Expert Review of Precision Medicine and Drug Development最新文献

{"title":"Personalizing treatments for patients based on cardiovascular phenotyping.","authors":"Jane A Leopold","doi":"10.1080/23808993.2022.2028548","DOIUrl":"https://doi.org/10.1080/23808993.2022.2028548","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiovascular disease persists as the leading cause of death worldwide despite continued advances in diagnostics and therapeutics. Our current approach to patients with cardiovascular disease is rooted in reductionism, which presupposes that all patients share a similar phenotype and will respond the same to therapy; however, this is unlikely as cardiovascular diseases exhibit complex heterogeneous phenotypes.</p><p><strong>Areas covered: </strong>With the advent of high-throughput platforms for omics testing, phenotyping cardiovascular diseases has advanced to incorporate large-scale molecular data with classical history, physical examination, and laboratory results. Findings from genomics, proteomics, and metabolomics profiling have been used to define more precise cardiovascular phenotypes and predict adverse outcomes in population-based and disease-specific patient cohorts. These molecular data have also been utilized to inform drug efficacy based on a patient's unique phenotype.</p><p><strong>Expert opinion: </strong>Multiscale phenotyping of cardiovascular disease has revealed diversity among patients that can be used to personalize pharmacotherapies and predict outcomes. Nonetheless, precision phenotyping for cardiovascular disease remains a nascent field that has not yet translated into widespread clinical practice despite its many potential advantages for patient care. Future endeavors that demonstrate improved pharmacotherapeutic responses and associated reduction in adverse events will facilitate mainstream adoption of precision cardiovascular phenotyping.</p>","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913616/pdf/nihms-1772637.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10698029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining immune checkpoint inhibitors with locoregional therapies in hepatocellular carcinoma","authors":"A. Rizzo, A. Ricci, G. Brandi","doi":"10.1080/23808993.2022.2020091","DOIUrl":"https://doi.org/10.1080/23808993.2022.2020091","url":null,"abstract":"The phase III IMbrave150 trial evaluating the combination of the PD-L1 inhibitor atezolizumab plus bevacizumab has recently represented an important step forward in the medical management of HCC [1]. According to the results of this study, advanced HCC patients receiving atezolizumab – bevacizumab reported statistically significant and clinically meaningful improvements in terms of overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and complete response rate, compared with sorafenib monotherapy [2,3]. Of note, immunotherapy seems to have find its role in the management of HCC as part of combinatorial strategies, as also witnessed by the recently published results of the phase I/II HIMALAYA trial [4]. In addition, an interesting line of research currently concerns the addition of locoregional therapies to immune checkpoint inhibitors, in order to produce a synergistic effect and improve clinical outcomes [5]. Locoregional treatments, including transarterial chemoembolization (TACE), radiofrequency ablation (RFA), selective internal radiation therapy (SIRT), and stereotactic body radiotherapy (SBRT), are considered of pivotal importance in the management of HCC patients [6]. These approaches are currently under evaluation in combination with immunotherapy, since locoregional therapies not only attack primary tumors but have been also suggested to boost antitumor immunity though the release of neoplasm antigens [7]. Recent years have seen the presentation or publication of several clinical trials combining immune checkpoint inhibitors with locoregional treatments (Table 1). A phase I/II trial published by Duffy and colleagues investigated the role of the combination of the CTLA-4 inhibitor tremelimumab plus TACE or RFA in Barcelona Clinic Liver Cancer (BCLC) Stage B and C HCC patients [8]. According to the results of this study, partial response (PR) was observed in 26.3% of cases, with 6-month PFS of 57.1% and median OS of 12.3 months (95% CI, 9.3–15.4). An interesting finding of this study concerns the HCVpositive population, with 12 of 14 HCC patients experiencing a notable reduction in viral load and a dramatical increase in CD8 + T cells reported in tumor biopsies after 6 weeks [8]. In another phase II trial conducted by Zhao and colleagues, the authors evaluated the role of thermal ablation plus a PD-1 inhibitor (pembrolizumab or nivolumab or JS001) in 50 HCC patients [9]. Median PFS, median Time to Progression (TTP), and median OS were 5 months (95% CI, 2.9–7.1), 6.1 months (95% CI, 2.6–11.2), and 16.9 months (95% CI, 7.7–26.1), respectively [9]. Another strategy under assessment is based on the combination of TACE plus immunotherapy. With efficacy data still pending, the preliminary results of the PETAL phase I/II study on conventional TACE followed by the PD-1 inhibitor pembrolizumab reported an acceptable safety profile for this combination [10]. Similarly, the IMMUTACE phase II trial is investigating the","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42826751","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":"Precision oncology in cholangiocarcinoma: current issues in clinical trial design and access to targeted therapies","authors":"A. Rizzo, A. Ricci, G. Gadaleta-Caldarola, G. Brandi","doi":"10.1080/23808993.2021.2008144","DOIUrl":"https://doi.org/10.1080/23808993.2021.2008144","url":null,"abstract":"Cholangiocarcinomas (CCAs) include a heterogeneous group of hepatobiliary tumors accounting for approximately the 10–15% of primary liver cancers [1]. Unfortunately, most of these tumors are diagnosed at an advanced stage, and more than ten years after the publication of the landmark phase III ABC-02 trial establishing gemcitabine-cisplatin as first-line standard for metastatic CCA, the prognosis of this patient population remains grim [2]. In fact, most of patients treated with front-line treatment fail to achieve a response or responses are short lived [3]. Recent years have witnessed the advent of molecular profiling in this setting, and new techniques and technologies have led to the identification of a variety of molecular alterations in CCA [4]. Over the last decade, several potentially actionable genetic aberrations have been highlighted, and precision oncology approaches have been evaluated and are under investigation in these hepatobiliary malignancies (Figure 1). A large number of anticancer agents are currently in development, including Fibroblast Growth Factor Receptor (FGFR) 2, Isocitrate Dehydrogenase 1 (IDH-1), and BRAF inhibitors [5]. FGFR2 aberrations have been reported in approximately the 20% of intrahepatic cholangiocarcinomas (iCCAs), with these alterations highlighted as most common in female patients and young adults [6]. Of note, FGFR2 aberrations are mainly represented by fusions, while mutations are detected only in a minority of patients. As regards IDH-1, missense mutations are the most frequent aberrations, involving a single residue in the active site of the enzyme [7]; typically, IDH-1 missense mutations have been reported to be more common in small duct type iCCAs and in poorly differentiated or undifferentiated forms [8]. Several other molecular aberrations have been observed in CCA patients, including BRCA mutations, NTRK fusions, and BRAF V600E mutations [9,10]. Nonetheless, several questions remain unanswered, and the adoption of precision oncology in CCA patients remains still far from everyday clinical practice, with some important exceptions. Among current obstacles, a crucial point to highlight is the limited access to anticancer treatments. For example, although the final overall survival (OS) analysis of the ClarIDHy phase III trial has been presented and on 25 August 2021 the FDA approved ivosidenib use in IDH-1 mutant iCCA, the IDH-1 inhibitor is not available in several countries, according to different choices by the regulatory agencies [11]. Second, biopsy samples are often inadequate for molecular profiling since tissue sampling has reported low sensitivity in the diagnosis of malignant biliary strictures; in fact, the highly desmoplastic nature of CCA severely limits the accuracy of pathological and cytological methodologies. On the basis of these premises, it is urgent to develop in this scenario novel strategies aimed at anticipating the diagnosis by detecting CCA at an early, resectable stage, a","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42393575","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":"Dopaminergic and other genes related to reward induced overeating, Bulimia, Anorexia Nervosa, and Binge eating","authors":"K. Blum, P. Thanos, Gene-Jack Wang, A. Bowirrat, Luis Llanos Gomez, D. Baron, Rehan Jalali, M. Gondré-Lewis, M. Gold","doi":"10.1080/23808993.2021.1994186","DOIUrl":"https://doi.org/10.1080/23808993.2021.1994186","url":null,"abstract":"ABSTRACT Introduction Eating Disorders and Obesity are a primary global public health concern. Areas Covered This article aims to trace the neurochemical mechanisms of unwanted eating disorders and target specific loci, within the Brain Reward Cascade (BRC) for therapeutic interventions. Changes due to BRC polymorphisms in functional connectivity and neurotransmission can manifest as overeating, Bulimia Nervosa, and Anorexia Nervosa, and other related eating disorders. Expert opinion Variations in dopamine function within the Ventral Tegmental Area (VTA), Nucleus Accumbens (NAc), and Ventral Striatum of individuals result in different outcomes related to maladaptive eating behaviors. The goal is to reduce maladaptive eating behaviors by implementing novel strategies that induce Dopamine Homeostasis within the BRC. Clinicians determine genetic risk severity and identify polymorphic targets for either pharmaceutical or nutraceutical interventions. Precision neuro-nutrient formulations of KB220 (Research ID Code) matched precisely to deficient neurotransmitter systems may promote the long-term development of ‘dopamine homeostasis’ to treat and prevent overeating, Bulimia, and Anorexia Nervosa.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46550213","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":"A profile on capmatinib in treating adult patients with metastatic NSCLC tumors with MET exon 14 skipping mutations","authors":"T. Hida","doi":"10.1080/23808993.2021.1999585","DOIUrl":"https://doi.org/10.1080/23808993.2021.1999585","url":null,"abstract":"ABSTRACT Introduction : Clinical studies of MET-targeted treatments have so far failed to provide adequate outcomes. Capmatinib, a newly designed MET receptor inhibitor, has demonstrated considerable anticancer efficacy in patients with advanced NSCLC who have a MET exon 14 skipping mutation. Areas covered : This review offers a summary of the findings from capmatinib clinical studies in NSCLC patients with a MET exon 14 skipping mutation, as well as preclinical data and post-market reporting of capmatinib. Expert opinion : Capmatinib has a tolerable safety profile and preliminary evidence of effectiveness in patients with a MET exon 14 skipping mutation, according to data from a phase 1 clinical study. The GEOMETRY mono-1 phase 2 study revealed objective response rates of 68% and 41%, and median OS of 20.8 and 13.6 months in treatment-naive and pretreated MET exon 14 skipping mutant patients, respectively. Furthermore, capmatinib penetrates the blood–brain barrier, and capmatinib activity in the brain was shown to be encouraging in the study. However, the effectiveness of immunotherapy for MET exon 14 skipping mutation remains debatable. To enhance therapy choices, researchers have begun to focus on the mechanisms of intrinsic and acquired resistance of the MET exon 14 skipping mutation.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45105946","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":"Capabilities of neural network technologies for extracting new medical knowledge and enhancing precise decision making for patients","authors":"L. Yasnitsky, A. Dumler, F. Cherepanov, V. L. Yasnitsky, Natalia A. Uteva","doi":"10.1080/23808993.2021.1993595","DOIUrl":"https://doi.org/10.1080/23808993.2021.1993595","url":null,"abstract":"ABSTRACT Objectives Currently, there is an active use of neural networks in various areas of human activity. Problems of recognition, diagnostics, optimization, forecasting, control, as well as obtaining new scientific knowledge are successfully solved. However, in medicine, due to the particular complexity of the human body, neural networks are mainly used only for solving the simplest problems of classification and diagnostics. The purpose of this article is to show that the possibilities of neural network modeling in medicine are much wider. Methods This goal is achieved by using special mathematical techniques developed by the authors that allow us to overcome these difficulties. Results The intellectual system created in this way made it possible to reveal a number of interesting scientific knowledge, which sometimes does not coincide with the generally accepted ideas of doctors. Virtual experiments conducted on computer models of patients using our intelligent system clearly demonstrate which lifestyle and medication variations can benefit a particular patient in the long term, and which can cause harm. Conclusion Our intellectual system allows us to identify new scientific knowledge, to carry out long-term forecasting of the development of the disease, to select the optimal courses of treatment and prevention of diseases.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41283522","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":"Genotype-Guided vs Clinically-Guided Stable Warfarin Dose Prediction and Stable Dose Establishment In A Predominantly Non-European Ancestry Population","authors":"Annesti F. Elmasri, Hee-soo Hur, Jin Han, James C. Lee","doi":"10.1080/23808993.2021.1989303","DOIUrl":"https://doi.org/10.1080/23808993.2021.1989303","url":null,"abstract":"ABSTRACT Background Warfarin dosing varies due to individual genetic and clinical factors. The utility of genotype‐guided warfarin dosing to improve stable warfarin dose is not extensively studied in non-European populations. Research design and methods Retrospective cohort study of patients initiating warfarin receiving genotype (PGx)‐guided or clinically guided dosing. Primary outcomes included dose discordance between estimated dose at discharge and eventual stable dose. Results No significant difference in warfarin dose discordance was observed (PGx: 9.1 ± 8.8 mg/week difference vs. Clinical: 7.9 ± 8.9 mg/week difference; P = 0.446). PGx‐guided dosing did not reduce time to achieve stable dose (1.8 ± 2.5 months vs. 2.1 ± 2.6 months; P = 0.508). Vitamin K intake level did not alter prediction accuracy or time to stable dose (PGx‐predicted: dose difference P = 0.493, time to stable dose P = 0.336; Clinically predicted: dose difference P = 0.145, time to dose INR P = 0.095). Conclusions PGx‐guided warfarin dosing did not improve eventual stable dose discordance or reduce the time to achieve stable dose in this predominantly non‐European cohort. Dietary vitamin K intake level did not impact warfarin dose discordance or time to achieve stable warfarin dose. Additional study is needed to identify populations that best benefit from PGx‐guided warfarin dosing.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42981298","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":"Atezolizumab plus vemurafenib and cobimetinib for the treatment of BRAF V600-mutant advanced melanoma: from an hypothetic triplet to an approved regimen","authors":"Aikaterini Katsandris, D. Ziogas, M. Kontouri, Stavroula Staikoglou, H. Gogas","doi":"10.1080/23808993.2021.1976637","DOIUrl":"https://doi.org/10.1080/23808993.2021.1976637","url":null,"abstract":"ABSTRACT Introduction Breakthrough changes in melanoma management induced by the introduction of BRAF/MEK inhibitors and immune checkpoint inhibitors (ICPIs) have motivated subsequent research to combine these strategies in the frontline approach of BRAFV600-mutant advanced melanoma. Initial preclinical data have shown that targeted agents may have a favorable immune impact on the tumor microenvironment and next, numerous trials tried to identify the optimal combination and sequence of immunotherapy and targeted therapy. Up until last year, when the first immune/targeted regimen including atezolizumab, vemurafenib and cobimetinib, was approved by the FDA. Areas covered Focusing on this first-in-class immune/targeted regimen, we describe here the entire process for its approval, from the bench of preclinical studies to the clinical evaluation of its efficacy and its toxicity profile on treated patients with advanced BRAF-mutant melanoma. All raised concerns about the use of atezolizumab/vemurafenib/cobimetinib triplet are thoroughly discussed. Expert opinion The atezolizumab/vemurafenib/cobimetinib triplet is an effective frontline option for advanced BRAF-mutant melanoma but its generalized implementation remains limited due to toxicity and cost. Results of ongoing trials are expected to identify more clearly the best candidates for such combinations and to update the role of immune/targeted triplets in melanoma treatment.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49442913","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":"Individualized management of cytomegalovirus in solid organ transplant recipients","authors":"H. Saeed, Matthew J. Thoendel, R. Razonable","doi":"10.1080/23808993.2021.1964951","DOIUrl":"https://doi.org/10.1080/23808993.2021.1964951","url":null,"abstract":"ABSTRACT Introduction Cytomegalovirus (CMV) is an opportunistic infection that affects immunocompromised solid organ transplant patients. Defining the imbalance between host and virus factors that predispose to its occurrence can assist in individualizing the approach to CMV prevention and treatment. Areas covered In this narrative review article, we provide an up to date overview of host, pathogen, and transplant-related factors that determine the risk and outcome of CMV infection in solid organ transplant recipients. We review the role of CMV-specific cell-mediated and humoral immune status, degree of lymphopenia, degree of viremia, and the dose and type of immunosuppressive regimen in defining the risk and determining the outcome of CMV. We propose that knowledge of these factors should be taken into account in optimizing the management strategies and individualize our approach to CMV prevention and treatment in the posttransplant setting. Expert opinion The management of CMV in transplant recipients is not a one-size-fits-all strategy. We highlight the spectrum of CMV risk and outcomes in solid organ transplant recipients based on host, virus, and transplant-related factors. We provide examples on how to incorporate these factors in the implementation of optimized antiviral prophylaxis, preemptive treatment of asymptomatic infection and management of susceptible, refractory, and resistant CMV disease.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44354255","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":"Targeted immunotherapies to consider for B Cell non-hodgkin lymphoma","authors":"E. Namoglu, M. Hughes, S. Nasta","doi":"10.1080/23808993.2021.1967142","DOIUrl":"https://doi.org/10.1080/23808993.2021.1967142","url":null,"abstract":"ABSTRACT Introduction Non-Hodgkin lymphoma is a disease spectrum of multiple subtypes with many potential targets. Given the heterogeneity and evolving landscape for targeted therapy, incorporation of therapeutics in this disease state is complex and dependent upon multiple factors. Areas covered Agents reviewed for either on- or off-label use include: monoclonal antibodies, antibody-drug conjugates, immunotherapy, cellular therapy, and bi-specific antibodies. In the current review, we discuss the most recently identified targets of interest and corresponding therapies. The authors aim to provide insight on where therapies may be incorporated for clinical utility in B cell non-Hodgkin lymphoma as well as future directions for new targets and combinations of these approaches. Expert opinion A multimodality approach to non-Hodgkin lymphoma will now be needed for early identification of potential targets and will be critical for treatment decisions. As each agent is defined in the relapsed refractory setting, the sequencing and combination of these agents will be critical, particularly with overlapping toxicities. The adoption in practice will depend not only on efficacy but ease of administration, limiting side effects and cost.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46060593","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}