tbuckley/cabot-search huggingface dataset:
Systematic review &amp; expert guidance on methods for sequencing of hepatitis C virus for detection of direct-acting antiviral resistance
Authors: S.R. Bartlett, J. Grebely, A.A. Eltahla, J.D. Reeves, A. Howe, V. Miller, R.A. Bull, F. Ceccherini-Silberstein, M.W. Douglas, G.J. Dore, P. Harrington, A.R. Lloyd, B. Jacka, G.V. Matthews, G.P. Wang, J.-M. Pawlotsky, J.J. Feld, J. Schinkel, F. Garcia, J. Lennerstrand, T.L. Applegate
Journal: Journal of Hepatology (2017)
Abstract 3079: Ethnicity and Risk Factors for Prospective Changes in the Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis
Authors: Matthew A Allison, Mary Cushman, Cam Soloman, Victor Aboyans, Mary McDermott, David Goff, Michael Criqui
Journal: Circulation (2008)

Background: In this study, we aimed to determine the traditional and novel CVD risk factors associated with conversion from a normal to either a low or high ABI. Methods: Subjects were participants...
Routine Imaging for Surveillance in Patients with Aggressive Non-Hodgkin Lymphoma in Complete Remission after Frontline Chemotherapy
Authors: Ka-Won Kang, Dae Sik Kim, Eun Sang You, Yong Park, Se Ryeon Lee, Hwa Jung Sung, Seok Jin Kim, Chul Won Choi, Byung Soo Kim
Journal: Blood (2016)
HLA-A 31:01 is not associated with the development of methotrexate pneumonitis in the UK population: results from a genome-wide association study
Authors: James Bluett, Sally-Ann Owen, Jonathan Massey, Ana Alfirevic, Munir Pirmohamed, Darren Plant, Suzanne M M Verstappen, Anne Barton
Journal: Annals of the Rheumatic Diseases (2017)

We read with interest the article by Furukawa et al 1 suggesting an association between HLA-A 31:01 and methotrexate (MTX)-induced interstitial lung disease (ILD) in Japanese patients with rheumatoid arthritis (RA). MTX-ILD or MTX-pneumonitis (MTX-P) is an idiosyncratic hypersensitivity reaction to MTX that usually occurs within the first year of MTX therapy, inducing inflammation, cytokine release and the activation of CD4+ T-lymphocytes within the lung parenchyma,2–4 with a reported prevalence of 1% of the Caucasian RA population prescribed MTX.5

To investigate this association further, we conducted a genome-wide association study. Rheumatologists working within the National Health Service in the UK identified Caucasian patients …
Management of drug-interactions with DAAs in Dutch human immunodeficiency virus/hepatitis C virus co-infected patients: adequate but not perfect
Authors: E.J. Smolders, C. de Kanter, C. Smit, J. Arends, K. Brinkman, B. Rijnders, M. van der Valk, P. Reiss, D. Burger
Journal: Journal of Hepatology (2017)
Concomitant Myeloproliferative Disorders (MPD) and Amyloidosis
Authors: Angeline J Pallante, Nelson Leung, Robert A. Kyle, Ayalew Tefferi, Stephen J. Russell, Thomas M. Habermann, Martha Q. Lacy, Suzanne R. Hayman, Aref Al-Kali, Craig Reeder, Angela Dispenzieri, Morie A. Gertz, Francis K Buadi, C. Christopher Hook, David Dingli, Animesh Pardanani
Journal: Blood (2016)
Nucleic acid polymer REP2139 monotherapy reveals a short halflife of serum HBsAg in HBeAg+ chronically infected hepatitis B virus patients
Authors: N. Borochov, S.J. Cotler, S.L. Uprichard, M. Al-Mahtab, M. Bazinet, A. Vaillant, H. Dahari
Journal: Journal of Hepatology (2017)
Plasma micoRNA-21, 26a, and 29a-3p as a predictive marker for treatment response following transarterial chemoembolization in patients with hepatocellular carcinoma
Authors: S.S. Kim, J.S. Nam, H.J. Cho, D.R. Kang, H.J. Kim, J.H. Won, J.W. Kim, S.W. Cho, J.Y. Cheong
Journal: Journal of Hepatology (2017)
Outcomes in Latin American NSCLC patients harboring wild-type or activating mutations of EGFR (CLICaP Registry).
Authors: Andres Felipe Cardona Zorrilla, Oscar Arrieta, Guillermo Federico Bramuglia, Alma Delia Campos-Parra, Henry Alberto Becerra Ramirez, Martin MARCELO Claudio, Eduardo Richardet, Silvia J Serrano, Pilar Archila, Rafael Rosell
Journal: Journal of Clinical Oncology (2012)

e18114 Background: Previous exploratory analysis of EGFR status in tumor samples from five LATAM countries suggested that frequency of mutations lies between that of Asian and Caucasian populations and therefore support the genetic heterogeneity of NSCLC around the world. Methods: We analyzed the EGFR sequence of tumor samples from advanced stage NSCLC patients previously participated in the CLICaP registry. We compared the outcomes (overall and progression free survival) of 175 patients (from Argentina, Colombia and México) with an activating EGFR mutation with 414 subjects without this condition. Results: Mutations were more frequent in women (57,1%), in patients who had never smoked (67,4%), and in those with adenocarcinomas (89,4%) (P&lt;0,002 for all comparisons). The mutations were deletions in exon 19 (58,3%) and L858R (36%). Median progression-free survival and overall survival for 175 patients who received tyrosine-kinase inhibitors (TKIs) were 13-mo (95%CI 11,2-14,8) months and 36-mo (95%CI 25,4-46,5), respectively. TKIs produced higher response rates (used as first or second line therapy) in the EGFR mutation-positive patients (70,8% vs. 29,2%; P&lt;0,001), as well as improved PFS (13,0 vs. 3,0; P&lt;0,001). OS is significantly different between treatment groups (36 vs. 14; P&lt;0,001). Conclusions: The analysis of a large comparative registry of Latin-American EGFR mutated and wild type patients confirms the results of individual clinical trials previously published.
High SVR rates with eight and twelve weeks of pangenotypic glecaprevir/pibrentasvir: integrated efficacy and safety analysis of genotype 1–6 patients without cirrhosis
Authors: M. Puoti, G. Foster, S. Wang, D. Mutimer, E. Gane, C. Moreno, T.T. Chang, S.S. Lee, R. Marinho, J.-F. Dufour, S. Pol, C. Hezode, S.C. Gordon, S.I. Strasser, P.J. Thuluvath, R. Liu, T. Pilot-Matias, F. Mensa
Journal: Journal of Hepatology (2017)
Directly observed therapy with sofosbuvir/ledipasvir for 8 weeks is highly effective in treatment-naïve, precirrhotic genotype 1 patients with borderline compliance receiving opioid agonist therapy
Authors: S. Moser, A. Schütz, K. Marchart, D. Kalchbrenner, G. Rechberger, J. Luhn, E. Gutic, H. Haltmayer, M. Gschwantler
Journal: Journal of Hepatology (2017)
A profile of lipid dysregulation in harlequin ichthyosis
Authors: S.C.I. Ip, D.L. Cottle, L.K. Jones, J.M. Weir, D.P. Kelsell, E.A. O'Toole, P.J. Meikle, I.M. Smyth
Journal: British Journal of Dermatology (2017)

Harlequin Ichythosis (HI) is a severe skin disease caused by mutations in the lipid transport protein, ABCA12. This disrupts extracellular lipid deposition; limiting barrier function and resulting in the differentiation of a thickened, restrictive epidermis. This phenotype is at least partially recapitulated in mouse models of disease. While patients1 (and HI mice2) exhibit a partial phenotypic correction after birth, they still require a life-long regime of frequent bathing, mechanical desquamation and emollient application.

This article is protected by copyright. All rights reserved.
Gene expression profiles that underlie biological events visualized by magnetic resonance spectra (MRS) of human prostate cancer: Choline kinase
Authors: Sandra M. Gaston, Jonathan G. Rogg, Jung M. Lee, Dang Vu, Dana L. Goldner, Mark J. Brice, Elizabeth M. Genega, Robert E. Lenkinski, William C. Dewolf
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

932 

Magnetic Resonance Spectroscopy (MRS) is an imaging technique that is under evaluation as a tool for prostate cancer staging in patients with clinically organ confined disease. The metabolic changes characteristic of MRS spectra of malignant areas of the prostate gland include increased choline and decreased citrate. It has been proposed that the elevated choline peak reflects tumor-associated cell membrane synthesis, with increased de novo formation of phosphatidylcholine. However, little is known about the changes in gene expression that underlie the choline spectra observed in human prostate cancers. We have profiled the expression of choline kinase (the first and probably regulatory enzyme in the Kennedy pathway responsible for de novo synthesis of choline containing membrane lipids) using tissue prints collected from radical prostatectomy specimens containing Gleason grade 6 (3+3), Gleason grade 7 (3+4) and/or Gleason grade 7 (4+3) prostate cancers. The patterns of choline kinase expression were compared to that of hepsin, a recently identified prostate tumor marker that has been found to be selectively upregulated in high grade PIN and in primary human prostate cancers. Tissue prints were collected from tissue slices taken at multiple levels of each radical prostatectomy specimen, and the prints were profiled for mRNA expression of tumor markers and reference genes using quantitative reverse transcriptase PCR (qrt-PCR). The tissue corresponding to the prints was processed for histopathological review using standard techniques (hematoxylin and eosin staining), and an experienced genitourinary pathologist assessed the distribution and grade of tumor (or tumors) in each specimen. Peaks of choline kinase mRNA expression co-localized with histologically evident prostate cancer within the gland. Interestingly, the ratio of choline kinase to hepsin mRNA increased sharply with tumor grade, with an approximately ten fold increase choline kinase/hepsin mRNA in Gleason grade 7 (4+3) as compared with Gleason grade 6 (3+3) prostate cancers. These findings suggest that the increased MRS choline peak characteristic of malignant areas of the prostate gland reflect clinically relevant changes in the biological characteristics of the tumor.
Allergen-specific immunotherapy modulates the balance of circulating Tfh and Tfr cells
Authors: Véronique Schulten, Victoria Tripple, Grégory Seumois, Yu Qian, Richard H. Scheuermann, Zheng Fu, Michela Locci, Sandy Rosales, Pandurangan Vijayanand, Alessandro Sette, Rafeul Alam, Shane Crotty, Bjoern Peters
Journal: Journal of Allergy and Clinical Immunology (2017)
Targeted therapy for patients with ALK positive NSCLC: Results from the transalpine cohort
Authors: C. Britschgi, M. Rechsteiner, R. Delaloye, M. Früh, G. Metro, O. Gautschi, S.I. Rothschild, R.A. Stahel, P.J. Wild, A. Curioni-Fontecedro
Journal: Annals of Oncology (2017)
Socioeconomic status and concomitant diseases in patients with prostate cancer.
Authors: Jonas Aronius, Birgitta Lilja, Jamilette Miranda, Bjorn Wettermark, Gunnar Ljunggren, Roger Henriksson
Journal: Journal of Clinical Oncology (2014)

e16076 Background: Prostate cancer remained the most common cancer disease in Sweden. The prognosis is relatively good (five year survival 87%, 2011). Today there is an ongoing discussion about how socioeconomic status (SES) and concomitant diseases could influence the outcome. This study aims to evaluate the potential association between tumor stage (TNM), concomitant diseases, SES and outcome among prostate cancer patients in a specific region of Sweden. Methods: This cross-sectional, retrospective registry study included 3.942 men diagnosed with prostate cancer (ICD-O-2: C61.9) during 2009-2010 in the region Stockholm-Gotland. The cohort was identified in the Swedish Cancer Registry. Data regarding other diagnoses, dispensed and administered drugs, surgery and radiotherapy and other diseases was collected through record linkage with other population based registries. Socioeconomic data on education, income and civil status was also used. Results: During the study period, 181 diagnosed patients died. For the remaining 3.761 patients alive the mean age was 68±9 (mean±sd) years. In this group drug treatment indicated for prostate cancer was recorded for 1.231 patients. Prostatectomy and orchiectomy were reported for 916, and 43 patients, respectively. Curative and palliative radiotherapy were documented for 631, and 36 patients, respectively. Circulatory, urogenital and musculoskeletal diseases were proportionally associated to age, with a total prevalence of 1.108, 1.054, and 603, respectively. The prevalence of digestive and endocrine diseases held no trend in relation to age groups. Older patients as well as patients with low education had more advanced primary tumors (T3-T4). Moreover, 125 patients had at least one additional cancer diagnosis. Conclusions: A more advanced tumor disease was positively related to higher age and lower education. Furthermore, circulatory, urogenital and musculoskeletal diseases were as expected also related to higher age. The severity of prostate cancer at diagnosis, treatment and comorbidity may be connected to patient SES.
Abstract B09: hnRNPA1 is a regulator of UNR IRES activity
Authors: Sebastian Lampe, Thilo Brauß, Michael Kunze, Anica Scholz, Sofia Winslow, Bernhard Brüne, Tobias Schmid
Journal: Cancer Research (2017)

Abstract Alternative translation initiation via internal ribosome entry sites (IRESs) allows for sustained expression of specific proteins under conditions, such as stress, where global translation is inhibited. As cells in tumors are constantly facing stress conditions, e.g. hypoxia or nutrient deprivation, it is not surprising that mRNAs encoding for oncogenes appear to be enriched in IRESs. IRES-dependent translation in eukaryotes commonly involves certain RNA-binding proteins, the so-called IRES trans-acting factors (ITAFs), that can directly interact with the IRESs to facilitate translation initiation. Upstream of N-Ras (UNR) is such an ITAF that can regulate the IRES activity of several cellular and viral IRESs. It is known that its 5' untranslated region (5' UTR) also contains an IRES that is regulated by polypyrimidine-tract binding protein (PTB), heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 and UNR itself. Prediction analyses indicated that hnRNPA1 might bind to the 5' UTR of UNR as well. hnRNPA1 was previously already shown to serve as an ITAF in the regulation of the IRES activities of numerous mRNAs including egr2 and sST2. The aims of this project were to determine the impact of hnRNPA1 on the IRES activity of UNR. To test, if hnRNPA1 interacts with the 5' UTR of UNR, as predicted, we employed RNA affinity chromatography. We found that hnRNPA1 indeed strongly bound to the UNR 5' UTR. To assess, if hnRNPA1 consequently affects UNR IRES activity, we overexpressed hnRNPA1. Overexpression of hnRNPA1 markedly increased UNR IRES activity. hnRNPA1 overexpression further induced total UNR protein expression, which indicates that elevated UNR IRES activity results in enhanced translation. With respect to the exact interaction sites, hnRNPA1 binding was predicted to occur at overlapping sites to the previously published PTB binding sites. Deletion of the hnRNPA1 binding sites not only decreased the UNR IRES activity, it further rendered it insensitive to elevated hnRNPA1 levels. Taken together, we found that the 5' UTR of UNR contains specific hnRNPA1 binding sites and that binding of hnRNPA1 at these sites enhances the UNR IRES activity. Our findings therefore add a new piece to the complex puzzle of UNR regulating ITAFs. Having established hnRNPA1 as a new regulator of UNR IRES activity, might further put hnRNPA1 forward as an interesting target to regulate UNR expression. Citation Format: Sebastian Lampe, Thilo Brauß, Michael Kunze, Anica Scholz, Sofia Winslow, Bernhard Brüne, Tobias Schmid. hnRNPA1 is a regulator of UNR IRES activity. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B09.
Workshop Report: Modulation of Antitumor Immune Responses by Dietary and Microbial Metabolites
Authors: Amit Kumar, Carolyne Smith, Christian Jobin, Giorgio Trinchieri, T. Kevin Howcroft, Harold Seifried, Michael Graham Espey, Roberto Flores, Young S. Kim, Phillip J. Daschner
Journal: JNCI Journal of the National Cancer Institute (2017)

The human microbiota maintains an enormous and diverse capacity to produce a diet-dependent metabolome that impacts both host tissue and microbial community homeostasis. Recent discoveries support a growing appreciation that microbial metabolites derived from bioactive foods are also important regulators of host immune and metabolic functions. To gain a better understanding of the current evidence for the roles of dietary and microbial metabolites in tumor immunity, the Division of Cancer Biology and the Division of Cancer Prevention, National Cancer Institute, cosponsored a workshop on August 31 and September 1, 2016, in Bethesda, Maryland. Workshop participants examined several lines of converging science that link nutrition, microbiology, and tumor immunology and identified key concepts and research opportunities that will accelerate our understanding of these interactions. In addition, the participants identified some of the critical gaps and research challenges that could be addressed through interdisciplinary collaborations, including future opportunities for translating new information into novel cancer prevention and treatment strategies based on targeting host immune functions that are altered by metabolite sensing pathways.
Price cap could mean patients miss out on newest stents, cardiologists warn
Authors: Sumi S Dutta
Journal: BMJ (2017)

Cardiologists in India have warned that the government’s uniform price cap on coronary stents may keep the latest models out of the Indian market and compromise safety during percutaneous coronary interventions in patients with complex arterial disease.

India’s National Pharmaceutical Pricing Authority (NPPA), the government agency that regulates prices, had in February this year imposed a price cap of INR30 000 (£360; €427; $464) on all drug eluting stents, some of which had previously been available to patients at prices of over INR180 000.

This is the first time that the government has put a coronary device on the national list of essential medicines, allowing it to be subject to price control. The NPPA had last year described India’s market for coronary stents …
Glanzmann’s Thrombasthenia Patients with No Mutations in Both the ITGA2B and ITGB3 Genes as Identified by Conformation Sensitive Gel Electrophoresis (CSGE)
Authors: Meganathan Kannan, Firdos Ahmad, Birendra K Yadav, Rajive Kumar, Jawed Fareed, Renu Saxena
Journal: Blood (2008)
Efficacy and safety of elbasvir/grazoprevir in treatment-naïve patients with chronic HCV GT 1, GT 4 and GT 6 infection (C-CORAL): a phase III randomized multinational clinical trial
Authors: L. Wei, K. Zhdanov, E. Burnevich, I.-S. Sheen, J. Heo, V.K. Nguyen, T. Tanwandee, P.-N. Cheng, D.Y. Kim, W.Y. Tak, S. Kizhlo, D. Zhongping, C.-Y. Peng, L.W. Liang, B. Evans, G. Hanna, E. Barr, M. Robertson, P. Ingravallo, R. Talwani, J. George
Journal: Journal of Hepatology (2017)
Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study
Authors: Aditya Sharma, Andrew Hill, Ekaterina Kurbatova, Martie van der Walt, Charlotte Kvasnovsky, Thelma E Tupasi, Janice C Caoili, Maria Tarcela Gler, Grigory V Volchenkov, Boris Y Kazennyy, Olga V Demikhova, Jaime Bayona, Carmen Contreras, Martin Yagui, Vaira Leimane, Sang Nae Cho, Hee Jin Kim, Kai Kliiman, Somsak Akksilp, Ruwen Jou, Julia Ershova, Tracy Dalton, Peter Cegielski
Journal: The Lancet Infectious Diseases (2017)
MAIT cell frequency and function in blood and liver of hepatitis C virus mono- and hepatitis C virus/human immunodeficiency virus co-infected patients with mild versus advanced fibrosis
Authors: B. Beudeker, G. van Oord, J. Arends, J.S. zur Wiesch, R. de Knegt, A. Verbon, A. Boonstra, M. Claassen
Journal: Journal of Hepatology (2017)
Real-world treatment utilization and results in the renaissance of HCV Care: analyses of treatment for 7,550 Patients from the TRIO Network
Authors: S. Flamm, B. Bacon, M. Curry, D. Dieterich, K. Kowdley, S. Milligan, N. Tsai, Z. Younossi, N. Afdhal
Journal: Journal of Hepatology (2017)
Identification of a nucleoside analog active against adenosine kinase–expressing plasma cell malignancies
Authors: Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J. Barelli, Michelle A. Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H. Shoemaker, J. David Warren, Olivier Elemento, Kenneth M. Kaye, Ethel Cesarman
Journal: Journal of Clinical Investigation (2017)

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.
Low rate of drug-drug interaction management during interferon-free simeprevir therapy – an integrated analysis of interventional and observational clinical studies
Authors: F. Marra, C. Höner zu Siederdissen, S. Khoo, M. Cornberg, M. Schlag, S. Ouwerkerk-Mahadevan, C. Bicer, I. Lonjon-Domanec, W. Jessner, M. Beumont-Mauviel, R. Kalmeijer, D. Back
Journal: Journal of Hepatology (2017)
Risk of hepatocellular carcinoma recurrence in hepatitis C cirrhotic patients treated with direct acting antivirals
Authors: G. Cabibbo, I. Cacciola, M.R. Cannavò, S. Madonia, V. Calvaruso, S. Petta, M. Di Stefano, L. Larocca, T. Prestileo, F. Tinè, A. Digiacomo, G. Bertino, L. Giannitrapani, F. Benanti, A. Davì, R. Volpes, L. Guarneri, A. Averna, I. Scalisi, C. Iacobello, G. Mazzola, F. Cartabellotta, V. Portelli, M. Russello, G. Scifo, G. Squadrito, G. Raimondo, A. Craxì, V. Di Marco, C. Cammà
Journal: Journal of Hepatology (2017)
A prospective study to evaluate the efficacy of a standardized low calorie diet according to PNPLA3 genotype in patients with Non Alcoholic Fatty Liver Disease (NAFLD) – 2 months data (interim analysis)
Authors: M. Teufelhart, H. Hofer, H. Haslacher, R. Winker, B. Meyer, P. Ferenci, B. Mehl, C. Rabitsch, S. Nistler, M. Trauner, T.-M. Scherzer
Journal: Journal of Hepatology (2017)
Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration
Authors: Inês Laíns, John B. Miller, Dong H. Park, Edem Tsikata, Samaneh Davoudi, Safa Rahmani, Jonathan Pierce, Rufino Silva, Teresa C. Chen, Ivana K. Kim, Demetrios Vavvas, Joan W. Miller, Deeba Husain
Journal: Ophthalmology (2017)
ENDURANCE-3: safety and efficacy of glecaprevir/pibrentasvir compared to sofosbuvir plus daclatasvir in treatment-naïve HCV genotype 3-infected patients without cirrhosis
Authors: G.R. Foster, E. Gane, A. Asatryan, T. Asselah, P.J. Ruane, S. Pol, F. Poordad, C.A. Stedman, G. Dore, S.K. Roberts, K. Kaita, J. Vierling, H.E. Vargas, J. Kort, C.-W. Lin, R. Liu, T. Ng, F. Mensa
Journal: Journal of Hepatology (2017)