Hormone Research in Paediatrics最新文献

{"title":"ISPAD Clinical Practice Consensus Guidelines 2024: Type 2 Diabetes in Children and Adolescents.","authors":"Amy S Shah, Margarita Barrientos-Pérez, Nancy Chang, Jun-Fen Fu, Tamara S Hannon, Megan Kelsey, Alexia S Peña, Orit Pinhas-Hamiel, Tatsuhiko Urakami, Brandy Wicklow, Jencia Wong, Farid H Mahmud","doi":"10.1159/000543033","DOIUrl":"10.1159/000543033","url":null,"abstract":"<p><p>Youth-onset type 2 diabetes (T2D) results from genetic, environmental, and metabolic causes that differ among individuals and populations. This chapter builds on the 2022 ISPAD guidelines and summarizes recent advances in the management of T2D in children and adolescents. Updates include diagnostic algorithm for youth with new onset T2D, algorithms and tables for treatment, management, and assessment of comorbidities and complications and recommendations on recently approved pharmacologic therapies for the treatment of youth-onset T2D and management strategies.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"542-570"},"PeriodicalIF":2.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828309","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":"Differential Methylation of CYP11B1 in Girls with High DHEAS Levels and Correlation with 11-Oxyandrogen Levels: A Pilot Study.","authors":"Fernando Rodríguez, Diana Ponce, José Patricio Miranda, José L Santos, Gordon B Cutler, Ana Pereira, Esteban Barnafi, Germán Iñiguez, Verónica Mericq","doi":"10.1159/000542963","DOIUrl":"10.1159/000542963","url":null,"abstract":"<p><strong>Introduction: </strong>Premature adrenarche in girls is defined biochemically by an increase in adrenal androgen (DHEAS) levels above the age-specific reference range before age 8 years. Recently, increased levels of 11-oxyandrogens have also been reported in girls with premature adrenarche. Epigenetic modifications, specifically CpG methylation, may affect gene expression and/or activity of steroidogenic enzymes during developmental changes in adrenal androgen secretion.</p><p><strong>Objective: </strong>The aim of the study was to determine whether circulating 11-oxyandrogen levels in post-menarcheal girls are associated with the methylation status of genes involved in 11-oxyandrogen steroidogenesis.</p><p><strong>Methods: </strong>Ninety-seven healthy girls followed since the age of 3 years were classified, according to DHEAS serum concentration at age 6-7 years, as normal DHEAS (<42 μg/dL [75th percentile for population]) or high DHEAS (≥42 μg/dL). At Tanner stage 2, the methylation status of CpG sites located in CYP11B1 and HSD11B2 genes was analyzed in genomic DNA from peripheral blood leukocytes by the melting curve analysis methylation assay. Eleven-oxyandrogen concentrations were assessed at 4 years post menarche.</p><p><strong>Results: </strong>Significantly lower methylation levels were detected in the CYP11B1 gene in girls with high versus normal serum DHEAS levels, with no differences found in HSD11B2 gene. Additionally, CYP11B1 methylation status correlated inversely with 11β-hydroxy-androstenedione and 11-ketotestosterone levels. Furthermore, CYP11B1 methylation in the full cohort correlated inversely with insulin concentration at Tanner 1 and with body mass index at Tanner stage 1 and 2.</p><p><strong>Conclusion: </strong>This pilot study proposes the hypothesis that a lower methylation of CYP11B1 may be a mechanism contributing to increased concentrations of 11-oxyandrogens in premature adrenarche and its associated metabolic risk.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828306","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":"Regional Deprivation and Diabetic Ketoacidosis at Type 1 Diabetes Diagnosis in Children and Adolescents: International Comparison among 6 Countries.","authors":"G Todd Alonso, Christina Reinauer, Georgina M Williams, Rosaria Gesuita, Craig Jefferies, Klemen Dovc, Julia M Grimsmann, Taylor M Triolo, Ambika Shetty, Reinhard W Holl, Valentino Cherubini","doi":"10.1159/000543139","DOIUrl":"10.1159/000543139","url":null,"abstract":"<p><strong>Introduction: </strong>The incidence of diabetic ketoacidosis (DKA) at the time of diagnosis of type 1 diabetes in youth varies between countries and is influenced by socioeconomic factors. We investigated the relationship between regional deprivation indices and DKA at the diagnosis of type 1 diabetes in six countries.</p><p><strong>Methods: </strong>We analyzed children 0.5-17.0 years old diagnosed with type 1 diabetes between 2019 and 2022 across six diabetes registries. Regional deprivation index within each country was standardized to compare each individual's socioeconomic status internationally. Log-binomial regression models assessed the association between the standardized deprivation index and DKA, with sex, age group, and year as covariates.</p><p><strong>Results: </strong>Among 21,020 children (mean age 9.08 [SD 4.19] years), the DKA rate of 36.5%. Cohorts were Germany (n = 13,561, DKA 32.5%), Italy (4,659, 42.5%), Colorado, USA (1,318, 54.9%), Wales (769, 35.2%), New Zealand (407, 43.7%), and Slovenia (306, 37.6%). Deprivation was associated with the increased risk of DKA in children 0.5-<6 (OR 1.16 [95% CI: 1.10-1.23], p < 0.0001) and 6-<12 years of age (1.05 [1.05-1.11], p = 0.02). Female sex increased risk of DKA (1.06 [1.00-1.13], p = 0.04). The proportion of DKA was lower in 2019 than in 2020, 2021, and 2022 (each p < 0.0001).</p><p><strong>Conclusion: </strong>Deprivation was significantly associated with the risk of DKA at the diagnosis of type 1 diabetes, and DKA was more common during the pandemic years 2020-2022 than in 2019. Younger children appear to be more vulnerable to deprivation than older patients. Understanding and reducing local and demographic-specific disparities are essential for effective intervention.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-8"},"PeriodicalIF":2.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817914","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":"ISPAD Clinical Practice Consensus Guidelines 2024: Screening, Staging, and Strategies to Preserve Beta-Cell Function in Children and Adolescents with Type 1 Diabetes.","authors":"Michael J Haller, Kirstine J Bell, Rachel E J Besser, Kristina Casteels, Jenny J Couper, Maria E Craig, Helena Elding Larsson, Laura Jacobsen, Karin Lange, Tal Oron, Emily K Sims, Cate Speake, Mustafa Tosur, Francesca Ulivi, Anette-G Ziegler, Diane K Wherrett, M Loredana Marcovecchio","doi":"10.1159/000543035","DOIUrl":"10.1159/000543035","url":null,"abstract":"<p><p>The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 T1D are included. Lastly, opportunities and challenges associated with the recent US Food and Drug Administration (FDA) approval of teplizumab as an immunotherapy to delay progression are discussed.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-17"},"PeriodicalIF":2.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812791","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":"International Society for Pediatric and Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Diabetes Technologies - Insulin Delivery.","authors":"Torben Biester, Cari Berget, Charlotte Boughton, Laura Cudizio, Laya Ekhlaspour, Marisa E Hilliard, Leenatha Reddy, Suzanne Sap Ngo Um, Melissa Schoelwer, Jennifer L Sherr, Klemen Dovc","doi":"10.1159/000543034","DOIUrl":"10.1159/000543034","url":null,"abstract":"<p><p>The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind insulin administration, with special emphasis on insulin pump therapy, especially on glucose-responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"592-618"},"PeriodicalIF":2.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806820","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":"Long-Term Treatment for Laron Syndrome with IGF-1 Injection over 22 Years in Saudi Arabia: A Cohort Study.","authors":"Abdullah Ali Alashwal, Areej Al-Fattani, Khushnooda Ramzan, Faiqa Imtiaz, Amal Binladen","doi":"10.1159/000543047","DOIUrl":"10.1159/000543047","url":null,"abstract":"<p><strong>Introduction: </strong>Laron syndrome (LS) is a rare autosomal recessive disorder caused by mutations in the growth hormone (GH) receptor gene, resulting in GH resistance and reduced levels of insulin-like growth factor 1 (IGF-1). Patients with LS exhibit severe growth retardation, low IGF-1 levels, elevated basal GH, and poor response to GH stimulation. Recombinant IGF-1 is the only approved treatment and has been shown to improve linear growth. This study evaluates the long-term efficacy and safety of IGF-1 therapy in a large cohort of LS patients treated at King Faisal Specialist Hospital and Research Center (KFSH &amp; RC), Riyadh, Saudi Arabia over 22 years.</p><p><strong>Methods: </strong>We conducted a retrospective review of medical records for 28 patients with growth hormone insensitivity syndrome, including 12 males and 16 females, treated with IGF-1 from 1998 to 2020. Patients were selected based on criteria including age over 2 years, height standard deviation score (SDS) ≤-2.8, normal or elevated GH secretion (>2.5 ng/mL), IGF-1 levels <50 ng/mL, and insensitivity to exogenous GH. IGF-1 was administered initially at 40 μg/kg/dose subcutaneously twice daily, escalating to a maximum of 120 μg/kg/dose as tolerated. Dosage was adjusted to minimize hypoglycemia risk, with blood glucose monitored frequently during hospitalization. In addition, molecular genetic results were reviewed for each patient in the cohort.</p><p><strong>Results: </strong>IGF-1 treatment significantly increased height velocity (HV) from a baseline of 3.4 cm/year to 6.5 cm/year in the first year (mean difference of 3.1 cm/year, p < 0.0001). In the second year, HV remained elevated at 5 cm/year (mean difference of 1.6 cm/year, p = 0.0015). Long-term follow-up over 10 years demonstrated sustained improvements in HV compared to baseline, with the most substantial gains occurring within the initial 5 years. Weight SDSs also showed significant improvement. Age at the start of therapy did not notably affect growth outcomes, though longer treatment durations were associated with greater growth. Ten disease-causing variants in the GHR gene were identified in 24 of the 28 LS patients.</p><p><strong>Conclusion: </strong>IGF-1 therapy significantly enhanced linear growth in children with Laron syndrome and was generally well tolerated. Although many patients did not reach normal adult height, the growth achieved with IGF-1 treatment was markedly better than expected without therapy. This study underscores the effectiveness of IGF-1 in improving growth outcomes and highlights the need for continued longitudinal studies to optimize treatment strategies and manage potential complications.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806821","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":"The Use of Automated Insulin Delivery around Physical Activity and Exercise in Type 1 Diabetes: A Position Statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD).","authors":"Othmar Moser, Dessi Zaharieva, Peter Adolfsson, Tadej Battelino, Richard M Bracken, Bruce A Buckingham, Thomas Danne, Elizabeth A Davis, Klemen Dovc, Gregory P Forlenza, Pieter Gillard, Sabine E Hofer, Roman Hovorka, Peter J Jacobs, Julia K Mader, Chantal Mathieu, Kirsten Nørgaard, Nick S Oliver, David N O'Neal, John Pemberton, Remi Rabasa-Lhoret, Jennifer L Sherr, Harald Sourij, Martin Tauschmann, Jane E Yardley, Michael C Riddell","doi":"10.1159/000542287","DOIUrl":"https://doi.org/10.1159/000542287","url":null,"abstract":"<p><p>Regular physical activity and exercise (PA) are cornerstones of diabetes care for individuals with type 1 diabetes. In recent years, the availability of automated insulin delivery (AID) systems has improved the ability of people with type 1 diabetes to achieve the recommended glucose target ranges. PA provides additional health benefits but can cause glucose fluctuations, which challenges current AID systems. While an increasing number of clinical trials and reviews are being published on different AID systems and PA, it seems prudent at this time to collate this information and develop a position statement on the topic. This joint European Association for the Study of Diabetes (EASD)/International Society for Pediatric and Adolescent Diabetes (ISPAD) position statement reviews current evidence on AID systems and provides detailed clinical practice points for managing PA in children, adolescents and adults with type 1 diabetes using AID technology. It discusses each commercially available AID system individually and provides guidance on its use in PA. Additionally, it addresses different glucose responses to PA and provides stratified therapy options to maintain glucose levels within the target ranges for these age groups.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-28"},"PeriodicalIF":2.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806823","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":"Endocrine management of transgender and gender diverse adolescents: expert opinion of the ESPE Working Group on Gender Incongruence and the Endo-ERN main thematic group on Sexual Development and Maturation.","authors":"Sabine E Hannema, Kanetee Busiah, Gary Butler, Hedi L Claahsen-van de Grinten, Martine Cools, Aneta M Gawlik-Starzyk, Daniel Klink, Katharina M Main, Laetitia Martinerie, Annette Richter-Unruh, Nicos Skordis, Martine Charlotte de Vries","doi":"10.1159/000542904","DOIUrl":"https://doi.org/10.1159/000542904","url":null,"abstract":"<p><p>Increasing numbers of transgender and gender diverse adolescents seek endocrine treatment to align their body to their gender identity. In this relatively young field of medicine, there is a limited body of evidence, and the available evidence generally is of low quality. However, in the absence of randomised trials, much can be learned from prospective observational studies. While evidence on somatic and psychosocial outcomes has increased in recent years, areas with little or no research rely on expert opinion. In order to reduce practice variation in paediatric endocrine care for transgender adolescents, we describe endocrine care for transgender and gender diverse adolescents in Europe in this statement, based on the available evidence as well as the experience of experts from the ESPE Working Group on Gender Incongruence and from the European Reference Network Endo-ERN, main thematic group 'Sexual Development and Maturation'. This document aims to provide practical information and tools for clinical care, with sections on the multidisciplinary team, counseling, fertility, hormone suppression, gender affirming hormone treatment, support for non-binary adolescents, long-term follow up and transition of care, altered treatment wishes, lifestyle and sexual health, and in addition includes a paragraph on ethical considerations regarding this care.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-41"},"PeriodicalIF":2.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768428","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":"Contribution of Sex Steroids in Management of Tall Stature: Is It Effective or Not?","authors":"Nese Akcan, Federica Verdecchia, Peter C Hindmarsh, Mehul Dattani","doi":"10.1159/000542553","DOIUrl":"10.1159/000542553","url":null,"abstract":"<p><strong>Introduction: </strong>Reduction in adult height by high-dose sex steroids was introduced decades ago. Here, we present the impact of lower doses of sex steroids on the predicted adult height (PAH) in children with tall stature.</p><p><strong>Methods: </strong>This single-center retrospective observational study included 22 tall children treated with low-dose sex steroids. Patients with familial tall stature, constitutional advance of growth, or Marfan syndrome were included. Anthropometric measurements at the commencement of treatment, six-monthly intervals on treatment, cessation of treatment, and at final assessment, were evaluated. Bone age (BA) determination, and PAH were made using both the tables of Bayley-Pinneau (BP) and Tanner-Whitehouse (TW) mark II methods.</p><p><strong>Results: </strong>The final height was significantly lower than the predicted height in girls whereas it was not significantly lower than predicted height in boys. In patients with Marfan syndrome, the final height was only lower than the prediction of TW rather than BP. Non-Marfan cases had significantly lower final height than both the predicted heights. Conversely, although there was a decrease in height SDS over time, this difference was not statistically significant in the study cohort. Starting treatment at early BA (<10 years) did not affect the last height SDS or the difference between predicted height and final height.</p><p><strong>Conclusion: </strong>Sex difference, sex steroid dosage, differences in treatment duration and differences in BA measurement method, PAH method, BA and chronological age at the start of treatment may all influence the therapy response. Shortcomings about these influences can be overcome in future prospective studies with a larger sample size.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768387","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":"Co-Occurrence of Two Rare Diseases: A Child with Phenylketonuria and WNT1 Osteoporosis.","authors":"Artemis Doulgeraki, Fan Wang, Anastasia Skouma, Eleana Petropoulou, Symeon Tournis, Alice Costantini, Outi Mäkitie","doi":"10.1159/000541378","DOIUrl":"10.1159/000541378","url":null,"abstract":"<p><strong>Introduction: </strong>Phenylketonuria (PKU), an inborn error of metabolism, when inadequately treated, may lead to nutritional deficits, which could affect bone health. This remains a controversial issue, given that in the majority of PKU cases, bone mineral density is within normal limits. On the other hand, WNT1 mutations are detrimental for bone, as they lead to primary osteoporosis.</p><p><strong>Case presentation: </strong>We present an eleven-year-old girl under a very strict diet for PKU (i.e., with low phenylalanine levels) and severe osteoporosis, signified by the presence of multiple vertebral fractures, which could not be attributed to her inborn error of metabolism. Family screening, including bone densitometry, revealed unexplained osteoporosis in her father and brother. Further genetic workup revealed a new WNT1, disease-causing mutation. The patient's dietary plan was modified, in order to achieve better metabolic control, and she was given vitamin D and calcium supplements. These measures led to great clinical and radiological improvement, without the use of bisphosphonates.</p><p><strong>Conclusion: </strong>In a patient with a chronic disorder known to affect the skeleton, the presence of disproportionally severe osteoporosis should prompt further diagnostic workup, in order to explain the severe bone phenotype, thus enabling more efficient and targeted therapeutic interventions.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739483","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}