tbuckley/cabot-search huggingface dataset:
Relationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific Mortality
Authors: Jiaqi Huang, Stephanie J. Weinstein, Kai Yu, Satu Männistö, Demetrius Albanes
Journal: Circulation Research (2019)

Rationale: Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and long-term mortality has not been conducted. Objective: Determine whether serum α-tocopherol (the predominant form of vitamin E) is related to long-term overall and cause-specific mortality and elucidate the dose-response relationships with better quantification of the associations. Methods and Results: We conducted a biochemical analysis of 29 092 participants in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) that originally tested vitamin E and β-carotene supplementation. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and during a 30-year follow-up we identified 23 787 deaths, including deaths from cardiovascular disease (9867), cancer (7687), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2698). After adjusting for major risk factors, we found that men with higher serum α-tocopherol had significantly lower all-cause mortality (hazard ratios=0.83, 0.79, 0.75, and 0.78 for quintile 2 (Q2)–Q5 versus Q1, respectively; P trend &lt;0.0001), and significantly decreased mortality from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, and other causes, with risk reductions from 17% to 47% for the highest versus lowest quintile. The α-tocopherol association with overall mortality was similar across subgroups of smoking intensity, years of smoking, alcohol consumption, trial supplementation, and duration of follow-up. The association was, however, significantly modified by baseline age and body mass index, with stronger inverse associations for younger men and men with a lower body mass index ( P interaction ≤0.006). Conclusions: In this long-term prospective cohort study, higher baseline serum α-tocopherol biochemical status was associated with lower risk of overall mortality and mortality from all major causes. Our data support the long-term health benefits of higher serum α-tocopherol for overall and chronic disease mortality and should be replicated in other more diverse populations.
Encorafenib plus cetuximab with or without binimetinib for BRAF V600E–mutant metastatic colorectal cancer: Expanded results from a randomized, 3-arm, phase III study vs the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC)
Authors: J. Tabernero, A. Grothey, E. Van Cutsem, R. Yaeger, H. Wasan, T. Yoshino, J. Desai, F. Ciardiello, F. Loupakis, Y Sang Hong, N. Steeghs, T.K. Guren, H.-T. Arkenau, P. García-Alfonso, A. Gollerkeri, M. Pickard, K. Maharry, J.L. Christy-Bittel, L. Anderson, S. Kopetz
Journal: Annals of Oncology (2019)
Updated results of a phase II study evaluating accelerator-based boron neutron capture therapy (AB-BNCT) with borofalan(10B) (SPM-011) in recurrent squamous cell carcinoma (R-SCC-HN) and recurrent and locally advanced non-SCC (R/LA-nSCC-HN) of the head and neck
Authors: K. Hirose, A. Konno, S. Yoshimoto, K. Ono, N. Otsuki, J. Hatazawa, J. Hiratsuka, Y. Takai
Journal: Annals of Oncology (2019)
Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy
Authors: H. Lee, I.D. Silva, M. Batten, U. Palendira, A. Ferguson, M.S. Carlino, A.M. Menzies, R.P. Saw, A.J. Spillane, R.A. Scolyer, G.V. Long, J. Wilmott
Journal: Annals of Oncology (2019)
Abstract #1645: First comprehensive report of strong interplay of genetic and environmental factors as well as high degree of ethnic and geographical variations in biology of Leukemia as manifested by frequencies of common fusion oncogenes of prognostic significance associated with different Leukemic subtypes in Pakistani population
Authors: Zafar Iqbal, Tanveer Akhtar, Mudassar Iqbal, Mubashar Naqvi, Zeba Aziz, Ammara Tahir, Tariq Gill, Abd ul-Qayyum, Abid Taj, Muhammad Khalid, Ijaz Shah, Abid Jameel, Muhammad Naeem, Najeeb Ur-Rehman, Shahid Baig, Muhammad Ferhan, Ahmad Khalid
Journal: Cancer Research (2009)

ABSTRACT: Leukemia is a heterogeneous genetic disease involving many fusion oncogenes frequencies of which can vary in different ethnic groups thus having implication in differential diagnosis, prognosis and treatment. We studied fusion-oncogenic frequencies in 471 Pakistani Leukemia patients using RT-PCR and Interphase-FISH and compared it with other populations. Significant differences were found between Pakistani and other populations with respect to frequencies of SIL-TAL1,TEL-AML1(adult ALL),BCR-ABL,E2A-PBX1,TEL-AML1,MLL-AF4(paediatric ALL) and BCR-ABL splice variants(CML) while no significant differences in frequencies of CBFB-MYH11,AML1-ETO(AML) and PML-PAR\#945;(APL)(p=0.01). Our data indicates strong interplay of genetic and environmental factors as well as high degree of ethnic variations in biology of Leukemia. This is the first comprehensive report about role of environmental factors in Leukemia genetics and will open new dimensions to study the role of ethnic variations and other environmental factors on biology and pathogenesis of Leukemia, leading to development of ethnic-specific disease markers and drug targets, ultimately paving the way for development of patient-specific/patient-tailored anti-leukemic therapies.$$table_{A6EE52E2-FDFF-4C5F-9D1A-A7C4FE64ED5A}$$ Table : Frequencies of Leukaemia-associated fusion genes in Pakistani and Western populations with statistical analysis (SD stands for significant difference between frequencies).  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1645.
Flavored Tobacco Product Use Among Middle and High School Students — United States, 2014–2018
Authors: Karen A. Cullen, Sherry T. Liu, Jennifer K. Bernat, Wendy I. Slavit, Michael A. Tynan, Brian A. King, Linda J. Neff
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

The 2009 Family Smoking Prevention and Tobacco Control Act prohibits the inclusion of characterizing flavors (e.g., candy or fruit) other than tobacco and menthol in cigarettes; however, characterizing flavors are not currently prohibited in other tobacco products at the federal level.* Flavored tobacco products can appeal to youths and young adults and influence initiation and establishment of tobacco-use patterns (1). The Food and Drug Administration (FDA) and CDC analyzed data from the 2014-2018 National Youth Tobacco Surveys (NYTS) to determine prevalence of current (past 30-day) use of flavored tobacco products, including electronic cigarettes (e-cigarettes), hookah tobacco, cigars, pipe tobacco, smokeless tobacco, bidis, and menthol cigarettes among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2018, an estimated 3.15 million (64.1%) youth tobacco product users currently used one or more flavored tobacco products, compared with 3.26 million (70.0%) in 2014. Despite this overall decrease in use of flavored tobacco products, current use of flavored e-cigarettes increased among high school students during 2014-2018; among middle school students, current use of flavored e-cigarettes increased during 2015-2018, following a decrease during 2014-2015. During 2014-2018, current use of flavored hookah tobacco decreased among middle and high school students; current use of flavored smokeless tobacco, cigars, pipe tobacco, and menthol cigarettes decreased among high school students. Full implementation of comprehensive tobacco prevention and control strategies, coupled with regulation of tobacco products by FDA, can help prevent and reduce use of tobacco products, including flavored tobacco products, among U.S. youths (2,3).
Bioactivation of Napabucasin Triggers Reactive Oxygen Species–Mediated Cancer Cell Death
Authors: Fieke E.M. Froeling, Manojit Mosur Swamynathan, Astrid Deschênes, Iok In Christine Chio, Erin Brosnan, Melissa A. Yao, Priya Alagesan, Matthew Lucito, Juying Li, An-Yun Chang, Lloyd C. Trotman, Pascal Belleau, Youngkyu Park, Harry A. Rogoff, James D. Watson, David A. Tuveson
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Napabucasin (2-acetylfuro-1,4-naphthoquinone or BBI-608) is a small molecule currently being clinically evaluated in various cancer types. It has mostly been recognized for its ability to inhibit STAT3 signaling. However, based on its chemical structure, we hypothesized that napabucasin is a substrate for intracellular oxidoreductases and therefore may exert its anticancer effect through redox cycling, resulting in reactive oxygen species (ROS) production and cell death. Experimental Design: Binding of napabucasin to NAD(P)H:quinone oxidoreductase-1 (NQO1), and other oxidoreductases, was measured. Pancreatic cancer cell lines were treated with napabucasin, and cell survival, ROS generation, DNA damage, transcriptomic changes, and alterations in STAT3 activation were assayed in vitro and in vivo. Genetic knockout or pharmacologic inhibition with dicoumarol was used to evaluate the dependency on NQO1. Results: Napabucasin was found to bind with high affinity to NQO1 and to a lesser degree to cytochrome P450 oxidoreductase (POR). Treatment resulted in marked induction of ROS and DNA damage with an NQO1- and ROS-dependent decrease in STAT3 phosphorylation. Differential cytotoxic effects were observed, where NQO1-expressing cells generating cytotoxic levels of ROS at low napabucasin concentrations were more sensitive. Cells with low or no baseline NQO1 expression also produced ROS in response to napabucasin, albeit to a lesser extent, through the one-electron reductase POR. Conclusions: Napabucasin is bioactivated by NQO1, and to a lesser degree by POR, resulting in futile redox cycling and ROS generation. The increased ROS levels result in DNA damage and multiple intracellular changes, one of which is a reduction in STAT3 phosphorylation.
SP0155 REASONS FOR QUANTITATIVE RESEARCH FOR HPR
Authors: Mwidimi Ndosi
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Health professionals in rheumatology are expected to provide care that is evidence-based. Evidence-based practice is the careful integration of best research evidence with clinical expertise, patient values and needs in the delivery of high-quality, cost-effective health care.<sup>1</sup> A sound understanding of quantitative methods is essential for correct evaluation of research and appropriate implementation into clinical practice. Quantitative methods are used in a wide range of topics, from validating patient-reported outcome measures, sample size estimation, assessing associations between variables or predicting risk factors and evaluating the effectiveness of interventions. Furthermore, quantitative methods can be used to pool the results of several studies into a meta-analysis and thus provide better estimates of effectiveness than what can be achieved in individual studies. This presentation will debate the case for quantitative research using examples of research conducted by health professionals in rheumatology. It is hoped that delegates will gain more confidence in using quantitative methods in their own research or evaluating evidence for clinical practice. <h3>Reference:</h3> [1] Sackett, D.L.; Straus, S.E.; Richardson, W.S.; Rosenberg, W.; Haynes, R.B. (2000). Evidence-based medicine: How to practice and teach EBM. 2. London: Churchill Livingstone. <h3>Disclosure of Interests:</h3> None declared
An RF hyperthermia electrode which generates no edge effect
Authors: N. Uchida, M. Moriyama, A. Kawaguchi, M. Yokokawa, S. Ikeda, H. Kitagaki, H. Kato
Journal: Journal of Clinical Oncology (2009)

e22229 Background: For local hyperthermia cancer therapy, radio frequency (RF) capacitive heating with a pair of electrodes is one of the most effective methods. RF hyperthermia with a conventional 2-dimensional square plate electrode produces an ‘edge effect‘ - the focusing of the RF current resulting in focal overheating. We designed and propose a novel hemispherical-shaped RF capacitive heating electrode that generates no edge effect. Methods: A CAD simulation (COMSOL Multiphysics 3.4) was done, and current and specific absorbance ratio (SAR) distributions of both the hemispherical and the conventional square plate shape electrodes were obtained by a 3-D finite element method. Results: The hemispherical electrode generated no focusing of current distribution, nor overheating with SAR elevation, while the square plate electrode produced an edge effect with local SAR elevation. Conclusions: The hemispherical electrode showed no edge effect from focal overheating. Our new electrode may be useful for local heating in the oral or vaginal cavity in clinical use. Phantom studies with a prototype electrode should be carried out for further confirmation. No significant financial relationships to disclose.
Updated Hodgkin's disease: B. Curability of localized disease. Combined radiation therapy and chemotherapy
Authors: M. Tubiana
Journal: JAMA (1973)

Severalrs ago, the value of a combination of radiotherapy and chemotherapy in the treatment of Hodgkin's disease was suggested by several authors,<sup>47-49</sup>but was debated by others.<sup>50</sup>Both radiotherapy and chemotherapy have since made considerable progress; however, there are still advantages to combining the modalities. Radiotherapy acts only on the neoplastic tissues that are located within the irradiated zones. For these tissues, the probability of recurrence decreases with the local radiation dose; but, it is never completely impossible. The dose is limited by the risk of local injury, especially in sensitive tissues such as the mediastinum or the spinal cord. The sequelae caused by the irradiation of the liver or of the lungs are so severe that their radical irradiation is practically impossible. Irradiation of the gonads in young patients carries genetic hazards that cannot be neglected. Extensive chemotherapy has become more and more efficient during the last decade. Aplasia of hematopoietic tissue represents the major limitating factor; in many cases this prevents sterilization of all the
Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone
Authors: Luz P. Blanco, Hege L. Pedersen, Xinghao Wang, Yaíma L. Lightfoot, Nickie Seto, Carmelo Carmona‐Rivera, Zu‐Xi Yu, Victoria Hoffmann, Peter S. T. Yuen, Mariana J. Kaplan
Journal: Arthritis & Rheumatology (2019)

A role for mitochondrial dysfunction has been proposed in the immune dysregulation and organ damage characteristic of systemic lupus erythematosus (SLE). Idebenone is a coenzyme Q10 synthetic quinone analog and an antioxidant that has been used in humans to treat diverse diseases in which mitochondrial function is impaired. This study was undertaken to assess whether idebenone ameliorates lupus in murine models.Idebenone was administered orally to MRL/lpr mice at 2 different doses (1 gm/kg or 1.5 gm/kg idebenone-containing diet) for 8 weeks. At peak disease activity, clinical, immunologic, and metabolic parameters were analyzed and compared to those in untreated mice (n = 10 per treatment group). Results were confirmed in the lupus-prone NZM2328 mouse model.In MRL/lpr mice, idebenone-treated mice showed a significant reduction in mortality incidence (P < 0.01 versus untreated mice), and the treatment attenuated several disease features, including glomerular inflammation and fibrosis (each P < 0.05 versus untreated mice), and improved renal function in association with decreased renal expression of interleukin-17A (IL-17A) and mature IL-18. Levels of splenic proinflammatory cytokines and inflammasome-related genes were significantly decreased (at least P < 0.05 and some with higher significance) in mice treated with idebenone, while no obvious drug toxicity was observed. Idebenone inhibited neutrophil extracellular trap formation in neutrophils from lupus-prone mice (P < 0.05) and human patients with SLE. Idebenone also improved mitochondrial metabolism (30% increase in basal respiration and ATP production), reduced the extent of heart lipid peroxidation (by one-half that of untreated mice), and significantly improved endothelium-dependent vasorelaxation (P < 0.001). NZM2328 mice exposed to idebenone also displayed improvements in renal and systemic inflammation, reducing the kidney pathology score (P < 0.05), IgG/C3 deposition (P < 0.05), and the gene expression of interferon, proinflammatory, and inflammasome-related genes (at least P < 0.05 and some with higher significance).Idebenone ameliorates murine lupus disease activity and the severity of organ damage, supporting the hypothesis that agents that modulate mitochondrial biologic processes may have a therapeutic role in human SLE.
A Crucial Role for Antigen Presenting Cells in Donor CD4+CD25+ Regulatory T Cell Mediated Suppression of Experimental Gvhd.
Authors: Isao Tawara, Tomomi Toubai, Chelsea Malter, Yaping Sun, Evelyn Nieves, Kathleen Lowler, Chen Liu, James LM Ferrara, Pavan Reddy
Journal: Blood (2009)
3D-bioprinting a genetically inspired cartilage scaffold with GDF5-conjugated BMSC-laden hydrogel and polymer for cartilage repair
Authors: Ye Sun, Yongqing You, Wenbo Jiang, Zanjin Zhai, Kerong Dai
Journal: Theranostics (2019)

Rationale: Articular cartilage injury is extremely common in congenital joint dysplasia patients.Genetic studies have identified Growth differentiation factor 5 (GDF5) as a shared gene in joint dysplasia and OA progression across different populations.However, few studies have employed GDF5 in biological regeneration for articular cartilage repair. Methods & Results:In the present study, we report identified genetic association between GDF5 loci and hip joint dysplasia with genome-wide association study (GWAS).GWAS and replication studies in separate populations achieved significant signals for GDF5 loci.GDF5 expression was dysregulated with allelic differences in hip cartilage of DDH and upregulated in the repaired cartilage in a rabbit cartilage defect model.GDF5 in vitro enhanced chondrogenesis and migration of bone marrow stem cells (BMSCs), GDF5 was tested in ectopic cartilage generation with BMSCs by GDF5 in nude mice in vivo.Genetically inspired, we further generated functional knee articular cartilage construct for cartilage repair by 3d-bioprinting a GDF5-conjugated BMSC-laden scaffold.GDF5-conjugated scaffold showed better cartilage repairing effects compared to control.Meanwhile, transplantation of the 3D-bioprinted GDF5-conjugated BMSC-laden scaffold in rabbit knees conferred long-term chondroprotection.Conclusions: In conclusion, we report identified genetic association between GDF5 and DDH with combined GWAS and replications, which further inspired us to generate a ready-to-implant GDF5-conjugated BMSC-laden scaffold with one-step 3d-bioprinting for cartilage repair.
Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis
Authors: S. Peters, S.S. Ramalingam, L. Paz-Ares, R. Bernabe Caro, B. Zurawski, S.-W. Kim, A. Alexandru, L. Lupinacci, E. de la Mora Jimenez, H. Sakai, I. Albert, A. Vergnenegre, M. Reck, H. Borghaei, J.R. Brahmer, K.J. O’Byrne, W.J. Geese, P. Bhagavatheeswaran, F.E. Nathan, M.D. Hellmann
Journal: Annals of Oncology (2019)
A phase II/III trial of high-dose, intermittent sunitinib in patients with recurrent glioblastoma: The STELLAR study
Authors: C.G. Brahm, M.E. van Linde, M. Labots, M.C.M. Kouwenhoven, E. Sanchez Aliaga, R.H. Enting, A.P.A. Appelman, J. Nuver, A.M.E. Walenkamp, H.M.W. Verheul
Journal: Annals of Oncology (2019)
A phase I study evaluating rovalpituzumab tesirine (ROVA-T) in frontline treatment of patients (pts) with extensive stage small cell lung cancer (ES-SCLC)
Authors: C. Hann, T. Burns, A. Dowlati, D. Morgensztern, M. Koch, Y.-W. Chang, P. Komarnitsky, C. Ludwig, H. Nimeiri, D.R. Camidge
Journal: Annals of Oncology (2019)
Potential for Lung Recruitment Estimated by the Recruitment-to-Inflation Ratio in Acute Respiratory Distress Syndrome. A Clinical Trial
Authors: Lu Chen, Lorenzo Del Sorbo, Domenico L. Grieco, Detajin Junhasavasdikul, Nuttapol Rittayamai, Ibrahim Soliman, Michael C. Sklar, Michela Rauseo, Niall D. Ferguson, Eddy Fan, Jean-Christophe M. Richard, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the presence of complete airway closure.Objectives: To validate a single-breath method for measuring recruited volume and test whether it differentiates patients with different responses to PEEP.Methods: Patients with acute respiratory distress syndrome were ventilated at 15 and 5 cm H2O of PEEP. Multiple pressure-volume curves were compared with a single-breath technique. Abruptly releasing PEEP (from 15 to 5 cm H2O) increases expired volume: the difference between this volume and the volume predicted by compliance at low PEEP (or above airway opening pressure) estimated the recruited volume by PEEP. This recruited volume divided by the effective pressure change gave the compliance of the recruited lung; the ratio of this compliance to the compliance at low PEEP gave the recruitment-to-inflation ratio. Response to PEEP was compared between high and low recruiters based on this ratio.Measurements and Main Results: Forty-five patients were enrolled. Four patients had airway closure higher than high PEEP, and thus recruitment could not be assessed. In others, recruited volume measured by the experimental and the reference methods were strongly correlated (R2 = 0.798; P < 0.0001) with small bias (-21 ml). The recruitment-to-inflation ratio (median, 0.5; range, 0-2.0) correlated with both oxygenation at low PEEP and the oxygenation response; at PEEP 15, high recruiters had better oxygenation (P = 0.004), whereas low recruiters experienced lower systolic arterial pressure (P = 0.008).Conclusions: A single-breath method quantifies recruited volume. The recruitment-to-inflation ratio might help to characterize lung recruitability at the bedside.Clinical trial registered with www.clinicaltrials.gov (NCT02457741).
Impact of cognitive-behavioral-therapy (CBT) on levels of anxiety, depression and distress in cancer patients (pts)
Authors: D. Tregnago, L. Carbognin, I. Trestini, A. Avancini, G. Sartori, E. Fiorio, V. Parolin, M. Lanza, M. Rimondini, L. Del Piccolo, E. Bria, M. Milella, S. Pilotto
Journal: Annals of Oncology (2019)
Randomized, double-blind, cross-over phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references
Authors: M. Velinova, A. Bellon, R. Nakov, S. Schussler, S. Schier-Mumzhiu, C. Schelcher, S.D. Koch, A. Skerjanec, J. Wang, A. Krendyukov, G.P. Otto
Journal: Annals of Oncology (2019)
Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first-line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study)
Authors: O. Caffo, E. Palesandro, F. Nole, D. Gasparro, C. Mucciarini, M. Aieta, V. Zagonel, R. Iacovelli, U.F.F. De Giorgi, S. Rossetti, L. Fratino, P. Ermacora, M. Nicodemo, M. Giordano, D. Sartori, D. Scapoli, E. Verri, F. Maines, G. Pappagallo, M. Aglietta
Journal: Annals of Oncology (2019)
Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer
Authors: M. Perez Hernandez, C. Cuscó, J. Bonelli, B. Farcic, A. Arias, A. Andreu, D. Martínez García, V. Soto Cerrato, J. Rocas, R. Pérez Tomás
Journal: Annals of Oncology (2019)