Revista De Investigacion Clinica-Clinical and Translational Investigation最新文献

{"title":"LINC01614 activated by SP1 promoted malignant behavior of triple-negative breast cancer cells via the WNT/b-Catenin signaling pathway.","authors":"Tao Chen, Kenzi Shi, Shengrong Sun","doi":"10.24875/RIC.24000093","DOIUrl":"10.24875/RIC.24000093","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer (BC), characterized by a dismal prognosis. Dysregulated long non-coding RNA LINC01614 might be a potential biomarker for BC as previously reported. Nevertheless, its functions and mechanism in TNBC cells are unclear.</p><p><strong>Objectives: </strong>The study aimed to study the effects of LINC01614 on TNBC cell migration, invasion, and epithelial-mesenchymal transition (EMT) process as well as the related mechanism.</p><p><strong>Methods: </strong>Reverse transcription quantitative polymerase chain reaction was performed to detect the expression of LINC01614 and SP1 in TNBC cells and tissues. The cellular localization of LINC01614 was determined by subcellular fraction assays. Cell counting kit-8 and Transwell invasion assays were conducted for measurement of TNBC cell viability and invasive ability. Cell migration was performed using wound healing assays and Transwell migration assays. Chromatin immunoprecipitation assays and luciferase reporter assays were used to explore the interaction between SP1 and LINC01614. Western blotting was used to assess protein levels of factors involved in EMT process and Wnt/ß-catenin signaling in TNBC cells.</p><p><strong>Results: </strong>LINC01614 expression was elevated in TNBC tissues and cells. LINC01614 knockdown inhibited cell viability as well as migratory and invasive abilities of TNBC cells. LINC01614 knockdown also obstructed EMT process, as shown by E-cadherin upregulation and vimentin downregulation in TNBC cells. SP1 directly bound to the promoter of LINC01614 and activated LINC01614 expression. SP1 overexpression reversed the suppressive effect of LINC01614 knockdown on TNBC cell migration, invasion, and EMT process. Protein levels of Wnt and ß-catenin were diminished by LINC01614 knockdown, and the trend was partially rescued by SP1 overexpression.</p><p><strong>Conclusion: </strong>SP1-induced LINC01614 promoted malignant behavior of TNBC cells by activating the Wnt/ß-catenin signaling pathway.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding Diagnostic Workup for hypertensive Intracerebral hemorrhage: a retrospective LATAM cerebrovascular registry comparison.","authors":"Amado Jiménez-Ruiz, Naomi N Becerra-Aguiar, Victor Aguilar-Fuentes, Juan C Ayala-Alvarez, Enrique Gómez-Figueroa, Carlos Cantú, Antonio Arauz, Fabiola Serrano-Arias, José L Ruiz-Sandoval","doi":"10.24875/RIC.24000142","DOIUrl":"https://doi.org/10.24875/RIC.24000142","url":null,"abstract":"<p><strong>Background: </strong>The leading cause of spontaneous intracerebral hemorrhage (ICH) is hypertensive arteriolopathy. In addition to age and hypertension history, patients usually present other comorbidities that potentially increase morbimortality. Ancillary studies other than non-contrast computerized tomography (NCCT) may help clarify the diagnosis and increase the detection of potentially modifiable vascular risk factors. Unfortunately, their use is not routinely performed.</p><p><strong>Objective: </strong>The study aimed to determine the frequency of ancillary studies performed in patients with hypertensive ICH.</p><p><strong>Methods: </strong>We performed a retrospective analysis of three Latin American cerebrovascular registries from academic medical centers, analyzing the results with descriptive statistics focusing on diagnosis and short-term outcomes.</p><p><strong>Results: </strong>We analyzed a total of 1,324 patients (mean age 64 years). Hypertension and obesity were the most prevalent risk factors. Only 14% underwent MRI, 10.3% extracranial ultrasonography, and 6.7% echocardiography. Among the three registries, the Latin America Stroke Registry performed more ancillary studies. Most of the patients presented a poor clinical outcome and in-hospital death.</p><p><strong>Conclusions: </strong>The use of ancillary studies in the diagnostic workup of ICH was poor in the three registries, and mortality was high. The lack of ancillary studies performed may negatively impact outcomes.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the HAS-BLED scale for the assessment of bleeding risk in patients on anticoagulation therapy with a diagnosis of venous thromboembolic disease.","authors":"Stephanie Ortiz-Gómez, Paula Ruiz-Talero, Oscar Muñoz","doi":"10.24875/RIC.24000147","DOIUrl":"https://doi.org/10.24875/RIC.24000147","url":null,"abstract":"<p><strong>Background: </strong>Several models have been developed to assess bleeding risk in patients with venous thromboembolism, such as HAS-BLED, but their external validity has not been adequately assessed.</p><p><strong>Objective: </strong>The objective of the study was to evaluate the discriminative ability and calibration of the HAS-BLED scale for predicting 1-month bleeding risk in patient's anticoagulated for venous thromboembolism.</p><p><strong>Materials and methods: </strong>External validation study of a prediction model based on a retrospective cohort of patients with venous thromboembolism treated between November 2019 and January 2022. Calibration of the HAS-BLED scale was evaluated using the Hosmer-Lemeshow test and the ratio of observed to expect events within each risk category. Discriminatory ability was assessed using the area under the curve (AUC) of a receiver operating characteristic curve.</p><p><strong>Results: </strong>We included 735 patients (median age 64 years, female sex 55.2%), pulmonary embolism was diagnosed in most patients (60.7%), and 4.9% presented bleeding events. Regarding calibration, the HAS-BLED scale systematically underestimates the risk both in the general population (ROE 3.76, p < 0.001) and in cancer patients (ROE 4.16). The Hosmer-Lemeshow test rejected the hypothesis of adequate calibration (p < 0.001). Discriminatory ability was limited both in the general population (AUC = 0.57, 95% confidence interval [CI]: 0.48-0.66) and in the subgroup with active cancer (AUC = 0.53, 95% CI: 0.36-0.69).</p><p><strong>Conclusion: </strong>The HAS-BLED scale in patients with venous thromboembolism underestimates the risk of bleeding at 1 month and has a low ability to discriminate high-risk patients. Cautious interpretation of the scale is recommended until additional evidence is available.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypes distribution of the SNP RS1477196 of FTO gen associated with primary knee osteoarthritis in females: an analysis using the 100Genomes database.","authors":"Ángel Roco-Videla, Sergio V Flores, Mariela Olguin-Barraza","doi":"10.24875/RIC.24000159","DOIUrl":"10.24875/RIC.24000159","url":null,"abstract":"","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curzerene suppresses hepatocellular carcinoma progression through the PI3K/AKT/MTOR pathway.","authors":"Yihui Luo, Zhenchang Wang, Jun'e Jiang, Shanshan Wu, Yang Zhai","doi":"10.24875/RIC.24000018","DOIUrl":"10.24875/RIC.24000018","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. Curzerene is a sesquiterpene and component of Curcuma rhizomes and has anti-tumor and anti-inflammatory properties.</p><p><strong>Objective: </strong>The study aimed to investigate the effects of curzerene on the malignant phenotypes and tumor growth in HCC.</p><p><strong>Methods: </strong>Various concentrations of curzerene were used to treat human HCC cells (Huh7 and HCCLM3). Cell viability, apoptosis, cell cycle, invasion, and migration were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, Transwell, and wound healing assays. Cell cycle-, apoptosis-, and signaling pathway-related proteins were analyzed by Western blot analysis. A mouse xenograft model was established to analyze the anti-tumor effects of curzerene in vivo.</p><p><strong>Results: </strong>Curzerene repressed the proliferation, invasion, and migration of Huh7 and HCCLM3 cells. Curzerene also induced G2/M cycle arrest and cell apoptosis. Curzerene downregulated the CDK1, cyclin B1, PCNA, Bcl-2, matrix metallopeptidases (MMP)2, and MMP9 protein expression and upregulated the Bax, cleaved caspase3, and cleaved poly ADPribose polymerase protein expression in HCC cells. Curzerene restrained the phosphorylation of PI3K, AKT, and the Mammalian target of rapamycin (mTOR) in Huh7 and HCCLM3 cells. The in vivo data revealed that curzerene inhibited HCC tumor growth and decreased the expression of phosphorylated mTOR in xenograft mouse models.</p><p><strong>Conclusion: </strong>Curzerene inhibited cell malignancy in vitro and tumor growth in vivo in HCC, suggesting that curzerene may be a candidate agent for anti-HCC therapy.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Deficiency/Dysregulation Associated Lymphoid Proliferations, EBV+ In Persons Living With HIV.","authors":"Johanna Cevallos, Carmen Lome-Maldonado, Leticia Quintanilla-Martínez, Ivonne Montes-Mojarro, Beda Islas-Muñoz, Ana F Ramírez, Leslie Chavez-Galán, Lucero Ramón-Luing, Patricia Volkow","doi":"10.24875/RIC.24000006","DOIUrl":"10.24875/RIC.24000006","url":null,"abstract":"<p><strong>Background: </strong>The 5^th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed.</p><p><strong>Objectives: </strong>To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoidproliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated.</p><p><strong>Materials and methods: </strong>HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, <i>in situ</i> hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data.</p><p><strong>Results: </strong>We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related.</p><p><strong>Conclusion: </strong>IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rediscovering extra-axial collections on medical imaging: subdural lymphatic hygroma.","authors":"José P Martínez-Barbero, Lucía Bueno-Caravaca, Antonio J Láinez-Ramos-Bossini","doi":"10.24875/RIC.24000042","DOIUrl":"10.24875/RIC.24000042","url":null,"abstract":"","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis.","authors":"Fei Zhang, Mi Zhang, Zhen Chen, Bo Yu, Xiaoqin He, Yongfang Luo, Fen Ai, Wenfeng Hu","doi":"10.24875/RIC.23000235","DOIUrl":"10.24875/RIC.23000235","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis.</p><p><strong>Objective: </strong>The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process.</p><p><strong>Methods: </strong>Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelialmesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR.</p><p><strong>Results: </strong>PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities.</p><p><strong>Conclusion: </strong>PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time matters: an insight into the relationship between chrononutrition and diabetes.","authors":"Rossy S López-Prieto, Alonso Romo-Romo, Paola Gómez-Avilés, Shubhangi Sharma-Sharma, Ximena Costilla-Orozco, Gabriela A Galán-Ramírez, Paloma Almeda-Valdés","doi":"10.24875/RIC.23000271","DOIUrl":"10.24875/RIC.23000271","url":null,"abstract":"<p><p>Chrononutrition is a branch of chronobiology that evaluates nutrients and the pathways implicated in their regulation in accordance with circadian rhythms. Sleep deprivation and disturbances have been strongly associated with the progression of different metabolic alterations, and the time of food intake plays a fundamental role in maintaining metabolic homeostasis. It has been demonstrated that not only the components of food are important, but quantity and quality are also crucial elements of a healthy eating pattern. Chrononutrition is an emerging tool that could help improve dietary interventions beyond those derived from consuming an adequate amount of each nutrient. Diabetes is a complex endocrine pathology characterized by sustained hyperglycemia. Dietary changes are a key component in obtaining adequate control and preventing long-term complications. Recent studies emphasize the use of chrononutrition and its components as a novel dietary intervention that could improve metabolic control. The use of chrononutrition as a dietary intervention is faced with challenges such as the presence of gaps in the literature that limit its implementation. This emphasizes the imperative need for additional research that can lead to an evidence-based use of this intervention.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is iron overload associated with worse outcomes in patients with chronic liver disease undergoing liver transplantation?","authors":"Sergio Rodriguez-Rodriguez, Antonio Olivas-Martinez, Jesus Delgado-de la Mora, Braulio Martinez-Benitez, Ignacio Garcia-Juarez, Roberta Demichelis-Gomez","doi":"10.24875/RIC.23000246","DOIUrl":"10.24875/RIC.23000246","url":null,"abstract":"<p><strong>Background: </strong>Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center.</p><p><strong>Methods: </strong>We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model.</p><p><strong>Results: </strong>Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055).</p><p><strong>Conclusion: </strong>Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.</p>","PeriodicalId":49612,"journal":{"name":"Revista De Investigacion Clinica-Clinical and Translational Investigation","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}