circulation (2016)

Introduction:  It has been shown that conventional stress testing parameters are not helpful in identifying occult coronary abnormalities, such as endothelial and microvascular dysfunction (MVD), in patients with angina in the absence of obstructive coronary artery disease (CAD). Abnormal heart rate recovery (HRR) has been shown to be a predictor of all-cause and cardiovascular mortality in both women and men. Recent guidelines have also recommended integrating this parameter when analyzing a routine exercise stress test to improve its diagnostic value.   Hypothesis:  We studied the ability of abnormal HRR during exercise stress testing to predict the presence of endothelial dysfunction and MVD in patients with angina in the absence of obstructive CAD.   Methods:  We studied 139 patients with angina found to have no obstructive CAD on coronary angiography who underwent endothelial function and MVD testing. Endothelial dysfunction was defined as a decrease in epicardial coronary diameter by > 20% after intracoronary acetylcholine. MVD was defined as an index of microvascular resistance (IMR) ≥ 25. HRR was defined as peak heart rate during exercise minus heart rate at one minute into recovery. Abnormal HRR was defined as ≤ 12 bpm.   Results:  The mean age of the population was 54.3 ± 11.5 years and 103 (74.3%) were women. Endothelial dysfunction was present in 93 (67.3%) patients, while 21 (15.3%) had MVD. On multiple variable logistic regression analysis, abnormal HRR independently predicted the presence of endothelial dysfunction and/or MVD (Table).   Conclusions:  Heart rate recovery, a non-ECG stress testing parameter that is easily obtained during a routine exercise stress test, provides important diagnostic information about underlying occult coronary abnormalities like endothelial dysfunction and/or MVD. Adding HRR to conventional stress testing may help in the management of patients with angina in the absence of obstructive CAD.
Anti-cancer drugs mediated PKCK2 activity downregulation sensitize TRAIL-resistant cancer cells toward TRAIL
Authors: Yoonmi Lee, Hyang Tae Choi, Hyeonseok Ko, Kunhong Kim
Journal: Cancer Research (2007)

LB-46  Tumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family of ligands, which can initiate apoptosis by engaging death receptors. TRAIL selectively induces apoptosis of a variety of tumor cells and transformed cells, but not most normal cells therefore TRAIL is a potent anti-cancer drug. However, many cancer cells are resistant to TRAIL-mediated apoptosis. Recently we demonstrated that protein kinase casein kinase (PKCK2) activity determines TRAIL resistance. PKCK2 activity is low in TRAIL-sensitive cancer cell lines but high in TRAIL-resistant cancer cell lines, and PKCK2 inhibitors sensitize TRAIL-resistant cancer cells to TRAIL. Therefore, we hypothesized that drugs which sensitize cancer cells to TRAIL, may function by inhibiting PKCK2 activity. Actinomycin D (ActD), Camptothecin-11 (CPT-11), or other anti-cancer drugs can sensitize cancer cells to TRAIL-mediated apoptosis. Treatment of HCE4 cancer cells, that are resistant to TRAIL, with ActD, CPT-11, or etoposide resulted in decreased PKCK2 activity. Very low concentrations of these anti-cancer drugs effectively sensitize HCE4 cells to TRAIL. We also found these anti-cancer drugs prime cancer cells for TRAIL-mediated apoptosis by processing procaspase-8 activity. These findings demonstrate that anti-cancer drugs including ActD, CPT-11, or etoposide decrease PKCK2 activity, and that PKCK2 play an important role in TRAIL signaling in HCE4 cells. Our results suggest that anti-cancer drugs that target TRAIL and down-regulate PKCK2 will be potentially useful therapeutic agents.
Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features
Authors: William L. Hwang, Rahul D. Tendulkar, Andrzej Niemierko, Shree Agrawal, Kevin L. Stephans, Daniel E. Spratt, Jason W. Hearn, Bridget F. Koontz, W. Robert Lee, Jeff M. Michalski, Thomas M. Pisansky, Stanley L. Liauw, Matthew C. Abramowitz, Alan Pollack, Drew Moghanaki, Mitchell S. Anscher, Robert B. Den, Anthony L. Zietman, Andrew J. Stephenson, Jason A. Efstathiou
Journal: JAMA Oncology (2018)

Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear.
THE ADDITION OF ANTI-ANGIOGENIC TYROSINE KINASE INHIBITORS TO CHEMOTHERAPY FOR ADVANCED NON-SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS
Authors: BT Li, C Hasovits, A Lee, Ae Li, Mustafa Khasraw, G Marx, N Pavlakis
Journal: Journal of Thoracic Oncology (2013)
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial
Authors: Christos E. Kyriakopoulos, Yu-Hui Chen, Michael A. Carducci, Glenn Liu, David F. Jarrard, Noah M. Hahn, Daniel H. Shevrin, Robert Dreicer, Maha Hussain, Mario Eisenberger, Manish Kohli, Elizabeth R. Plimack, Nicholas J. Vogelzang, Joel Picus, Matthew M. Cooney, Jorge A. Garcia, Robert S. DiPaola, Christopher J. Sweeney
Journal: Journal of Clinical Oncology (2018)

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P &lt; .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.
A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood AML.
Authors: R J Jaju, O A Haas, M Neat, J Harbott, J Boultwood, V Saha, B W Krings, U Muller, S W Morris, J S Wainscoat, L Kearney
Journal: Blood (1998)
Effect of early and systematic integration of palliative care in patients with advanced cancer: a randomised controlled trial
Authors: Gaëlle Vanbutsele, Koen Pardon, Simon Van Belle, Veerle Surmont, Martine De Laat, Roos Colman, Kim Eecloo, Veronique Cocquyt, Karen Geboes, Luc Deliens
Journal: The Lancet Oncology (2018)
microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11
Authors: Wei-Luo Cai, Wen-Ding Huang, Bo Li, Tian-Rui Chen, Zhen-Xi Li, Cheng-Long Zhao, Heng-Yu Li, Yan-Mei Wu, Wang-Jun Yan, Jian-Ru Xiao
Journal: Molecular Cancer (2018)

Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer. In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis. Herein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis. Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.
ARIEL4: An international, multicenter randomized phase 3 study of the PARP inhibitor rucaparib vs chemotherapy in germline or somatic <i>BRCA1-</i> or <i>BRCA2-</i>mutated, relapsed, high-grade ovarian carcinoma.
Authors: Amit M. Oza, Domenica Lorusso, Ana Oaknin, Tamar Safra, Elizabeth Swisher, Igor Bondarenko, Tomasz Huzarski, Jaroslav Klat, Róbert Póka, Luciana Spillari Viola, Chris Tankersley, Lara Maloney, Sandra Goble, Caro Unger, Heidi Giordano, Rebecca Sophie Kristeleit
Journal: Journal of Clinical Oncology (2017)

TPS5603 Background: In high-grade epithelial ovarian carcinoma (OC), ≈18% of patients (pts) have tumors with a germline BRCA1 or BRCA2 mutation; ≈7% have tumors with a somatic BRCA1 or BRCA2 mutation (Pennington et al. Clin Cancer Res. 2014;20:764-75). The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is approved in the United States for treatment of pts with OC associated with a deleterious BRCA1 or BRCA2 mutation (germline and/or somatic) who have received ≥2 chemotherapies. Although PARP inhibitors have demonstrated clinical activity in OC in both treatment and maintenance settings, comparison to standard of care (SOC) has only been evaluated in the maintenance setting. Randomized studies are needed to assess the benefit-risk profile of PARP inhibitors vs current SOC as treatment for BRCA1- or BRCA2-mutated, relapsed, high-grade OC. Methods: ARIEL4 (NCT02855944) is evaluating rucaparib vs chemotherapy as treatment for pts with germline or somatic BRCA1- or BRCA2-mutated, relapsed, high-grade OC (regardless of histology) who have received ≥2 prior chemotherapy regimens. Approximately 345 pts will be randomized 2:1 to receive rucaparib (600 mg BID) (n = 230) or chemotherapy (n = 115) and stratified by progression-free interval after their most recent platinum regimen. Pts with platinum-resistant (progressive disease [PD] 1– &lt; 6 mo after last platinum) or partially platinum-sensitive disease (PD 6– &lt; 12 mo after last platinum) will be randomized to rucaparib or weekly paclitaxel; pts with platinum-sensitive disease (PD ≥12 mo after last platinum) will be randomized to rucaparib or platinum-based therapy (single-agent or doublet at the discretion of the investigator). Pts receiving chemotherapy have the option to cross over to rucaparib upon radiographic disease progression. The primary endpoint is progression-free survival. Secondary endpoints include investigator-assessed objective response rate (ORR) (RECIST version 1.1), ORR/CA-125 response, duration of response, overall survival, and pt-reported outcomes. Safety will be summarized descriptively using standard adverse event reporting. Clinical trial information: NCT02855944.
Prevalence of Cardiac Amyloidosis in Patients Referred for Transcatheter Aortic Valve Replacement
Authors: Paul R. Scully, Thomas A. Treibel, Marianna Fontana, Guy Lloyd, Michael Mullen, Francesca Pugliese, Neil Hartman, Philip N. Hawkins, Leon J. Menezes, James C. Moon
Journal: Journal of the American College of Cardiology (2018)

Valve ReplacementAortic stenosis (AS) is the most common valve disease in the developed world.Symptomatic severe
BAFF and CD4+ T cells are major survival factors for long-lived splenic plasma cells in a B-cell–depletion context
Authors: Lan-Huong Thai, Simon Le Gallou, Ailsa Robbins, Etienne Crickx, Tatiana Fadeev, Zhicheng Zhou, Nicolas Cagnard, Jérôme Mégret, Christine Bole, Jean-Claude Weill, Claude-Agnès Reynaud, Matthieu Mahévas
Journal: Blood (2018)
Lessons from pathological analysis of recurrent early esophageal squamous cell neoplasia after complete endoscopic radiofrequency ablation
Authors: Wen-Lun Wang, I-Wei Chang, Chien-Chuan Chen, Chi-Yang Chang, Cheng-Hao Tseng, Chi-Ming Tai, Jaw-Town Lin, Hsiu-Po Wang, Ching-Tai Lee
Journal: Endoscopy (2018)

Endoscopic radiofrequency ablation (RFA) is a treatment option for early esophageal squamous cell neoplasia (ESCN); however, long-term follow-up studies are lacking. The risks of local recurrence and "buried cancer" are also uncertain.Patients with flat-type ESCN who were treated with balloon-type ± focal-type RFA were consecutively enrolled. Follow-up endoscopy was performed at 1, 3, and 6 months, and then every 6 months thereafter. Endoscopic resection was performed for persistent and recurrent ESCN, and the histopathology of resected specimens was assessed.A total of 35 patients were treated with RFA, of whom 30 (86 %) achieved a complete response, three were lost to follow-up, and five (14 %) developed post-RFA stenosis. Two patients had persistent ESCN and received further endoscopic resection, in which the resected specimens all revealed superficial submucosal invasive cancer. Six of the 30 patients with successful RFA (20 %) developed a total of seven episodes of local recurrence (mean size 1.4 cm) during the follow-up period (mean 40.1 months), all of which were successfully resected endoscopically without adverse events. Histological analysis of the resected specimens revealed that six (86 %) had esophageal glandular ductal involvement, all of which extended deeper than the muscularis mucosae layer. Immunohistochemistry staining for P53 and Ki67 suggested a clonal relationship between the ductal involvement and epithelial cells. None of the tumors extended out of the ductal structure; no cases of cancer buried beneath the normal neosquamous epithelium were found.Because ductal involvement is not uncommon and may be related to recurrence, the use of RFA should be conservative and may not be the preferred primary treatment for early ESCN.
The Tandem Duplicator Phenotype Is a Prevalent Genome-Wide Cancer Configuration Driven by Distinct Gene Mutations
Authors: Francesca Menghi, Floris P. Barthel, Vinod Yadav, Ming Tang, Bo Ji, Zhonghui Tang, Gregory W. Carter, Yijun Ruan, Ralph Scully, Roel G.W. Verhaak, Jos Jonkers, Edison T. Liu
Journal: Cancer Cell (2018)