F&S reviews最新文献

{"title":"Prevalence of adenomyosis in symptomatic adolescents and young women: a systematic review and meta-analysis","authors":"Paolo Vercellini M.D. , Camilla Buffo R.M. , Veronica Bandini M.D. , Sonia Cipriani Sc.D. , Francesca Chiaffarino M.Sc. , Paola Viganò Ph.D. , Edgardo Somigliana M.D., Ph.D.","doi":"10.1016/j.xfnr.2024.100083","DOIUrl":"10.1016/j.xfnr.2024.100083","url":null,"abstract":"<div><h3>Objective</h3><div>Many adolescents and young women experience dysmenorrhea, a condition that is often trivialized or overlooked but can cause a substantial deterioration in health-related quality of life. Therefore, we conducted a systematic review and meta-analysis to investigate the overall prevalence of symptomatic individuals with ultrasound/magnetic resonance imaging–diagnosed adenomyosis in the 12–25 year-age group. This could inform management and treatment decisions.</div></div><div><h3>Evidence Review</h3><div>The PubMed/Medline, Embase, and Scopus databases were searched for full-length, English-language reports published between 2015 and 2024. This systematic review with meta-analysis was conducted and reported following the Joanna Briggs Institute methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. We included observational studies that assessed the number of patients with adenomyosis among adolescents and young women, the majority of whom presented with dysmenorrhea. The methodological quality of the included studies and their potential risk of bias were ascertained using the Joanna Briggs Institute Critical Appraisal Tool for Prevalence Studies. The main outcome was the prevalence of adenomyosis among symptomatic adolescents (midpoint of the study age range, <20 years) and young women (midpoint of the study age range, ≥20 years). Three meta-analyses, categorized by age, were performed using Stata to pool adenomyosis prevalence data from selected studies. The risk of endometriosis in women with and without adenomyosis was ultimately assessed as an exploratory and confirmatory investigation by combining the odds ratio estimates from each study using the random-effects model.</div></div><div><h3>Results</h3><div>Six studies comprising 1,300 individuals met the inclusion criteria. The prevalence of adenomyosis ranged from 5.9% to 46.0%, with an overall weighted mean of 20.7% (95% confidence interval [CI], 11.5–31.6) with high heterogeneity (<em>I</em><sup><em>2</em></sup> = 94.8%). The aggregate estimates were as 16.9% (95% CI, 8.8%–27.0%) in the adolescent subgroup and 29.7% (95% CI, 17.5%–43.5%) in the young woman subgroup. The risk of endometriosis in patients with adenomyosis was significantly higher than that in patients without adenomyosis, with a pooled odds ratio of 3.39 (95% CI, 2.11–5.45), without statistically significant heterogeneity across studies.</div></div><div><h3>Conclusion</h3><div>The findings of the present review should assist clinicians in developing a high index of suspicion for adenomyosis when adolescents and young women present with chronic severe dysmenorrhea and menorrhagia. Limiting the diagnostic delay and considering secondary prevention medical interventions may improve the quality of life and limit the risk of disease progression. Further rigorous prospective analytic studies are required to better defi","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promises and pitfalls of preimplantation genetic testing for polygenic disorders: a narrative review","authors":"Jaime A. Roura-Monllor M.D., M.S. ,&nbsp;Zachary Walker M.D. ,&nbsp;Joel M. Reynolds Ph.D. ,&nbsp;Greysha Rivera-Cruz M.D. ,&nbsp;Avner Hershlag M.D. ,&nbsp;Gheona Altarescu M.D. ,&nbsp;Sigal Klipstein M.D. ,&nbsp;Stacey Pereira Ph.D. ,&nbsp;Gabriel Lázaro-Muñoz Ph.D., J.D. ,&nbsp;Shai Carmi Ph.D. ,&nbsp;Todd Lencz Ph.D. ,&nbsp;Ruth Bunker Lathi M.D.","doi":"10.1016/j.xfnr.2024.100085","DOIUrl":"10.1016/j.xfnr.2024.100085","url":null,"abstract":"<div><div>Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. Preimplantation genetic testing for polygenic disorders makes use of polygenic risk scores for conditions that are multifactorial and are significantly influenced by environmental and lifestyle factors. If current predictions are accurate, then absolute risk reductions range from approximately 0.02% to 10.1%, meaning that between 10 and 5,000 in vitro fertilization patients would need to be tested with PGT-P to prevent 1 offspring from becoming affected in the future, depending on the condition and the number of embryos available. Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention; however, clinicians and professional organizations have many reservations. The use of PGT-P raises multiple social and ethical concerns including the need for adequate counseling, the setting of realistic expectations, the application of distributive justice, the impact of environmental and social determinants of health, and the potential exacerbation of health inequities. Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patients’ unrealistic expectations regarding “healthiest disease-free” embryos. Furthermore, current evidence lacks long-term outcome data and generalizability. Before offering PGT-P to patients, additional clinical validation studies are needed. Also, ethical and social considerations raised by PGT-P should be carefully delineated. Systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable before the ethical implementation of PGT-P.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of alpha-Klotho protein in male and female reproduction. A systematic review","authors":"Noemie Sachs-Guedj M.D. ,&nbsp;Piotr Sokol M.D. ,&nbsp;Tania Quesada-López Ph.D. ,&nbsp;Thomas Freour Pharm.D., Ph.D. ,&nbsp;Nikolaos P. Polyzos Ph.D. ,&nbsp;Francisca Martinez Ph.D.","doi":"10.1016/j.xfnr.2024.100084","DOIUrl":"10.1016/j.xfnr.2024.100084","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this systematic review is to provide the first comprehensive overview of the current knowledge regarding the role of the alpha-Klotho protein in male and female fertility, focusing on the testicle, spermatozoa, ovary, and oocyte.</div></div><div><h3>Evidence Review</h3><div>A comprehensive literature search was conducted up to March 2024 to determine the role of Klotho (KL, alpha-Klotho) in human reproductive tissues. The search terms included the following: “Klotho” AND “Sperm” OR “Testicle” OR “Oocyte” OR “Ovary” OR “Reproduction” OR “Fertility” OR “Infertility” OR “Gamete” OR “Gonad.” Following Cochrane methodology, the search covered MEDLINE, EMBASE, Cochrane Library, National Center for Biotechnology Information Gene, Tabula Sapiens, GTEx, Trip Database, Google Scholar, medRxiv, Open Grey, Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry, including all relevant studies up to March 2024 without language or publication status restrictions. The focus was on the role of alpha-Klotho in fertility, including studies involving animals and humans and basic experimental or observational designs. After removing duplicates, 2 investigators (N.S-.G., F.M.) independently screened titles and abstracts, with disagreements resolved by a third investigator (P.S.). The search identified a total of 258 articles, of which 18 were selected for the review. Final eligibility was determined by 4 investigators (N.S-.G., P.S., T.Q-.L., F.M.).</div></div><div><h3>Results</h3><div>The Klotho protein levels decrease with age. This decline influences male fertility by impacting spermatogenesis, sperm maturation, androgen production, and local homeostasis. In women, KL influences ovulatory function by inhibiting hypothalamic gonadotropin-releasing hormone secretion, regulating growth hormone secretion and oocyte quality, and controlling granulosa cells and follicular apoptosis. Overall, animal and human studies indicate that Klotho is an important factor in fertility, contributing to sperm quality and oocyte maturation and development. Additionally, the antioxidant properties of KL may help preserve the integrity of sperm cells and could serve as an effective antioxidant for the cryopreservation of ovarian tissue.</div></div><div><h3>Conclusion</h3><div>Further research is warranted to fully understand the mechanisms underlying the role of KL protein in human fertility, both as a potential biomarker and as a therapeutic target for infertility treatments and fertility preservation strategies. Advances in functional genetic variations studies will clarify the pathways linking genotype to phenotype in reproductive health.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134271","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":"Epithelial-mesenchymal transition links inflammation and fibrosis in the pathogenesis of endometriosis: a narrative review","authors":"Zoé I. Vincent-Mistiaen Ph.D.","doi":"10.1016/j.xfnr.2025.100089","DOIUrl":"10.1016/j.xfnr.2025.100089","url":null,"abstract":"<div><div>Endometriosis, a chronic inflammatory condition, is characterized by the growth of endometrial-like tissue outside the uterus, leading to debilitating pain and infertility. Although retrograde menstruation is widely accepted as a mechanism for the dissemination of endometrial cells to ectopic sites, the processes that enable their survival, invasion, and lesion formation remain incompletely understood. Epithelial-mesenchymal transition (EMT) has emerged as a potential driver, promoting cellular plasticity that supports ectopic implantation and invasion. Epithelial-mesenchymal transition is closely linked to inflammation, with transforming growth factor-β–mediated pathways playing a central role in driving these transitions. Chronic inflammation also induces fibroblast-myofibroblast transition (FMT) and smooth muscle metaplasia, processes that exacerbate fibrosis through excessive extracellular matrix deposition and fibroblast activation. These fibrotic changes worsen symptoms and contribute to disease progression. This review explores EMT and FMT as key mechanistic links between inflammation and fibrosis and discusses how targeting these pathways could offer novel therapeutic strategies to disrupt fibrotic progression, alleviate symptoms, and improve patient outcomes. Additionally, EMT and FMT markers hold promise as diagnostic tools, offering potential for earlier detection and more precise staging of endometriosis.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertoprotective agents and tumor response: a narrative review","authors":"Addison W. Alley M.D. ,&nbsp;Jonathan E. Constance Ph.D. ,&nbsp;Joseph M. Letourneau M.D.","doi":"10.1016/j.xfnr.2025.100087","DOIUrl":"10.1016/j.xfnr.2025.100087","url":null,"abstract":"<div><div>As advances in cancer therapy have significantly improved mortality rates, there is increasing emphasis on improving quality of life for cancer survivors. One such area of focus is in maintaining fertility, as both chemotherapy and radiation therapy carry significant risks of causing infertility through various mechanisms of gonadal injury. Although fertility preservation options exist, such as sperm or egg banking, they are not always available or indicated for all patients. Fertoprotective agents are proposed substances that may serve to protect the gonad from the harmful impacts of cancer therapy to maintain fertility. However, caution must be taken to evaluate whether these agents could act similarly to protect the tumor from anticancer therapies. In this narrative review, we first describe the various mechanisms by which chemotherapy or radiation therapy can cause gonadal harm. We then review the available research on fertoprotective agents and their proposed mechanisms of gonadal protection. Finally, we discuss what evidence exists for interaction with cancer therapy for each agent, with an emphasis on opportunities for future research.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421240","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":"Polycystic ovary syndrome and miscarriage: a narrative review","authors":"Leeann M. Bui M.D. ,&nbsp;Lusine Aghajanova M.D., P.h.D. ,&nbsp;Ruth B. Lathi M.D. ,&nbsp;Anna Sokalska M.D., Ph.D.","doi":"10.1016/j.xfnr.2024.100078","DOIUrl":"10.1016/j.xfnr.2024.100078","url":null,"abstract":"<div><p>Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. Although women with PCOS are often identified when presenting for oligomenorrhea or infertility care, PCOS is also linked to several metabolic morbidities, which may predispose to poor reproductive outcomes. Research has also suggested a possible independent association between PCOS and miscarriage, although available data are conflicting. This review focuses on the current literature regarding the risk of miscarriage and recurrent pregnancy loss in women with PCOS. First, we give an overview of the prevalence of miscarriage and recurrent pregnancy loss in this population and identify study limitations that contribute to the conflicting data regarding the potential association. Subsequently, we review the current literature on obesity, insulin resistance and hyperinsulinemia, thrombophilia, hyperandrogenism, oocyte, and embryo quality and viability, endometrial receptivity, oxidative stress and chronic inflammation, in addition to the efficacy of potential risk-mitigating interventions for miscarriage in women with PCOS.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"5 4","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169030","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":"Fertility, family building, and contraception in adolescents and young adults with sickle cell disease: a scoping review","authors":"Jenna Reich M.D. ,&nbsp;Devin Murphy M.D. ,&nbsp;Leena Nahata M.D. ,&nbsp;Susie Creary M.D. ,&nbsp;Amani Sampson M.S. ,&nbsp;Likolani Arthurs M.D. ,&nbsp;Dorice Vieira M.P.H. ,&nbsp;Gwendolyn P. Quinn Ph.D.","doi":"10.1016/j.xfnr.2024.100077","DOIUrl":"10.1016/j.xfnr.2024.100077","url":null,"abstract":"<div><h3>Objective</h3><p>To identify the current state of knowledge among adolescent and young adults (AYAs) with sickle cell disease (SCD) on fertility, family building, and contraception. We aimed to identify recommendations and guidance for communication strategies and counseling methods in these areas.</p></div><div><h3>Design</h3><p>Full-text publications were included if they focused on individuals with SCD, were published in English in peer-reviewed journals, and addressed patient or family knowledge of fertility, family building, or contraception. A comprehensive search using PubMed, CINAHL, Ovid MEDLINE, Embase, and PsycINFO was performed. Multiple reviewers independently assessed each abstract for inclusion, and a senior librarian resolved disagreements.</p></div><div><h3>Results</h3><p>Of 2,885 publications screened, 314 underwent full review, and 11 were included. Of the included studies, three discussed fertility only, two discussed family building only, two discussed contraception only, two discussed contraception and fertility, one discussed contraception and family building, and one discussed fertility and family building. Two overarching gaps were identified: a lack of counseling related to reproductive healthcare provided to AYAs with SCD and limited knowledge regarding their own disease sequelae.</p></div><div><h3>Conclusion</h3><p>Many AYAs are not counseled and are not knowledgeable about their fertility risks, family building options, and contraception choices. Furthermore, previous counseling guidelines on these subjects are limited, leading to incomplete and highly variable discussions between patient and clinicians on these subjects. This review highlights counseling recommendations and areas in which more concrete guidelines and evidence are important for the standardization of comprehensive reproductive healthcare in the AYA SCD population.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"5 4","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150784","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":"Stressed out: how forces from uterine contractions influence fibroid progression, a Narrative Review","authors":"Megan R. Sax M.D. ,&nbsp;Carolyn Nietupski B.S. ,&nbsp;Rachel E. Warwar M.D. ,&nbsp;Andreja Moset Zupan B.S. ,&nbsp;Emily G. Hurley M.D. ,&nbsp;Stacey C. Schutte Ph.D.","doi":"10.1016/j.xfnr.2024.100079","DOIUrl":"10.1016/j.xfnr.2024.100079","url":null,"abstract":"<div><div>Uterine fibroids are exposed to significant mechanical forces due to routine, monthly uterine contractions and have also been found to generate contractions in the junctional zone or inner myometrium. These are not the only mechanical forces that uterine fibroids experience but also compression and strain, or percent change in length, due to the stiff extracellular matrix of the fibroids. The forces may vary by location within the tumor. Strong uterine contractions not only cause pain but may also contribute to uterine fibroid growth, which, in turn, may lead to worsening symptom severity. This review discusses uterine contractions in the nonpregnant uterus and what is known about the impacts of mechanical forces on uterine fibroid cells.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"5 4","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewer of the Year 2023: F&S Reviews celebrates excellence in our world-class reviewers","authors":"","doi":"10.1016/j.xfnr.2024.100076","DOIUrl":"10.1016/j.xfnr.2024.100076","url":null,"abstract":"","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"5 3","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141413124","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":"Biomarkers to predict improvement of sperm parameters and hypogonadism after varicocele repair","authors":"","doi":"10.1016/j.xfnr.2024.100074","DOIUrl":"10.1016/j.xfnr.2024.100074","url":null,"abstract":"<div><p>Approximately 15% of couples in the US are affected by infertility, with male factor infertility acting as the sole or contributing factor in 20% and 40% of cases, respectively. Of the numerous potential causes of male infertility, varicocele is the most common and correctable. Although there are several hypotheses for the mechanism by which varicocele may cause symptoms such as infertility, pain, or hypogonadism, many patients with varicocele remain asymptomatic, and it remains unclear why only a subset of men with varicocele develop symptomatic pathology. Biomarkers are measurable indicators of disease presence or progression and have been proposed for use in the diagnosis and management of men with various reproductive conditions, including varicocele. This study examines a range of markers, including proteins, ribonucleic acid, deoxyribonucleic acid, and metabolites. Proteins implicated in heat shock reactions, oxidative stress, and mitochondrial function, including heat shock protein family A member 2, apolipoprotein A2, and TOM22, have been investigated within the context of varicocele when compared with their expression in healthy men. Additionally, potential biomarkers associated with sperm motility and spermatogenesis, such as serpin family A member 5 and adenosine triphosphate synthase delta domain protein, have been identified with studies showing improvement in concentrations post varicocelectomy. The pursuit of noninvasive biomarkers has gained significance for predicting improvement in fertility and assessing responses to varicocelectomy, offering opportunities for early intervention, minimizing unnecessary surgeries, and optimizing patient outcomes. This review consolidates current knowledge, underscores existing gaps, and outlines future research directions refining diagnostic and therapeutic strategies for varicocele-related infertility.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"5 3","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141034040","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}