Endocrine最新文献

{"title":"Long-term follow-up of treatment outcomes in Graves' disease and toxic nodular disease.","authors":"David Veríssimo, Beatriz Pereira, Joana Vinhais, Catarina Ivo, Ana C Martins, João N E Silva, Dolores Passos, Luís Lopes, João J de Castro, Mafalda Marcelino","doi":"10.1007/s12020-024-04000-1","DOIUrl":"10.1007/s12020-024-04000-1","url":null,"abstract":"<p><strong>Purpose: </strong>Hyperthyroidism guidelines have not been updated over the past five years, despite numerous data on the subject, and recent studies providing a wide variation in treatment success rates. We aim to compare the effectiveness and safety of treatment modalities in patients with Graves' disease or toxic nodular disease.</p><p><strong>Methods: </strong>Single center retrospective cohort study of Graves' disease and toxic nodular disease patients treated between 1983 and 2023.</p><p><strong>Results: </strong>A total of 411 patients were treated for hyperthyroidism, 245 due to Graves' disease and 166 due to or toxic nodular disease, followed for a median of 7 years. In Graves' disease, 90.2% were treated with antithyroid drugs over 250 cycles, achieving 41.7% cumulative remission. Half of all relapses (50.9%) occurred in the first year, 76.3% in the first three years, and 98.3% within nine years. Treatment periods of 12-24 months showed higher remission and lower relapse rates than longer periods. I-131 was used in 103 cycles with 82.5% remission and 7.1% relapse. A total of 29 thyroidectomies resulted in 100% remission, with no relapse. In toxic nodular disease, surgery was the most frequently used treatment (54.5%), followed by I-131 (37.1%).</p><p><strong>Conclusion: </strong>Our findings support antithyroid drugs as the preferential first-line treatment for Graves' disease, allowing for euthyroidism with minimal adverse effects. Given the propensity for relapse, we suggest a rigorous monitoring, particularly within the first three years. In toxic nodular disease, surgery should be the preferred option, with I-131 being reserved for single adenomas and small goiters.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"234-242"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996751","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":"Therapeutic efficacy and patient compliance of levothyroxine liquid and softgel formulations taken with meals: a systematic review.","authors":"Vittorio Oteri, Salvatore Volpe, Mariarita Lopes, Giulia Sceusa, Andrea Tumminia, Antonino Belfiore, Francesco Frasca, Damiano Gullo","doi":"10.1007/s12020-024-04016-7","DOIUrl":"10.1007/s12020-024-04016-7","url":null,"abstract":"<p><strong>Purpose: </strong>Levothyroxine (L-T4) is the drug of choice for treating primary hypothyroidism. L-T4 tablets should be taken at least 30 min before breakfast. Several studies have suggested that serum thyroid profile is not affected by concomitant intake of liquid/softgel L-T4 with meals. Our aim is to review the evidence on therapeutic efficacy and patient compliance with the liquid and softgel formulation of L-T4 taken with meals, also compared with the standard tablet therapy regimen, in hypothyroid patients.</p><p><strong>Methods: </strong>We performed a systematic review of literature by searching PubMed, Embase, and Cochrane Library databases. PRISMA guidelines were applied, and the risk of bias of the included studies was assessed using the RoB 2 and ROBINS tools. The methodological quality was assessed following the GRADE criteria.</p><p><strong>Results: </strong>We included 13 studies, accounting for a total of 1697 patients. The timing of liquid L-T4 intake from breakfast did not affect the therapeutic efficacy of the treatment. No significant differences in the absorption of liquid L-T4 were found when administered together with different foods, beverages, drugs, or other supplements. TSH levels are not influenced by taking softgel L-T4 at breakfast; the efficacy of softgel and liquid formulation is similar when they are taken with a meal, but superior to that of tablet formulation. Shifting from L-T4 tablets taken 30 min before breakfast to liquid/softgel formulation taken with the meal improved medication adherence and perceived quality of life of patients.</p><p><strong>Conclusion: </strong>Liquid and softgel formulation of L-T4 can be taken at breakfast or close to meals, without losing therapeutic efficacy. These formulations could also improve patient compliance and quality of life compared to L-T4 tablet therapy taken 30 min before breakfast.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"48-58"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on redifferentiation strategies for radioactive iodine-refractory differentiated thyroid carcinoma.","authors":"Theodora Pappa, Lori Wirth","doi":"10.1007/s12020-024-04018-5","DOIUrl":"10.1007/s12020-024-04018-5","url":null,"abstract":"<p><strong>Purpose: </strong>Although most patients with differentiated thyroid carcinoma (DTC) have an excellent prognosis, a subset will experience radioactive iodine refractory (RAI-R) disease, associated with recurrence, distant metastases and worse prognosis. In recent years, redifferentiation has emerged as an attractive approach for patients with RAI-R DTC, a strategy to induce iodine uptake in RAI-R DTC tumor cells and ultimately prolong time to initiation of systemic therapy.</p><p><strong>Methods: </strong>An overview and critical appraisal of the existing literature on redifferentiation will be presented in this review under the lens of the genotype-specific targeted therapy administered with redifferentiation intent.</p><p><strong>Results/conclusions: </strong>Due to the significant heterogeneity across studies, it will be key to harmonize research methodology and support future larger, multicenter prospective trials in order to identify the most suitable candidates for this therapeutic strategy.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134209","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":"Radioligand therapy in sympathetic-adrenal-medullary axis tumors: state of art and perspectives.","authors":"Ilham Badrane, Luca Urso, Alfredo Campennì, Corrado Cittanti, Maria Luisa De Rimini, Mirco Bartolomei","doi":"10.1007/s12020-024-04062-1","DOIUrl":"10.1007/s12020-024-04062-1","url":null,"abstract":"<p><p>The approval in 2017 by the European Medicines Agency (EMA) and in 2018 by the US Food and Drug Administration (FDA) of radioligand therapy (RLT) led to its wide application in therapeutic management of neuroendocrine neoplasms (NENs). However, the indications are currently limited to certain specific histotypes belonging to the broader NEN's family, mainly advanced well-differentiated gastro-entero-pancreatic NENs. As a consequence, several other tumors of the NEN spectrum that can potentially benefit, due to their biological characteristics, from RLT are still ineligible and can be considered \"RLT-orphans\". Among those, the subgroup of NENs originating from the sympathetic-adrenal-medullary (SAM) axis can be listed. This paper discusses the state of art and perspectives of the theragnostic applications in pheochromocytomas and paragangliomas, considering both the traditional theragnostic model - with radiolabelled metaiodobenzylguanidine (MIBG) - and the innovative one with radiolabeled somatostatin analogs (SSAs), that will hopefully become available for these patients in the near future.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"67-72"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382153","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":"Prognostic significance of metastatic lymph node size and extra-nodal extension in papillary thyroid carcinoma according to the 9th edition of general rules for the description of thyroid cancer risk stratification: a single center validation study.","authors":"Haruhiko Yamazaki, Soji Toda, Rika Sasaki, Aya Saito","doi":"10.1007/s12020-024-03974-2","DOIUrl":"10.1007/s12020-024-03974-2","url":null,"abstract":"<p><strong>Purpose: </strong>In the 9th edition of general rules for the description of thyroid cancer (GRDTC), the N factor was subdivided according to the maximum diameter of metastatic lymph nodes, presence of extra-nodal extension (ENE), and location of mediastinal lymph nodes. This study aimed to investigate the clinical usefulness of the 9th GRDTC risk stratification in papillary thyroid carcinoma (PTC) patients with lymph node metastasis.</p><p><strong>Methods: </strong>A total of 703 PTC patients with lymph node metastasis who underwent initial thyroidectomy at our institution between January 2000 and October 2023 were included.</p><p><strong>Results: </strong>Among the 703 patients with PTC, the 10-year cause specific survival rates of patients with pN1a-1 (n = 383), pN1a-2 (n = 13), pN1b-1 (n = 234), and pN1b-2 (n = 73) were 97.9%, 100%, 95.4%, and 76.2%, respectively (p < 0.001). Therefore, the pN1b-2 classification identified patients with a worse prognosis among those with pN1b. Among the 664 patients with M0 PTC, the 10-year disease free survival (DFS) rates of the patients with pN1a-1 (n = 378), pN1a-2 (n = 13), pN1b-1 (n = 215), and pN1b-2 (n = 58) were 86.9%, 62.5%, 79.9%, and 59.4%, respectively (p < 0.001). The pN1b-2 category was associated with worse DFS in pN1b patients.</p><p><strong>Conclusions: </strong>The 9th edition of the GRDTC may be useful for stratifying the prognosis of patients with PTC. The risk assessment of PTC-related death and recurrence will be more accurate by considering the size of lymph node metastasis and ENE in GRDTC.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"188-195"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789613","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":"New Onset Diabetes After COVID 19 (NODAC) is predominantly due to exacerbated Insulin Resistance (IR) rather than beta cell dysfunction: Lessons from tertiary care hospital data during confluence of two epidemics.","authors":"Juhi Jamwal, Ankit Chhabra, Ajaz Qadir, Mohd Ashraf Ganie, Syed Mudasir Qadri, Adnan Lone, Naveed Nazir Shah","doi":"10.1007/s12020-024-04006-9","DOIUrl":"10.1007/s12020-024-04006-9","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate determinants of new onset diabetes after COVID-19 (NODAC) and its recovery at 6 months.</p><p><strong>Methods: </strong>This was an observational follow up study conducted from August, 2020 to July, 2023, recruiting patients with preexisting DM and COVID 19 patients with no history of DM. Multivariate regression analysis was used to determine the factors responsible for severity of COVID 19 infection in preexisting DM group. Clinical, laboratory and glycometabolic parameters were estimated at baseline and 6 months in NODAC and euglycemic group to determine the factors responsible for NODAC and its persistence at 6 months.</p><p><strong>Results: </strong>Of 1310 patients, 855 (65.3%) COVID 19 patients were further divided based on their glycemic status: preexisting DM (19%), NODAC (8.5%) and euglycemia (72.5%). Older age and male gender were independent risk factors for severe COVID 19 disease in patients with preexisting diabetes. Prevalence of NODAC in present study was 8.5%. Patients with NODAC had higher mean fasting blood glucose (FBG), random blood glucose (RBG) and HbA1c at baseline as compared to COVID with euglycemic group with no difference in serum C-peptide levels. Female gender, family history of DM, signs of insulin resistance, higher BMI, WHR, HbA1c, serum insulin levels, FBG and RBG predicted persistence of NODAC at 6 months.</p><p><strong>Conclusion: </strong>Preexisting DM is a risk factor for severe COVID 19 disease. Patients with NODAC have evidence of persistence insulin resistance on follow up, underscoring the need for long term glycemic monitoring.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"126-135"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074374","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 impact of metformin on mortality in patients with type 2 diabetes mellitus: a prospective cohort study.","authors":"Bocheng Zhang, Ying Cao, Zhenan Qu, Yulan Sun, Xiaoyuan Tian","doi":"10.1007/s12020-024-04012-x","DOIUrl":"10.1007/s12020-024-04012-x","url":null,"abstract":"<p><strong>Background: </strong>Metformin, a widely used antihyperglycemic drug, has shown efficacy in treating type 2 diabetes mellitus (T2DM) and is associated with potential benefits beyond glycemic control. This study investigates the impact of metformin on mortality in T2DM patients using a prospective cohort design utilizing data from the National Health and Nutrition Examination Survey (NHANES).</p><p><strong>Methods: </strong>In NHANES 1999-2014, a total of 5813 representative participants aged 20 and above with T2DM were included in the analysis. We utilized Kaplan-Meier survival curves and multivariate Cox regression analysis to investigate the impact of metformin on both all-cause mortality and cause-specific mortality among patients with T2DM.</p><p><strong>Results: </strong>Kaplan-Meier analysis showed a significant reduction in all-cause and cause-specific mortality in metformin users compared to non-users (p < 0.05). Multivariate Cox regression confirmed these findings, indicating that metformin use was associated with a 18% reduction in all-cause mortality (HR = 0.82, 95% CI = 0.73-0.92, p < 0.001) and 25% reduction in cardiovascular mortality (HR = 0.75, 95% CI = 0.60-0.94, p = 0.01).</p><p><strong>Conclusion: </strong>Our results suggest that metformin significantly reduces all-cause and cardiovascular mortality in T2DM patients, highlighting its potential benefits beyond glycemic control. These results contribute to the existing literature by providing robust evidence from a large prospective cohort study. However, further research is needed to validate these findings and elucidate the underlying mechanisms controlling the effects of metformin on mortality outcomes in individuals with T2DM.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"136-143"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074375","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":"Addressing the growing concern of adolescent overweight: a call for action.","authors":"Yanggang Hong","doi":"10.1007/s12020-024-03985-z","DOIUrl":"10.1007/s12020-024-03985-z","url":null,"abstract":"","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"346-347"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890670","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":"Correlation of bone age development with overweight and obesity in 23,305 children from Beijing.","authors":"Bo Zhou, Xia Qu, Minjun Li, Xi Wang, Qi Xu, Jianhong Wang, Xiaoli Liu, Lili Zhang, Ting Zhang, Jialu Gu, Lijun Zhou, Nan Peng, Wenquan Niu, Lin Wang","doi":"10.1007/s12020-024-03988-w","DOIUrl":"10.1007/s12020-024-03988-w","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to observe the influence of differential nutritional status on bone age (BA) change according to body mass index (BMI) and analyze the risk of advanced bone age in children with overweight and obesity.</p><p><strong>Methods: </strong>In total 23,305 children from Beijing were included in this cross-sectional study. Childhood overweight and obesity were defined according to the China and World Health Organization growth criteria. The data were analyzed by the R coding platform version 4.3.0.</p><p><strong>Results: </strong>Under the Chinese criteria, 29%, 15%, and 4% of boys with overweight; 33%, 33%, and 3% of boys with obesity; 39%, 25%, and 2% of girls with overweight; and 37%, 42% and 1% of girls with obesity had advanced, significantly advanced and delayed BA, respectively. After adjustment, overweight (odds ratio, 95% confidence interval, P under the Chinese criteria: 2.52, 2.30-2.75, <0.001 and 4.54, 4.06-5.09, <0.001) and obesity (4.31, 3.85-4.82, <0.001 and 14.01, 12.39-15.85, <0.001) were risk factors for both advanced BA and significantly advanced BA.</p><p><strong>Conclusions: </strong>Different nutritional statuses lead to differences in children's BA development. Children with overweight and obesity have higher rates of advanced BA under two growth criteria, and girls have more advances in BA than boys do. Overweight and obesity are risk factors for advanced BA.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"304-313"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid hormones for euthyroid patients with simple goiter growing over time: a survey of European thyroid specialists.","authors":"Enrico Papini, Roberto Attanasio, Miloš Žarković, Endre Vezekenyi Nagy, Roberto Negro, Petros Perros, Juan Carlos Galofré, Chagit Adler Cohen, Ersin Akarsu, Maria Alevizaki, Göksun Ayvaz, Tomasz Bednarczuk, Biljana Nedeljković Beleslin, Eszter Berta, Miklos Bodor, Anna Maria Borissova, Mihail Boyanov, Camille Buffet, Maria-Cristina Burlacu, Jasmina Ćirić, Juan J Díez, Harald Dobnig, Valentin Fadeyev, Benjamin C T Field, Dagmar Führer-Sakel, Tommi Hakala, Jan Jiskra, Peter Andreas Kopp, Michael Krebs, Michal Kršek, Mikael Lantz, Ivica Lazúrová, Laurence Leenhardt, Vitaliy Luchytskiy, Francisca Marques Puga, Anne McGowan, Miguel Melo, Saara Metso, Carla Moran, Tatyana Morgunova, Dan Alexandru Niculescu, Božidar Perić, Tereza Planck, Eyal Robenshtok, Patrick Olivier Rosselet, Marek Ruchala, Kamilla Ryom Riis, Alla Shepelkevich, Mykola Tronko, David Unuane, Irfan Vardarli, W Edward Visser, Andromachi Vryonidou, Younes Ramazan Younes, Laszlo Hegedüs","doi":"10.1007/s12020-024-04002-z","DOIUrl":"10.1007/s12020-024-04002-z","url":null,"abstract":"<p><strong>Background: </strong>Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines.</p><p><strong>Purpose: </strong>To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice.</p><p><strong>Methods: </strong>Online survey on the use of TH for growing SG among thyroid experts from 28 European countries.</p><p><strong>Results: </strong>The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak.</p><p><strong>Conclusions: </strong>Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":"262-272"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113971","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}