Reproduction & fertility最新文献

{"title":"The impact of the microbiota-gut-brain axis on endometriosis-associated symptoms: mechanisms and opportunities for personalised management strategies.","authors":"Francesca Hearn-Yeates, Andrew W Horne, Siobhain O'Mahony, Philippa T K Saunders","doi":"10.1530/RAF-23-0085","DOIUrl":"10.1530/RAF-23-0085","url":null,"abstract":"<p><p>Endometriosis is a chronic inflammatory condition affecting one in 10 women and those assigned female at birth, defined by the presence of endometrial-like tissue outside the uterus. It is commonly associated with pain, infertility, and mood disorders, and often comorbid with other chronic pain conditions, such as irritable bowel syndrome. Recent research has identified a key role for the microbiota-gut-brain axis in health and a range of inflammatory and neurological disorders, prompting an exploration of its potential mechanistic role in endometriosis. Increased awareness of the impact of the gut microbiota within the patient community, combined with the often-detrimental side effects of current therapies, has motivated many to utilise self-management strategies, such as dietary modification and supplements, despite a lack of robust clinical evidence. Current research has characterised the gut microbiota in endometriosis patients and animal models. However, small cohorts and differing methodology has resulted in little consensus in the data. In this narrative review, we summarise research studies that have investigated the role of gut microbiota and their metabolic products in the development and progression of endometriosis lesions, before summarising insights from research into co-morbid conditions and discussing the reported impact of self-management strategies on symptoms of endometriosis. Finally, we suggest ways in which this promising field of research could be expanded to explore the role of specific bacteria, improve access to 'microbial' phenotyping, and to develop personalised patient advice for reduction of symptoms such as chronic pain and bloating.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917624","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":"Lessons learned from bovine subclinical endometritis: A systematic review exploring its potential relevance to chronic endometritis in women.","authors":"Kaltrina Krasniqi, Naomi Black, Erin Williams, Osvaldo Bogado Pascottini, Sarah Thornton, Siobhan Quenby, Joshua Odendaal","doi":"10.1530/RAF-23-0035","DOIUrl":"10.1530/RAF-23-0035","url":null,"abstract":"<p><p>Chronic endometritis (CE) in humans is asymptomatic inflammation of the endometrium, associated with poor reproductive outcomes. Similarly asymptomatic endometrial inflammation in cows, termed subclinical endometritis (SCE), is associated with adverse reproductive outcomes. While the pathophysiology and treatment options for CE in humans remains poorly defined, the financial implications of SCE in dairy cows mean it has been intensively researched. We performed a systematic review with an emergent theme thematic analysis of studies of SCE in cows, to determine potential areas of interest in human CE research. A literature search for studies of subclinical endometritis in cows published between 1990 and November 2021 was performed across Embase, Medline, Scopus and CINAHL. Studies of symptomatic or clinical endometritis were excluded. Thematic analysis across two broad themes were explored: diagnostic methods and pathophysiology of SCE. In total, 44 bovine studies were included. 12 studies reported on diagnostic methodology. The primary emergent theme was the use of cytology for the diagnosis of SCE. This method has a lower sensitivity than histopathology but is less invasive and more specific than alternative techniques of ultrasound, vaginoscopy, or metabolic markers. The subthemes related to pathophysiology were identified as type of endometritis, metabolic stress, artificial insemination, infective causes, and altered cellular pathways. Despite the lack of symptoms, cellular pathways of inflammation including NFkB, MAPK, and inflammasomes were found to be activated. The key themes related to the diagnosis and pathophysiology of SCE in cows identified in this systematic review highlight potential areas for future research into human CE.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909720","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":"Harnessing the power within: engineering the microbiome for enhanced gynecologic health.","authors":"Caitriona Brennan, Kristina Chan, Tanya Kumar, Erica Maissy, Linda Brubaker, Marisol I Dothard, Jack A Gilbert, Katharine E Gilbert, Amanda L Lewis, Varykina G Thackray, Amir Zarrinpar, Rob Knight","doi":"10.1530/RAF-23-0060","DOIUrl":"10.1530/RAF-23-0060","url":null,"abstract":"<p><strong>Abstract: </strong>Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions.</p><p><strong>Lay summary: </strong>Manipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11046331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186766","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":"Oogonial stem cells: the unexpected superheroes.","authors":"Rita L Sousa","doi":"10.1530/RAF-24-0004","DOIUrl":"10.1530/RAF-24-0004","url":null,"abstract":"","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11046342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186768","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":"Sex: the last real binary?","authors":"Shiuli Bhattacharyya","doi":"10.1530/RAF-24-0005","DOIUrl":"10.1530/RAF-24-0005","url":null,"abstract":"<p><p>The rights of transgender and intersex people have become a contentious issue in our current political climate. Whether it be the rights of intersex athletes such as Caster Semenya (who identifies as a woman) to compete in elite sport, or the rights of transgender women to use women's only spaces, there is an increasingly fierce debate as to the legitimacy of people's gender and sexual identities and what parameters should be used to define them. A common argument accepted by most in our society is that while gender may be a spectrum, sex is an inalienable binary.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11046348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141299","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":"Microbiome: Mammalian milk microbiomes: sources of diversity, potential functions, and future research directions.","authors":"Michael L Power, Carly R Muletz-Wolz, Sally L Bornbusch","doi":"10.1530/RAF-23-0056","DOIUrl":"10.1530/RAF-23-0056","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;Milk is an ancient, fundamental mammalian adaptation that provides nutrition and biochemical communication to offspring. Microbiomes have been detected in milk of all species studied to date. In this review, we discuss: (a) routes by which microbes may enter milk; (b) evidence for proposed milk microbiome adaptive functions; (c) variation in milk microbiomes across mammals; and (d) future research directions, including suggestions for how to address outstanding questions on the viability and functionality of milk microbiomes. Milk microbes may be sourced from the maternal gastrointestinal tract, oral, skin, and mammary gland microbiomes and from neonatal oral and skin microbiomes. Given the variety of microbial sources, stochastic processes strongly influence milk microbiome assembly, but milk microbiomes appear to be influenced by maternal evolutionary history, diet, environment, and milk nutrients. Milk microbes have been proposed to colonize the neonatal intestinal tract and produce gene and metabolic products that influence physiology, metabolism, and immune system development. Limited epidemiological data indicate that early-life exposure to milk microbes can result in positive, long-term health outcomes. Milk microbiomes can be modified by dietary changes including providing the mother with probiotics and prebiotics. Milk replacers (i.e. infant formula) may benefit from supplementation with probiotics and prebiotics, but data are lacking on probiotics' usefulness, and supplementation should be evidence based. Overall, milk microbiome literature outside of human and model systems is scarce. We highlight the need for mechanistic studies in model species paired with comparative studies across mammals to further our understanding of mammalian milk microbiome evolution. A broader study of milk microbiomes has the potential to inform animal care with relevance to ex situ endangered species.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Lay summary: &lt;/strong&gt;Milk is an ancient adaptation that supports the growth and development of mammalian neonates and infants. Beyond its fundamental nutritional function, milk influences all aspects of neonatal development, especially immune function. All kinds of milks so far studied have contained a milk microbiome. In this review, we focus on what is known about the collection of bacterial members found in milk microbiomes. Milk microbiomes include members sourced from maternal and infant microbiomes and they appear to be influenced by maternal evolutionary history, diet, milk nutrients, and environment, as well as by random chance. Once a neonate begins nursing, microbes from milk colonize their gut and produce byproducts that influence their physiology, metabolism, and immune development. Empirical data on milk microbiomes outside of humans and model systems are sparse. Greater study of milk microbiomes across mammals will expand our understanding of mammalian evolution and improve the health of animals under ","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11046322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186767","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":"Cumulus matrix selection leads to isolation of spermatozoa with better motility, morphology, and lower DNA fragmentation.","authors":"Maria Handzhiyska, Rumiana Ganeva, Dimitar Parvanov, Margarita Ruseva, Petar Eftimov, Vilyana Georgieva, Denitsa Velikova, Georgi Stamenov","doi":"10.1530/RAF-23-0052","DOIUrl":"10.1530/RAF-23-0052","url":null,"abstract":"<p><p>The objective of this study was to compare the motility, morphology, and levels of DNA fragmentation of spermatozoa subjected to conventional swim-up or cumulus matrix (CM) sperm selection. Semen samples were collected from 60 normozoospermic men at a private hospital between December 2021 and March 2022. After liquefaction, semen samples were separated into two portions - one part was subjected to conventional swim-up preparation and the remaining spermatozoa were subjected to CM selection. The CM was obtained by mechanical isolation from healthy donor oocytes. Semen analysis and evaluation of sperm were performed according to WHO 6th Edition Laboratory Manual and Kruger's strict criteria, respectively. Sperm DNA fragmentation (SDF, %) of the two preparations was evaluated using Halosperm G2 detection kit (Halotech, Madrid, Spain). Wilcoxon rank-sum test was used to compare the characteristics of spermatozoa obtained by the two preparations. Spermatozoa selected by CM showed significantly better rapidly progressive motility (43.5% vs. 30.6%, respectively, p<0.001), higher percentage of morphologically normal forms (14.0% vs. 9.0%, respectively, p<0.05), and lower levels of SDF (26.0% vs. 45.0%, p<0.05) in comparison to those prepared by conventional swim-up. Moreover, the incidence of multiple sperm defects was considerably lower in the samples that underwent CM selection compared to those that did not (30.0% vs. 49.0%, respectively, p<0.05).The selection by CM significantly increases sperm motility and reduces morphologically abnormal spermatozoa and DNA fragmentation rates in comparison to the conventional swim-up preparation. The application of this selection technique may increase chances of successful IVF outcomes.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867092","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":"Assessment of the impact of direct in vitro PFAS treatment on mouse spermatozoa.","authors":"Leah Calvert, Jacinta H Martin, Amanda L Anderson, Ilana R Bernstein, Nathan D Burke, Geoffry N De Iuliis, Andrew L Eamens, Matthew D Dun, Brett D Turner, Shaun D Roman, Mark P Green, Brett Nixon","doi":"10.1530/RAF-23-0087","DOIUrl":"10.1530/RAF-23-0087","url":null,"abstract":"<p><strong>Abstract: </strong>Poly- and per-fluoroalkyl substances (PFAS) are synthetic environmentally persistent chemicals. Despite the phaseout of specific PFAS, their inherent stability has resulted in ubiquitous and enduring environmental contamination. PFAS bioaccumulation has been reported globally with omnipresence in most populations wherein they have been associated with a range of negative health effects, including strong associations with increased instances of testicular cancer and reductions in overall semen quality. To elucidate the biological basis of such effects, we employed an acute in vitro exposure model in which the spermatozoa of adult male mice were exposed to a cocktail of PFAS chemicals at environmentally relevant concentrations. We hypothesized that direct PFAS treatment of spermatozoa would induce reactive oxygen species generation and compromise the functional profile and DNA integrity of exposed cells. Despite this, post-exposure functional testing revealed that short-term PFAS exposure (3 h) did not elicit a cytotoxic effect, nor did it overtly influence the functional profile, capacitation rate, or the in vitro fertilization ability of spermatozoa. PFAS treatment of spermatozoa did, however, result in a significant delay in the developmental progression of the day 4 pre-implantation embryos produced in vitro. This developmental delay could not be attributed to a loss of sperm DNA integrity, DNA damage, or elevated levels of intracellular reactive oxygen species. When considered together, the results presented here raise the intriguing prospect that spermatozoa exposed to a short-term PFAS exposure period potentially harbor an alternate stress signal that is delivered to the embryo upon fertilization.</p><p><strong>Lay summary: </strong>PFAS are synthetic chemicals widely used in non-stick cookware, food packaging, and firefighting foam. Such extensive use has led to concerning levels of environmental contamination and reports of associations with a spectrum of negative health outcomes, including testicular cancer and reduced semen quality. To investigate the effects of PFAS on male reproduction, we incubated mouse sperm in a cocktail of nine PFAS at environmentally relevant concentrations before checking for a range of functional outcomes. This treatment strategy was not toxic to the sperm; it did not kill them or reduce their motility, nor did it affect their fertilization capacity. However, we did observe developmental delays among pre-implantation embryos created using PFAS-treated sperm. Such findings raise the intriguing prospect that PFAS-exposed sperm harbor a form of stress signal that they deliver to the embryo upon fertilization.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898424","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":"Algorithm vs. clinical experience: controlled ovarian stimulations with follitropin-delta and individualised doses of follitropin-alpha/beta.","authors":"Irene Gazzo, Francesca Bovis, Denise Colia, Fausta Sozzi, Mauro Costa, Paola Anserini, Claudia Massarotti","doi":"10.1530/RAF-23-0045","DOIUrl":"10.1530/RAF-23-0045","url":null,"abstract":"<p><p>In the registrational trials, follitropin delta was compared with a fixed dose of 150 UI of follitropin alpha/beta, finding higher chances to reach a target response of 8-14 oocytes compared to controls. For this reason, follitropin delta is marketed as particularly useful in expected hyper-responder patients. The main outcome of this study is to report if comparable results are reached in a real-life scenario with follitropin alpha/beta personalized doses, based on patients' characteristics. This is a retrospective study performed in two public fertility centres. All first cycles from January 2020 to June 2022 with either follitropin delta (cases) or alpha/beta (controls) in patients with antiMüllerian hormone >2.5 ng/ml were compared by an inverse probability weighting approach based on propensity score. The follitropin total dose was higher in controls (1179.06 ± 344.93 vs. 1668.67 ± 555.22 IU, p<0.001). The target response of 8-14 oocytes was reached by 40.2% of cases and 40.7% of controls (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.65-1.53, p=0.98). Fewer than 8 oocytes were collected in 24.1% of cases and 22% of controls (OR 1.10, 95% CI 0.71-1.69, p=0.67); more than 14 oocytes in 35.7% of cases and 37.3% of controls (OR 0.83, 95% CI 0.54-1.28, p=0.40). Our experience did not find worse results in term of proportion of patients who reached the target response with an algorithm-chosen dose of follitropin delta compared to a personalised starting dose of follitropin alpha/beta, with follitropin delta having the advantage of objectivity. Larger numbers are needed to confirm these results.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708943","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":"Effects of bovine ovarian storage conditions and vitrification on isolated preantral follicle viability.","authors":"Yasmin Franko, Marcia de Almeida Monteiro Melo Ferraz","doi":"10.1530/RAF-23-0071","DOIUrl":"10.1530/RAF-23-0071","url":null,"abstract":"<p><strong>Lay summary: </strong>The decreasing rate of successful pregnancies, both naturally and through assisted conception, has led to innovations in the way eggs, sperm, and embryos are stored. Despite these advances, the use of assisted reproductive techniques to preserve endangered or rare species remains unexplored. Since the location where samples are collected and facilities are often far apart, we aim to address part of this challenge by comparing different methods to store and handle ovarian tissue before freezing. This may pave the way for further research in preserving endangered species, despite the challenges posed by the distance between sample collection sites and suitable facilities.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":"5 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565514","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}