Hematology/oncology and stem cell therapy最新文献

{"title":"A flow cytometric approach to compare stem cell apoptosis in aplastic anemia and hypoplastic myelodysplastic syndrome.","authors":"Medhat Ibrahim, Ashraf Khodeary, Shereen P Aziz, Mahmoud G Mahmoud, Asmaa A Abdel-Baset, Tamer Mohamed, Sherif A Sayed","doi":"10.4103/hemoncstem.HEMONCSTEM-D-24-00008","DOIUrl":"10.4103/hemoncstem.HEMONCSTEM-D-24-00008","url":null,"abstract":"<p><strong>Background and objectives: </strong>Aplastic anemia (AA) is a disease caused by bone marrow (BM) failure. There are many similarities between AA and hypoplastic myelodysplastic syndrome (MDS); hence, differentiating them could be problematic. The current study aimed to use the new technique of flow cytometry as a possible diagnostic tool for AA and hypoplastic MDS.</p><p><strong>Patients and methods: </strong>The BM mononuclear cell (BMMC) and blood samples from 44 participants (17 patients with AA, 13 with hypoplastic MDS, and 14 healthy controls) were collected. The flow cytometric analysis of the cluster of differentiation 34 (CD34) levels and cell apoptosis was performed for all sample types.</p><p><strong>Results: </strong>Patients with hypoplastic MDS showed a high percentage of CD34+ cells with low apoptosis, while those with AA showed a low percentage of CD34+ cells with high apoptosis.</p><p><strong>Conclusions: </strong>Despite the similarity in the clinical presentation of hypoplastic MDS and AA, they are biologically different disorders. Increased CD34+ cell numbers with high viability may provide a useful and accurate tool for the differential diagnosis of hypoplastic MDS from AA.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 3","pages":"184-189"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485229","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":"Clinical characteristics and outcomes of Fusarium infections in adult patients after hematopoietic stem cell transplantation: A meta-summary of case reports.","authors":"Leong Tung Ong","doi":"10.4103/hemoncstem.HEMONCSTEM-D-24-00009","DOIUrl":"10.4103/hemoncstem.HEMONCSTEM-D-24-00009","url":null,"abstract":"<p><p>Fusarium infections have increased, particularly among patients with hematological malignancies and in those receiving hematopoietic stem cell transplantation (HSCT). This meta-summary summarizes the clinical characteristics, treatment, and outcomes of Fusarium infections in HSCT recipients. The PubMed, ScienceDirect, and Ovid SP databases were searched from inception to January 2024 to identify relevant case reports. A total of 31 patients diagnosed with Fusarium infections after HSCT were included. The most common infection sites were the skin and soft tissues (74.2%), blood (54.8%), and lungs (41.9%). Fusarium species complex was identified in 67.7% of the patients, and the most common species was Fusarium solani (51.6%). Of the included patients, 58.1% received antifungal monotherapy, whereas 41.9% received antifungal combination therapy. The overall mortality rate was 74.2%. Cutaneous infection was associated with a low mortality rate. The median time to mortality was 28 days. Fusarium infections commonly present as disseminated infections in HSCT recipients.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 3","pages":"168-175"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485230","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":"Special Report: Summary of the eighth workshop of the worldwide network for blood and marrow transplantation on the status and issues related to hematopoietic stem cell transplantation in near-east countries, held in Pakistan from September 22 to 23, 2022.","authors":"Hildegard T Greinix, Raheel Iftikhar, Qamar Un Nisa Chaudhry, Parvez Ahmed, Murtadha Al-Khabori, Javid Gaziev, Amir Ali Hamidieh, Shahrukh Hashmi, Mohiuddin Khan, Bishesh Sharma Poudyal, Marwan Shaheen, Walid Rasheed, Sebastian Galeano, Yoshihisa Kodera, Dietger Niederwieser, Syed Osman Ahmed, Yoshiko Atsuta, Helen Baldomero, Cristobal Frutos, Minako Iida, Shinichiro Okamoto, Damiano Rondelli, Joseph Schwartz, Adriana Seber, Daniel Weisdorf, Nina Worel, Efstratios Chatzixiros, Mickey Bc Koh, Mahmoud Aljurf","doi":"10.4103/hemoncstem.HEMONCSTEM-D-24-00011","DOIUrl":"10.4103/hemoncstem.HEMONCSTEM-D-24-00011","url":null,"abstract":"<p><p>The eighth workshop of the Worldwide Network for Blood and Marrow Transplantation (WBMT) was held in Islamabad, Pakistan, from September 22 to 23, 2022, aiming to foster hematopoietic stem cell transplant (HSCT) activity in the World Health Organization (WHO) Eastern Mediterranean Region (EMRO). Participating countries, including Pakistan, Oman, Iran, and Saudi Arabia, reported increased HSCT in the last few years, whereas others from the EMRO and beyond, including Qatar, United Arab Emirates, Nepal, and Bangladesh, started HSCT recently and have developed HSCT programs with excellent results. During educational sessions and open dialog, participating teams and international experts from the WBMT shared their experience and discussed minimum essential requirements for establishing and expanding HSCT in emerging countries, indications for HSCT training and dissemination of knowledge, stem cell donor selection and safety, quality assurance in transplant centers, and the value and importance of transplant outcome databases. International support, collaboration, and local engagement, including government participation and WHO assistance, are valuable in increasing HSCT access worldwide.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 3","pages":"190-199"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485234","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":"Tumor Seeding Post Nutritional Support Implementation: A Rare Complication; A Scoping Review.","authors":"Jumanah S Alawfi, Reem M Ragea, Sadeem S Alrubaian","doi":"10.56875/2589-0646.1119","DOIUrl":"10.56875/2589-0646.1119","url":null,"abstract":"<p><p>Patients with cancer are at risk of malnutrition because of reduced food intake, thus making oral intake challenging. Thus, nutritional support is used to provide the nutrient requirements. Feeding tube site implantation among patients with cancer has been reported after endoscopic feeding gastrostomy installation. This manuscript aims to further explore this phenomenon using a structured database review. Among 33 seeding cases included in this review, case reports (70 %) were the most common study design, predominantly using percutaneous endoscopic gastrostomy via the pull method. The duration between tube implantation and seeding detection ranged from 7.12 ± 3.7 months, with some missing data among the included studies. The most common primary cancer diagnosis was head and neck cancer. Tumor seeding was higher among male patients than that in female patients. However, large-scale, statistically powered studies are needed to further investigate this complication.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 2","pages":"95-109"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338489","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":"Age-related Morphofunctional Changes in Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells.","authors":"Felipe A Rós, Péricles N M da Costa, Jonathan Milhomens, Débora G L de La-Roque, Fernanda U Ferreira, Juliana de Matos Maçonetto, Camila C de Oliveira Menezes Bonaldo, Julianne V de Carvalho, Patrícia V B Palma, Wassim El Nemer, Dimas T Covas, Simone Kashima","doi":"10.56875/2589-0646.1115","DOIUrl":"10.56875/2589-0646.1115","url":null,"abstract":"<p><strong>Background and objectives: </strong>Bone marrow mesenchymal stromal cells (BM-MSCs) are key elements of the hematopoietic niche and participate in the regulatory mechanisms of hematopoietic stem cells (HSCs). Hematological diseases can affect MSCs and their functions. However, the dysregulations caused by sickle cell disease (SCD) are not fully elucidated. This work explored changes in BM-MSCs and their relationship with age using sickle cell mice (Townes-SS).</p><p><strong>Materials and methods: </strong>BM-MSCs were isolated from Townes-SS, and control groups 30- and 60-day-old Townes-AA and C57BL/6 J.</p><p><strong>Results: </strong>The BM-MSCs showed no morphological differences in culture and demonstrated a murine MSC-like immunophenotypic profile (Sca-1+, CD29+, CD44+, CD90.2+, CD31-, CD45-, and CD117-). Subsequently, all BM-MSCs were able to differentiate into adipocytes and osteocytes in vitro. Finally, 30-day-old BM-MSCs of Townes-SS showed higher expression of genes related to the maintenance of HSCs (Cxcl12, Vegfa, and Angpt1) and lower expression of pro-inflammatory genes (Tnfa and Il-6). However, 60-day-old BM-MSCs of Townes-SS started to show expression of genes related to reduced HSC maintenance and increased expression of pro-inflammatory genes.</p><p><strong>Conclusion: </strong>These results indicates age as a modifying factor of gene expression of BM-MSCs in the context of SCD.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 2","pages":"120-129"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338483","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":"Predicting Stage Progression in Binet Stage a Chronic Lymphocytic Leukemia.","authors":"Salem H Alshemmari, Mazyad Almazyad, Ahmed Alsarraf, Anita Kunhikrishnan, Asha M Isaac, Andy Kaempf","doi":"10.56875/2589-0646.1117","DOIUrl":"10.56875/2589-0646.1117","url":null,"abstract":"<p><strong>Introduction: </strong>The variable clinical course of chronic lymphocytic leukemia (CLL) and the lack of consensus on follow-up and treatment strategies have necessitated a prognostic model for identifying high-risk patients at the time of diagnosis.</p><p><strong>Methods: </strong>We involved a retrospective analysis of demographic and clinical characteristics of 212 patients diagnosed with Binet stage A CLL and thus eligible for risk stratification by both the International Prognostic Score for Early-stage CLL (IPS-E) and the alternative IPS-E (AIPS-E). We evaluated the applicability of these prognostic indices in our young, Middle Eastern cohort (median age 59 at diagnosis).</p><p><strong>Results: </strong>During the study period with a median follow-up of 3.5 years, 67 patients (32 %) experienced progression to first treatment and cumulative incidence of treatment was 13 % at 1 year and 28 % at 3 years after diagnosis. Sixty-nine (51 % of the 136 with a known value) patients harbored an unmutated immunoglobulin heavy chain gene (IGHV) and 21 (10 %) an 11q or 17p deletion with 11 % lacking FISH results. For each early-stage CLL prognostic index, more patients were identified as high-risk for disease progression (51 % of 124 patients evaluable for IPS-E; 42 % of 109 patients evaluable for AIPS-E) than intermediate-risk and low-risk. Multivariable models involving the IPS-E and AIPS-E components revealed that unmutated IGHV and elevated absolute lymphocyte count were significant predictors of earlier treatment requirement. Both prognostic scores were discriminative of time to first treatment (log-rank p < 0.001; c-statistics of 0.74 for IPS-E and 0.69 for AIPS-E).</p><p><strong>Conclusion: </strong>Although clarity on clinical behavior with regard to initiation of treatment remains elusive, IPS-E and AIPS-E are valuable tools for identifying high-risk patients.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 2","pages":"137-145"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338487","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":"Use of Endpoints in Phase III Randomized Controlled Trials for Hematopoietic Stem Cell Transplantation Over the Last 15 Years: A Systematic Review.","authors":"Moazzam Shahzad, Muhammad Fareed Khalid, Muhammad Kashif Amin, Mohammad Ammad-Ud-Din, Usman Ilyas, Ali H Mushtaq, Atif Butt, Iqra Anwar, Sibgha Gull Chaudhary, Nausheen Ahmed, Leyla Shune, Anurag K Singh, Sunil H Abhyankar, Joseph P McGuirk, Muhammad Umair Mushtaq","doi":"10.56875/2589-0646.1118","DOIUrl":"10.56875/2589-0646.1118","url":null,"abstract":"<p><p>This systematic review aimed to evaluate the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and analyze their trends in time and study sponsorship status. The Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006 to 2021 reported 197 primary and 600 secondary endpoints. Overall survival (OS, 17 %), progression-free survival (PFS, 15 %), graft versus host disease (GVHD, 8 %), event-free survival (EFS, 8 %), and organ function (8 %) were the most common primary endpoints. GVHD (12.3 %, n = 74), safety/toxicity/adverse events (11.8 %, n = 71), OS (11.5 %, n = 69), PFS (9.3 %, n = 56), and relapse rate (RR; 7.5 %, n = 45) were the most common secondary endpoints during 2006-2021. After 2013, an increase was noted in the use of PFS as a primary endpoint (12 %-18 %, p = 0.196), while the use of OS as a primary endpoint declined (20 %-13 %, p = 0.170). An increase was observed in using the secondary endpoints RR (5 %-10 %, p = 0.047) and NRM (3 %-6 %, p = 0.047). EFS was used more (14 % vs. 4 %, p = 0.012) than ORR (11 % vs. 2 %, p = 0.003) as a primary endpoint in pharmaceutical-compared to non-pharmaceutical-sponsored studies. As secondary endpoints, the use of EFS (4 % vs. 1 %, p = 0.013) and ORR (4 % vs. 1 %, p = 0.028) was higher, whereas that of organ systems/functions (1.5 % vs. 5.5 %, p = 0.022) and GVHD (6.5 % vs. 15 %, p = 0.002) was lower in pharmaceutical-compared to non-pharmaceutical sponsored studies. GVHD-free relapse-free survival was reported as a primary endpoint in 2 % of studies, while only 5 % reported quality of life as a secondary endpoint. We described commonly used endpoints in HSCT phase III RCTs and patterns in their use over time by funding source and study intervention category.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 2","pages":"88-94"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338490","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":"Factors Influencing Life Space Mobility in Cancer Survivors Following Hematopoietic Stem Cell Transplantation - Physical Function, Depression, Fatigue, Neighborhood Walkability, and Employment Status.","authors":"Junichiro Inoue, Takashi Saito, Daisuke Makiura, Rei Ono, Hisayo Doi, Kimikazu Yakushijin, Yoshitada Sakai","doi":"10.56875/2589-0646.1120","DOIUrl":"10.56875/2589-0646.1120","url":null,"abstract":"<p><strong>Background/objective: </strong>The level of physical activity in the daily lives of cancer survivors following hematopoietic stem cell transplantation (HSCT) is crucial for maintaining their physical and mental health. Considering that life space mobility (LSM) may limit physical activity, maintaining and expanding LSM is particularly essential for post-HSCT survivors. This study aimed to identify factors influencing LSM in post-HSCT survivors.</p><p><strong>Methods: </strong>Thirty cancer survivors after HSCT (14 women, mean age 52.0 ± 12.3 years, 196-3017 days post-HSCT) were included in this cross-sectional study. The assessment encompassed patient characteristics, employment status, life space (Life Space Assessment; LSA), physical function (handgrip strength, isometric knee extension strength, 5 chair standing test, walking speed), depression (Self-rating Depression Scale; SDS), fatigue (Cancer Fatigue Scale), and neighborhood walkability (Walk Score^®). The association between LSA and each factor was compared by correlation analysis. Subsequently, multiple regression analysis was conducted, with LSA as the dependent variable and independent variables being outcome measures exhibiting a significant correlation with LSA.</p><p><strong>Results: </strong>Variables significantly correlated with LSA included SDS (r =-0.65, p < .01), employment status (r=-0.60, p < .01), handgrip strength (r = 0.43, p = .02), and isometric knee extension strength (r = 0.40, p = .03). Results of multiple regression analysis show that SDS (β = -0.53, p < .01), employment status (β = 0.48, p < .01), and isometric knee extension strength (β = 0.27, p = .02) were significantly associated with LSA (R² = 0.74).</p><p><strong>Conclusion: </strong>Depression, employment status, and isometric knee extension strength were identified as factors related to LSM in post-HSCT survivors.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 2","pages":"146-153"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338485","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":"Sickle Cell Disease Phenotypes and Obstructive Sleep Apnea; Are They Related?","authors":"Suhail Al-Saleh, Norah Alshehri, Sara Alsiddiqi, Mohmmed Rayis, Safa Eltahir, Khaled AlDajjam, Mohammed Alzaid, Wadha Alotaibi","doi":"10.56875/2589-0646.1116","DOIUrl":"10.56875/2589-0646.1116","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to compare the polysomnographic features between Arab-Indian and Benin phenotypes of sickle cell disease (SCD).</p><p><strong>Materials and methods: </strong>This prospective cross-sectional study was conducted in the Children's Hospital at King Fahad MedicalCity, in Riyadhwhere childrenwere recruited fromthe pediatric hematology clinic and pediatric sleepmedicine. All families were approached and patients who met the inclusion criteria and agreed to participate were included in the study.</p><p><strong>Results: </strong>Eighty four children (37 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.65, 11) years and their body mass index z score was -1.45 (-2.195, -1.45). The evidence of obstructive sleep apnea (OSA) was more prominent in the Benin phenotype (66.7%) in comparison to those of the Arab-Indian (35.2%) phenotype ( p = 0.006). Additionally, 56.7% of Benin had moderate to severe OSA whereas Arab-Indian had 18% with a ( p = 0.0003). Controlling for other factors, the odds ratio (confidence interval) of having OSA in Benin phenotype was 4.68 (1.42-15.38) times higher as compared to Arab-Indian phenotype.</p><p><strong>Conclusion: </strong>The risk of having OSA as well as the severity of OSA is higher in Benin phenotype as compared to Arab-Indian phenotype which indicates the presence of potential OSA risk factors other than the SCD itself.</p>","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 2","pages":"130-136"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338488","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":"Evaluation of Janus Kinase 2 Exon 12 Mutations in Patients With JAK2V617F-negative Polycythemia Vera.","authors":"Sahar Khosravi, Bahram Chahardouli, Pouyan Ebrahimi, Fatemeh N Babaei, Kamran Alimoghadam, Shahrbano Rostami","doi":"10.56875/2589-0646.1121","DOIUrl":"10.56875/2589-0646.1121","url":null,"abstract":"","PeriodicalId":516321,"journal":{"name":"Hematology/oncology and stem cell therapy","volume":"17 2","pages":"154-158"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338484","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}