tbuckley/cabot-search huggingface dataset:
Variation in Mutational Robustness between Different Proteins and the Predictability of Fitness Effects
Authors: Peter A. Lind, Lars Arvidsson, Otto G. Berg, Dan I. Andersson
Journal: Molecular Biology and Evolution (2016)

Random mutations in genes from disparate protein classes may have different distributions of fitness effects (DFEs) depending on different structural, functional, and evolutionary constraints. We measured the fitness effects of 156 single mutations in the genes encoding AraC (transcription factor), AraD (enzyme), and AraE (transporter) used for bacterial growth on l-arabinose. Despite their different molecular functions these genes all had bimodal DFEs with most mutations either being neutral or strongly deleterious, providing a general expectation for the DFE. This contrasts with the unimodal DFEs previously obtained for ribosomal protein genes where most mutations were slightly deleterious. Based on theoretical considerations, we suggest that the 33-fold higher average mutational robustness of ribosomal proteins is due to stronger selection for reduced costs of translational and transcriptional errors. Whereas the large majority of synonymous mutations were deleterious for ribosomal proteins genes, no fitness effects could be detected for the AraCDE genes. Four mutations in AraC and AraE increased fitness, suggesting that slightly advantageous mutations make up a significant fraction of the DFE, but that they often escape detection due to the limited sensitivity of commonly used fitness assays. We show that the fitness effects of amino acid substitutions can be predicted based on evolutionary conservation, but those weakly deleterious mutations are less reliably detected. This suggests that large-effect mutations and the fraction of highly deleterious mutations can be computationally predicted, but that experiments are required to characterize the DFE close to neutrality, where many mutations ultimately fixed in a population will occur.
Adipocyte Differentiation of SOD2−/− Mouse Bone Marrow Stromal Cells Is Associated with Decreased Antioxidant Reserves and Is Reversed by the Antioxidant WR2721 (Amifostine).
Authors: Michael W. Epperly, Stanislav Lechpammer, Suhua Nie, Julie Glowacki, Joel S. Greenberger
Journal: Blood (2004)
The Impact of Anemia on Overall Survival in Patients with Myelofibrosis Treated with Ruxolitinib: An Exploratory Analysis of the Comfort Studies
Authors: Vikas Gupta, Claire N. Harrison, Elizabeth O. Hexner, Haifa Kathrin Al-Ali, Lynda Foltz, Michael Montgomery, Wei Peng, Prashanth Gopalakrishna, Hagop Kantarjian, Srdan Verstovsek
Journal: Blood (2015)
NRAS:BCL-2 Complex Localization Determines Anti-Apoptotic Features Associated with Progressive Disease in Myelodysplastic Syndromes (MDS)
Authors: Rose Ann Padua, Carole Le Pogam, Patricia Krief, Stephanie Beurlet, Bruno Cassinat, Hélène Cavé, Olivier Kosmider, Niclas Setterblad, Christophe Leboeuf, Laure Sarda-Mantel, Florence Hervatin, Pascal Merlet, Maria-Elena Noguera, Anne Janin, Marika Pla, Michaela Fontenay, Lionel Ades, Pierre Fenaux, Christine Chomienne, Nader Omidvar
Journal: Blood (2012)
CD8-Depleted Donor Lymphocyte Infusions Can Improve Both T- and B-Cell Reconstitution after Allogeneic Stem Cell Transplantation from Haploidentical Family Donors
Authors: Anna Dodero, Cristiana Carniti, Anna Raganato, Antonio Vendramin, Simona Di Terlizzi, Lucia Farina, Francesco Spina, Franca Fossati Bellani, Marco Milanesi, Paolo Longoni, Lorenza Gandola, Claudia Lombardo, Paolo Corradini
Journal: Blood (2008)
PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis
Authors: Xiaorong Zhou, Barrett L. Updegraff, Yabin Guo, Michael Peyton, Luc Girard, Jill E. Larsen, Xian-Jin Xie, Yunyun Zhou, Tae Hyun Hwang, Yang Xie, Jaime Rodriguez-Canales, Pamela Villalobos, Carmen Behrens, Ignacio I. Wistuba, John D. Minna, Kathryn A. O'Donnell
Journal: Cancer Research (2016)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths worldwide. Given the efficacy of membrane proteins as therapeutic targets in human malignancies, we examined cell-surface receptors that may act as drivers of lung tumorigenesis. Here, we report that the PROTOCADHERIN PCDH7 is overexpressed frequently in NSCLC tumors where this event is associated with poor clinical outcome. PCDH7 overexpression synergized with EGFR and KRAS to induce MAPK signaling and tumorigenesis. Conversely, PCDH7 depletion suppressed ERK activation, sensitized cells to MEK inhibitors, and reduced tumor growth. PCDH7 potentiated ERK signaling by facilitating interaction of protein phosphatase PP2A with its potent inhibitor, the SET oncoprotein. By establishing an oncogenic role for PCDH7 in lung tumorigenesis, our results provide a rationale to develop novel PCDH7 targeting therapies that act at the cell surface of NSCLC cells to compromise their growth. Cancer Res; 77(1); 187-97. ©2016 AACR.
Citrate Effects and Bone Mineral Density (BMD) in Serial Long-Term Apheresis Donors.
Authors: Charles Bolan, Jeremiah Ronquillo, Yu Ying Yau, Robert Wesley, Stacey Cecco, Firoozeh Alvandi, James Reynolds, Phyllis Byrne, Cynthia Matthews, Cathy Cantilena, Michael Collins, Nadja Rehak, Susan Leitman
Journal: Blood (2006)
Prevalence and Risk Factors of Elevated Tricuspid Regurgitant Jet Velocity in Children with Sickle Cell Disease: Association with Age, Hemolysis, Oxygen Saturation and CD36 Deficiency.
Authors: Francoise Bernaudin, Cecile Arnaud, Annie Kamdem, Elodie Fauveau, Anne Le Roux, Nadia Medejel, Isabelle Hau, Fouad Madhi, Ketty Lee, Christophe Delacourt
Journal: Blood (2009)
Lymphocyte-Activating Chemokines Are Potent Inducers of Sudden Arrest and Firm Adhesion in Mesenchymal Stromal Cells (MSCs) Under Shear Flow
Authors: Felicia Ciuculescu, Melanie Giesen, Erika Deak, Erhard Seifried, Tanja Nicole Hartmann, Reinhard Henschler
Journal: Blood (2008)
AB0387 Efficacy of 12-Month Therapy with Methotrexate Solution for Subcutaneous Injection (SC MTX) in Patients with Early RA with Different Body Mass Index (BMI): Table 1.
Authors: G.I. Gridneva, Y. Muraviev
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The levels of inflammation markers, specifically C-reactive protein (CRP), are known to be elevated in patients with excessive body weight. <h3>Objectives</h3> To evaluate the efficacy of 12-month therapy with SC MTX in patients with recently emerged RA with different BMI. <h3>Methods</h3> MTX-naive patients with active early RA (&lt;6 months) diagnosed in accordance with ACR/EULAR 2010 or ACR 1987 (DAS28&gt;3.2) before inclusion were eligible for the 12-month open study. Patients were divided into 3 groups depending on the BMI: I ≤25 kg/m<sup>2</sup>, II =25–30 kg/m<sup>2</sup>, III ≥30 kg/m<sup>2</sup>. Monotherapy with SC MTX once weekly was administered to all patients; starting dose – 10–15 mg per week with escalation of 5 mg every 1–2 weeks (maximum dose – 30 mg per week) until treatment targets were reached (DAS28≤2.6) or adverse events (AE) appeared. Given that patients received almost identical single doses of SC MTX, but had different BMI, we have calculated the dose in mg per m<sup>2</sup>, calling it the actual dose (AD). Folic acid was administered at the dose of at least 5 mg per week on any day(s) except for the date of SC MTX administration. Disease activity was determined using DAS28<sub>ESR,</sub> DAS28<sub>CRP</sub> and SDAI. Remission was determined in accordance with ACR/EULAR 2011 criteria. <h3>Results</h3> 47 patients (38 female, 9 male) with mean RA duration of 4.2±1.7 months and mean age of 51.0±13.2 years were included. There were no differences between groups defined on the basis of BMI in gender, disease duration, rheumatoid factor, baseline disease activity. The majority of patients have not received DMARD or glucocorticoids (GC) before. After 3, 6 and 12 months of monotherapy with SC MTX we received different results between groups (see table). AE were similar in all groups at each time point. <h3>Conclusions</h3> Treatment effect of SC MTX in patients with recently emerged RA correlates with BMI and is significantly increased in patients with normal BMI (≤25 kg/m<sup>2</sup>) than in patients with excessive body weight or obesity. <h3>Disclosure of Interest</h3> None declared
E-cigarettes raise teens’ risk of persistent cough and wheeze, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Teenagers who use e-cigarettes have twice the risk of respiratory symptoms such as persistent cough, bronchitis, and wheeze as those who have never used the devices, a large US study has found.1

Use of e-cigarettes among teenagers is increasing dramatically, and public health experts are concerned that these devices may increase cigarette smoking. But there has been limited information on the effect of chronic e-cigarette use on respiratory health.

Researchers analysed responses to a questionnaire from 2086 teenagers aged 16 to 18 years who were taking part in the ongoing Southern California Children’s Health study, to investigate the long term effects …
Direct Upregulation of Iron Regulatory Hormone Hepcidin by Interferon Alpha
Authors: Kazuhiko Ichiki, Katsuya Ikuta, Hiroki Tanaka, Yusuke Sasaki, Yasushi Shimonaka, Katsunori Sasaki, Satoshi Ito, Motohiro Shindo, Takaaki Ohtake, Yoshihiro Torimoto, Yutaka Kohgo
Journal: Blood (2011)
ATF3 expression in cardiomyocytes preserves homeostasis in the heart and controls peripheral glucose tolerance
Authors: Roy Kalfon, Lilach Koren, Sharon Aviram, Ortal Schwartz, Tsonwin Hai, Ami Aronheim
Journal: Cardiovascular Research (2016)

Obesity and type 2 diabetes (T2D) trigger a harmful stress-induced cardiac remodeling process known as cardiomyopathy. These diseases represent a serious and widespread health problem in the Western world; however the underlying molecular basis is not clear. ATF3 is an 'immediate early' gene whose expression is highly and transiently induced in response to multiple stressors such as metabolic, oxidative, endoplasmic reticulum and inflammation, stressors that are involved in T2D cardiomyopathy. The role of ATF3 in diabetic cardiomyopathy is currently unknown. Our research has aimed to study the effect of ATF3 expression on cardiomyocytes, heart function and glucose homeostasis in an obesity-induced T2D mouse model. We used wild type mice (WT) as well as mutant mice with a cardiac-specific ATF3 deficiency (ATF3-cKO). Mice were fed a high-fat diet (HFD) for 15 weeks. HFD induced high ATF3 expression in cardiomyocytes. Mice were examined for cardiac remodeling processes and the diabetic state was assessed. HFD-fed ATF3-cKO mice exhibited severe cardiac fibrosis, higher levels of heart hypertrophic markers, increased inflammation and worse cardiac function, as compared to WT mice. Interestingly, HFD-fed ATF3-cKO mice display increased hyperglycemia and reduced glucose tolerance, despite higher blood insulin levels, as compared to HFD-fed WT mice. Elevated levels of the cardiac inflammatory cytokines IL-6 and TNFα leading to impaired insulin signalling may partially explain the peripheral glucose intolerance. Cardiac ATF3 has a protective role in dampening the HFD-induced cardiac remodeling processes. ATF3 exerts both local and systemic effects related to T2D-induced cardiomyopathy. This study provides a strong relationship between heart remodeling processes and blood glucose homeostasis.
THU0154 Effects of Etanercept Biomimics on Lipid Profiles in Patients with Rheumatoid Arthritis
Authors: R. Zhu, H. Shen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To compare the modifications in lipid profiles among patients with RA receiving anti-TNF-α agents – one Etanercept biomimics plus disease modifying anti-rheumatic drugs (DMARDs) versus DMARDs, explore the relationship between dyslipidemia, inflammation in RA patients. <h3>Methods</h3> 100 newly diagnosed RA patients were randomly divided into biological agent treatment group and non-biological agent treatment group, each group included 50 patients. At baseline and at 12 and 24 weeks, levels of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), as well as the atherogenic index of plasma (AIP) was calculated, antibodies against cyclic citrullinated peptide (ACCP), carotid intima-media thickness (CIMT)were studied at baseline and 24 weeks. Statistical analyses are performed with SPSS software version 19.0. <h3>Results</h3> Baseline values for lipid levels were similar in both groups. Pearson correlation test was carried out and found that CIMT and ESR, CRP, AIP were positively correlated, and HDL, Apo-Al were negatively correlated at baseline. At 12 weeks and 24 weeks in the biological agent treatment group, the levels of HDL, Apo-Al were increased and levels of Lpa, AIP were decreased when compared to the baseline, and at 24 weeks, CIMT was decreased compared to the baseline. At 24 weeks in the non-biological agents treatment group, the level of HDL was increased, levels of LDL, Lpa, CIMT, AIP were all decreased compared to the baseline. At 12 weeks in the biological agent treatment group, the levels of AIP, Lpa were lower than non-biological agent group, levels of TC, HDL, Apo-Al were higher than non-biological agent group, and at 24 weeks in the biological agent treatment group, the levels of Apo-B, Lpa were lower than non-biological agent group, level of LDL, Apo-Al were higher than non-biological agent group (all P&lt;0.05). <h3>Conclusions</h3> (1) Inflammatory status may affect the lipid profiles and the endothelial function and is associated with the atherosclerosis. (2) The Etanercept biomimics and DMARDs both can improve lipid profiles, and the protective effect of the Etanercept biomimics on cardiovascular complications is superior to traditional DMARDs, but the medication9s effect lasts shorter lengths of time, therefore further studies and large samples are needed in the future. <h3>Disclosure of Interest</h3> None declared
Diagnosis, Treatment, and Clinical Management of Pulmonary Arterial Hypertension in the Contemporary Era
Authors: Bradley A. Maron, Nazzareno Galiè
Journal: JAMA Cardiology (2016)

Pulmonary arterial hypertension (PAH) is characterized by severe remodeling of the distal pulmonary arteries, increased pulmonary vascular resistance, and right ventricular dysfunction that promotes heart failure. Once regarded as largely untreatable, evidence-based decision making now guides clinical management of PAH and improves outcomes. However, misconceptions regarding the approach to PAH in the modern era are common and associated with substandard clinical care.
Variation of T-Reg and CD 200+ T- Lymphocytes After in Vitro Treatment with Active Drugs against CLL.
Authors: Nunziatina Parrinello, Piera La Cava, Daniele Tibullo, Cesarina Giallongo, Annalisa Chiarenza, Alessandra Romano, Maide Cavalli, Anna Triolo, Giuseppe A Palumbo, Francesco Di Raimondo
Journal: Blood (2009)
Human Vascular Progenitor Cells Can Guide Mesodermal Lineage Choice of Mesenchymal Stem and Progenitor Cells After Co-Transplantation In Vivo.
Authors: Andreas Reinisch, Nathalie Etchart, Nicole A Hofmann, Anna Ortner, Eva Rohde, Katharina Schallmoser, Christine Beham-Schmid, Christian Dullin, Clemens Diwoky, Alexander Hofmeister, Rudolf Stollberger, Frauke Alves, Dirk Strunk
Journal: Blood (2010)
Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic Control of the Membrane Metallo-Endopeptidase
Authors: Zijie Feng, Lei Wang, Yanmei Sun, Zongzhe Jiang, John Domsic, Chiying An, Bowen Xing, Jingjing Tian, Xiuheng Liu, David C. Metz, Xiaolu Yang, Ronen Marmorstein, Xiaosong Ma, Xianxin Hua
Journal: Cancer Research (2016)

Neuroendocrine tumors (NET) often harbor loss-of-function mutations in the MEN1 and DAXX tumor suppressor genes. Here, we report that the products of these genes, menin and Daxx, interact directly with each other to suppress the proliferation of NET cells, to a large degree by inhibiting expression of the membrane metallo-endopeptidase (MME). Menin and Daxx were required to enhance histone H3 lysine9 trimethylation (H3K9me3) at the MME promoter, as mediated partly by the histone H3 methyltransferase SUV39H1. Notably, the menin T429K mutation associated with a NET syndrome reduced Daxx binding, MME repression, and proliferation of NET cells. Conversely, inhibition of MME in NET cells repressed proliferation and tumor growth in vivo Our findings reveal a previously unappreciated cross-talk between two crucial tumor suppressor genes thought to work by independent pathways, focusing on MME as a common target of menin/Daxx to treat NET. Cancer Res; 77(2); 401-11. ©2016 AACR.
CC-486 in Patients with Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML): Safety, Tolerability, and Response
Authors: Michael R. Savona, Kathryn Kolibaba, Paul Conkling, Edwin C. Kingsley, Carlos Becerra, John Morris, Robert M. Rifkin, Eric Laille, Amy Kellerman, Stacey M. Ukrainskyj, Qian Dong, Barry S. Skikne
Journal: Blood (2014)
Macrophage Colony-Stimulating Factor Attenuated the Severity of Chronic Graft-Versus-Host Disease after Unrelated Bone Marrow Transplantation
Authors: Fumihiko Kimura, Ken Sato, Hideki Akiyama, Hiroshi Sao, Shin-ichiro Okamoto, Naoki Kobayashi, Masamichi Hara, Keisei Kawa, Kazuo Motoyoshi
Journal: Blood (2008)
Performance of the ASAS classification criteria for axial and peripheral spondyloarthritis: a systematic literature review and meta-analysis
Authors: Alexandre Sepriano, Roxana Rubio, Sofia Ramiro, Robert Landewé, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2017)

To summarise the evidence on the performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) (also imaging and clinical arm separately), peripheral (p)SpA and the entire set, when tested against the rheumatologist's diagnosis ('reference standard').A systematic literature review was performed to identify eligible studies. Raw data on SpA diagnosis and classification were extracted or, if necessary, obtained from the authors of the selected publications. A meta-analysis was performed to obtain pooled estimates for sensitivity, specificity, positive and negative likelihood ratios, by fitting random effects models.Nine papers fulfilled the inclusion criteria (N=5739 patients). The entire set of the ASAS SpA criteria yielded a high pooled sensitivity (73%) and specificity (88%). Similarly, good results were found for the axSpA criteria (sensitivity: 82%; specificity: 88%). Splitting the axSpA criteria in 'imaging arm only' and 'clinical arm only' resulted in much lower sensitivity (30% and 23% respectively), but very high specificity was retained (97% and 94% respectively). The pSpA criteria were less often tested than the axSpA criteria and showed a similarly high pooled specificity (87%) but lower sensitivity (63%).Accumulated evidence from studies with more than 5500 patients confirms the good performance of the various ASAS SpA criteria as tested against the rheumatologist's diagnosis.
Evaluating the Impact of Florida’s “Stand Your Ground” Self-defense Law on Homicide and Suicide by Firearm
Authors: David K. Humphreys, Antonio Gasparrini, Douglas J. Wiebe
Journal: JAMA Internal Medicine (2016)

In 2005, Florida amended its self-defense laws to provide legal immunity to individuals using lethal force in self-defense. The enactment of "stand your ground" laws in the United States has been controversial and their effect on rates of homicide and homicide by firearm is uncertain.To estimate the impact of Florida's stand your ground law on rates of homicide and homicide by firearm.Using an interrupted time series design, we analyzed monthly rates of homicide and homicide by firearm in Florida between 1999 and 2014. Data were collected from the Wide-ranging Online Data for Epidemiologic Research (WONDER) web portal at the Centers for Disease Control and Prevention. We used seasonally adjusted segmented Poisson regression models to assess whether the onset of the law was associated with changes in the underlying trends for homicide and homicide by firearm in Florida. We also assessed the association using comparison states without stand your ground laws (New York, New Jersey, Ohio, and Virginia) and control outcomes (all suicides and suicides by firearm in Florida). October 1, 2005, the effective date of the law, was used to define homicides before and after the change.Monthly rates of homicide, firearm-related homicide, suicide, and suicide by firearm in Florida and the 4 comparison states.Prior to the stand your ground law, the mean monthly homicide rate in Florida was 0.49 deaths per 100 000 (mean monthly count, 81.93), and the rate of homicide by firearm was 0.29 deaths per 100 000 (mean monthly count, 49.06). Both rates had an underlying trend of 0.1% decrease per month. After accounting for underlying trends, these results estimate that after the law took effect there was an abrupt and sustained increase in the monthly homicide rate of 24.4% (relative risk [RR], 1.24; 95%CI, 1.16-1.33) and in the rate of homicide by firearm of 31.6% (RR, 1.32; 95% CI, 1.21-1.44). No evidence of change was found in the analyses of comparison states for either homicide (RR, 1.06; 95% CI, 0.98-1.13) or homicide by firearm (RR, 1.08; 95% CI, 0.99-1.17). Furthermore, no changes were observed in control outcomes such as suicide (RR, 0.99; 95% CI, 0.94-1.05) and suicide by firearm (RR, 0.98; 95% CI, 0.91-1.06) in Florida between 2005 and 2014.The implementation of Florida's stand your ground self-defense law was associated with a significant increase in homicides and homicides by firearm but no change in rates of suicide or suicide by firearm.
The Effect of Prophylactic Recombinant Factor IX and Glycopegylated Factor IX to Normalize Articular Wound Healing Following Hemarthrosis Examined in Hemophilia B Mice
Authors: Junjiang Sun, Eric Livingston, Tom Knudsen, Dougald M. Monroe, Mirella Ezban, Ted Bateman, Paul E. Monahan
Journal: Blood (2015)
FLAG-IDA Regimen (Fludarabine, Cytarabine, Idarubicin and G-CSF) in the Treatment of Patients with High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndromes.
Authors: Pau Montesinos, Javier de la Rubia, Guillermo Orti, Jaime Sanz, David Martinez, Ninotchka Mendoza, Miguel Scaff, Mariliz Paciello, Monica Romero, Guillermo Martin, Ignacio Lorenzo, Jesus Martinez, Lorenzo Algarra, Isidro Jarque, Mariluz Perez-Sirvent, Guillermo Sanz, Miguel A. Sanz
Journal: Blood (2007)
Fresh fruit consumption in relation to incident diabetes and diabetic vascular complications: findings from the China Kadoorie Biobank Study
Authors: Huaidong Du, Liming Li, Derrick Bennett, Yu Guo, Iain Turnbull, Ling Yang, Fiona Bragg, Zheng Bian, Yiping Chen, Junshi Chen, Iona Millwood, Sam Sansome, Liangcai Ma, Ying Huang, Ningmei Zhang, Xiangyang Zheng, Qiang Sun, Timothy J Key, Rory Collins, Richard Peto, Zhengming Chen
Journal: The Lancet Diabetes & Endocrinology (2016)
EVI1 Overexpression in Pediatric Acute Myeloid Leukemia Associated with Unfavorable Subtypes.
Authors: Brian V Balgobind, Sanne Lugthart, Iris H.I.M. Hollink, Susan T.J.C.M. Arentsen-Peters, Elisabeth R van Wering, Sibold S.N. de Graaf, Dirk Reinhardt, Gertjan Kaspers, Jan Stary, Jan Trka, Martin Zimmermann, Ruud Delwel, Rob Pieters, Christian M Zwaan, Marry M van den Heuvel-Eibrink
Journal: Blood (2008)
Trametinib plus 4-Methylumbelliferone Exhibits Antitumor Effects by ERK Blockade and CD44 Downregulation and Affects PD-1 and PD-L1 in Malignant Pleural Mesothelioma
Authors: Hiroyuki Cho, Seiji Matsumoto, Yoshiko Fujita, Ayumi Kuroda, Toshi Menju, Makoto Sonobe, Nobuyuki Kondo, Ikuko Torii, Takashi Nakano, Primo N. Lara, David R. Gandara, Hiroshi Date, Seiki Hasegawa
Journal: Journal of Thoracic Oncology (2016)