tbuckley/cabot-search huggingface dataset:
Morning bright light treatment for sleep-wake disturbances in Primary Biliary Cholangitis (PBC)
Authors: M. Turco, N. Cazzagon, I. Franceschet, G. Frighetto, F. Giordani, N. Cellini, G. Mazzotta, R. Costa, B. Middleton, D. Skene, S. Montagnese, A. Floreani
Journal: Journal of Hepatology (2018)
Fertility and Birth Outcomes in Women With Epilepsy Seeking Pregnancy
Authors: Page B. Pennell, Jacqueline A. French, Cynthia L. Harden, Anne Davis, Emilia Bagiella, Evie Andreopoulos, Connie Lau, Nichelle Llewellyn, Sarah Barnard, Stephanie Allien
Journal: JAMA Neurology (2018)

Prior studies report lower birth rates for women with epilepsy (WWE) but have been unable to differentiate between biological and social contributions. To our knowledge, we do not have data to inform WWE seeking pregnancy if their likelihood of achieving pregnancy is biologically reduced compared with their peers.To determine if WWE without a prior diagnosis of infertility or related disorders are as likely to achieve pregnancy within 12 months as their peers without epilepsy.The Women With Epilepsy: Pregnancy Outcomes and Deliveries study is an observational cohort study comparing fertility in WWE with fertility in control women (CW) without epilepsy. Participants were enrolled at 4 academic medical centers and observed up to 21 months from November 2010 to May 2015. Women seeking pregnancy aged 18 to 40 years were enrolled within 6 months of discontinuing contraception. Exclusion criteria included tobacco use and a prior diagnosis of infertility or disorders that lower fertility. Eighteen WWE and 47 CW declined the study, and 40 WWE and 170 CW did not meet study criteria. The Women With Epilepsy: Pregnancy Outcomes and Deliveries electronic diary app was used to capture data on medications, seizures, sexual activity, and menses. Data were analyzed from November 2015 to June 2017.The primary outcome was proportion of women who achieved pregnancy within 12 months after enrollment. Secondary outcomes were time to pregnancy using a proportional hazard model, pregnancy outcomes, sexual activity, ovulatory rates, and analysis of epilepsy factors in WWE. All outcomes were planned prior to data collection except for time to pregnancy.Of the 197 women included in the study, 142 (72.1%) were white, and the mean (SD) age was 31.9 (3.5) years among the 89 WWE and 31.1 (4.2) among the 108 CW. Among 89 WWE, 54 (60.7%) achieved pregnancy vs 65 (60.2%) among 108 CW. Median time to pregnancy was no different between the groups after controlling for key covariates (WWE: median, 6.0 months; 95% CI, 3.8-10.1; CW: median, 9.0 months; 95% CI, 6.5-11.2; P = .30). Sexual activity and ovulatory rates were similar in WWE and CW. Forty-four of 54 pregnancies (81.5%) in WWE and 53 of 65 pregnancies (81.5%) in CW resulted in live births. No epilepsy factors were significant.Women with epilepsy seeking pregnancy without prior known infertility or related disorders have similar likelihood of achieving pregnancy, time to pregnancy, and live birth rates compared with their peers without epilepsy.
A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors
Authors: R. Ferrarotto, G. Eckhardt, A. Patnaik, P. LoRusso, L. Faoro, J.V. Heymach, A.M. Kapoun, L. Xu, P. Munster
Journal: Annals of Oncology (2018)

Brontictuzumab is a monoclonal antibody that targets Notch1 and inhibits pathway activation. The purpose of this first-in-human study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, immunogenicity and preliminary efficacy of brontictuzumab in patients with solid tumors.Subjects with selected refractory solid tumors were eligible. Brontictuzumab was administered intravenously at various dose levels and schedule during dose escalation, and at 1.5 mg/kg every 3 weeks (Q3W) during expansion. Evidence of Notch1 pathway activation as determined by an immunohistochemistry assay was required for entry in the expansion cohort. Adverse events were graded according to the NCI-CTCAE v 4.03. Efficacy was assessed by RECIST 1.1.Forty-eight subjects enrolled (33 in dose escalation and 15 in the expansion phase). The MTD was 1.5 mg/kg Q3W. Dose-limiting toxicities were grade 3 diarrhea in two subjects and grade 3 fatigue in one subject. The most common drug-related adverse events of any grade were diarrhea (71%), fatigue (44%), nausea (40%), vomiting (21%), and AST increase (21%). Brontictuzumab exhibited nonlinear pharmacokinetics with dose-dependent terminal half-life ranging 1-4 days. Clinical benefit was seen in 6 of 36 (17%) assessable subjects: 2 had unconfirmed partial response (PR) and 4 subjects had prolonged (≥ 6 months) disease stabilization (SD). Both PRs and three prolonged SD occurred in adenoid cystic carcinoma (ACC) subjects with evidence of Notch1 pathway activation. Pharmacodynamic effects of brontictuzumab were seen in patients' blood and tumor.Brontictuzumab was well tolerated at the MTD. The main toxicity was diarrhea, an on-target effect of Notch1 inhibition. An efficacy signal was noted in subjects with ACC and Notch1 pathway activation.NCT01778439.
Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes
Authors: Marie-Victoire Sénat, Helene Affres, Alexandra Letourneau, Magali Coustols-Valat, Marie Cazaubiel, Helene Legardeur, Julie Fort Jacquier, Nathalie Bourcigaux, Emmanuel Simon, Anne Rod, Isabelle Héron, Virginie Castera, Loic Sentilhes, Florence Bretelle, Catherine Rolland, Mathieu Morin, Philippe Deruelle, Celine De Carne, François Maillot, Gael Beucher, Eric Verspyck, Raoul Desbriere, Sandrine Laboureau, Delphine Mitanchez, Jean Bouyer
Journal: JAMA (2018)

<h3>Importance</h3> Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. <h3>Objective</h3> To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. <h3>Design, Settings, and Participants</h3> The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. <h3>Interventions</h3> Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. <h3>Main Outcomes and Measures</h3> The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. <h3>Results</h3> Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, −∞ to 10.5%;<i>P</i>=.19). <h3>Conclusion and Relevance</h3> This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01731431
Response by Wong et al to Letter Regarding Article, “Importance of Routine Antihuman/Leukocyte Antibody Monitoring: De Novo Donor Specific Antibodies Are Associated With Rejection and Allograft Vasculopathy After Heart Transplantation”
Authors: Ka L. Wong, Byron H. Smith, Walter K. Kremers, Naveen L. Pereira
Journal: Circulation (2018)
Metastatic gastroenteropancreatic neuroendocrine tumors treated with somatostatin analogues: Ten years experience in a third level hospital in Mexico City.
Authors: Alberto Pimentel, Abdel Karim Dip Borunda, Luis Jonathan Bueno Rosario, Gloria Martinez Martinez, Miguel Angel Pluma, Miguel Quintana, Juan ALEJANDRO Silva, Samuel Rivera
Journal: Journal of Clinical Oncology (2018)

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.
Should we recommend e-cigarettes to help smokers quit?
Authors: Paul Aveyard, Deborah Arnott, Kenneth C Johnson
Journal: BMJ (2018)

Smokers want to vape, it can help them quit, and it's less harmful than smoking, say <b>Paul Aveyard</b> and <b>Deborah Arnott</b>. But <b>Kenneth C Johnson</b> argues that smokers who vape are generally less likely to quit and is concerned about youth vaping as a gateway to smoking, dual use, and potential harms from long term use
TCTAP A-132 Deliverability and 6-month Outcome of Patients Treated with Long 30mm to 40mm SeQuent® Please NEO Drug Coated Balloons
Authors: Yusheng James Weng, Hee Hwa Ho, Timothy James Watson, Jason Kwon Kong Loh, Fahim Haider Jafary, Paul JL. Ong
Journal: Journal of the American College of Cardiology (2018)
MVisAGe Identifies Concordant and Discordant Genomic Alterations of Driver Genes in Squamous Tumors
Authors: Vonn Walter, Ying Du, Ludmila Danilova, Michele C. Hayward, D. Neil Hayes
Journal: Cancer Research (2018)

Abstract Integrated analyses of multiple genomic datatypes are now common in cancer profiling studies. Such data present opportunities for numerous computational experiments, yet analytic pipelines are limited. Tools such as the cBioPortal and Regulome Explorer, although useful, are not easy to access programmatically or to implement locally. Here, we introduce the MVisAGe R package, which allows users to quantify gene-level associations between two genomic datatypes to investigate the effect of genomic alterations (e.g., DNA copy number changes on gene expression). Visualizing Pearson/Spearman correlation coefficients according to the genomic positions of the underlying genes provides a powerful yet novel tool for conducting exploratory analyses. We demonstrate its utility by analyzing three publicly available cancer datasets. Our approach highlights canonical oncogenes in chr11q13 that displayed the strongest associations between expression and copy number, including CCND1 and CTTN, genes not identified by copy number analysis in the primary reports. We demonstrate highly concordant usage of shared oncogenes on chr3q, yet strikingly diverse oncogene usage on chr11q as a function of HPV infection status. Regions of chr19 that display remarkable associations between methylation and gene expression were identified, as were previously unreported miRNA–gene expression associations that may contribute to the epithelial-to-mesenchymal transition. Significance: This study presents an important bioinformatics tool that will enable integrated analyses of multiple genomic datatypes. Cancer Res; 78(12); 3375–85. ©2018 AACR.
A Method to Summarize Toxicity in Cancer Randomized Clinical Trials
Authors: Mariana Carbini, Mayte Suárez-Fariñas, Robert G. Maki
Journal: Clinical Cancer Research (2018)

Purpose: Despite development of clinical "value frameworks" by national and international groups, there remains no generally accepted method to summarize toxicity in cancer clinical trials. We explored ways to simplify toxicity data of an arm of a cancer clinical trial to a single value, termed a "weighted toxicity score" (WTS).Experimental Design: We compiled 58 randomized clinical trials of FDA-approved kinase-directed inhibitors. We generated 5 models, each of which assigned different weights for each observed grade 1 to 4 toxicities. For each model, we calculated WTS values as different weighted averages of the sum of the toxicities. We correlated each WTS with the dose reduction rate in each trial, using the dose reduction rate as a clinically relevant surrogate of treatment that is too toxic. The WTS method yielding the strongest correlation with frequency of dose reduction was declared the best model.Results: Nineteen of 58 trials were placebo controlled and had complete data. Of the 5 models examined, differences in dose reduction rates correlated best with differences in WTS using a model with a clinician-weighted scale for toxicities (model M5). The WTS difference thus serves as a surrogate for a desired dose reduction rate difference and could be used to adjust dose/schedule as patients are accrued to a clinical trial.Conclusions: The WTS distills a tabular listing of toxicities of a treatment into a single value, and provides a simple method that can be incorporated into value frameworks, or used to guide discussion of the risks and benefits of systemic therapy. Clin Cancer Res; 24(20); 4968-75. ©2018 AACRSee related commentary by Vaishampayan, p. 4918.
A Near-Disaster in Rescuing Wide Complex Tachycardia—Can We Always Trust External Defibrillators?
Authors: Idris Ali Amghaiab, Khalid Abozguia, Fathi I. Ali
Journal: JAMA Internal Medicine (2018)

This case report presents the elecrocardiographic findings of a man in his 50s with dizziness, shortness of breath, and tachycardia in whom electrical cardioversion was unsuccessful until the sixth attempt.
Constitutively active erythropoietin receptor variants in human ovarian and breast cancers
Authors: Geza Acs, Gyorgy Paragh, Xiaowei Xu, Suresh Kumar
Journal: Cancer Research (2008)

3428   The erythropoietin receptor (EpoR) serves as a specific receptor for erythropoietin (Epo). Epo stimulates the proliferation and inhibits the apoptosis of erythroblasts in the bone marrow, and plays a role in the protection of neurons and cardiac muscle cells from hypoxic damage. Human recombinant Epo (rHuEpo) is widely used in the management of cancer and therapy related anemia in patients with malignant neoplasms. Although rHuEpo is effective in correcting anemia and improving quality of life, recent clinical trials suggested that its use may be associated with earlier tumor recurrence/progression and decreased survival. Various human cancer cells were recently shown to express EpoR and  in vitro  studies suggested that Epo can stimulate signaling mechanisms and proliferation in some cancer cells providing a potential biologic basis for the observed adverse effects rHuEpo in cancer patients. Other studies, however, found that exogenous Epo failed to stimulate tumor growth in  in vivo  tumor models. Given the lack of biologic response to Epo despite the presence of high levels of EpoR in some tumor cells, we tested the hypothesis that EpoR is constitutively active and contributes to tumor growth independent of Epo in such tumors. We found that despite expression of high levels of EpoR, exogenous Epo fails to stimulate EpoR-related signaling mechanisms, proliferation or invasiveness in A2780 human ovarian carcinoma cells. We have specifically down-regulated EpoR expression in A2780 cells using a short hairpin RNA (shRNA) expression plasmid and found that blocking EpoR expression resulted in markedly suppressed cell proliferation and invasiveness  in vitro . EpoR-specific shRNA also abrogated ovarian cancer cell growth  in vivo . Western blot analysis revealed a decrease in the activation status of EpoR signaling pathway components in A2780/EpoR shRNA tumors compared to controls. In order to examine the potential mechanisms of constitutive EpoR signaling in breast and ovarian cancer cells, we measured the mRNA expression levels of all eight exons of the EpoR gene. We found that, in contrast to UT-7 cells expressing functional, wild type EpoR, mRNA regions coding for the extracellular portion of EpoR were expressed at significantly lower levels compared to C-terminal regions, suggesting the presence of altered EpoR mRNA species in these cancer cells. Increased ratio of C- vs N-terminal EpoR mRNA levels determined by qualitative RT PCR in archived breast cancer samples significantly correlated with lymphatic invasion and nodal metastasis. A SMART RACE PCR assay confirmed the presence of altered EpoR mRNA variants in breast and ovarian cancer cells, in contrast to the full length wild type EpoR mRNA present in UT7 cells. Our findings suggest that variant forms of EpoR may be constitutively active in some cancer cells and provide the first evidence for the potential role of an Epo independent EpoR mediated pathway in tumor growth.
Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study
Authors: Magnus Ekström, Anna Bornefalk-Hermansson, Nicholas Wysham, David C. Currow, Neil MacIntyre, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Elizabeth A. Regan, Stephanie Santorico, Edwin K. Silverman, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, Elizabeth A. Regan, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, Carla G. Wilson, John E. Hokanson, John Hughes, Gregory Kinney, Sharon M. Lutz, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Dawn L. DeMeo, Craig Hersh, Francine L. Jacobson, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Marilyn G. Foreman, Eugene Berkowitz, Gloria Westney, Russell Bowler, David A. Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs Pharm.D, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, MeiLan K. Han, Ella Kazerooni, Carlos H. Martinez, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.
Imputation-based analysis of <i>MICA</i> alleles in the susceptibility to ankylosing spondylitis
Authors: Adrian Cortes, Dafna Gladman, Soumya Raychaudhuri, Jing Cui, Lawrie Wheeler, Matthew A Brown
Journal: Annals of the Rheumatic Diseases (2018)

genetic variation within the major histocompatibility complex (MHC), and the class I HLA-B*27 allele confers the major genetic risk factor to AS[1].Additionally, strong evidence for non-HLA-B*27 independent
Resequencing a core collection of upland cotton identifies genomic variation and loci influencing fiber quality and yield
Authors: Zhiying Ma, Shoupu He, Xingfen Wang, Junling Sun, Yan Zhang, Guiyin Zhang, Liqiang Wu, Zhikun Li, Zhihao Liu, Gaofei Sun, Yuanyuan Yan, Yinhua Jia, Jun Yang, Zhaoe Pan, Qishen Gu, Xueyuan Li, Zhengwen Sun, Panhong Dai, Zhengwen Liu, Wenfang Gong, Jinhua Wu, Mi Wang, Hengwei Liu, Keyun Feng, Huifeng Ke, Junduo Wang, Hongyu Lan, Guoning Wang, Jun Peng, Nan Wang, Liru Wang, Baoyin Pang, Zhen Peng, Ruiqiang Li, Shilin Tian, Xiongming Du
Journal: Nature Genetics (2018)
Cost-effectiveness of scaling up Hepatitis C virus prevention, testing and treatment interventions among people who inject drugs in the US
Authors: C. Barbosa, H. Fraser, T. Hoerger, A. Leib, J. Evans, J. Havens, L. Nerlander, K. Page, A. Young, A. Kral, J. Zibbell, S. Hariri, C. Vellozzi, J. Ward, P. Vickerman
Journal: Journal of Hepatology (2018)
The reproducibility of COPD blood eosinophil counts
Authors: Thomas Southworth, Gussie Beech, Philip Foden, Umme Kolsum, Dave Singh
Journal: European Respiratory Journal (2018)

Post hoc and pre-specified analyses of chronic obstructive pulmonary disease (COPD) randomised controlled trials have shown that higher blood eosinophil counts predict greater inhaled corticosteroid (ICS) effects on exacerbation prevention [1–5]. COPD patients with higher blood eosinophil counts have greater eosinophil numbers in sputum, bronchoalveolar lavage and bronchial tissue, and more reticular basement membrane thickening [6]. Furthermore, increased sputum eosinophil counts are associated with reduced airway presence of pathogenic bacteria in COPD [7]. Eosinophilic COPD therefore has distinct biological features associated with increased ICS responsiveness. Blood eosinophil counts in COPD are stable over the long term <http://ow.ly/aDlN30jVBCg>
Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer
Authors: Matthew D. Hellmann, Margaret K. Callahan, Mark M. Awad, Emiliano Calvo, Paolo A. Ascierto, Akin Atmaca, Naiyer A. Rizvi, Fred R. Hirsch, Giovanni Selvaggi, Joseph D. Szustakowski, Ariella Sasson, Ryan Golhar, Patrik Vitazka, Han Chang, William J. Geese, Scott J. Antonia
Journal: Cancer Cell (2018)