tbuckley/cabot-search huggingface dataset:
SIRT1 Regulates N6‐Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2‐Dependent FTO SUMOylation
Authors: Xiaoming Liu, Jianye Liu, Wen Xiao, Qinghai Zeng, Hao Bo, Yuxing Zhu, Lian Gong, Dong He, Xiaowei Xing, Ruhong Li, Ming Zhou, Wei Xiong, Yanhong Zhou, Jianda Zhou, Xiaohui Li, Fei Guo, Canxia Xu, Xiong Chen, Xiaoyan Wang, Fen Wang, Qiang Wang, Ke Cao
Journal: Hepatology (2020)

Background and Aims Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase silent information regulator 1 (SIRT1) was discovered in HCC, and its presence is positively correlated with malignancy and metastasis. N 6 ‐methyladenosine (m 6 A) is the most prominent modification, but the exact mechanisms on how SIRT1 regulates m 6 A modification to induce hepatocarcinogenesis remain unclear. Approach and Results Here we demonstrate that SIRT1 exerts an oncogenic role by down‐regulating fat mass and obesity‐associated protein (FTO), which is an m 6 A demethylase. A crucial component of small ubiquitin‐related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)‐216 site that promotes FTO degradation. Moreover, Guanine nucleotide‐binding protein G (o) subunit alpha (GNAO1) is identified as m 6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m 6 A + GNAO1 and down‐regulates its mRNA expression. Conclusions We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m 6 A + of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a target of SIRT1 for therapeutic agents to treat HCC.
A modified CA-125 progression criterion in ovarian cancer (OC) patients (pts) receiving maintenance treatment following complete clinical response (cCR) to primary therapy
Authors: P. Liu, J. Moon, D. S. Alberts, B. J. Monk, M. Brady, M. Markman
Journal: Journal of Clinical Oncology (2006)

5080 Background: CA-125 progression criterion for OC by Vergote et al (JNCI 2000; 92:1534) has been widely adopted, with 35 U/ml as the most commonly used normal limit. Based on recent findings (ASCO Proceedings 2005, #5013), primary therapy cCR OC pts with nadir CA-125 ≤10 versus &gt;10–20 versus &gt;20–35 have different prognosis. We propose to modify the CA-125 progression criterion in this setting as follows: for pts with nadir ≤10, value ≥20 that is confirmed equals progression; for pts with nadir &gt;10, value ≥ 2×nadir that is confirmed equals progression. This new criterion essentially treats 10 U/ml as the normal limit. Methods: The proposed criterion combined with RECIST was tested on SWOG 9701/GOG 178 pts (n = 287) and compared to the existing criterion. All pts achieved cCR from primary therapy and entered the above maintenance trial with CA125 ≤35. Results: Of 91 pts last known to be progression-free by existing criterion, 10 (11%) new progressions were called. Available CA-125 values continued to rise in all except 1 case (1%). For 196 pts with known progressive disease, the progression date was unchanged by the new criterion in 42%, and was earlier by ≤60 days in 31%, 61–180 days in 16% and &gt;180 days in 11% (overall median days early = 56). Conclusions: In a series of 39 primary therapy cCR pts with CA-125 ≤35, Santillan et al found a progressive low-level increase in CA-125 to be strongly predictive of disease recurrence (JCO 2005; 23:9338). Similarly, initial testing of the proposed CA-125 criterion demonstrated a low false positive rate and early detection of disease progression &gt;2 months in approximately 30% of the same first line complete responders with progressive disease during or after maintenance treatment. Such pts can potentially benefit from starting alternative treatments early. The proposed criterion should be further investigated. No significant financial relationships to disclose.
Novel toxicity endpoint for dose-finding designs evaluating molecularly targeted agents (MTA).
Authors: Monia Ezzalfani, Sarah Zohar, Sumithra J. Mandrekar, Gilles Vassal, Marie-Cécile Le Deley
Journal: Journal of Clinical Oncology (2013)

2577 Background: The emergence of MTA in oncology has revolutionized the phase I design paradigm. The usual dose-limiting toxicity (DLT) endpoint is an oversimplification of the complex toxicity profile resulting in loss of information. Moreover, MTAs can induce less DLTs but more multiple moderate toxicities that may lead to dose reduction in long lasting treatment. We thus sought to develop a new toxicity endpoint, the Total Toxicity Profile (TTP), to incorporate multiple toxicities. Methods: We reanalysed the phase I trial that evaluated erlotinib (75, 100, 125, 150 mg/m 2 ) in children with brain stem glioma (NCT00418327). Only 2/21 patients experienced protocol defined DLTs, but multiple moderate toxicities were observed. The TTP endpoint is a weighted combination of all toxicities experienced by the patient (Euclidean norm of the weights), where the weights (ranging from 0 to 10) reflect the clinical importance of each grade and type of toxicity. The weights and the acceptable toxicity target (target TTP) were elicited from 3 clinicians using hypothetical patient cohorts with various toxicity outcomes. They were asked to make a decision of where the next cohort of patients would be treated: higher, lower or same dose level. The target TTP was defined as the mean of TTPs of the cohorts associated with a decision to repeat the dose. We used the TTP-driven Quasi-Likelihood Continual Reassessment Method (QL-CRM) to re-estimate the recommended dose. Results: Clinicians identified 5 main dermatological toxicity types possibly attributable to erlotinib. The consensus weights (table below) as well as the target TTP (set at 4.66) were easily obtained, confirming the feasibility of the process. The weights differed from the CTCAE grades, confirming the interest of the approach. The recommended dose based on the retrospective analysis of all grades toxicity was lower than that identified by the DLT-driven CRM (100 instead of 125mg/m 2 ). Conclusions: By neglecting multiple moderate toxicities, DLT-driven designs may over-estimate the recommended dose when investigating MTA. Our proposal is an appealing alternative design for MTA. [Table: see text]
Surgical skills video-based assessment tool for dermatology residents: A prospective pilot study
Authors: Pooja Chitgopeker, Kirk Sidey, Adam Aronson, Jina Chung, Gretchen Roth, Brian Swick, Hillary Johnson-Jahangir, Marta VanBeek, Karolyn A. Wanat, Nkanyezi Ferguson
Journal: Journal of the American Academy of Dermatology (2020)
Psychosocial impact of parental cancer on Moroccan children: Result of an exploratory study.
Authors: Saoussane Kharmoum, Yassir Sbitti, Mounia Amzerin, Mohamed Mesmoudi, Jinane Kharmoum, Hind Mrabti, Hassan Errihani
Journal: Journal of Clinical Oncology (2013)

e20624 Background: Cancer diagnosis and treatment of a parent has considerable impact on the lives of their children. The aim is to identify whether the diagnosis of parental cancer is associated with an increased risk of psychosocial difficulties amongst children and adolescents in Moroccan population. Methods: At the National Institute of Oncology in Rabat, from September to December 2009, 194 Children and adolescents whose parents were diagnosed with a cancer were interviewed. We used a questionnaire covering socio-epidemiological characteristics exploring the disease repercussions to their psychic. Results: There were 52% son and 48% daughters, aged between 10-15 years old (yo) in 26%, 15 - 20 yo in 44% and 20-22 yo in 30% of cases respectively. 67% were studying. Communication difficulties between parents with cancer and their children were observed in 100%. 20% of children were not aware of their parents' cancer. Only the children who were informed about their parents’ cancer were interviewed. All of them had traumatism, initial denial and anguish of loss of the parent. Guilt feelings were present in 90% of cases. 87% of them felt abandoned. The fear of having a stepfather or stepmother was observed in 41.2% of daughters and 12.8% of son, especially when the parent who had the cancer was the mother. Fear of inheriting cancer was seen in 80% of daughters whose mothers were suffering from breast cancer. The process of parentification was benign in 54% and destructive in 23% of cases. Enuresis was present in 30% of cases (20.6% in daughters 9.4% in son). Introversion was seen in 70% of cases. 30% of children noted a regression in their school abilities. Toxic habits appeared in 15% of cases. Conclusions: The result of this transversal study suggests that Moroccan children who have parents suffering from cancer, experiment an important distress. Unfortunately, the Moroccan parents do not use the services of psychological assistance. Thus, we should be vigilant to detect any potential psycho-pathologic disorders and to enable the family to live as normal as possible.
PERFORMANCE AND ACCURACY OF NATURAL LANGUAGE PROCESSING TO IDENTIFY DISEASE ETIOLOGY FROM NON-STRUCTURED CARDIAC MAGNETIC RESONANCE IMAGING ELECTRONIC MEDICAL RECORD REPORTS
Authors: Duygu Kocyigit, Alex Milinovich, Chan M. Lee, Micheal Silverman, Maleeha Ahmad, Mazen Hanna, Andrej Gabrovesk, Jian Jin, W.H. Wilson Tang, Richard A. Grimm, Leslie Cho, Brian P. Griffin, Scott D. Flamm, Deborah Kwon
Journal: Journal of the American College of Cardiology (2020)
RECURRENT REACTIVATED CHAGAS DISEASE MIMICKING ACUTE CELLULAR REJECTION IN A HEART TRANSPLANT PATIENT PREVIOUSLY TREATED WITH TRYPANOCIDAL THERAPY
Authors: Jonathan Nattiv, Grace Liu, Pooya Banankhah, Joseph Rahman, Kruti Pandya, Aaron M. Wolfson, Eugene Christopher DePasquale, Ajay Vaidya
Journal: Journal of the American College of Cardiology (2020)
Healthcare and homelessness: remember homeless migrants, especially refused asylum seekers
Authors: Rebecca G Macfarlane
Journal: BMJ (2020)

Bax and Middleton discuss healthcare for people experiencing homelessness.1 As is often the case in commentaries and strategies on homelessness, however, they do not mention migrant homelessness.2

Homeless people who are seeking protection from returning to their countries of origin face specific problems. They live not only in destitution but also in constant fear …
Interdomain spacing and spatial configuration drive the potency of IgG-[L]-scFv T cell bispecific antibodies
Authors: Brian H. Santich, Jeong A. Park, Hoa Tran, Hong-Fen Guo, Morgan Huse, Nai-Kong V. Cheung
Journal: Science Translational Medicine (2020)

T cell–bispecific antibody antitumor function is maximized through optimal interdomain spacing and dual cis-configurations.
Efficacy and toxicity of q 2 weeks docetaxel versus weekly versus q 3 weeks in metastatic castration-resistant prostate cancer (CRPC).
Authors: Akshiv Malhotra, Paula Rosenbaum, Bernard J. Poiesz
Journal: Journal of Clinical Oncology (2013)

e16087 Background: Standard treatment for metastatic CRPC is docetaxel 75 mg/m 2 q3weeks. Methods: We retrospectively studied patients treated with q 1, 2, or 3 weeks docetaxel regimens at 30, 60 and 75 mg/m 2 , respectively. The choice of regimen and duration of treatment was decided by their oncologist. Patients who had been in a clinical trial previously, or treated with any other chemotherapy before docetaxel were excluded. On this basis 41 patients were studied. Prostate specific antigen (PSA) was used as the primary method to assess response and progression. Response was a decline of &gt;/=50% from baseline value with no clinical or radiographic evidence of disease progression. For patients whose PSA did not decrease, progression was a &gt;/= 25% increase from baseline. If the PSA decreased without reaching response criteria, progression was a &gt;/= 25% increase from nadir. In those who responded, progression was a &gt;/= 50% increase from nadir. The increase had to be at least 5ng/ml. Toxicity was graded on the basis of CTCAE version 4.0. Response rate and toxicity in the 3 arms was compared using a two by two square t-test. Results: There were 12, 14 and 15 patients in the q1w, q2w and q3w arms, respectively. Response rates, mean progression free survival (PFS), median PFS, mean overall survival (OS), median OS, mean cumulative dose (MCD) and toxicity are shown in table 1. Toxicity was similar in the q1w, q2w and q3w arms, except grade 1/2 neuropathy was higher in the q2w arm vs. the q1w arm (p=0.005). Conclusions: The MCD, response rates, PFS and OS in the q1w and q3w arms were similar to previously published reports. Patients in the q2w arm received a statistically significant higher MCD. Our data suggest a better outcome in the q2w arm as compared to the q1w and q3w arms. However, given the small number of patients studied, the results are not statistically significant. Toxicity was similar save for grade1/2 neuropathy. [Table: see text]
Efficacy of a tetravalent dengue vaccine in healthy children aged 4–16 years: a randomised, placebo-controlled, phase 3 trial
Authors: Shibadas Biswal, Charissa Borja-Tabora, Luis Martinez Vargas, Hector Velásquez, Maria Theresa Alera, Victor Sierra, Edith Johana Rodriguez-Arenales, Delia Yu, V Pujitha Wickramasinghe, Edson Duarte Moreira, Asvini D Fernando, Dulanie Gunasekera, Pope Kosalaraksa, Felix Espinoza, Eduardo López-Medina, Lulu Bravo, Suely Tuboi, Yanee Hutagalung, Pedro Garbes, Ian Escudero, Martina Rauscher, Svetlana Bizjajeva, Inge LeFevre, Astrid Borkowski, Xavier Saez-Llorens, Derek Wallace, Alys Concepción, Ana Cecilia Villarreal, Asvini Fernando, Charissa Borja-Tabora, Chukiat Sirivichayakul, Delia Yu, Dulanie Gunasekera, Eduardo López-Medina, Edith Johanna Rodriguez-Arenales, Edson Duarte Moreira, Felix Espinoza, Hector Velásquez, Humberto Reynales, Kleber Luz, Jose Jimeno, LakKumar Fernando, Lulu Bravo, Luis Martinez Vargas, Luis Rivera, Maria Theresa Alera, Onanong Manacharoen, Pio Lopez, Pope Kosalaraksa, V. Pujitha Wickramasinghe, Reynaldo Dietze, Rivaldo Venâncio da Cunha, Veerachai Watanaveeradej, Victor Sierra, Xavier Saez-Llorens, Shibadas Biswal, Manja Brose, Martina Rauscher, Svetlana Bizjajeva, Inge LeFevre, Astrid Borkowski, Derek Wallace, Ian Escudero, Kelley Moss, Pedro Garbes, Seetha Meyer, Yanee Hutagalung, Suely Tuboi, Vianney Tricou
Journal: The Lancet (2020)
Trastuzumab and vinorelbine or taxane chemotherapy for HER2+ metastatic breast cancer: The TRAVIOTA study
Authors: H. J. Burstein, A. Keshaviah, A. Baron, R. Hart, R. Lambert-Falls, P. K. Marcom, R. Gelman, E. P. Winer
Journal: Journal of Clinical Oncology (2006)

650 Background: The optimal trastuzumab/chemotherapy regimen for advanced breast cancer is not known. We performed a multicenter, randomized clinical trial to compare TRastuzumab And VInorebline Or TAxane (TRAVIOTA) chemo- and bio-therapy combination treatment given on a weekly schedule for HER2+ metastatic breast cancer. Patients and Methods: Eligible patients had stage IV breast cancer, measurable disease (by RECIST criteria), HER2+ tumors (IHC 3+ or FISH+), no prior chemotherapy or trastuzumab for advanced breast cancer, and LVEF &gt; 50%. Patients were randomized 1:1 to trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter) with either weekly vinorelbine (25 mg/m 2 ) or weekly taxane (paclitaxel 80 mg/m 2 or docetaxel 35 mg/m 2 , selected by the treating investigator). The primary endpoint was response rate. The study opened in August 2001 and planned to accrue 250 patients. It was closed in December 2003 having accrued only 85 patients. Results are presented for the 81 patients who received any protocol-based therapy. Results: Patients receiving trastuzumab and vinorelbine tended to have higher response rates and TTP than those assigned trastuzumab and taxane therapy but the results were not statistically significant (see Table ). Vinorelbine therapy was associated with more frequent grade 3 or 4 hematological toxicity and dose delay because of myelosuppression. Other toxicities generally reflected the known side effects of the chemotherapy agents. Conclusions: The TRAVIOTA study suggests at least comparable clinical activity of trastuzumab with vinorelbine as with weekly taxane chemotherapy in HER2+ metastatic breast cancer, with side effect profiles consistent with previous experience with these regimens. [Table: see text] [Table: see text]
LONG-TERM OUTCOMES AFTER SURGICAL CORRECTION OF TETRALOGY OF FALLOT: VALVE-SPARING REPAIR DECREASES RE-INTERVENTION AND OVERALL BURDEN OF RESIDUAL LESIONS COMPARED TO TRANSANNULAR PATCHES
Authors: Samuel Blais, Ariane Marelli, Alain Vanasse, Christian Drolet, Adrian Dancea, Nagib Dahdah, Frederic Dallaire
Journal: Journal of the American College of Cardiology (2020)
Alterations of natural killer cell receptors as biomarkers associated with the severity of the disease in prostate cancer.
Authors: Christine Pasero, Gwenaelle Gravis, Palma Rocchi, Sylvaine Just-Landi, Philippe Livrati, Jeanne Thomassin, Serge Brunelle, Naji Salem, Jochen Walz, Daniel Olive
Journal: Journal of Clinical Oncology (2012)

e15155 Background: Recently, therapeutic vaccines and monoclonal antibody-based therapies have been investigated as promising new treatments against prostate cancer (PC). Natural killer (NK) cells which have anti-tumoral activity thus represent promising candidates for immunotherapy. Our group have reported major impairments of NK in acute myeloid leukemia and recently in metastatic breast cancer. The aim of this work was to evaluate the phenotype and function of NK cells in patients with localized and metastatic PC to determine their role in disease progression. Methods: Activating and inhibitory receptors were analyzed in peripheral NK cells from 14 patients with localized PC, 33 with metastatic disease and 30 healthy donors. NK function was evaluated by measuring CD107 degranulation. Results: The ratio mean fluorescence intensity RMFI (MFI receptor/MFI control isotype) of the activating receptor NKp30 was significantly lower in patients (7.30 +/- 0.68, p=0.0059) than in HD (10.99 +/- 1.34), whereas NKp46 was lower in the metastatic patients only (11.76 +/- 1.18) compared to the localized cases (21.86 +/- 4.25) and HD (19.13 +/- 2.39). The RMFI of 2B4 (47.14 +/- 7.99), the percentage of positive cells for the inhibitory receptor ILT2 (49.34 +/- 3.90, p=0.0003) and the maturation marker CD57 (41.13 +/- 4.69, p=0.0014) were significantly upregulated in patients compared with HD (2B4 23.09 +/- 4.74, ILT2 20.65 +/- 3.09, CD57 21.36 +/- 3.07), with a more pronounced increase in the metastatic groups. The RMFI of other receptors such as NKG2D or CD94 does not differ. NK cells from patients were significantly less effective (17.90% +/- 1.48, p&lt;0.0001) than NK from HD (30.31% +/- 2.70) to degranulate against the K562 target or prostate tumor cell lines. Conclusions: We observed an altered phenotype of NK cells in PC, correlated with decreased NK cell function, with alterations more pronounced during metastatic progression. Prostate tumor cells could have the ability to impair NK cell visibility through the modulation of their receptors and consequently decrease their cytotoxic function. This highlights the possibility of restoring NK cells cytotoxicity as a future therapy against PC.
ASSOCIATION OF CORONARY ARTERY CALCIUM AND ABDOMINAL AORTA CALCIUM WITH INCIDENT FATAL AND NON-FATAL CARDIOVASCULAR DISEASE EVENTS: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS STUDY
Authors: Paul Jurgens, John Jeffrey Carr, James Terry, Jamal S. Rana, David R. Jacobs, Daniel Duprez
Journal: Journal of the American College of Cardiology (2020)
Impact of the new American College of Cardiology/American Heart Association definition of hypertension on atherosclerotic vascular events in systemic lupus erythematosus
Authors: Konstantinos Tselios, Dafna D Gladman, Jiandong Su, Murray Urowitz
Journal: Annals of the Rheumatic Diseases (2020)

Background The 2017 American College of Cardiology/American Heart Association guidelines defined hypertension at ≥130/80 mm Hg. Studies on patients with connective tissue diseases were not considered. Our aim was to assess the impact of this definition on atherosclerotic vascular events (AVEs) in systemic lupus erythematosus. Patients methods Individuals from the Toronto Lupus Clinic with at least 2 years of follow-up and no prior AVE were divided in three groups according to their mean blood pressure (BP) over that period (≥140/90 mm Hg, 130-139/80-89 mm Hg and &lt;130/80 mm Hg). They were followed until the first occurrence of an AVE (fatal or non-fatal coronary artery disease, cerebrovascular event and peripheral vascular disease) or last visit. Groups were compared as per the baseline atherosclerotic risk factors. A multivariable time-dependent analysis was performed to adjust for the presence of other risk factors. Results Of 1532 patients satisfying the inclusion criteria, 155 (10.1%) had a BP ≥140/90 mm Hg, 316 (20.6%) 130–139/80–89 mm Hg and 1061 (69.3%) were normotensives. After a mean follow-up of 10.8 years, 124 AVEs were documented. The incidence rates were 18.9, 11.5 and 4.5 per 1000 patient-years for the three groups, respectively (p=0.0007 between the 130–139/80–89 mm Hg group and the normotensives). A mean BP of 130–139/80–89 mm Hg over the first 2 years was independently associated with the occurrence of AVEs (HR 1.73, 95% CI 1.13 to 2.65, p=0.011). Conclusion Patients with lupus with a sustained mean BP of 130–139/80–89 mm Hg over 2 years had a significantly higher incidence of AVEs compared with normotensive individuals. This BP level should be the target for antihypertensive therapy to minimise their cardiovascular risk.
RELATIONSHIP BETWEEN HIGH-SENSITIVITY TROPONIN, PERFUSION ABNORMALITIES, AND CORONARY FLOW RESERVE IN ACUTE CORONARY SYNDROMES
Authors: Jacob R. Nelson, Ryan E. Cooney, Justin A. Pieper, Vaiibhav N. Patel, Sylvia G. Escolero, Adam B. Stein, Richard L. Weinberg, Venkatesh L. Murthy
Journal: Journal of the American College of Cardiology (2020)
TACE plus sorafenib for the treatment of advanced hepatocellular carcinoma.
Authors: Vijay Sukhdeo Palwe, Rajnish Vasant Nagarkar
Journal: Journal of Clinical Oncology (2013)

e15178 Background: Hepatocellular carcinoma (HCC) is considered to be a hypervascular tumor. Therefore, Trans Arterial Chemo Embolization (TACE) and inhibition of angiogenesis appear rational treatment strategies for those patients who have localised disease not amenable to surgical resection. TACE causes increased hypoxia leading to an up regulation in hypoxia inducible factor-1α (HIF-1α), which in turn up regulates vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor, and increases tumor angiogenesis. The present study investigated for the combination of TACE and Sorafenib, a multikinase inhibitor with anti-angiogenic activities approved for the treatment of HCC. Methods: Patients included histologically confirmed, unresectable hepatocellular carcinoma beyond Milan criteria, no extrahepatic spread, Child Pugh score ≤8, ECOG PS 0-2, platelets &gt;100K/µl, and bilirubin &lt;2.5 mg/dl. We present our experience with 42 patients of HCC treated with Trans Arterial Chemo Embolisation (TACE) with Cisplatin, Lipodol and PVA of which 14 pts received TACE along with Sorafenib. Results: Between May 2007 to Jan 2013, 42 patients were enrolled. Patients received a mean of 1.45 TACE interventions (range 1-4). The longest survival was 53 months after 1 st TACE and median overall survival was 443 days. Grade 3 and 4 toxicities were noted in 18% and 7% of patients. Conclusions: TACE is a very good method for palliation of unresectable hepatocellular carcinoma (HCC) with improved survival and quality of life.The combination of TACE with sorafenib is tolerable for most patients and associated with a promising rate of radiographic response and OS.
ECHOCARDIOGRAPHIC/CATHETERIZATION DISCORDANCE IN LOW VS. HIGH GRADIENT AND LOW VS. NORMAL FLOW AORTIC STENOSIS
Authors: Ramy Mando, George S. Hanzel, Aimee Hite, Priscilla Sigua-Arce, Michael Gallagher, Wei Lau, Philippe Pibarot, Francis Shannon, Amr E. Abbas
Journal: Journal of the American College of Cardiology (2020)