tbuckley/cabot-search huggingface dataset:
Abstract 14810: Gender Differences in the Prevalence of Physical Frailty in Heart Failure
Authors: Mary C Davis, Christopher S Lee, Amy Corcoran, Nandita Gupta, Izabella Uchmanowicz, Quin E Denfeld
Journal: Circulation (2020)

Introduction: The intersection of frailty and heart failure (HF) continues to garner interest. Almost half of patients with HF are frail; however, gender differences in the prevalence of frailty in HF are poorly understood. The objective of this study was to quantify gender differences in the prevalence of frailty in HF. Methods: Data from a subset of studies from a previous meta-analysis were analyzed if they included prevalence of frailty by gender. We performed a random-effects meta-analysis to quantify the relative and absolute risk of frailty in women compared to men with HF overall, and divided into Physical and Multidimensional Frailty measures. Risk ratios (RR) along with their confidence intervals (CI) were estimated. Results: Thirteen studies involving 3,662 women and men with HF were included in this meta-analysis. The estimated prevalence of frailty in HF was 51.4% for women and 33.9% for men. The overall absolute risk increase for women compared to men with HF being frail was 14% (z = 3.92, p &lt; 0.001). Overall, women with HF had a 42.1% higher risk of being frail (RR = 1.42 (CI = 1.19-1.69), p &lt; 0.001) compared to men with HF, and there was significant heterogeneity in RRs across studies ( I 2 = 81.7%). Among studies that used Physical Frailty measures, women with HF had a 43.7% higher risk of being frail (RR = 1.44 (CI = 1.20-1.73), p &lt; 0.001) compared with men. Among studies that used Multidimensional Frailty measures, there was no significant difference in risk of frailty between women and men (RR = 1.36 (CI = 0.94,1.96), p = 0.105). Conclusions: In HF, frailty affects women significantly more than men, although this was only noted among studies that measured physical frailty, and there was significant heterogeneity across studies. Future work should focus on elucidating potential causes of gender differences in frailty in HF.
P15.07 Safety and Efficacy Profile of TQB-2450 Alone/with Anlotinib in Previously-Treated Advanced NSCLC: A Phase IB Single-Arm Trial
Authors: B. Han, W. Zhang, C. Shi, T. Chu, H. Zhong, Y. Zhang, Y. Lou, Y. Dong, F. Qian, W. Zhou, Y. Chen, Z. Yang
Journal: Journal of Thoracic Oncology (2021)
Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial
Authors: Stefan T Engelter, Christopher Traenka, Henrik Gensicke, Sabine A Schaedelin, Andreas R Luft, Barbara Goeggel Simonetti, Urs Fischer, Patrik Michel, Gaia Sirimarco, Georg Kägi, Jochen Vehoff, Krassen Nedeltchev, Timo Kahles, Lars Kellert, Sverre Rosenbaum, Regina von Rennenberg, Roman Sztajzel, Stephen L Leib, Simon Jung, Jan Gralla, Nicole Bruni, David Seiffge, Katharina Feil, Alexandros A Polymeris, Levke Steiner, Janne Hamann, Leo H Bonati, Alex Brehm, Gian Marco De Marchis, Nils Peters, Christoph Stippich, Christian H Nolte, Hanne Christensen, Susanne Wegener, Marios-Nikos Psychogios, Marcel Arnold, Philippe Lyrer, Timo Kahles, Krassen Nedeltchev, Valerian Altersberger, Leo H Bonati, Alex Brehm, Nicole Bruni, Gian Marco De Marchis, Stefan T Engelter, Thomas Fabbro, Urs Fisch, Joachim Fladt, Henrik Gensicke, Lisa Hert, Philippe A Lyrer, Marina Maurer, Nils Peters, Alexandros Polymeris, Marios-Nikos Psychogios, Sabine Schaedelin, Christoph Stippich, Sebastian Thilemann, Christopher Traenka, Benjamin Wagner, Marcel Arnold, Urs Fischer, Barbara Goeggel Simonetti, Jan Gralla, Mirjam Heldner, Simon Jung, Stephen L Leib, David J Seiffge, Hubertus Mueller, Lukas Sveikata, Roman Sztajzel, Hubertus Mueller, Pamela Correia, Ashraf Eskandari, Ivo Meyer, Patrik Michel, Stefania Nannoni, Suzette Remillard, Gaia Sirimarco, Alexandros Zachariadis, Georg Kaegi, Anna Mueller, Jochen Vehoff, Janne Hamann, Andreas R Luft, Levke Steiner, Susanne Wegener, Hebun J Erdur, Christian H Nolte, Regina von Rennenberg, Jan F Scheitz, Katharina Feil, Lars Kellert, Hanne Christensen, Sverre Rosenbaum
Journal: The Lancet Neurology (2021)
Abstract P08: Adenosine-based cancer immunotherapy for COVID-19
Authors: Giulia Monticone, Alistair Ramsay, Lucio Miele
Journal: Clinical Cancer Research (2021)

Abstract Cancer immunotherapy has shaped the way in which we design cancer treatments, introducing the paradigm of taking advantage of our immune system to fight cancer. We propose that the same concept could be applied to infectious diseases and, especially, to those that hamper the immune system like COVID-19. It is well known that an adaptive immune response is able to eradicate viral infections and CD8+ T-cells are key in such anti-viral response. Furthermore, several studies reported that the number of CD8+ T-cells is reduced in COVID-19 patients since the beginning of SARS-CoV-2 infection and further decreased in severe cases. CD8+ T-cells often show signs of exhaustion, loss of T-cell functions and suppression in COVID-19 patients, suggesting that hampering CD8+ T-cells could be a way by which SARS-CoV-2 infection progresses. Importantly, the number of CD8+ T cells appears to re-increase in patients that are recovering from COVID-19, suggesting that CD8+ T-cells could be a key factor that determines whether our body can recover from the disease. We propose that therapies that boost CD8+ T cells could be effective in clearing SARS-CoV-2 infection in COVID-19. To test this, we will take advantage of the adenosine-mediated immunomodulation. Adenosine, an ATP metabolite that is produced during inflammation, hypoxia and in the tumor microenvironment, was found to suppress the immune response through activation of adenosine receptors present on immune cells. Small molecules antagonists that block one of these receptors, adenosine A2A receptor (A2AR) antagonists, are currently being studied to boost anti-cancer T-cell mediated immune responses. Our data show that treatment with an A2AR antagonist restores and stabilizes Notch1, a key pathway for T-cell functions, along with production of INF-gamma and Granzyme B and proliferation in CD8+ T-cells. As a proof of concept, our data indicates that treatment with an A2AR antagonist increases CD8+ T-cells anti-cancer response in tumor-derived organoids, suggesting that the treatment boosts CD8+ T-cells-mediated immune response. Ongoing work aims to test whether the A2AR antagonist treatment restores several parameters of T-cell function that are specifically modified in COVID-19. This analysis will help to predict the action of the A2AR antagonist on T-cells in vivo and we ultimately aim to test this treatment in a mouse model for COVID-19. Overall, our work could introduce a new paradigm and new therapies for COVID-19 and other infectious diseases. Citation Format: Giulia Monticone, Alistair Ramsay, Lucio Miele. Adenosine-based cancer immunotherapy for COVID-19 [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P08.
P36.08 Effect of Soluble CD39 and PD-L1 Levels on Diagnosis and Prognosis of Lung Cancer Patients with Malignant Pleural Effusion
Authors: M. Chen, X. Li, B. Wan, S. Zhu, C. Chen, F. Zhang, Y. Song, T. Lv
Journal: Journal of Thoracic Oncology (2021)
P59.07 Molecular Profiling of Human Non-Small Cell Lung Cancer by Single-Cell RNA-Seq
Authors: J. Wang, J. He, F.C. Tang, Q.Q. Li, R. Wang, Z.L. Yang, W. Li, Z.J. Wang, H. Bai, L. Wen, Y.H. Tian, Y.B. Gao
Journal: Journal of Thoracic Oncology (2021)
P90.04 RAS Precision Medicine Trans-Atlantic Partnership: Multi-Centre Pooled Analysis of RAS Pathway Mutations in Advanced NSCLC
Authors: H. Adderley, M. Aldea, J. Aredo, M. Carter, M. Church, F. Blackhall, M.G. Krebs, H.A. Wakelee, B. Besse, D. Planchard, D. Vasseur, C. Massard, C. Lindsay
Journal: Journal of Thoracic Oncology (2021)
P72.01 Stress-Induced Upregulation of TNFSF4 in Cancer Associated Fibroblasts Facilitates Chemoresistance of Lung Adenocarcinoma
Authors: Y. Li, L. Miao, Y. Wang, M. Shi, N. Kang, Y. Zhou, H. Chen, G. Huang
Journal: Journal of Thoracic Oncology (2021)
Applicability of lung ultrasound in COVID-19 diagnosis and evaluation of the disease progression: A systematic review
Authors: A.O. Peixoto, R.M. Costa, R. Uzun, A.M.A. Fraga, J.D. Ribeiro, F.A.L. Marson
Journal: Pulmonology (2021)

The COVID-19 pandemic originated in China and within about 4 months affected individuals all over the world. One of the limitations to the management of the COVID-19 is the diagnostic imaging to evaluate lung impairment and the patients' clinical evolution, mainly, in more severe cases that require admission into the intensive care unit. Among image examinations, lung ultrasound (LU) might be a useful tool to employ in the treatment of such patients.
Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition
Authors: Lawrence Corey, Peter B. Gilbert, Michal Juraska, David C. Montefiori, Lynn Morris, Shelly T. Karuna, Srilatha Edupuganti, Nyaradzo M. Mgodi, Allan C. deCamp, Erika Rudnicki, Yunda Huang, Pedro Gonzales, Robinson Cabello, Catherine Orrell, Javier R. Lama, Fatima Laher, Erica M. Lazarus, Jorge Sanchez, Ian Frank, Juan Hinojosa, Magdalena E. Sobieszczyk, Kyle E. Marshall, Pamela G. Mukwekwerere, Joseph Makhema, Lindsey R. Baden, James I. Mullins, Carolyn Williamson, John Hural, M. Juliana McElrath, Carter Bentley, Simbarashe Takuva, Margarita M. Gomez Lorenzo, David N. Burns, Nicole Espy, April K. Randhawa, Nidhi Kochar, Estelle Piwowar-Manning, Deborah J. Donnell, Nirupama Sista, Philip Andrew, James G. Kublin, Glenda Gray, Julie E. Ledgerwood, John R. Mascola, Myron S. Cohen
Journal: New England Journal of Medicine (2021)

Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.
Tunable electroconductive decellularized extracellular matrix hydrogels for engineering human cardiac microphysiological systems
Authors: Jonathan H. Tsui, Andrea Leonard, Nathan D. Camp, Joseph T. Long, Zeid Y. Nawas, Rakchanok Chavanachat, Alec S.T. Smith, Jong Seob Choi, Zhipeng Dong, Eun Hyun Ahn, Alejandro Wolf-Yadlin, Charles E. Murry, Nathan J. Sniadecki, Deok-Ho Kim
Journal: Biomaterials (2021)
Eribulin Plus Pembrolizumab in Patients with Metastatic Triple-Negative Breast Cancer (ENHANCE 1): A Phase Ib/II Study
Authors: Sara M. Tolaney, Kevin Kalinsky, Virginia G. Kaklamani, David R. D'Adamo, Gursel Aktan, Michaela L. Tsai, Ruth M. O'Regan, Peter A. Kaufman, Sharon T. Wilks, Eleni Andreopoulou, Debra A. Patt, Yuan Yuan, Grace Wang, Claudio Savulsky, Dongyuan Xing, Ella Kleynerman, Vassiliki Karantza, Sami Diab
Journal: Clinical Cancer Research (2021)

Abstract Purpose: As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase Ib/II study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings. Patients and Methods: In this open-label, single-arm, phase Ib/II study, eligible patients had mTNBC, measurable disease, and ≤2 prior systemic anticancer therapies in the metastatic setting. Patients were enrolled by number of prior systemic anticancer therapies (stratum 1: 0 vs stratum 2: 1–2) in the metastatic setting and further analyzed by tumor programmed death-ligand 1 (PD-L1) expression status. All patients received intravenous eribulin 1.4 mg/m2 on day 1 and day 8, plus intravenous pembrolizumab 200 mg on day 1, of 21-day cycles. The primary objectives were the safety, tolerability, and objective response rate (ORR) of this combination. Results: The study included 167 patients (phase Ib, n = 7; phase II, n = 160). The most common treatment-emergent adverse events were fatigue (66%), nausea (58%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). ORRs were 25.8% [95% confidence interval (CI): 15.8–38.0] for stratum 1 (n = 66) and 21.8% (95% CI: 14.2–31.1) for stratum 2 (n = 101). Patients with PD-L1–positive tumors (combined positive score ≥1) had numerically higher ORR than those with PD-L1–negative tumors, particularly in stratum 1 [stratum 1: 34.5% (95% CI: 17.9–54.3) vs 16.1% (95% CI: 5.5–33.7); stratum 2, 24.4% (95% CI: 12.9–39.5) vs 18.2% (95% CI: 8.2–32.7)]. Conclusions: Eribulin plus pembrolizumab was generally well tolerated and showed promising antitumor activity in mTNBC. Efficacy outcomes appeared influenced by line of therapy and PD-L1 status.
P74.02 Treatment Patterns of EGFR mt+ NSCLC IV pts: Real World Data of the NOWEL Network
Authors: J. Roeper, M. Falk, M. Tiemann, L. Heukamp, C. Wesseler, G.h. Wiest, S. Sackmann, D. Ukena, F. Griesinger
Journal: Journal of Thoracic Oncology (2021)
Abstract 13268: Gold Nanoparticles for Detection of Vascular Inflammation in Experimental Carotid Atherosclerosis and Aortic Aneurysms
Authors: Hisanori Kosuge, Maki Nakamura, Ayako Oyane, Kazuko Tajiri, Nobuyuki Murakoshi, Satoshi Sakai, Akira Sato, Masaki Ieda, Kazutaka Aonuma
Journal: Circulation (2018)

Introduction: Inflammation contributes to progression of both atherosclerosis and abdominal aortic aneurysms (AAA). Macrophages are important targets for imaging vascular inflammation. Gold nanopar...
NIMG-64. DISTINCT IMAGING PATTERNS OF PSEUDOPROGRESSION IN GLIOMA PATIENTS FOLLOWING PROTON VERSUS PHOTON RADIATION THERAPY
Authors: Jerome Graber, Reed Ritterbusch, Lia Halasz
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Radiologic Assessment in Neuro-Oncology (RANO) criteria define pseudoprogression (Ps) after photon radiation for gliomas, as occurring less than twelve weeks from radiation, within the high dose radiation field. However, some patients receiving proton manifest lesions that appear subjectively different from photon Ps based on timing and location (more than six months from radiation and deeper to the prior tumor), which would be called tumor progression by RANO. We retrospectively reviewed MRI changes after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) distinct from photon pseudoprogression or tumor progression. METHODS Post-treatment MRIs of patients with gliomas were reviewed, along with clinical and pathological data. 77 proton patients were reviewed for the presence of ProPs, and 64 photon patients were reviewed for imaging changes. Data collected included the location, timing, and morphology of the lesions, tumor type, chemotherapy, and clinical symptoms. RESULTS 16 (21%) of the patients who received protons had imaging changes unique to protons, at a mean of 14.6 months after radiation. We established the following criteria to characterize ProPs: not immediately in or adjacent to the resection cavity; ~ 2cm opposite from target beam entry; can resolve without treatment; subjectively multifocal, patchy, small (&amp;lt; 1cm). None of the photon patients had lesions that met our criteria for ProPs (p&amp;lt; 0.001). CONCLUSION Patients who receive protons can have a unique subtype of pseudoprogression (Ps), which we refer to as proton pseudoprogression (or ProPs). These lesions could be mistaken for tumor progression, but typically resolve spontaneously. ProPs can possibly be explained by the increased relative biological effectiveness of protons and beam angle selection which may deposit at ~2cm deep to the target. Recognizing these lesions can prevent unnecessary treatment for mistaken tumor progression, especially in the context of clinical trials that include proton.
OA04.04 Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer
Authors: J.K. Sabari, C.A. Shu, K. Park, N. Leighl, P. Mitchell, S. Kim, J. Lee, D. Kim, S. Viteri, A. Spira, J. Han, J. Trigo, C.K. Lee, K.H. Lee, N. Girard, T. Yang, K. Goto, R.E. Sanborn, J.C. Yang, J. Xie, A. Roshak, M. Thayu, R.E. Knoblauch, B.C. Cho
Journal: Journal of Thoracic Oncology (2021)

Despite sharing similar tumor biology to other epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) tumors, no targeted therapies have been approved for NSCLC harboring EGFR Exon 20 insertion mutations (Exon20ins). The standard of care remains platinum-based chemotherapy for the front-line, with no clear subsequent options available. Amivantamab (JNJ-61186372) is a novel, fully human EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations, as well as MET mutations and amplifications, and has received FDA Breakthrough Therapy Designation for the treatment of patients with EGFR Exon20ins NSCLC after platinum-based chemotherapy.
High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial
Authors: Atul Anand, Kuan Ken Lee, Andrew R. Chapman, Amy V. Ferry, Phil D. Adamson, Fiona E. Strachan, Colin Berry, Iain Findlay, Anne Cruikshank, Alan Reid, Paul O. Collinson, Fred S. Apple, David A. McAllister, Donogh Maguire, Keith A.A. Fox, David E. Newby, Chris Tuck, Ronald Harkess, Catriona Keerie, Christopher J. Weir, Richard A. Parker, Alasdair Gray, Anoop S.V. Shah, Nicholas L. Mills, Bill Alexander, Shannon Amoils, Roma Armstrong, Anda Bularga, Bernard L. Croal, Dimitrios Doudesis, Colin M. Fischbacher, Ian Ford, Takeshi Fujisawa, Ronnie Harkess, Dorien M. Kimenai, Stephen J. Leslie, Pamela Linksted, Matthew T.H. Lowry, Claire MacDonald, Lucy Marshall, Filip Mendusic, John Norrie, Imran Sadat, Catherine L. Stables, Jennifer Stevens, Stacey D. Stewart, Laura Stirling, Caelan Taggart, Ryan Wereski, Stephen Young
Journal: Circulation (2021)

High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early rule-out pathway is safe and effective for patients with suspected acute coronary syndrome.
Leprosy post-exposure prophylaxis risks not adequately assessed – Author's reply
Authors: Jan Hendrik Richardus, Liesbeth Mieras, Paul Saunderson, Eliane Ignotti, Marcos Virmond, Mohammad A Arif, Basu Dev Pandey, Arielle Cavaliero, Peter Steinmann
Journal: The Lancet Global Health (2021)

We thank Diana Lockwood and colleagues for their concerns about leprosy post-exposure chemoprophylaxis with single-dose rifampicin (SDR-PEP) for contacts of people diagnosed with leprosy.1 Some of their concerns against SDR-PEP are based on misunderstandings of the outcome of the COLEP trial.
MA04.04 Assessing the Methodological Quality of Quality-of-Life Analyses in First-Line Lung Cancer Trials: A Systematic Review
Authors: F. Waisberg, C. Lopez, J. Burton, I. Hirsch, D. Enrico, P. Mandó, C. Martin, M. Chacón, N. Seetharamu
Journal: Journal of Thoracic Oncology (2021)
Label-Free Deep Profiling of the Tumor Microenvironment
Authors: Sixian You, Eric J. Chaney, Haohua Tu, Yi Sun, Saurabh Sinha, Stephen A. Boppart
Journal: Cancer Research (2021)

Abstract Label-free nonlinear microscopy enables nonperturbative visualization of structural and metabolic contrast within living cells in their native tissue microenvironment. Here a computational pipeline was developed to provide a quantitative view of the microenvironmental architecture within cancerous tissue from label-free nonlinear microscopy images. To enable single-cell and single-extracellular vesicle (EV) analysis, individual cells, including tumor cells and various types of stromal cells, and EVs were segmented by a multiclass pixelwise segmentation neural network and subsequently analyzed for their metabolic status and molecular structure in the context of the local cellular neighborhood. By comparing cancer tissue with normal tissue, extensive tissue reorganization and formation of a patterned cell–EV neighborhood was observed in the tumor microenvironment. The proposed analytic pipeline is expected to be useful in a wide range of biomedical tasks that benefit from single-cell, single–EV, and cell-to-EV analysis. Significance: The proposed computational framework allows label-free microscopic analysis that quantifies the complexity and heterogeneity of the tumor microenvironment and opens possibilities for better characterization and utilization of the evolving cancer landscape.
State‐Level HCC Incidence and Association With Obesity and Physical Activity in the United States
Authors: Yi‐Te Lee, Jasmine J. Wang, Michael Luu, Hsian‐Rong Tseng, Nicole E. Rich, Shelly C. Lu, Nicholas N. Nissen, Mazen Noureddin, Amit G. Singal, Ju Dong Yang
Journal: Hepatology (2021)

Background and Aims Hepatocellular carcinoma (HCC) remains a leading cause of cancer‐related mortality, with a disproportionate impact on racial/ethnic minority groups. However, state‐level variation in racial/ethnic disparities and temporal trends of HCC incidence remain unknown. Therefore, we aimed to characterize (1) state‐level racial/ethnic disparity in HCC incidence, (2) state‐level temporal changes in HCC incidence, and (3) the ecological correlation between HCC incidence and obesity/physical activity levels in the USA. Approach and Results Trends in HCC incidence between 2001 and 2017 were calculated using data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and End Results, and annual percent change in rates were calculated. State‐level percent of obesity and level of physical activity were obtained from the Centers for Disease Control and Prevention, and the correlation among obesity, physical activity, and state‐specific average annual percent change was tested by Pearson correlation coefficient. There were striking state‐level racial/ethnic disparities in HCC incidence; incidence rate ratios ranged between 6.3 and 0.9 in Blacks, 6.1 and 1.7 in Asians/Pacific Islanders, 3.8 and 0.9 in Hispanics, and 6.0 and 0.9 in American Indians/Alaska Natives (compared with Whites as reference). Despite overall decreasing HCC incidence rates after 2015, HCC incidence continued increasing in 26 states over recent years. HCC incidence trends had a moderate correlation with state‐level obesity ( r = 0.45, P &lt; 0.001) and a moderate inverse correlation with state‐level physical activity ( r = −0.40, P = 0.004). Conclusions There is wide state‐level variation in racial/ethnic disparity of HCC incidence. There are also disparate incidence trends across states, with HCC incidence continuing to increase in over half of the states. Regional obesity and lack of physical activity have moderate correlations with HCC incidence trends, suggesting that interventions targeting these factors may help curb rising HCC incidence.
High-Throughput Sequencing of IgG B-Cell Receptors Reveals the Frequent Usage of the Rearranged IGHV4-28//IGHJ4 Gene in Primary Immune Thrombocytopenia in Adults
Authors: Naohito Fujishima, Masaru Togashi, Ryo Hasegawa, Ken Watanabe, Akiko Saga, Ayumi Omokawa, Tomoo Saga, Shigeharu Ueki, Naoto Takahashi, Kazutaka Kitaura, Ryuji Suzuki, Makoto Hirokawa
Journal: Blood (2017)