Expert Review of Precision Medicine and Drug Development最新文献

{"title":"Slotting metabolomics into routine precision medicine","authors":"M. Mussap, A. Noto, C. Piras, L. Atzori, V. Fanos","doi":"10.1080/23808993.2021.1911639","DOIUrl":"https://doi.org/10.1080/23808993.2021.1911639","url":null,"abstract":"ABSTRACT Introduction Despite an impressive amount of metabolomics studies in animal models and humans, most findings have not yet translated into the clinical setting, and the road ahead remains still long. Areas covered This review provides the most challenging applications of clinical metabolomics testing in human health and disease. Personalized clinical metabolomics testing is incorporated within the test panel to diagnose inborn errors of metabolism, optimize dietary regimens, and discover and develop new drugs. The potential routine utilization of metabolomics in precision medicine has been revised in cancer and nutrition. The association between metabolomics with artificial intelligence and machine learning may open emerging perspectives for more effective utilization and timely introduction of clinical metabolomics testing in the care of patients with acute and chronic diseases. Expert opinion In conclusion, slotting metabolomics into routine precision medicine implies the direct relationship between metabolomic results and clinical decision-making, similarly to any other clinical test result, as well as it requires the application of clinical laboratory standards, protocols, training, the oversight to a global biochemical profiling technology, and the availability of metabolic profiles from reference populations, defining cutoff values and decision levels.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1911639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42840621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ivosidenib in IDH-mutant cholangiocarcinoma: where do we stand?","authors":"A. Rizzo, A. Ricci, G. Brandi","doi":"10.1080/23808993.2021.1915126","DOIUrl":"https://doi.org/10.1080/23808993.2021.1915126","url":null,"abstract":"ABSTRACT Introduction: Cholangiocarcinomas (CCAs) are rare and heterogeneous malignancies associated with poor prognosis, with most of the patients presenting with advanced disease at diagnosis. The recent advent of molecular profiling has led to the identification of several druggable genetic aberrations, and among these, there is an increasing interest in isocitrate dehydrogenase-1 (IDH-1) mutations, with the IDH-1 inhibitor ivosidenib that has reported interesting results in advanced CCA patients. Areas covered: Herein, we will critically discuss the current state of the art of ivosidenib in IDH-mutant CCA, especially focusing on efficacy and safety results of recent trials assessing this IDH-1 inhibitor. Expert opinion: According to the results of phase I studies and the recently published ClarIDHy phase III trial, the IDH-1 inhibitor ivosidenib seems to be associated with a manageable safety profile and interesting antitumor efficacy. In particular, the ClarIDHy showed that ivosidenib treatment reported improved progression-free survival (PFS) compared to placebo in previously treated patients, with median PFS of 2.7 and 1.4 months, respectively. However, several questions remain unanswered and the effective impact of ivosidenib in IDH-mutant CCA remains open.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1915126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44246783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dacomitinib as first-line treatment for EGFR mutation-positive non-small cell lung cancer","authors":"T. Reungwetwattana, N. Rohatgi, T. Mok, K. Prabhash","doi":"10.1080/23808993.2021.1909420","DOIUrl":"https://doi.org/10.1080/23808993.2021.1909420","url":null,"abstract":"ABSTRACT Introduction: Dacomitinib is a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). Recent results from ARCHER 1050, the first randomized, open-label, Phase 3 trial of a second-generation vs. a first-generation EGFR TKI, showed that dacomitinib improves progression-free survival and overall survival compared with gefitinib as a first-line treatment in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). Areas covered: We review the efficacy and safety of dacomitinib as a first-line treatment of EGFR mutation-positive NSCLC, including the management of toxicity, and evaluate the activity of dacomitinib against brain metastases. Additionally, the optimal treatment sequence given EGFR TKI choice, resistance mechanisms, activity against rare mutations, and real-world dosing is discussed. Expert opinion: The introduction of EGFR TKIs has changed the treatment strategy for patients with EGFR mutation-positive NSCLC. The second- and third-generation EGFR TKIs are the result of research elucidating mechanisms of resistance to first-generation EGFR TKIs. There is now more than one treatment option for patients with EGFR mutation-positive advanced NSCLC that improves survival, highlighting the need to more clearly understand the use of the right drug for the right person at the right time and how the appropriate treatment sequence may provide optimal outcomes for these patients.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1909420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45533208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized patient care with aggressive hematological malignancies in non-responders to first-line treatment","authors":"K. Miura, N. Iriyama, Y. Hatta, M. Takei","doi":"10.1080/23808993.2021.1903314","DOIUrl":"https://doi.org/10.1080/23808993.2021.1903314","url":null,"abstract":"ABSTRACT Introduction Whereas most patients with aggressive hematological malignancies can achieve disease remission after receiving current standard first-line chemotherapies, the prognosis of those with primary refractory disease remains poor. Conventional salvage chemotherapies are usually unsuccessful, but significant advances have been achieved in precision medicine for these patients in recent years. Areas covered This article presents a comprehensive review of current personalized care for patients with primary refractory aggressive hematological malignancies, focusing on acute leukemias and aggressive non-Hodgkin lymphomas. Expert opinions Salvage treatment for refractory acute myeloid leukemia (AML) should be personalized by the FMS-like tyrosine kinase 3 (FLT3) mutation status. Additionally, treatment for isocitrate dehydrogenase 1 or 2 (IDH1/2)-mutated refractory AML can be specified. Inotuzumab ozogamicin and blinatumomab are essential drugs for refractory B-cell acute lymphoblastic leukemia. These antibodies can be selected based on the disease status, such as measurable residual disease. For refractory diffuse large B-cell lymphoma, treatment options are different according to the cell-of-origin. Finally, accurate pathological phenotyping is an essential first step to optimize refractory peripheral T-cell lymphoma treatment. Although novel personalized approaches have improved the clinical outcomes of these patients, consolidation with hematopoietic stem cell transplantation has a vital role in most cases.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1903314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42194701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting and targeting NTRK gene fusions in cholangiocarcinoma: news and perspectives","authors":"A. Rizzo, A. Ricci, G. Brandi","doi":"10.1080/23808993.2021.1910023","DOIUrl":"https://doi.org/10.1080/23808993.2021.1910023","url":null,"abstract":"Cholangiocarcinomas (CCAs) are rare and aggressive tumors accounting for less than 1% of all malignancies worldwide and approximately the 10–15% of all primary liver cancers [1]. Unfortunately, advanced CCA carries a poor prognosis and the benefit provided from systemic treatments is modest [2]. In the last decade, CCA has emerged as a disease entity presenting several potentially druggable mutations, and the advent of next-generation sequencing (NGS) has led to a new era in CCA management [3]. In fact, a number of potential therapeutic targets have been described, including fibroblast growth factor receptor (FGFR) fusions, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations, and BRAF mutations [4]. In particular, some molecularly targeted treatments have been shown to improve progression-free survival (PFS) and overall survival (OS), with these therapies that add to the armamentarium of therapeutic options currently available for CCA patients [5]. Few data are available on the putative role of other molecular aberrations which have already provided interesting results in other solid tumors, including neurotrophic tropomyosin receptor kinase (NTRK) fusions. Several genes have been suggested to represent fusions partner of NTRK, including the transcription factor ETV6 and BCAN. Notably enough, NTRK1, NTRK2, and NTRK3 gene fusions have been suggested to act as oncogenic drivers in a range of solid tumors, including gastrointestinal cancers such as CCA [6]; these fusions have been highlighted in around 1% of all pediatric and adult malignancies, with recent studies suggesting their role as promising therapeutic targets for anticancer treatment [7]. In particular, the frequency of these fusions seems to vary from less than 1% in cancer types such as colorectal, lung, pancreatic, breast cancers, melanoma and other hematological and solid tumors, up to 25% in tumors including thyroid, spitzoid, and gastrointestinal stromal tumors, to more than 90% in rare cancer types such as secretory breast carcinoma, mammary analogue secretory carcinoma, congenital infantile fibrosarcoma, and congenital mesoblastic nephroma [6–8]. Typically, these molecular aberrations occur following the fusion of the C-terminal tyrosine kinase with a N-terminal fusion partner, leading to ligand-independent phosphorylation. Consequently, several pathways are activated, resulting in cellular growth and increase proliferation [8]. In recent years, several methods have been used to diagnose NTRK fusions. Among these, fluorescent in situ hybridization reverse-transcriptase PCR, and NGS; in addition, beyond tumor-based approaches, NTRK fusions can be potentially detected also through plasma-based cell-free DNA testing. As regards biliopancreatic malignancies, in a report presented at ESMO World Congress on Gastrointestinal Cancer 2020, Demols and colleagues explored the prevalence of NTRK gene fusions in 149 CCAs and pancreatic adenocarcinomas through the use of different techniques [9","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1910023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49594347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future perspective: precision medicine to improve treatment results in the settings of allogenic stem cell transplantation for acute myelogenous leukemia","authors":"H. Reikvam, Silje Johansen, C. Koenecke","doi":"10.1080/23808993.2021.1897464","DOIUrl":"https://doi.org/10.1080/23808993.2021.1897464","url":null,"abstract":"Acute myelogenous leukemia (AML) is a malignant disease of the blood and bone marrow, characterized by proliferation, lack of apoptosis, and block in differentiation of leukemic blasts [1]. These immature cells compromise normal bone marrow function, resulting in severe bone marrow failure, with anemia, thrombocytopenia, and granulocytopenia [1]. The disease has a highly malignant and aggressive course, and without treatment the patients will usually die within weeks to months. Except for promyelocytic AML, the only possibility for a longtime cure is intensive chemotherapy, and in high-risk patients combined with allogenic hematopoietic stem cell transplantation (allo-HSCT) [1,2]. Allo-HSCT is the most potent antileukemic treatment, by utilization of the immune mediated graft versus leukemia (GVL) effect derived from immune competent donor cells. However, alloHSCT is associated with a high degree of morbidity and mortality, especially due to severe graft versus host disease (GVHD). Furthermore, the occurrence of relapse of the disease even after transplantation is still prevalent, especially for patients present with genetic markers associated with inferior prognosis at the time of diagnosis [2,3]. In the following, we will discuss the current and future aspects of allo-HSCT in the setting of AML, untangling the possibilities to optimize the treatment approaches based on precision medicine.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1897464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46736678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is there a worthwhile value in personalizing radiation therapy for breast cancer patients? Time for a new paradigm in the older adult population","authors":"V. Salvestrini, M. Mariotti, M. Banini, C. Becherini, L. Visani, V. Scotti, I. Desideri, L. Livi, I. Meattini","doi":"10.1080/23808993.2021.1897463","DOIUrl":"https://doi.org/10.1080/23808993.2021.1897463","url":null,"abstract":"Over the past few decades, the world population has increased dramatically including a large number of elderly people. This explosion in population aging comes with a rising number of older adults who have potential multiple comorbidities and chronic illnesses, including cancer. Indeed, the prevalence of multimorbidity in older patients ranges from 55 to 98% [1]. Older cancer population represents a major public health issue and tailoring of treatment for these patients represents a paradigmatic example of treatment optimization. The number of elderly living with cancer disease is high due to the possibility of early diagnosis in the last years and the recent advances in cancer treatment strategy. Breast cancer is the most common malignancy among women, and it is estimated that around 20% of newly diagnosed patients will be aged more than 70 years. It has been widely reported that breast cancer-related mortality increases with age, regardless of disease stage. A specific management for this elder population is not defined because clinical trials usually do not include this subset of patients. The International Society of Geriatric Oncology in conjunction with the European Society of Breast Cancer Specialists recommended that any decision to treat cancer in the older adult woman with cancer must be individual and based on specific evaluation of the elderly woman and cancer. Physiological age, life expectancy, treatment tolerance, patient preference, potential barriers to the proposed treatments, competitive causes of mortality, and broad geriatric evaluation must be deeply considered [2]. Many investigators are recently focusing their efforts on optimization of cancer treatment strategy in older patients. With this regard, the ongoing COVID-19 pandemic has reinforced the urgent need also to minimize exposure of our patients to virus without compromising oncological outcome [3]. Currently, the standard of care for most patients affected by early invasive breast cancer still remains whole breast irradiation (WBI) after breastconserving surgery (BCS), since WBI showed a decrease in first recurrence also in low-risk elderly patients, with a lower absolute 10-year risk reduction of any locoregional or distant relapse [4,5]. The randomized CALGB 9343 trial evaluating 636 patients aged more than 70 years affected by invasive breast cancer treated with BCS and adjuvant tamoxifen with or without postoperative WBI demonstrated a significant decrease in the local relapse rate in favor of the group of patients receiving postoperative radiation therapy (RT) [6]. Shorter courses using moderate hypofractionated schedules should currently represent the standard of care for WBI, since a level-1 evidence exists on equivalent local control and late toxicity rates [7]. A brand-new approach to optimization of RT is the ultra-hypofractionated schedule given over just oneweek, feasible option in selected low-risk patients. The FAST Forward trial compared 26 Gy or 27 Gy ","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1897463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44763778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The value of genotyping patients for the presence of HLA-C in the personalized treatment of psoriasis","authors":"M. Galluzzo, V. Manfreda, Alessandra Petruzzellis, L. Bianchi, M. Talamonti","doi":"10.1080/23808993.2021.1878022","DOIUrl":"https://doi.org/10.1080/23808993.2021.1878022","url":null,"abstract":"ABSTRACT Introduction: Some cases of psoriasis still unfortunately do not respond, do not respond adequately or lose response to biotechnological therapies available to help control psoriasis. The common solution is to switch to other biological drugs, with a corresponding increase in pharmaceutical costs. Genetic polymorphisms have also recently been shown to influence the response of psoriasis patients to biological drugs. Areas covered: The PubMed databases were searched for articles regarding HLA-C and response to biological therapies. Additional publications were collected from references identified in articles and related citations in PubMed. Expert opinion: The clinical response to a specific biological drug may be correlated with genetic variations. Since genetic variations lead to different molecular pathways, identifying genetic markers in psoriasis patients that can predict a response to biologics is of fundamental importance. In this sense, recent evidences published in literature, suggest that HLA-C*06:02 typifies a molecularly different subtype of psoriasis whose maintenance and amplification are strongly controlled by IL12/23 signaling and therefore more responsive to the selective blockade of this signaling pathway, and it is not yet possible to exclude that this allele also influences the response to the most recent anti-IL-17 drugs.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1878022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41851470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of primary renal cell carcinoma to determine treatment approaches","authors":"V. Stühler, S. Rausch, A. Stenzl, J. Bedke","doi":"10.1080/23808993.2021.1874822","DOIUrl":"https://doi.org/10.1080/23808993.2021.1874822","url":null,"abstract":"ABSTRACT Introduction To date, there is no validated predictive biomarker available that guides treatment selection between an immune-based or an anti-VEGF-based regimen in patients with metastatic renal cell carcinoma (mRCC). Here, valid biomarkers could increase the benefit of therapy and thereby safe unnecessary toxicity. Recently, phase II and III clinical trials have shown a correlation between molecular clusters and responses to targeted therapy with tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) or as combination of both in patients with clear-cell mRCC. Areas covered This review discusses recent advances in the discovery of predictive biomarkers, highlighting the growing role of genetic analysis for treatment selection and its potential impact on precision medicine in mRCC. In this context, we extensively analyzed the available literature from Pubmed’s archives on this topic. Expert opinion Molecular subclassification which predicts responses to TKI, or ICI therapy is an exciting step toward personalized medicine in mRCC, but this still requires validation. However, intratumoral heterogeneity in relationship to the predictive power of molecular analysis of the primary tumor and circulating tumor DNA is challenging and requires further analysis.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1874822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44334175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial independent validation of a genomic heart failure survival prediction algorithm","authors":"G. Bondar, I. Silacheva, T. Bao, S. Deshmukh, N. Kulkarni, T. Nakade, T. Grogan, D. Elashoff, M. Deng","doi":"10.1080/23808993.2021.1882847","DOIUrl":"https://doi.org/10.1080/23808993.2021.1882847","url":null,"abstract":"ABSTRACT Background Biological determinants of survival in advanced heart failure (AdHF) are linked to systems biological properties of disease severity including age, comorbidities, and frailty. We hypothesize that an algorithm trained to predict the survival in severely ill mechanical circulatory support (MCS) AdHF patients can be independently validated in AdHF-cohorts of varying severity undergoing etiology-specific interventions including heart transplantation (HTx), transcatheter aortic valve replacement (TAVR), and continued guidelines directed medical therapy (GDMT). Research Design & Methods We independently validated our previously published multi-dimensional algorithm, based on 4 clinical parameters and 12 transcriptomic biomarkers, and trained in AdHF patients undergoing MCS-surgery (n = 29), in AdHF patients undergoing TAVR, HTx, MCS, and GDMT-interventions (n = 48). Results In the independent validation cohort, our algorithm demonstrated 71% sensitivity, 90% specificity, 56% positive predictive value, and 95% negative predictive value, allowing for construction of a prototype survival prediction score. While prediction of 1-year survival using clinical parameters alone achieved an AUC = 0.69, addition of 12 differentially expressed genes to the clinical model improved the AUC = 0.90. Conclusions Our initial validation data suggests that the proposed multi-dimensional algorithm is applicable across various AdHF-risk groups and Surgical-Interventional Therapies (S/IT), increasing survival prediction accuracy compared to clinical data alone and warranting further study in larger cohorts.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1882847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46192690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}