Expert Review of Precision Medicine and Drug Development最新文献

{"title":"Guiding treatment selection with immunotherapy compared to targeted therapy agents in patients with metastatic kidney cancer","authors":"M. Rosellini, Andrea Marchetti, Elisa Tassinari, Giacomo Nuvola, Alessandro Rizzo, M. Santoni, V. Mollica, F. Massari","doi":"10.1080/23808993.2022.2156786","DOIUrl":"https://doi.org/10.1080/23808993.2022.2156786","url":null,"abstract":"ABSTRACT Introduction Kidney cancer treatment has been first revolutionized by the advent of targeted therapies (TKIs and mTOR inhibitors) and then by the approval of immunotherapy and immunocombinations. Whereas immunocombinations represent the most used first-line therapy in intermediate/poor risk patients with clear-cell tumors, cabozantinib and nivolumab are both effective compounds at progression, and till today it is not totally clear what to prefer. No standard treatments are approved in post-second-line setting and in non-clear carcinoma. Areas covered The aim of this review is to summarize the main evidence supporting the use of targeted therapies and immunotherapy, in every setting of clear-cell and non-clear cell renal cell carcinoma, while also providing an insight into promising ongoing and upcoming trials. Expert opinion We speculate on what could help physicians in guiding the therapeutic decision-making process in advanced kidney cancer. International mRCC Database Consortium criteria are still recommended for the choice of primary treatments, despite presenting several limitations in the current immunotherapy-era. Multiple predictors of response to immunotherapy or targeted therapies are emerging but validated biomarkers are awaited. Furthermore, we discuss therapeutic sequences in kidney cancer, guessing how physicians may prefer immunotherapy or TKI as later-line strategies on the basis of previous treatments. Summary The therapeutic armamentarium for advanced clear cell RCC has been revolutionized by the approval of novel immune-based combinations in the last decade. Anti-VEGF TKI as a first-line treatment still represents a valid choice in good risk patients or in subjects who are not able to receive immunocombinations. Several compounds are available in second-line after TKI monotherapy, but no specific indications are available after immunocombinations. Cabozantinib seems to be the option with the strongest rationale and the most widely investigated, but the issue is still open. No standard therapy is approved for non-clear cell patients, although cabozantinib is emerging as the most promising option. Data regarding immunotherapy are still awaited. Prospective and molecular-driven trials enrolling non-clear patients are required. No predictive biomarkers have been validated to guide physician’s treatment choice, toward TKIs or either immunotherapic compounds. Future efforts are necessary to improve the predictive role of novel emerging biomarkers in both clear cell and non-clear cell histologies, such as gene expression profiling and tumor microenvironment features.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44241389","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":"PD-L1 assessment in breast cancer immunotherapy: a critical overview","authors":"A. Ricci, Alessandro Rizzo, G. Palmiotti, G. Brandi","doi":"10.1080/23808993.2022.2094766","DOIUrl":"https://doi.org/10.1080/23808993.2022.2094766","url":null,"abstract":"The advent of immune checkpoint inhibitors (ICIs) has recently made a breakthrough in several hematological and solid tumors including, among others, non-small-cell lung cancer, renal cell carcinoma, melanoma, urothelial carcinoma, and hepatocellular carcinoma [1–3]. These agents are able to enhance antitumor activity, leading to an increase in the cytotoxicity of T cells and the blocking of downregulators of immunity such as programmed cell death protein 1 (PD-1) and its ligand PD-L1, cytotoxic T-lymphocyte antigen 4 (CTLA-4), and lymphocyte activating-3 (LAG-3) [4]. ICIs have also been recently assessed in breast cancer (BC), as monotherapy or in combination with other anticancer agents. First, monotherapy with ICIs has reported disappointing results in unselected triple-negative BC (TNBC), with approximately one-quarter of patients achieving response [5]; in fact, the KEYNOTE-086 and the KEYNOTE-119 trials evaluating pembrolizumab monotherapy highlighted response rates lower than 10%, and these findings have also been confirmed by clinical studies evaluating other immunotherapies, such as single-agent atezolizumab [6]. Thus, several combination treatments have been investigated, based on the synergistic effect of ICIs plus other anticancer agents with different mechanism of action. Among these combinatorial strategies, and following the results of landmark trials, chemoimmunotherapy has entered into clinical practice as new front-line treatment in TNBC patients with metastatic disease and PD-L1 overexpression or elevated combined positive score (CPS) [7]. Moreover, a large number of phase I to III clinical trials are assessing immunebased combinations, with these studies having the potential to further shape the direction of firstand later-line therapy in this patient population. However, a high unmet need in BC immunotherapy remains the lack of biomarkers predictive of response to ICIs. In fact, if PD-L1 is considered the most reliable predictor, its assessment presents several limitations, and it is far from being standardized [8]. The expression of PD-L1 is typically detected on tumor cells (TC) or immune cells (IC), and in recent years, PD-L1 assessment has emerged as an important predictive biomarker of response to immunotherapy in several tumor types (e.g. nonsmall-cell lung cancer, head and neck cancer, and gastric cancer) [9,10]. As regards BC, PD-L1 status has been associated with a prognostic value, and high PD-L1 expression seems to predict worse clinical outcomes in triple-negative BC patients [11]. PD-L1 has been validated as a predictor of response to chemoimmunotherapy in metastatic BC and has entered into everyday clinical practice, following the results of recently published IMpassion130 and KEYNOTE-355 phase III clinical trials [12,13]. The IMpassion130 compared chemoimmunotherapy with atezolizumab–nab-paclitaxel versus placebo plus nabpaclitaxel as front-line treatment in TNBC patients with metastatic disease [12]; the copri","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44040888","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":"Therapeutic potential of GABAA receptor subunit expression abnormalities in fragile X syndrome","authors":"Mathijs B. van der Lei, R. Kooy","doi":"10.1080/23808993.2021.2008168","DOIUrl":"https://doi.org/10.1080/23808993.2021.2008168","url":null,"abstract":"ABSTRACT Introduction Many studies have reported brain region and age-dependent alterations in the expression of several subunits of the GABAA receptor in Fmr1 KO mice. GABAA receptors are located synaptic and extrasynaptic with differential subunit compositions and characteristics. Interestingly, the activity of many subunits of the GABAA receptor is amendable by differential pharmacological treatment. Areas Covered The purpose of this review is to summarize the expression of GABAA receptor subunits in different brain regions of Fmr1 KO mice across different ages. The decreased expression of the synaptic α2 subunit in juvenile, and the decreased expression of the extrasynaptic δ subunit in both juvenile and adult Fmr1 KO mice, are among the most consistent abnormalities reported. Both subunits are suitable for treatment and currently available compounds are discussed in this review along with their therapeutic potential. Expert Opinion Pharmacological treatment targeting specific subunits of the GABAA receptor has shown selective improvements in fragile X syndrome. To our knowledge, combinatorial therapies targeting multiple subunits of the GABAA receptor have not been explored. We here argue that such a combination therapy could induce a synergistic effect to ameliorate the clinical symptoms of fragile X syndrome.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42488143","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":"Prediction and early diagnosis of immune-checkpoint inhibitor-induced inflammatory arthritis from molecular biomarkers – Where are we now?","authors":"Christopher Aboo, Tue Wenzel Krastrup, H. Tenstad, Jie Ren, S. A. Just, M. Ladekarl, A. Stensballe","doi":"10.1080/23808993.2022.2156785","DOIUrl":"https://doi.org/10.1080/23808993.2022.2156785","url":null,"abstract":"ABSTRACT Introduction Immune-checkpoint inhibitors (ICI) works by blocking inhibitory signals of T cells. This produces an effective anti-tumor response but can also cause immune-related adverse events (irAEs). Most irAEs are transient, but ICI-induced inflammatory arthritis (ICI-IIA) might become chronic and affect the quality-of-life, or even necessitate treatment discontinuation. However, there exist no tools to identify patients that are susceptible to develop ICI-IIA. Areas covered This non-systematic review briefly presents a sparse number of studies, that have tried to identify circulating biomarkers for early prediction of ICI-IIA. Challenges, recommendations, and possibilities related to biomarker discovery in the context of ICI-IIA are then covered. Expert opinion Improved diagnosis adapted from rheumatological settings is needed for future studies to avoid a major pitfall of bad endpoints. Synovial tissue biopsies, omics technologies and particularly integration of multiple omics data is useful when searching for biomarkers of ICI-IIA and can also help unravel underlying biological mechanisms. Future biomarkers could ultimately aid clinical decision-making and facilitate early prophylaxis, pave the way for new treatment or even translational models to study autoimmune arthritis.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45829306","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":"Accelerating precision ophthalmology: recent advances","authors":"Loay Rahman, Ammaarah Hafejee, Rajeevan Anantharanjit, Wei Wei, M. Cordeiro","doi":"10.1080/23808993.2022.2154146","DOIUrl":"https://doi.org/10.1080/23808993.2022.2154146","url":null,"abstract":"ABSTRACT Introduction The future of ophthalmology is precision medicine. With a growing incidence of lifestyle-associated ophthalmic disease such as diabetic retinopathy, the use of technology has the potential to overcome the burden on clinical specialists. Advances in precision medicine will help improve diagnosis and better triage those with higher clinical need to the appropriate experts, as well as providing a more tailored approach to treatment that could help transform patient management. Areas covered A detailed literature review was conducted using OVID Medline and PubMed databases to explore advances in precision medicine within the areas of retinal disease, glaucoma, cornea, cataracts and uveitis. Over the last three years [2019 – 2022] are explored, particularly discussing technological and genomic advances in screening, diagnosis, and management within these fields. Expert opinion Artificial intelligence and its subspecialty deep learning provide the most substantial ways in which diagnosis and management of ocular diseases can be further developed within the advancing field of precision medicine. Future challenges include optimal training sets for algorithms and further developing pharmacogenetics in more specialized areas.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46231060","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":"Predictors of response for hepatocellular carcinoma immunotherapy: is there anything on the horizon?","authors":"Alessandro Rizzo, A. Ricci","doi":"10.1080/23808993.2022.2075724","DOIUrl":"https://doi.org/10.1080/23808993.2022.2075724","url":null,"abstract":"ABSTRACT Introduction Hepatocellular carcinoma (HCC) remains an important cause of cancer-related death, representing the sixth most commonly diagnosed malignancy worldwide. Novel systemic treatment options have recently emerged for advanced diseases, including immune checkpoint inhibitors (ICIs), as monotherapy or in combination with other anticancer agents. However, several questions remain unanswered, including the identification of predictors of response to immunotherapy in this setting. Areas Covered Herein, we will provide a critical overview of current knowledge regarding predictive biomarkers of response to ICIs in HCC patients. A literature search was conducted in December 2021 of PubMed/Medline, Cochrane library, and Scopus databases. Expert Opinion Several critical issues regarding the role of ICIs in advanced HCC remain unsolved, with the identification of predictive biomarkers representing an unmet need. Further efforts aimed at identifying reliable predictors and the effective role of PD-L1 status, TMB, MSI, and other biomarkers are warranted.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42272331","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":"Non-alcoholic fatty liver disease - opportunities for personalized treatment and drug development","authors":"Aurino M. Kemas, Sonia Youhanna, V. Lauschke","doi":"10.1080/23808993.2022.2053285","DOIUrl":"https://doi.org/10.1080/23808993.2022.2053285","url":null,"abstract":"ABSTRACT Introduction Non-alcoholic fatty liver disease (NAFLD) constitutes a highly prevalent liver disorder whose rise in prevalence is closely connected to the growing rates of obesity, dyslipidemia, and type 2 diabetes. Importantly, kinetics and likelihood of NAFLD onset and its progression to non-alcoholic steatohepatitis (NASH) and fibrosis differs considerably between individuals. In recent years, the understanding of NAFLD pathogenesis has increased substantially and a multitude of factors, genetic predispositions, molecular signatures or NAFLD-related liver injury and comorbidities have been identified. Areas Covered This article summarizes inter-individual differences in NAFLD, including genetic variations, epigenetic and metabolic alterations and differences in the microbiome. We also discuss how these features might be leveraged for treatment personalization. Expert opinion The complexity and heterogeneity of NAFLD provides considerable challenges for drug developers and has resulted in numerous costly project failures. We expect that increased knowledge and appreciation of patient-specific factors will facilitate better patient stratification and identification of those individuals that benefit most from a given therapeutic strategy. Furthermore, we anticipate that pathophysiologically relevant in vivo and ex vivo disease models as well as large-scale chemogenomic projects hold promise to drastically improve NAFLD drug development to complement lifestyle and surgical interventions with pharmacological approaches.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43318378","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":"Ramucirumab or merestinib in biliary tract cancer: new combinations, old mistakes?","authors":"Alessandro Rizzo, Alessandro Di Federico, G. Palmiotti, G. Brandi","doi":"10.1080/23808993.2022.2095903","DOIUrl":"https://doi.org/10.1080/23808993.2022.2095903","url":null,"abstract":"Biliary tract cancers (BTCs) encompass a heterogeneous group of rare malignancies accounting for approximately the 10–15% of primary liver cancers [1]. Most of these hepatobiliary tumors are diagnosed at a metastatic stage, and more than a decade after the publication of the ABC-02 trial establishing gemcitabine plus cisplatin as front-line standard for metastatic BTC, the prognosis of this patient population remains grim [2]. BTC include intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder carcinoma (GBC); recent years have registered that the incidence of BTC has progressively increased worldwide, and a proportion of cases ranging from 60% to 70% is diagnosed with advanced stage – locally advanced or metastatic disease. Surgical resection represents the only potentially curative treatment option for BTC patients, but even following radical surgery with curative intent, 5-year overall survival (OS) is only 20–35%. Systemic treatment options for BTC are limited, and more than a decade after the practice-changing ABC-02 phase III trial, cisplatin-gemcitabine remains the standard first-line therapy for patients with metastatic disease. Recent years have witnessed the advent of molecular profiling in this setting, and new techniques and technologies have led to the identification of several molecular alterations in BTC [3]. Thus, precision oncology approaches have been widely evaluated and are currently under assessment in BTC patients, as shown by the recent development of a wide range of agents targeting Fibroblast Growth Factor Receptor (FGFR) 2, Isocitrate Dehydrogenase 1 (IDH-1), and BRAF [4–6]. However, a number of molecularly targeted therapies, including antiangiogenic agents, have shown limited efficacy in BTC, and several questions regarding the effective role of these anticancer treatments remain unanswered. A recently published phase 2 trial has evaluated the addition of ramucirumab or merestinib to first-line cisplatin-gemcitabine, reporting no improvement of progression-free survival (PFS) in patients with locally advanced or metastatic BTC [7]. Ramucirumab is a fully humanized monoclonal antibody with a high binding affinity for the extracellular domain of VEGFR-2, with preclinical studies showing that targeting of this VEGF family receptor was associated with inhibition of VEGF-mediated signaling, proliferation and migration of human endothelial cells, and antitumor activity in animal models. Conversely, merestinib is a small molecule inhibitor of MET and several other receptor tyrosine kinases such as MST1R, FLT3, AXL, MERTK, TEK, ROS1, NTRK1/2/3, and DDR1/2. Aiming to interpret the results of the study conducted by Valle and colleagues, some comments come to mind. First, the rationale for this international, double-blind, phase 2 study regarding antiangiogenic agents was probably based on the limited availability of treatments in advanced BTC at the time this trial was designed. Several st","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44903206","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":"Challenges in biomarker-based clinical trials for patients with gastrointestinal malignancies","authors":"J. Kratz, Wei Zhang, M. Patel, N. Uboha","doi":"10.1080/23808993.2022.2106852","DOIUrl":"https://doi.org/10.1080/23808993.2022.2106852","url":null,"abstract":"ABSTRACT Introduction The goal of precision oncology is to match each patient with the most appropriate therapeutic agent based on patient- and tumor-specific characteristics. Many therapeutics in development target tumors with specific biomarkers, in addition to considering tumor histologic classification and clinical presentation. Areas Covered Appropriate patient selection for research studies is critical to elucidate the potential effectiveness of therapies in development, as well as to spare the toxicities from ineffective therapies in patients who are unlikely to benefit. Biomarker-based clinical studies provide a platform to bring forward the expanse of therapeutics beyond the use of chemotherapy, including novel immunotherapeutic and targeted strategies. There are a number of issues to be considered when developing these types of studies. They range from biomarker validity to patient enrollment and trial availability. In this review, we discuss challenges that are frequently confronted in the design, enrollment, and analysis of biomarker-based clinical trials for patients with gastrointestinal (GI) cancers. Expert opinion The challenges encountered in biomarker-based trials for patients with GI cancers must be considered and addressed early during drug development to ensure proper therapy and patient selection in a timeframe acceptable for both patient diseases and rapidly changing oncology standards.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48204554","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":"Personalised pharmacotherapy options for soft tissue sarcomas","authors":"S. Arifi","doi":"10.1080/23808993.2022.2038562","DOIUrl":"https://doi.org/10.1080/23808993.2022.2038562","url":null,"abstract":"ABSTRACT Introduction Soft tissue sarcomas (STS) are a rare and heterogeneous group of tumors. The role of molecular testing to inform diagnosis, disease prognosis, and therapy has become critical to optimal treatment. Areas covered This review reports updated data on precision therapy in patients with STS, particularly those of immediate utility in clinical practice. Expert opinion There is a high unmet need for effective systemic therapy for patients with STS. In the era of precision medicine, doxorubicin-based chemotherapy is still the standard of care in first-line treatment for the majority of histologic subtypes with a median overall survival of only 20 months. Precision therapy for STS has only been partially effective. A new wave of targeted therapeutic agents has been approved with preferential benefit in subgroups of patients. Immunotherapy is now undergoing clinical trials. There is a heterogeneity in the benefit of immune checkpoint inhibitors across subtypes. Strategies targeted to antigen bearing sarcomas including vaccine and adoptive T-cell have yielded promising results in selected histotypes.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49556230","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}