Cancer pathogenesis and therapy最新文献

{"title":"Nomogram for predicting the risk and prognosis of lung metastasis of four subtypes of breast cancer: A population-based study from SEER","authors":"Yuanfang Xin ,&nbsp;Guoxin Zhang ,&nbsp;Qiuxia Dong ,&nbsp;Yaobang Liu ,&nbsp;Xingfa Huo ,&nbsp;Yumei Guan ,&nbsp;Yonghui Zheng ,&nbsp;Qianqian Fang ,&nbsp;Dengfeng Ren ,&nbsp;Fuxing Zhao ,&nbsp;Zitao Li ,&nbsp;Xinlan Liu ,&nbsp;Jiuda Zhao","doi":"10.1016/j.cpt.2024.08.001","DOIUrl":"10.1016/j.cpt.2024.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) is the most diagnosed cancer worldwide, and patients' survival decreases with metastasis. We conducted a retrospective study using data derived from the Surveillance, Epidemiology, and End Results (SEER) database and clinicopathological data to construct a clinical predictive model to predict the risk and prognosis of lung metastasis (LM) in patients with different subtypes of BC and validate its performance.</div></div><div><h3>Methods</h3><div>A total of 1650 patients from the SEER database between 2011 and 2015 were enrolled in this study. Cox regression analysis was performed to identify prognostic factors for breast cancer lung metastasis (BCLM). A nomogram was constructed using the independent prognostic factors. The concordance index (C-index), area under the curve (AUC) value, calibration curve, and decision curve analysis (DCA) were used to test the prediction accuracy of the nomogram. External validation (<em>n</em> = 112) was performed using clinical data from the Affiliated Hospital of Qinghai University and the General Hospital of Ningxia Medical University.</div></div><div><h3>Results</h3><div>Multivariate Cox regression analyses suggested that age, grade, surgery, chemotherapy, subtype, and liver, bone, and brain metastases were independent prognostic factors for overall survival (OS). Kaplan–Meier survival analysis showed that the median survival times of patients with human epidermal growth factor receptor 2 (HER2)-positive, luminal A, luminal B, and triple-negative BC were 25 (95% confidence interval [CI], 20–37), 27 (95% CI, 23–29), 35 (95% CI, 30–44), and 12 (95% CI, 11–14), respectively. The C-indexes of the nomogram for predicting OS of the SEER training, SEER validation, and clinical validation cohorts were 0.7, 0.6, and 0.6, respectively, and the calculated AUCs at 3 years were 0.765, 0.794, and 0.799, respectively. The calibration curve indicates that the nomogram possessed a high level of accuracy.</div></div><div><h3>Conclusions</h3><div>Our nomogram demonstrates significant predictive value, indicating that molecular subtypes, brain metastasis, and liver metastasis are closely associated with the prognosis of patients with LM. This information can guide clinical practice.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 154-162"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609836","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":"Dynamics of epithelial–mesenchymal plasticity driving cancer drug resistance","authors":"Rashmi Bangarh ,&nbsp;Reena V. Saini ,&nbsp;Adesh K. Saini ,&nbsp;Tejveer Singh ,&nbsp;Hemant Joshi ,&nbsp;Seema Ramniwas ,&nbsp;Moyad Shahwan ,&nbsp;Hardeep Singh Tuli","doi":"10.1016/j.cpt.2024.07.002","DOIUrl":"10.1016/j.cpt.2024.07.002","url":null,"abstract":"<div><div>Epithelial–mesenchymal transition (EMT) promotes several cancers by increasing tumor cell motility, disrupting epithelial cell phenotypes, apical–basal polarity, and intracellular connections, and enhancing tumor resistance to immunotherapy and chemotherapy. Mesenchymal–epithelial transition (MET), the opposite of EMT, causes tumor metastasis. EMT drives primary tumor cells, whereas MET inhibits them. Importantly, the complex network of EMT includes cell–cell interactions in the tumor microenvironment. Transcription factors, post-translational regulation, cytokine-mediated signaling, and microRNAs control EMT. In this review, we discussed how molecular mechanisms, signaling networks, and epithelial/mesenchymal states affect cancer treatment resistance and the tumor microenvironment. Research on immunotherapy and chemotherapy problems associated with EMT suggests that targeting EMT might be a potential cancer treatment resistance strategy.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 120-128"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141704522","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":"Predictive models and therapeutic strategies for breast cancer","authors":"Lei Liu,&nbsp;Peng Yuan,&nbsp;Xue Wang","doi":"10.1016/j.cpt.2024.06.008","DOIUrl":"10.1016/j.cpt.2024.06.008","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 85-86"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141701936","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":"Factors affecting the place of death in patients with liver cancer in China, 2013–2020: A population-based study","authors":"Xiaosheng Ding ,&nbsp;Weiwei Shi ,&nbsp;Jinlei Qi ,&nbsp;Juan An ,&nbsp;Weiran Xu ,&nbsp;Hui Shi ,&nbsp;Xixi Zheng ,&nbsp;Xiaoyan Li","doi":"10.1016/j.cpt.2024.04.001","DOIUrl":"10.1016/j.cpt.2024.04.001","url":null,"abstract":"<div><h3>Background</h3><div>Despite the country's substantial liver cancer burden, there is limited research on the factors influencing the place of death (POD) of patients with liver cancer in China. This study aimed to delineate POD distribution among patients with liver cancer, identify the factors associated with hospital deaths, and offer valuable insights for the government to develop healthcare policies.</div></div><div><h3>Methods</h3><div>Data from 2013 to 2020 were obtained from the National Mortality Surveillance System (NMSS) of China. This analysis focused on the distribution of POD among individuals who succumbed to liver cancer. Variations in characteristic distributions across different categories were evaluated using a chi-squared test. We also applied a multilevel logistic regression analysis to identify the factors associated with hospital liver cancer deaths. The proportional change in variance was computed to evaluate the contributions of different factors in the model.</div></div><div><h3>Results</h3><div>From 2013 to 2020, the NMSS reported a total of 608,789 liver cancer-related deaths, of which 440,079 (72.29%) died at home, and 158,291 (26.00%) died in the hospital. Home remained the preferred POD among patients with liver cancer. The results demonstrated that female patients, aged between 0 and 14 years, of Han ethnicity, living in urban areas, unmarried, highly educated, and either employed in a professional, staff, or civil servant capacity, or retired patients tended to end their lives in the hospital.</div></div><div><h3>Conclusions</h3><div>In China, home continues to be the predominant POD for patients with liver cancer, with demographic and socioeconomic factors significantly influencing whether a hospital is their POD. Enhancing healthcare policymakers' understanding of the factors influencing the place of death for patients with liver cancer may assist in creating a more equitable distribution of healthcare resources and providing a variety of choices for minorities with distinct preferences for end-of-life care.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 163-172"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140778926","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":"Cardiotoxicity in platinum-based chemotherapy: Mechanisms, manifestations, and management","authors":"Betty Rachma ,&nbsp;Merlyna Savitri ,&nbsp;Henry Sutanto","doi":"10.1016/j.cpt.2024.04.004","DOIUrl":"10.1016/j.cpt.2024.04.004","url":null,"abstract":"<div><div>Platinum-based chemotherapy, a cornerstone in the treatment of various malignancies, is often limited by its potential cardiotoxic effects. Understanding these effects is crucial for optimizing patient outcomes and guiding treatment decisions. This review explores the mechanisms, clinical manifestations, detection, management, and future directions in the research of cardiotoxicity associated with platinum-based chemotherapy. The mechanisms discussed here include oxidative stress, reactive oxygen species production, DNA damage, and alterations in signaling pathways. Clinical manifestations range from mild symptoms to severe complications, including Takotsubo cardiomyopathy, as highlighted by recent case studies. The role of diagnostic tools such as echocardiography, cardiac magnetic resonance imaging, and cardiac biomarkers in early detection is emphasized, underscoring the importance of regular cardiac monitoring. Management strategies focus on cardioprotective agents, alternative chemotherapy regimens, and emerging therapeutic approaches, including the potential of nano liposomal and cubosomal formulations. The review also delves into the future of personalized medicine in predicting and managing cardiotoxicity, advocating for ongoing research to mitigate these adverse effects. This comprehensive overview aims to enhance the understanding of cardiotoxicity in platinum-based chemotherapy, informing clinical practices and promoting patient-centric care.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 101-108"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780765","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":"Risk of autoimmunity, cancer seeding, and adverse events in human trials of whole-tissue autologous therapeutic vaccines","authors":"Garrett Gianneschi ,&nbsp;Anthony Scolpino ,&nbsp;James Oleske","doi":"10.1016/j.cpt.2024.05.003","DOIUrl":"10.1016/j.cpt.2024.05.003","url":null,"abstract":"<div><h3>Background</h3><div>Whole-tissue autologous therapeutic vaccines (WATVs) are a form of cancer immunotherapy that use a patient's own pathological tissue. Concerns exist regarding the potential of WATVs to induce autoimmunity or the spread of cancer; however, their adverse events (AEs) have not been adequately studied. This literature review primarily aimed to evaluate the risks of autoimmunity and cancer seeding associated with using WATVs in human clinical trials. Its secondary objectives included assessing the incidence of AEs graded 1–5 using the Common Terminology Criteria for Adverse Events v5.0.</div></div><div><h3>Methods</h3><div>The inclusion criteria were any clinical trial using human subjects in which at least part of the cancer vaccine was derived from the patient's own tumor tissue, which likely preserved the unique tumor-associated antigens (TAAs) present in the patient's tumor (i.e., whole-tissue). Tumor vaccine trials that used limited TAAs or highly processed tumor antigens were excluded. Published clinical trials were searched using Google Scholar until March 2024. The authors elaborated on the risk of bias in such cases, as indicated. All reviewed publications were searched for evidence of autoimmunity, cancer seeding, and other AEs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement guided the review.</div></div><div><h3>Results</h3><div>Data from 55 human clinical trials, abstracts, case reports, and unpublished data were analyzed, including 3323 patients treated with WATVs for various cancers. The primary outcomes were: (1) no documented cases of WATV-induced autoimmunity, (2) no documented cases of WATV-induced spreading or seeding of noninfectious cancers, and (3) the observed 0.24% (2/838) risk of spreading or seeding infectious cancers was attributed to inadequate sterilization. The secondary outcomes were: (1) no deaths were attributed to WATV therapy, (2) 0.18% (6/3323) incidence of grade 4 AEs, (3) 0.42% (14/3323) incidence of grade 3 AEs, (4) the incidence of grades 1–2 AEs was 52.21% (478/916).</div></div><div><h3>Conclusions</h3><div>WATVs carry no risk of inducing autoimmunity and essentially no risk of cancer seeding if properly sterilized. WATVs also exhibit a side effect profile comparable to that of routine vaccinations, with common, mild, and transient adverse effects. The combined risk of grade 3 and 4 AEs was 0.60% (20/3323). No deaths were causally associated with WATV treatment.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 129-134"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609834","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":"Handy “tools” for studying brain tumors","authors":"Gangfeng Yu,&nbsp;Fanghui Lu,&nbsp;Liangxue Zhou","doi":"10.1016/j.cpt.2024.06.009","DOIUrl":"10.1016/j.cpt.2024.06.009","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 87-88"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141713150","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":"A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer","authors":"Jianqiong Yin ,&nbsp;Jing Huang ,&nbsp;Min Ren ,&nbsp;Rui Tang ,&nbsp;Linshen Xie ,&nbsp;Jianxin Xue","doi":"10.1016/j.cpt.2024.06.004","DOIUrl":"10.1016/j.cpt.2024.06.004","url":null,"abstract":"<div><h3>Background</h3><div>To date, no direct comparisons have been performed to compare the effectiveness of all epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) against <em>EGFR</em> mutation-positive non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of EGFR-TKIs in patients with <em>EGFR</em> mutation-positive NSCLC.</div></div><div><h3>Methods</h3><div>We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Pooled estimations of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity (grade ≥ 3 adverse events) were performed within the Bayesian framework.</div></div><div><h3>Results</h3><div>Twenty-three trials involving 11 treatments were included. All EGFR-TKIs improved PFS relative to chemotherapy, except for icotinib (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.26–1.44). All EGFR-TKIs demonstrated significant ORR benefits over chemotherapy. Osimertinib seemed to prolong PFS compared with icotinib (HR = 0.29, 95% CI: 0.1–0.86), gefitinib (HR = 0.39, 95% CI: 0.21–0.74), and erlotinib (HR = 0.53, 95% CI: 0.29–1.0). In addition, osimertinib showed favorable superiority in improving OS compared with chemotherapy (HR = 0.6, 95% CI: 0.43–0.82), gefitinib (HR = 0.61, 95% CI: 0.45–0.83), erlotinib (HR = 0.65, 95% CI: 0.48–0.89), and afatinib (HR = 0.65, 95% CI: 0.44–0.94). Among these regimens, afatinib showed the highest ORR (cumulative probability: 96.96%). Icotinib was associated with minimal toxicity among the EGFR-TKIs, followed by furmonertinib and osimertinib. Moreover, the toxicity spectra differed among the EGFR-TKIs. Subgroup analyses of patients with two common types of <em>EGFR</em> mutations indicated that furmonertinib possessed the greatest PFS benefit in patients with exon 19 deletion, and lazertinib showed the greatest PFS benefit in patients with Leu858Arg mutation. We also identified differences between EGFR-TKIs in prolonging PFS in patients with brain metastasis.</div></div><div><h3>Conclusions</h3><div>Osimertinib is the first choice of treatment with considerable efficacy and safety for <em>EGFR</em> mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 135-146"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609835","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":"Overview of skin cancer types and prevalence rates across continents","authors":"Amdad Hossain Roky ,&nbsp;Mohammed Murshedul Islam ,&nbsp;Abu Mohammed Fuad Ahasan ,&nbsp;Md Saqline Mostaq ,&nbsp;Md Zihad Mahmud ,&nbsp;Mohammad Nurul Amin ,&nbsp;Md Ashiq Mahmud","doi":"10.1016/j.cpt.2024.08.002","DOIUrl":"10.1016/j.cpt.2024.08.002","url":null,"abstract":"<div><div>Skin cancer is one of the most prevalent cancers in the world, and its incidence and mortality rates are increasing continuously, mostly in regions with white-skinned inhabitants. The types of skin cancer vary in their origin and clinical appearances and also differ in their extensiveness. The continents of the world have different scenarios of skin cancer prevalence. This review aims to explore the different types of skin cancer, their clinical features, and their worldwide prevalence based on the literature. Literature from different electronic databases, including Google Scholar, ResearchGate, PubMed, Scopus, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Elsevier, and Springer, were collected through a literature search using specific keywords such as “skin cancer”, “skin cancer types”, “melanoma”, “non-melanoma”, “skin cancer continental prevalence” or similar keywords. The search included English publications from 2000 to 2024. Melanoma skin cancer (MSC) ranks 17th in global prevalence, with the highest incidence and deaths occurring in Europe, However, Australia and New Zealand record the highest incidence and mortality rates. Asia has a lower incidence rate of melanoma, but a higher mortality rate. Superficial spreading melanoma (SSM) is the most common type of MSC. Non-melanoma skin cancers (NMSCs) have the highest incidence in North America, with the highest number of deaths occurring in Asia, Australia and New Zealand have the highest incidence rates for basal cell carcinoma (BCC). BCC is the most commonly diagnosed skin cancer worldwide and the most prevalent form of NMSCs; however, squamous cell carcinoma is the most aggressive form of NMSCs, causing more deaths. NMSCs are the most prevalent cancers worldwide, causing most skin cancer-related deaths. The prevalence of skin cancer rising globally, with several continents experiencing higher incidence and mortality rates. The types and subtypes of skin cancer are becoming more common among clinically diagnosed cancers. This review comprehensively describes skin cancer types and their prevalence worldwide. However, the actual prevalence of skin cancer in these countries should be investigated. Further research on the prevalence of skin cancer across different continents is required to develop more effective cancer management strategies and control the spread of the disease.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 89-100"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609830","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":"Integrating multi-omics methods for personalized treatment of refractory chronic myelomonocytic leukemia with NRAS and TET2 mutations","authors":"Chuandong Hou ,&nbsp;Bo Yang ,&nbsp;Yue Wang ,&nbsp;Lili Cai ,&nbsp;Ran Qin ,&nbsp;Bo Guo ,&nbsp;Jie Geng ,&nbsp;XueChun Lu","doi":"10.1016/j.cpt.2024.12.001","DOIUrl":"10.1016/j.cpt.2024.12.001","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 2","pages":"Pages 173-175"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609730","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}