European Journal of Medical Research最新文献

{"title":"Integrated weighted gene co-expression network analysis and machine learning analysis identifies SEC14L5 as a potential biomarker for polycystic ovary syndrome.","authors":"Zhe Wang, Fei Yu, Pei He, Rui Hua, Yinghe Zhao, Hongchuan Tan, Song Quan, Mian Liu","doi":"10.1186/s40001-026-04076-7","DOIUrl":"https://doi.org/10.1186/s40001-026-04076-7","url":null,"abstract":"<p><strong>Background and aims: </strong>To identify novel biomarkers and therapeutic targets for polycystic ovary syndrome (PCOS) using integrated bioinformatics approaches.</p><p><strong>Methods: </strong>We integrated two microarray datasets (GSE34526, n = 10; GSE137684, n = 12) and validated findings in an independent RNA-seq dataset (GSE168404, n = 10). We employed weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and three machine learning algorithms to investigate differentially expressed genes (DEGs) and module genes.</p><p><strong>Results: </strong>We retrieved gene expression datasets GSE34526 and GSE137684, utilizing the limma package to identify DEGs between PCOS and control subjects. WGCNA revealed 122 upregulated and 431 downregulated genes across 11 distinct modules, with the darkslateblue module containing 143 genes showing the highest Pearson correlation coefficient. Enrichment analyses indicated significant associations with pathways related to lipid metabolism, glucose metabolism, neutrophil regulation, and various immune functions. These findings were validated in an in vitro PCOS cell model.</p><p><strong>Conclusions: </strong>Our study highlights SEC14L5 as a key differentially expressed gene in PCOS, providing a promising target for clinical research and treatment of PCOS patients.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369414","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":"Exosome genomics in inflammatory bowel disease: mechanisms and diagnostic potential.","authors":"Liuqing Xu, Zanwei Tu, Xiaofang Cheng, Jing Liu","doi":"10.1186/s40001-026-04082-9","DOIUrl":"https://doi.org/10.1186/s40001-026-04082-9","url":null,"abstract":"<p><p>Exosomes, as crucial mediators of intercellular communication, shuttle a variety of biomolecules including lipids, proteins, and RNAs. In recent years, research has focused on their diagnostic and therapeutic potential, attributed to the cell-of-origin specificity of their components and their stability in bodily fluids. However, clinical translation of exosome-based applications remains challenged by the high heterogeneity of exosomes and the complexity of isolation and characterization techniques. The global incidence of inflammatory bowel disease (IBD) is on the rise, with its pathogenesis involving multiple factors such as genetics, immune dysregulation, and intestinal dysbiosis. Exosome-related studies have furnished multidimensional tools to address the research challenges in IBD; particularly, the integration of multi-omics technologies and engineering strategies has facilitated the translation of IBD research from the basic to the clinical setting. This review summarizes the basic background of exosomes and exosomics technologies, elaborates on the regulatory roles of exosomes and the functional implications of exosomics, and focuses on the applications of exosomes in IBD.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369410","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":"Correction: Application of risk prediction model to evaluate the effect of mechanical ventilation on postoperative pulmonary complications in thoracic surgery.","authors":"Li Wang, Xiaoyun He, Minxi Zhao, Jun Liu","doi":"10.1186/s40001-026-04121-5","DOIUrl":"10.1186/s40001-026-04121-5","url":null,"abstract":"","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of fospropofol disodium versus propofol for general anesthesia induction: a systematic review and meta-analysis.","authors":"Yunpeng Xu, Qian Liu, Zi Yang, Lei Zhu, Xiaojing Jia, Hong Guo, Yang Jiao, Kangtai Wang, Jian Liu","doi":"10.1186/s40001-026-04165-7","DOIUrl":"https://doi.org/10.1186/s40001-026-04165-7","url":null,"abstract":"<p><strong>Background: </strong>Propofol is a widely used agent for general anesthesia induction, with well-established anesthetic efficacy. However, its use is frequently associated with adverse reactions such as injection pain and circulatory depression. Fospropofol disodium, a water-soluble prodrug of propofol, has the potential to alleviate these issues. This study aimed to systematically review and meta-analyze the differences in efficacy and safety between fospropofol disodium and propofol for general anesthesia induction.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data, VIP, and SinoMed, covering studies up to July 2025. Additional searches were performed in Google Scholar, ClinicalTrials.gov, and the Chinese Clinical Trial Registry (ChiCTR). Randomized controlled trials (RCTs) comparing fospropofol disodium and propofol for anesthesia induction were included. Data were analyzed using Review Manager 5.4 and Stata 15.1. Study quality was assessed using the Cochrane Risk of Bias tool.</p><p><strong>Results: </strong>A total of nine RCTs were included. Compared to propofol, fospropofol disodium (≥ 20 mg/kg) showed no significant difference in induction success rate (RR = 0.99; 95% CI 0.97 to 1.01; P = 0.15; high-certainty), but was associated with a significantly longer anesthesia induction time (SMD = 2.76; 95% CI 2.11 to 3.41; P < 0.00001; moderate-certainty). No significant difference was observed in recovery time (SMD = 0.19; 95% CI - 0.27 to 0.64; P = 0.42; low-certainty). For hemodynamic change during induction, there were no significant differences in heart rate (MD = - 1.54; 95% CI -3.15 to 0.07; P = 0.06; moderate-certainty) or mean arterial pressure (MD = - 2.91; 95% CI - 6.55 to 0.74; P = 0.12; moderate-certainty). Regarding adverse event indicators, fospropofol disodium significantly reduced the incidence of injection pain and bradycardia (RR = 0.23; 95% CI 0.18 to 0.29; P < 0.00001; moderate- to high-certainty; RR = 0.69; 95% CI 0.56 to 0.86; P = 0.0008). However, it was associated with significantly higher rates of pruritus and paresthesia compared to propofol (RR = 20.57; 95% CI 9.78 to 43.27; RR = 21.36; 95% CI 12.01 to 38.01; P < 0.00001; high-certainty).</p><p><strong>Conclusions: </strong>This meta-analysis suggests that high-dose fospropofol disodium achieves a comparable induction success rate to propofol and provides clear advantages in reducing injection pain and bradycardia. However, these benefits should be weighed against its delayed onset and the markedly higher rates of paresthesia and pruritus. Overall, fospropofol disodium may serve as a feasible alternative for selected patients. Given the limited current evidence, further high-quality RCTs are needed to clarify its indications and long-term safety profile. Research registration This study was registered in PROSPERO (CRD420251110352).</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369353","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":"Heterogeneous associations between molecular subtypes of small cell lung cancer and survival prognosis: a systematic review highlighting knowledge gaps.","authors":"Shumeng Li, Hui Li, Jinghong Wu, Lin Cheng, Ganlin Zhang, Teng Ma, Guowang Yang","doi":"10.1186/s40001-026-04052-1","DOIUrl":"https://doi.org/10.1186/s40001-026-04052-1","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) is a heterogeneous disease with different pathogenic mechanisms. A range of molecular classification systems has been proposed based on the tumor's molecular characteristics. However, the relationship between these various molecular subtypes and survival prognosis remains unclear and has not been incorporated into clinical practice. Therefore, we conducted a systematic review of studies investigating the relationship between molecular subtypes of SCLC and patient survival prognosis.</p><p><strong>Method: </strong>A comprehensive search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases, utilizing combinations of terms related to SCLC, molecular subtypes, and survival prognosis. Two independent reviewers were tasked with data extraction and quality assessment.</p><p><strong>Results: </strong>Following a comprehensive review of the pertinent literature, eight studies were included. Some methodological heterogeneity across these studies contributed to frequently inconsistent conclusions. Our findings tend to suggest that the inflammatory subtype (SCLC-I), which belongs to the non-neuroendocrine (non-NE) subtype, exhibits a survival advantage in most cases, while the ASCL1-dominant subtype (SCLC-A), which belongs to the NE subtype, shows a poorer survival prognosis, except in some exceptional cases.</p><p><strong>Conclusions: </strong>This is one of the first comprehensive systematic reviews to explore the relationship between molecular subtypes and survival prognosis in SCLC. Future high-quality studies employing standardized subtype definitions are warranted to validate these prognostic associations and enable definitive conclusions. Furthermore, emerging multi-omics and integrated spatial analyses have revealed novel subtypes and predictors, which are significantly associated with survival prognosis.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369403","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":"Correction: CMTM6 drives glioblastoma progression by promoting M2 polarization and suppressing antigen presentation in microglia/macrophages.","authors":"Xiang Li, Wenbo Han, Wenpei Cai, Ruoxin Yang, Gaojie Bai, Changxiu Sun, Shiyuan Ge, Cheng Zhang, Xinyi Han, Han Yang, Yi Chen, Qiao Shan, Xiaohui Li, Xueli Tian, Yuan Lyu, Junqi Li, Xinjun Wang","doi":"10.1186/s40001-026-03917-9","DOIUrl":"10.1186/s40001-026-03917-9","url":null,"abstract":"","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective cohort study on the interaction between arterial stiffness and insulin resistance in chronic heart failure.","authors":"Lingyu Ma, Wei Guo, Jinhua Bi, Xiaoli Liu, Xue Bao, Guo Song, Rong Gu","doi":"10.1186/s40001-026-04146-w","DOIUrl":"https://doi.org/10.1186/s40001-026-04146-w","url":null,"abstract":"<p><strong>Background: </strong>Arterial stiffness and insulin resistance are established risk factors for chronic heart failure (CHF), yet their interaction in CHF remains unclear.</p><p><strong>Methods: </strong>We analyzed 1,162 hospitalized CHF patients at Nanjing Drum Tower Hospital. Estimated pulse wave velocity (ePWV) was calculated using a nonlinear function of age and mean blood pressure, and the triglyceride-glucose index (TyG) was calculated based on fasting triglyceride and plasma glucose levels. Participants were stratified into four groups by the medians of ePWV and TyG. Restricted cubic spline (RCS) analysis examined nonlinear associations, while Cox proportional hazards regression assessed cardiovascular mortality risk; additive and multiplicative interactions between ePWV and TyG were further evaluated.</p><p><strong>Results: </strong>During a median follow-up of 921 days, 121 cardiovascular deaths occurred. RCS revealed a nonlinear J-shaped association between ePWV and cardiovascular mortality risk (inflection point: 11.36 m/s; 95% CI 11.35-11.38, P for nonlinearity = 0.013). In the combined analysis comparing with the dual-low group, cardiovascular mortality risk was significantly elevated when both markers were above the median (HR = 2.99, 95% CI 1.73-5.17). Controlling for one of the two factors below the median, the isolated elevation of the other marker did not lead to a significant increase in risk. Additive interaction analysis indicated a synergistic effect (RERI = 1.52, 95% CI 0.28-2.99; AP = 0.52, 95% CI 0.08-0.81), whereas multiplicative interaction was nonsignificant (P = 0.065). Findings were consistent across subgroups and robust to sensitivity analyses.</p><p><strong>Conclusion: </strong>In CHF, concomitant elevation of ePWV and TyG conferred a 2.99-fold increased risk, with 52% attributable to their interaction.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369377","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":"PABPC1 regulates EOPE pathogenesis through modulating TMBIM4 mRNA expression and stability.","authors":"Shuyu Zhao, Nan Lv, Tianyi Liu, Yuhong Sun, Peiling Li","doi":"10.1186/s40001-026-04149-7","DOIUrl":"https://doi.org/10.1186/s40001-026-04149-7","url":null,"abstract":"<p><p>Preeclampsia (PE), a rare complication with a high incidence and mortality rate, causes tremendous mental and physical impairment to pregnant women. Emerging studies have identified that PE was primarily induced by inadequate trophoblast migration and invasion. Poly(A) Binding Protein Cytoplasmic 1 (PABPC1) is a critical modulator of mRNA translation and stability, with established role in modulating proliferation, apoptosis, and invasion of tumor cells. Transmembrane BAX Inhibitor Motif Containing 4 (TMBIM4), which negatively regulates apoptosis, is downregulated in placental tissues of patients with early-onset preeclampsia (EOPE). Notably, 3'UTR motif of TMBIM4 mRNA contains PABPC1 binding site. Here, we investigated the functional role of PABPC1 on regulating proliferation and invasion of trophoblast cells, and how PABPC1 modulated mRNA stability of TMBIM4. HTR-8/SVneo cells transfected with silencing or overexpressed PABPC1 plasmid were applied as the in vitro model. The results revealed that PABPC1 facilitated cell proliferation, migration, and invasion as well as inhibited apoptosis. Moreover, Sprague Dawley rats were received intraperitoneal lipopolysaccharides administration at 40 μg/kg on gestational days 14.5, 15.5, and 16.5. Upregulated PABPC1 ameliorated elevated blood pressure and severe kidney impairment. Furthermore, for the rescue experiments, the effect of PABPC1 on boosting cell proliferation and invasion was blocked by silencing TMBIM4. More interestingly, according to RIP-qPCR and dual luciferase reporter assays, PABPC1 enhanced TMBIM4 expression through enhancing its mRNA stability via binding to its 3'UTR. Taken together, PABPC1 suppressed EOPE development through boosting trophoblast proliferation and invasion by elevating TMBIM4 mRNA stability. Our findings firstly elucidated the vital effect of PABPC1 on EOPE pathogenesis and highlighted that PABPC1 upregulation might be developed as a promising strategy for EOPE treatment.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364463","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":"Autophagy promotes the brain metastasis of cisplatin-resistant lung cancer cells through the KLF4/KLF2/IL15 signaling pathway.","authors":"Yong Cai, Wentao Zhao, Jiying Wang","doi":"10.1186/s40001-026-04166-6","DOIUrl":"https://doi.org/10.1186/s40001-026-04166-6","url":null,"abstract":"<p><strong>Background: </strong>Patients with lung cancer often develop brain metastases. The mechanism underlying the enhanced metastatic potential of drug-resistant lung cancer cells is unclear. Previously, we demonstrated that hypoxia-induced autophagy promotes cisplatin resistance. However, the effect of autophagy induction on pro-metastatic gene expression during drug resistance development has not been examined.</p><p><strong>Objective: </strong>This study aimed to explore the molecular mechanism underlying autophagy mediated brain metastasis.</p><p><strong>Methods: </strong>This study evaluated autophagy activation in cisplatin-resistant A549 (A549/DDP) and SK-MES-1 (SK-MES-1/DDP) cells. Differential gene analysis using GSE213102, GSE108214, GSE110495, GSE161116, and GSE73158 datasets revealed that IL-15 is a key component in the interplay between cisplatin resistance, autophagy, and brain metastasis. Next, the mechanism through which A549/DDP cells suppress natural killer (NK) cell activation was examined. The regulatory effects of the transcription factors KLF4 and KLF2 on IL15 were investigated using the luciferase reporter, chromatin immunoprecipitation, and DNA pull-down assays. In vivo brain metastasis was modeled in mice via carotid artery injection.</p><p><strong>Results: </strong>Drug-resistant cells exhibited enhanced autophagy activation and ATG5 upregulation. IL-15 was downregulated in drug-resistant cells, impairing NK cell activation by downregulating IFN-γ, granzyme B, and perforin. Mechanistically, ATG5 upregulated KLF4/KLF2, which subsequently repressed IL15. KLF4 could directly bind the IL15 promoter, while KLF2 inhibited NF-κB (p50/p65)-driven IL15 transcription by interacting with PCAF. IL-15 overexpression suppressed the brain metastasis of A549/DDP cells in mice.</p><p><strong>Conclusion: </strong>The autophagy-ATG5-KLF4/KLF2 axis may downregulate IL-15 in cisplatin-resistant lung cancer cells, suppressing NK cell activation and promoting brain metastasis. These findings offer useful insights into the mechanisms underlying the brain metastasis of lung cancer and provide valuable reference for the development of preventive and therapeutic strategies for this pathological condition.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364441","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":"Musculoskeletal consequences of coeliac disease.","authors":"Filippo Migliorini, Francesco Simeone, Luise Schäfer, Dragana Katusic, Raju Vaishya, Michael Kurt Memminger","doi":"10.1186/s40001-026-04010-x","DOIUrl":"https://doi.org/10.1186/s40001-026-04010-x","url":null,"abstract":"<p><p>Coeliac disease is no longer confined to the gastrointestinal tract. Increasing evidence has positioned it as a systemic condition with profound implications for bone, muscle, and joint health. Yet, the musculoskeletal consequences of coeliac disease remain largely under-recognised, underdiagnosed, and undertreated. This narrative review critically explores the multifaceted pathophysiology linking gluten sensitivity to skeletal fragility, sarcopenia, and autoimmune arthropathies, integrating findings from paediatric to elderly populations. Nutritional deficiencies, chronic inflammation, immune dysregulation, and alterations in gut microbiota emerge as central contributors to musculoskeletal decline. Clinical evidence highlights increased fracture risk, early-onset osteoporosis, muscle wasting, and functional impairment, even in asymptomatic individuals or those with potential coeliac disease. Diagnostic and therapeutic strategies require a multidisciplinary approach that combines gluten exclusion, biomarker surveillance, physical rehabilitation, and targeted nutritional support. By unveiling the often-overlooked musculoskeletal burden of coeliac disease, this review calls for broader clinical awareness and a re-evaluation of management priorities in both gastroenterology and musculoskeletal medicine.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364393","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}