Systems Biology in Reproductive Medicine最新文献

{"title":"Aberrant epithelial differentiation may contribute to endometrial polyp formation: insights from single-cell analysis.","authors":"Amruta D S Pathare, Ankita Lawarde, Katrin Täär, Sergio Vela Moreno, Apostol Apostolov, Vijayachitra Modhukur, Darja Tarassova, Alberto Sola-Leyva, Andres Salumets, Merli Saare, Maire Peters","doi":"10.1080/19396368.2026.2628916","DOIUrl":"https://doi.org/10.1080/19396368.2026.2628916","url":null,"abstract":"<p><p>Endometrial polyps (EPs) are benign overgrowths of the endometrium causing abnormal uterine bleeding and infertility. Despite their clinical significance, the molecular mechanisms underlying their development and recurrence remain poorly understood, warranting comprehensive transcriptomic investigation. We hypothesized that transcriptomic differences, particularly at the single-cell level as revealed through cellular trajectory analysis, distinguish EPs from adjacent endometrium. To investigate this, paired EP and adjacent endometrium (adEN) samples were collected from 12 women undergoing hysteroscopic polypectomy (proliferative phase, <i>n</i> = 9; secretory phase, <i>n</i> = 3) and analyzed using bulk and single-cell RNA sequencing (scRNA-seq). Bulk RNA-seq revealed high transcriptional similarity between EPs and adENs, with only a few differentially expressed genes (FDR < 0.05) in proliferative-phase EPs, including upregulation of <i>KMT2B</i> and <i>DLEC1</i> and downregulation of <i>COL9A1</i> and <i>RAB3C</i>, potentially reflecting epigenetic regulation and protective mechanisms against tumorigenesis. scRNA-seq identified eight major cell clusters namely stromal, epithelial, endothelial, immune, perivascular, macrophage, B cell, and ciliated populations in both tissues. Pseudotime analysis revealed a mid-transcriptional arrest and enrichment of <i>MECOM/EYA2</i>-positive intermediate epithelial states in EPs, in contrast to the late, mature epithelial stage seen in the adENs. This aberrant epithelial maturation may be associated with impaired perivascular and endothelial differentiation, potentially contributing to defective vascular remodeling and polyp persistence. In conclusion, while EPs exhibit global transcriptomic similarity to adENs, single-cell and pseudotime analyses suggest subtle but significant disruptions in epithelial differentiation and vascular remodeling that might be involved in EPs development. Study limitations include scRNA-seq restricted to the proliferative phase, which may limit generalizability. Nevertheless, future functional studies using primary epithelial organoids derived from EPs may provide a physiologically relevant model to evaluate targeted therapeutic strategies including hormonal interventions with potential applications in infertility management.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"131-148"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228785","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":"Bioethics in assisted reproduction and embryology.","authors":"George Anifandis, Helen G Tempest, Dimitrios Ioannou, Peter Sutovsky, Christina Messini, Katerina Chatzimeletiou, Eleni Zagelidou, Georgia Kokkali","doi":"10.1080/19396368.2026.2618252","DOIUrl":"https://doi.org/10.1080/19396368.2026.2618252","url":null,"abstract":"<p><p>The use of assisted reproductive therapies, advances in embryo research, and developments in scientific fields such as gene editing and <i>in vitro</i> gametogenesis have attracted the attention of bioethicists for years. On one side, the 14-day rule has faced criticism from embryo researchers advocating for its extension. On the other side, the increasing number of cryopreserved embryos worldwide has raised practical and ethical concerns about their fate. While advancements in scientific research, especially gene editing and in-vitro gametogenesis (IVG), are not yet fully applicable, their potential future use appears to pose significant bioethical questions. In this review, we examine the evolving bioethics of embryo research, focusing on the 14-day rule, the challenges surrounding surplus cryopreserved embryos, and the future dilemmas posed by CRISPR-based gene editing, IVG, and preimplantation genetic testing for polygenic risk (PGT-P). We also highlight the critical role of multidisciplinary, patient-centered counseling in ART practice, to foster informed consent, realistic expectations, and psychosocial well-being. Finally, we underscore the need for anticipatory ethical frameworks and open-society engagement that integrate public deliberation with scientific progress to ensure that reproductive innovation proceeds responsibly, preserving both human dignity and social justice.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"87-100"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046985","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":"SBiRM 2026.","authors":"Stephen A Krawetz","doi":"10.1080/19396368.2025.2605839","DOIUrl":"https://doi.org/10.1080/19396368.2025.2605839","url":null,"abstract":"","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"1-2"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913055","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":"Metabolomic analysis of follicular fluid in women with unexplained infertility.","authors":"Durva Panchal, Aishani Bose, Grishma Desai, Priyanka Vora, Priyanka Parte","doi":"10.1080/19396368.2026.2637454","DOIUrl":"https://doi.org/10.1080/19396368.2026.2637454","url":null,"abstract":"<p><p>Unexplained infertility (UI) affects ∼10% of infertile couples, yet standard diagnostic protocols fail to identify a cause. Follicular fluid (FF), which supports oocyte development, contains metabolites that may reflect underlying molecular disturbances. In this exploratory study, we investigated the FF metabolome of women with UI and compared it with controls to explore metabolic alterations associated with UI. FF was collected during oocyte retrieval from 20 women undergoing IVF (ten with UI, ten with male factor infertility), matched for age, BMI, stimulation, and fertilization protocols. Metabolomic profiling was performed using hydrophilic interaction and reversed-phase liquid chromatography coupled to Q-TOF-MS/MS, followed by metabolite identification (XCMS Online and MetaboAnalyst) and KEGG pathway analysis. Approximately 2000 features were detected. Differential metabolites were identified by OPLS-DA (VIP > 2) and validated using univariate metrics such as fold change (|log₂FC| > 1), statistical significance (<i>p</i> < 0.05), and ROC analysis (AUC > 0.8). Twelve metabolites, including diacylglycerols, phosphatidic acids, vitamin D3 derivatives (VitD3-glucosiduronate, 1α-hydroxy-2β-(5-hydroxypentoxy)-VitD3), asparaginyl-asparagine, 3α-hydroxy-6-oxo-5β-cholan-24-oic acid, Leu-Pro-Ala-Ser-Phe, triacylglycerols, phosphatidylcholine, and lactosyl-ceramide were significantly decreased, while Ile-Lys-Val-Val was increased in women with UI. Pathway analysis highlighted disruptions in glycerophospholipid, glycerolipid, steroid, and linoleic acid metabolism. Consistent with the untargeted findings, targeted analysis demonstrated significantly reduced levels of follicular 25-hydroxyvitamin D [25(OH)D] in women with UI despite uniform oral supplementation, indicating dysregulated follicular vitamin D availability. Whilst the study was limited by sample size, the metabolome analysis was performed in triplicate for each sample, thus providing preliminary insights into the metabolic disruptions in FF from women with UI.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"168-184"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373211","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":"Future directions in infertility research: the role of generative AI and large language models.","authors":"Hasan M Jamil","doi":"10.1080/19396368.2026.2627889","DOIUrl":"https://doi.org/10.1080/19396368.2026.2627889","url":null,"abstract":"<p><p>Male infertility remains an understudied yet significant contributor to global reproductive health challenges, with up to 50% of infertility cases involving a male factor and a large proportion still classified as idiopathic. Recent advances in generative artificial intelligence (AI), particularly large language models (LLMs), offer a transformative opportunity to tackle persistent gaps in understanding the genetic, epigenetic, and environmental determinants of male infertility. This chapter explores the scientific potential of LLMs and related AI technologies in accelerating discov-eries across the male reproductive research continuum - from interpreting complex genomic data and identifying novel gene - environment interactions to enhancing sperm quality assessment and predicting an unborn child's long-term health risks stemming from paternal factors. Real-world examples and emerging case studies illustrate how generative AI can help fertility researchers learn rapidly, synthesize massive volumes of literature, generate hypotheses, design experiments, and reveal patterns that conventional analyses may miss. The narrative further reflects on the implications of using AI to forecast offspring health <i>via</i> polygenic risk scoring and in silico developmental simulations, highlighting both technical promise and ethical considerations. Written from the perspective of a computational scientist collaborating with fertility experts, this chapter demonstrates how interdisciplinary approaches, amplified by LLMs, can lower barriers between computer science and reproductive biology. By embracing generative AI responsibly - with attention to data quality, interpretability, and social responsibility - male infertility researchers stand poised to unlock novel insights that will benefit not only current patients but also future generations.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"185-210"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469103","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":"The biology and clinical aspects of female infertility.","authors":"Mitko Madjunkov, Svetlana Madjunkova, Clifford Librach","doi":"10.1080/19396368.2025.2593345","DOIUrl":"10.1080/19396368.2025.2593345","url":null,"abstract":"<p><p>Female infertility is a multifactorial condition with complex biological and clinical underpinnings. Biologically, female-related infertility may stem from disruptions in the hypothalamic-pituitary-ovarian (HPO) axis, impaired folliculogenesis, oocyte maturation defects, uterine abnormalities, endometrial dysfunction, and fallopian tube abnormalities. This review highlights key genetic mechanisms contributing to reproductive dysfunction and their relevance to diagnosis and treatment. Chromosomal abnormalities, including Turner syndrome and X-autosome translocations, also contribute to infertility and recurrent pregnancy loss (RPL). Age-related declines in oocyte quality and quantity-due to increased aneuploidy significantly impact fertility after the mid-30s. Clinical causes such as polycystic ovary syndrome (PCOS), luteal phase defects, and endometriosis contribute to infertility through hormonal imbalance, inflammation, and impaired implantation. Environmental and lifestyle factors-like endocrine-disrupting chemicals, obesity, smoking, and stress-further influence reproductive function. Evaluation requires a multidisciplinary approach combining hormonal profiling, imaging, and genetic diagnostics. Ovarian reserve assessment using anti-Müllerian hormone (AMH) and antral follicle count (AFC), hormonal evaluation along with ultrasound and hysterosalpingography, are central to clinical workups. Next-generation sequencing is enhancing the role of genetic screening in unexplained infertility and specific conditions like POI and endometriosis. Treatment options-ranging from ovulation induction to surgery and assisted reproductive technologies (ART)-are increasingly personalized based on underlying causes and patient profiles. Despite advances, many cases remain idiopathic, highlighting the need for deeper molecular research and refined phenotyping. This review emphasizes the importance of precision medicine and an evidence-based, patient-centered approach to improve fertility outcomes across a broad spectrum of infertility etiologies.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"23-54"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960291","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":"HDAC6 interacting-microtubule associated proteins (HMAPs) identified in human sperm.","authors":"Veena Chawan, Aniket Patankar, Smita Yevate, Rahul Gajbhiye, Sinetra Kushte, Kedar Ganla, Priyanka Parte","doi":"10.1080/19396368.2026.2631565","DOIUrl":"10.1080/19396368.2026.2631565","url":null,"abstract":"<p><p>Sperm flagellar axoneme comprises microtubules (MT) and associated machinery and is an integral determinant of sperm motility. Reports from our lab show reduced levels of acetyl α-tubulin, and HDAC6, along with compromised axoneme polymerization in sperm of asthenozoospermic men. These observations prompted us to identify the sperm repertoire of HDAC6-interacting proteins(HIPs) associated with the MTs. HIPs and Microtubule associated protein (MAP) fractions, respectively, were isolated from sperm of normozoospermic individuals, subjected to tandem mass spectrometry(MS) using a bottom-up approach and proteins in the two groups were identified. 1224 and 315 proteins were identified in the respective groups. Seven clusters of HIPs were among the top 20 significant clusters. Proteins were manually curated from these relevant clusters and overlapped with the MAPs dataset which identified 14 HDAC6 interacting proteins to be associated with MTs (HMAPs). On further analysis with MAP analyzer-LZTFL1, RAB7A, AIFM1 demonstrated low specificity toward MT whereas MYH10 and CFAP53 demonstrated high specificity. Among these HMAPs, EEF1A2, MYH10, ANXA1, TUFM, SOD1, and SRSF7 are known to interact with HDAC6 as documented in the BioGRID database. Interaction of CFAP53 with HDAC6 was validated by double immunofluorescence staining and co-immunoprecipitation in rat sperm. LFQ-DDA analysis of these HMAPs, revealed significantly lower abundance of CFAP53 and TUFM with higher abundance of MYH10 in asthenozoospermic men. Their differential expression in men with poor sperm motility as well as enrichment of acetylation on these HMAPs highlights their association with HDAC6 in maintaining axonemal stability/dynamicity and acetylation-deacetylation to the extent required for sperm motility, although interpretation is limited by the small sample size, restricted availability of human sperm for experimental validation, and reliance on <i>in silico</i> acetylation predictions.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"149-167"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318285","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":"Novel <i>DNAH1</i> variants in Chinese males with MMAF-associated asthenoteratozoospermia.","authors":"Kun Ye, LeiYu Deng, Fei Huang, Feiyan Mao, Jinhao Liu, Erkai Liu, Hongbo Zhang, Jianlin Chen, Jia Deng, Aimin Deng, Zenghui Mao, Hualin Huang","doi":"10.1080/19396368.2026.2619009","DOIUrl":"https://doi.org/10.1080/19396368.2026.2619009","url":null,"abstract":"<p><p>Asthenoteratozoospermia is a major contributor to male infertility, with multiple morphological abnormalities of the flagellum (MMAF) representing a genetically heterogeneous disorder characterized by structural defects in sperm flagella. To identify the genetic determinants underlying MMAF-associated infertility, we conducted a comprehensive and systematic investigation involving Chinese infertile couples exhibiting the MMAF phenotype and undergoing assisted reproductive technology (ART). Our integrated approach combined whole-exome sequencing (WES) with Sanger sequencing for variant validation, complemented by scanning and transmission electron microscopy (SEM/TEM) to elucidate ultrastructural features. Molecular analyses included quantitative real-time PCR (qRT-PCR) and immunofluorescence (IF) to evaluate both transcriptional and translational alterations. We identified novel variants in six loci of dynein axonemal heavy chain 1 (<i>DNAH1</i>), including both missense and frameshift variants, across three unrelated families. Affected spermatozoa demonstrated characteristic morphological and ultrastructural abnormalities, while qRT-PCR and IF analyses revealed altered expression patterns of <i>DNAH1</i>. Personalized ART strategies enabled successful pregnancies in individuals harboring <i>DNAH1</i> variants. While the limited sample size reflects the rarity of this genetic disorder, functional validation beyond expression analysis and structural prediction remains limited. Larger cohorts and in-depth biochemical assays will be required to generalize the findings. Nonetheless, our findings provide important insights into the genetic mechanisms of MMAF and its clinical management.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"116-130"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094171","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":"Molecular mechanisms of folliculogenesis and oogenesis.","authors":"Mohamed Aboul Ezz, Ahmed Zaky Balboula","doi":"10.1080/19396368.2026.2631558","DOIUrl":"10.1080/19396368.2026.2631558","url":null,"abstract":"<p><p>Folliculogenesis is a complex, multi-stage process crucial for the establishment and maintenance of female fertility through the production of a developmentally competent oocyte. Folliculogenesis, including follicular formation, activation, growth and maturation, relies on a finely tuned spatiotemporal crosstalk between germ cells, somatic cells, and the hypothalamic-pituitary-ovarian axis. This work provides a comprehensive overview of the cellular dynamics and molecular mechanisms underlying each stage of follicular development. A particular emphasis is placed on the interaction of growth factors, transcriptional networks, signaling pathways and endocrine cues that collectively govern follicular fate and oocyte quality. Disruptions in these interactions lead to emergence of pathological conditions such as premature ovarian insufficiency and age-related infertility. We further highlight the dual aspects of oocyte maturation, nuclear and cytoplasmic, as major determinants of developmental competence, and explore the role of spindle dynamics, organelle redistribution and epigenetic reprograming in this process. The bidirectional communication between oocytes and cumulus cells, mediated by paracrine signaling and jap junctions, is underscored as a pivotal regulator of oocyte metabolic activity, redox homeostasis, and meiotic competence. A better understanding of the oocyte-cumulus cell interaction offers new approaches for refining the <i>in vitro</i> maturation systems and improving assisted reproductive technologies. A special attention is given to the emerging use of cumulus cell-derived biomarkers for noninvasive assessment of oocyte quality and prediction of preimplantation embryo development. Taken together, this article presents an integrated framework to guide future research in reproductive biology, regenerative medicine, and fertility preservation.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"211-240"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertilization and oocyte activation: overview, updates, and novel hypotheses from a molecular perspective.","authors":"Valentina Di Nisio, Peter Sutovsky, Sevastiani Antonouli, Christina Messini, Katerina Chatzimeletiou, Georgia Kokkali, George Anifandis","doi":"10.1080/19396368.2026.2618253","DOIUrl":"https://doi.org/10.1080/19396368.2026.2618253","url":null,"abstract":"<p><p>The multifaceted process of fertilization encompasses a precisely orchestrated cascade of molecular and morphological modifications of the participating male and female gametes. Fertilization culminates in the union of the maternal and paternal genomes and ultimately spark the development of a new individual. During the last decade, extensive new knowledge has been gained concerning the candidate cellular and molecular mechanisms that guide each step of the process from the sperm journey through the female reproductive tract to the gamete fusion and oocyte activation. In this review, we aim at summarizing the main molecular mechanisms of sperm and oocyte activation and fertilization from the moment sperm enters the female reproductive system up to zygote formation. Focusing on molecular determinants including but not limited to ligands, receptors, and signal transducers, we describe well established and novel molecular candidates that pave the way throughout this complex process and highlight the need for further investigation toward clinical application in assisted reproductive therapy.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"101-115"},"PeriodicalIF":2.2,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047035","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}