Clinical & Translational Oncology最新文献

{"title":"Management and outcome of children with high-risk neuroblastoma: insights from the Spanish Society of Pediatric Hematology and Oncology (SEHOP) neuroblastoma group on refractory and relapse/progressive disease.","authors":"Blanca Martínez de Las Heras, Pedro M Rubio-Aparicio, Alba Rubio-San-Simón, Lucas Moreno, Paula Mazorra, Ricardo López Almaraz, Mercedes Llempén López, Julia Balaguer Guill, Vanessa Segura, Mar Bermúdez, Irene Jiménez, Désirée Ramal, Adela Cañete","doi":"10.1007/s12094-025-03853-w","DOIUrl":"https://doi.org/10.1007/s12094-025-03853-w","url":null,"abstract":"<p><strong>Purpose: </strong>Outcome for children with refractory and relapse/progressive high-risk neuroblastoma (HR-NB) remains poor, without an internationally agreed standard second-line approach. Heterogeneity in patients' disease and treatment strategies challenges clinical management. The survival rate for patients with resistant disease does not exceed 20% at 5 years. The study's aim was to analyze refractory and progressive HR-NB patients in a real-world setting to evaluate current clinical practices and optimize future approaches.</p><p><strong>Methods: </strong>Data from patients diagnosed with refractory and relapse/progressive (R/R-P) HR-NB between January 2019 and December 2021 at six of the major Spanish neuroblastoma treating hospitals were collected and analyzed.</p><p><strong>Results: </strong>A total of 67 episodes of R/R-P HR-NB were included. Treatments applied included chemotherapy (97%), immunotherapy (48%), consolidation (21%), local treatment (surgery and/or radiotherapy) (45%) and maintenance (16%), and were administered within a clinical trial (CT) in 34% of the episodes. Biopsy was performed in 37% of the tumors and 30% were profiled. Event-free survival (EFS) in our cohort was 20.9% and overall survival (OS) 32%. Significant survival advantage (in both OS and EFS) was observed in refractory episodes compared to relapse/progressive, in first events compared to successive, and when response or disease stabilization was achieved. MYCN status, presence of lymph node metastases, use of irinotecan or topotecan, and radiotherapy were also univariate predictors of OS.</p><p><strong>Conclusions: </strong>Treatment of refractory and relapse/progressive HR-NB is highly heterogeneous. We confirm a poor outcome, although certain epidemiological and treatment-related factors have prognostic value. Molecular profiling and inclusion in CTs should be improved.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2025 Updated version v1.0 SEOM-GEMCAD-TTD clinical guidelines for the systemic treatment of metastatic colorectal cancer (2022).","authors":"Ana Fernández Montes, Vicente Alonso, Enrique Aranda Aguilar, Elena Élez, Pilar García Alfonso, Cristina Grávalos Castro, Joan Maurel, Ruth Vera García, Rosario Vidal Tocino, Jorge Aparicio Urtasun","doi":"10.1007/s12094-025-03860-x","DOIUrl":"https://doi.org/10.1007/s12094-025-03860-x","url":null,"abstract":"","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A PET/CT-based 3D deep learning model for predicting spread through air spaces in stage I lung adenocarcinoma.","authors":"Cheng Zheng, Yujie Cai, Jiangfeng Miao, BingShu Zheng, Yan Gao, Chen Shen, ShanLei Bao, ZhongHua Tan, ChunFeng Sun","doi":"10.1007/s12094-025-03870-9","DOIUrl":"https://doi.org/10.1007/s12094-025-03870-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluates a three-dimensional (3D) deep learning (DL) model based on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting the preoperative status of spread through air spaces (STAS) in patients with clinical stage I lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>A retrospective analysis of 162 patients with stage I LUAD was conducted, splitting data into training and test sets (4:1). Six 3D DL models were developed, and the top-performing PET and CT models (ResNet50) were fused for optimal prediction. The model's clinical utility was assessed through a two-stage reader study.</p><p><strong>Results: </strong>The fused PET/CT model achieved an area under the curve (AUC) of 0.956 (95% CI 0.9230-0.9881) in the training set and 0.889 (95% CI 0.7624-1.0000) in the test set. Compared to three physicians, the model demonstrated superior sensitivity and specificity. After the artificial intelligence (AI) assistance's participation, the diagnostic accuracy of the physicians improved during their subsequent reading session.</p><p><strong>Conclusion: </strong>Our DL model demonstrates potential as a resource to aid physicians in predicting STAS status and preoperative treatment planning for stage I LUAD, though prospective validation is required.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabazitaxel versus abiraterone or enzalutamide for metastatic castration-resistant prostate cancer following docetaxel failure: a systematic review and meta-analysis.","authors":"Izael Pereira da Silva, Lucas Guimarães Campos Roriz de Amorim, Gabriel Vieira Piredda, Marcelo Mass-Lindenbaum, Francisco Cezar Aquino de Moraes, Pedro F S Freitas, Bárbara Vieira Lima Aguiar Melão, Helisandro Montenegro Brandão, Karine Martins da Trindade","doi":"10.1007/s12094-025-03851-y","DOIUrl":"https://doi.org/10.1007/s12094-025-03851-y","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment for metastatic castration-resistant prostate cancer (mCRPC) includes chemotherapy and inhibition of the androgen receptor pathway. However, the optimal treatment sequence in this scenario is not yet fully understood. Therefore, we conducted a systematic review and meta-analysis comparing cabazitaxel versus abiraterone or enzalutamide for efficacy and safety outcomes as second-line therapy in mCRPC patients after docetaxel failure.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and Cochrane databases for interventional studies comparing cabazitaxel versus abiraterone or enzalutamide for patients with mCRPC who have experienced treatment failure with docetaxel as their first-line therapy. We computed hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Eight studies, comprising 1,897 patients were included, of whom 548 (28.8%) received cabazitaxel. Mean follow-up time ranged from 3 to 16.4 months. Median age ranged from 68.1 to 73.9 years in the cabazitaxel group, and 68.0 to 73.1 years in the abiraterone or enzalutamide group. In our meta-analysis, cabazitaxel significantly improved progression-free survival (PFS) rates (HR 0.60; 95% CI 0.47-0.78; p < 0.001) compared to abiraterone or enzalutamide. There were no differences between groups in overall survival (HR 0.76; 95% CI 0.46-1.24; p = 0.27), therapy-related grade ≥ 3 adverse events (AEs) (OR 3.00; 95% CI 0.72-12.40; p = 0.12), and PSA decline ≥ 50% (OR 1.20; 95% CI 0.51-2.80; p = 0.67).</p><p><strong>Conclusions: </strong>In this systematic review and meta-analysis of men with mCRPC after docetaxel failure, second-line therapy with cabazitaxel was associated with a longer PFS compared with abiraterone or enzalutamide, though without a significant difference in OS.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.","authors":"Louis Boafo Kwantwi, James Danquah Boafo, Bevelyn Emefa Egleh, Mingfeng Li","doi":"10.1007/s12094-025-03874-5","DOIUrl":"https://doi.org/10.1007/s12094-025-03874-5","url":null,"abstract":"<p><p>Increasing knowledge of the immunosuppressive tumor microenvironment in cancer-related processes has led to the developing of novel immune-based therapies that have changed the cancer treatment paradigm. In the tumor microenvironment, the plethora of soluble factors secreted by tumor cells interacts with immune cells and non-immune components to deliver signals necessary for tumor progression. Accordingly, targeting tumor-derived factors inducing this immunosuppressive tumor microenvironment has become an appealing therapeutic potential in advancing cancer treatment. CCL20, a chemokine best known to induce leucocyte migration in response to pathological and inflammatory conditions, has been implicated in tumor proliferation, angiogenesis, metastasis, immunosuppression, and therapeutic resistance. Notably, CCL20 and its receptor CCR6 are important in tumor microenvironment interactions. This review discusses the interaction between the CCL20-CCR6 axis and the tumor microenvironment and how these interactions promote tumor progression. Also, an outline of studies utilizing CCL20 in combination with other standard cancer treatments has been shed.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory biomarker analysis from a phase III study of the PI3K inhibitor, copanlisib, in combination with rituximab in patients with indolent non-Hodgkin lymphoma, a retrospective study.","authors":"Shalini Chaturvedi, Anke Weispfenning, Tine Descamps, Sara Bellinvia, David Bauer, Rong Du, Teresa Lunt, Lidia Mongay Soler, Barrett H Childs, Pier Luigi Zinzani","doi":"10.1007/s12094-025-03869-2","DOIUrl":"https://doi.org/10.1007/s12094-025-03869-2","url":null,"abstract":"<p><strong>Purpose: </strong>There has been increased difficulty in developing safe and effective treatment using PI3K inhibitors in heme malignancies, despite the role of PI3K/AKT being well defined in this population. This study was an attempt to conduct exploratory biomarker analysis retrospectively from the phase III CHRONOS-3 trial with the aim to identify a sub-set of patients that could benefit from treatment.</p><p><strong>Patients and methods: </strong>Patients with CD20-positive indolent B-cell lymphoma were randomized 2:1 to receive intravenous copanlisib plus rituximab (C + R) or placebo plus rituximab (P + R). Biomarker analyses were performed to examine potential associations between treatment outcome and phosphatase and tensin homolog (PTEN) protein expression, EZH2 and BCL2 mutation status via next-generation sequencing, and plasma cytokine levels.</p><p><strong>Results: </strong>PTEN presence was associated with significant improvements in progression-free survival (PFS) for C + R over P + R in patients with iNHL (P = 0.001) and FL (P = 0.012). Both the mutant and wild-type EZH2 FL patients had equal PFS benefits when treated with copanlisib. A significant improvement in PFS was observed for patients with mutant versus wild-type BCL2 FL in the C + R arm (P = 0.002). Overall survival (OS) was significantly improved for patients with iNHL and low or undetectable versus high baseline IL-2 levels in the C + R arm (P < 0.0001, unadjusted).</p><p><strong>Conclusions: </strong>PTEN presence, BCL2 mutations, and low or undetectable baseline IL-2 levels were associated with improved patient survival following treatment with C + R, supporting a potential role for these biomarkers in guiding treatment selection for patients with indolent non-Hodgkin lymphoma.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical metric of tumor mutational burden depicts colorectal cancer patients at the extremes.","authors":"Ming Zheng","doi":"10.1007/s12094-025-03873-6","DOIUrl":"https://doi.org/10.1007/s12094-025-03873-6","url":null,"abstract":"<p><strong>Purpose: </strong>Rare cases of colorectal cancer patients with exceptionally good or poor prognosis often remain overlooked, limiting insights into prognostic factors and underlying mechanisms.</p><p><strong>Methods: </strong>This study developed an analytical framework to investigate cancer patients at the extremes using tumor mutational burden (TMB). By analyzing data from 1277 colorectal cancer patients who did not receive immunotherapy, this analysis assessed how patient survival varies with a broad range of TMB levels.</p><p><strong>Results: </strong>Among patients with TMB ≤ 10 mutations per megabase (mut/Mb), increasing TMB was associated with worse survival outcomes. In contrast, patients with TMB > 10 mut/Mb showed  increasingly improved survival. Notably, a small subgroup (3.83%) with TMB > 60 mut/Mb had significantly better survival outcomes.</p><p><strong>Conclusions: </strong>These findings highlight TMB's dual role in colorectal cancer progression. This study suggests that atypical patients can coexist within the same \"disease continuum\" with typical patients, under the universal context unified by a shared cancer hallmark. TMB provides a useful biomarker for identifying these extremes, offering a clinical metric to better predict patient outcomes and personalize treatment strategies.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic cell immunotherapy has its antitumor action improved by the LPS in the maturation process.","authors":"Angela Maria Moed Lopes, Jéssica Ferreira Vieira, Saulo Fernando Moreira da Silva, Eddie Fernando Candido Murta, Márcia Antoniazi Michelin","doi":"10.1007/s12094-025-03858-5","DOIUrl":"https://doi.org/10.1007/s12094-025-03858-5","url":null,"abstract":"<p><p>Immunotherapy with dendritic cells (DCs) in cancer patients aims to activate the immune response to eliminate neoplastic cells. The present study aimed to investigate lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells in investigating antitumor immune response in experimental breast cancer. For this, we submitted bone marrow pluripotent cells of Balb/c mice differentiated by GM-CSF and IL-4 to maturation with TNF-α and tumor lysate (DCs protocol) or with TNF-α, LPS, and tumor lysate (LPS/DCs protocol). Both immunotherapies were tested in 4T1 breast cancer to evaluate their impact on splenic and tumor microenvironment. We observed that DCs and LPS/DCs reduce the tumor growth rate (p < 0.0001). Besides, the LPS/DCs vaccine shows higher splenic and intratumoral T helper lymphocytes (p < 0.001). Both vaccines increased the production of IFN-γ in the tumor microenvironment (p < 0.0001). The LPS/DCs induced lower Treg lymphocytes and macrophages in the tumor microenvironment (p < 0.0001). The results allow us to conclude that bone marrow-derived dendritic cells stimulated with LPS have been shown to reduce tumor growth rate efficiently and could be better immunotherapy in breast cancer by reducing immunosuppressive cells and increasing antitumoral immune cells in the tumor microenvironment.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A population-based study of incidence trends of head and neck epithelial cancers in northeastern Spain, 1994-2018.","authors":"Jordi Rubió-Casadevall, Jan Trallero, Carla Calvo, Montse Puigdemont, Marià Carulla, Arantza Sanvisens, Alberto Ameijide, Anna Vidal, Clàudia Pla, Jordi Marruecos, Rafael Marcos-Gragera, Jaume Galceran","doi":"10.1007/s12094-025-03855-8","DOIUrl":"https://doi.org/10.1007/s12094-025-03855-8","url":null,"abstract":"<p><strong>Background: </strong>Head and neck cancer (HNC) is the seventh most common cancer worldwide. Incidence rates of these tumors vary between countries and change over time depending on the prevalence of risk factors such as tobacco and alcohol consumption, betel nut chewing habits or human papillomavirus infection. This makes it necessary to periodically study HNC incidence trends in each geographic area.</p><p><strong>Methods: </strong>To determine trends in the incidence of HNC, all cancer cases diagnosed in Girona and Tarragona (northeastern Spain) between 1994 and 2018, except mesenchymal and hematological neoplasms, were included. Crude and standardized incidence rates and the annual percentage change (APC) were calculated.</p><p><strong>Results: </strong>We identify 7,966 cases of HNC, 83.7% in men. A significant decrease in incidence, with an APC of  - 1.83, was observed in all HNC as a whole and in cancers of the lip (APC =  - 5.34), salivary glands (APC =  - 2.22), nasopharynx (APC =  - 2.01), hypopharynx (APC =  - 3.15), and larynx (APC =  - 1.97). In men, a significant decline in incidence was observed in overall HNC and in cancers of the lip, oral cavity, salivary glands, nasopharynx, hypopharynx, and larynx. In women, a significant increase was identified in overall HNC and in cancers of oral cavity, oropharynx, hypopharynx, and larynx.</p><p><strong>Conclusion: </strong>A decline in the overall incidence of HNC has been observed in this area of southern Europe, mainly based on a decrease in men of cancers of the lip, oral cavity, salivary glands, nasopharynx, hypopharynx, and larynx.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel hypermethylation marker, ZSCAN18, and construction of a diagnostic model in cervical cancer.","authors":"Jinhao Yang, Shuang Chen, Yuqing Liu, Ping Wang, Jing Zhao, Jianying Yi, Jin Wei, Rong Wang","doi":"10.1007/s12094-025-03864-7","DOIUrl":"https://doi.org/10.1007/s12094-025-03864-7","url":null,"abstract":"<p><strong>Purpose: </strong>Cervical cancer (CC), a common female malignancy, has been linked to alterations in DNA methylation. This study employed an integrated \"dry-wet lab\" strategy combining bioinformatics, machine learning, and experimental validation to identify novel methylation biomarkers for CC.</p><p><strong>Methods: </strong>Methylome and transcriptome data from the TCGA and GEO cohorts (n=349 discovery, n=414 validation) were analyzed to identify differentially methylated CpGs. The top candidates were validated by pyrosequencing, methylation-specific PCR, and quantitative assays. Diagnostic models were developed, and functional studies were performed for the target markers.</p><p><strong>Results: </strong>Eighteen differentially methylated CpGs were identified, with five top candidates (three in the ZSCAN18 promoter) showing diagnostic potential. ZSCAN18 promoter methylation levels and positivity rates were significantly greater in CC tissues than in normal tissues (p<0.05), reaching 77.8% (21/27) in ThinPrep cytology test (TCT) samples. The ridge regression diagnostic model achieved an AUC of 0.9421 in the validation cohort. Similarly, ZSCAN18 overexpression suppressed CC cell proliferation (p<0.05).</p><p><strong>Conclusions: </strong>This study established a rapid, effective and systematic systemic research strategy to screen novel methylation markers for CC. ZSCAN18 promoter methylation correlates with cervical lesion severity, and the diagnostic model enhances the diagnostic ability. These findings highlight the dual role of ZSCAN18 as a diagnostic marker and potential therapeutic target.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}