medRxiv - Endocrinology最新文献

{"title":"Free fatty acids accelerate β-cell death in type 1 diabetes","authors":"Emily C Elliott, Soumyadeep Sarkar, Lisa Bramer, Meagan Burnet, Young-Mo Kim, Xiaoyan Yi, Igor L Estevao, Marian Rewers, Xiaolu A Cambronne, Kendra Vehik, Rafael Arrojo e Drigo, Thomas O Metz, Decio L Eizirik, Bobbie-Jo M Webb-Robertson, Raghavendra G Mirmira, Ernesto S Nakayasu","doi":"10.1101/2024.09.16.24313433","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313433","url":null,"abstract":"Type 1 diabetes (T1D) results from autoimmune destruction of the insulin-producing pancreatic beta cells. The body lipid metabolism is strongly regulated during this process but there is a need to understand how this regulation contributes to the beta-cell death. Here, we show that fatty acids are released from plasma lipoproteins in children during islet autoimmunity, prior to T1D onset. These fatty acids (FFAs) enhanced cytokine-mediated apoptosis in cultured insulin-producing cells by downregulating the production of nicotinamide adenosine dinucleotide (NAD) via its salvage pathway, as well as deregulated central carbon metabolism and impaired levels of ATP. Downregulation of the NAD salvage pathway and central carbon metabolism enzymes were further observed during T1D development, supporting that the pathways for NAD and energy production are compromised in vivo. Our findings show that fatty acids are released during islet autoimmunity, accelerating disease development through impaired NAD metabolism.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269085","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":"Detection of enterovirus RNA in pancreas and lymphoid tissues of organ donors with type 1 diabetes","authors":"Jutta E Laiho, Sami Oikarinen, Sofia Morfopoulou, Maarit Oikarinen, Ashlie Renner, Daniel Depledge, Matthew C Ross, Ivan C Gerling, Judith Breuer, Joseph F Petrosino, Vincent Plagnol, Alberto Pugliese, Antonio Toniolo, Richard E Lloyd, Heikki Hyoty","doi":"10.1101/2024.09.11.24313112","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313112","url":null,"abstract":"Aims/hypothesis The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. Methods We analysed pancreas, spleen, pancreatic lymph nodes, and duodenum samples from the following donor groups: a) donors with type 1 diabetes (n=71), with (n=35) or without (n=36) insulin-containing islets, (b) donors with single or double islet autoantibody positivity without diabetes (n=22) and c) autoantibody-negative donors without diabetes (control donors) (n=74). Five research laboratories participated in this collaborative effort using approaches for unbiased discovery of RNA viruses (two RNA-Seq platforms), targeted detection of Enterovirus A-D species using RT-PCR, and tests for virus growth in cell-culture. Results Direct RNA-Seq did not detect virus signal in pancreas samples, whereas RT-PCR detected enterovirus RNA confirmed by sequencing in low amounts in pancreas samples in three of the five donor groups, namely donors with type 1 diabetes with insulin-containing islets, 16% (5/32) donors being positive, donors with single islet autoantibody positivity with 53% (8/15) donors being positive, and non-diabetic donors with 8% (4/49) being enterovirus RNA positive. Detection of enterovirus RNA was significantly more frequent in single islet autoantibody-positive donors compared to donors with type 1 diabetes with insulin-deficient islets (p-value <0.001) and control donors (p-value 0.004). In some donors, pancreatic lymph nodes were also positive. RT-PCR detected enterovirus RNA also in spleen of a small number of donors and virus enrichment in susceptible cell lines before RT-PCR resulted in much higher rate in spleen positivity, particularly in donors with type 1 diabetes. Interestingly, the enterovirus strains detected did not cause a typical lytic infection, possibly reflecting their persistence-prone nature. Conclusions/interpretation This was the largest coordinated effort to examine the presence of enterovirus RNA in pancreas of organ donors with type 1 diabetes, using a multitude of assays. These findings are consistent with the notion that both the subjects with type 1 diabetes and those with islet autoantibodies may carry a low-grade enterovirus infection in the pancreas and lymphoid tissues.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255302","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":"Sex and age differences in cardiovascular risk factors and lifestyle at the onset of diabetes mellitus: a cross-sectional study in Spanish Primary Health Care.","authors":"Pilar Vich-Perez, Belen Taulero-Escalera, Victoria Garcia-Espinosa, Laura Villanova-Cuadra, Paula Regueiro-Toribio, Ignacio Sevilla-Machuca, Julia Timoner-Aguilera, Mario Martinez-Grandmontagne, Tania Abos-Pueyo, Cristina Alvarez-Hernandez-Canizares, German Reviriego-Jaen, Alberto Serrano-Lopez-Hazas, Ines Gala-Molina, Mar Sanz-Pascual, Miguel A Salinero-Fort, LADA-PC consortium","doi":"10.1101/2024.09.11.24313481","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313481","url":null,"abstract":"Aims\u0000To describe the main characteristics of patients recently diagnosed with diabetes\u0000mellitus in terms of comorbidities, cardiovascular risk factors and healthy lifestyle by\u0000sex and age group.\u0000Methods\u0000A cross-sectional, multicenter, observational study of 681 patients aged >30 years\u0000diagnosed with diabetes mellitus in the previous 4 years was performed. The patients\u0000were treated in primary care centers in Madrid (Spain). The variables were obtained\u0000from their electronic medical records, physical examination, complete analysis, and\u0000lifestyle questionnaires.\u0000Results\u0000The main comorbidities were: hypercholesterolemia (64.4%; 95% CI, 60.6-68.2),\u0000hypertension (55.2%; 95% CI, 51.3-59.1), obesity (58.9%; 95% CI, 55.2-62.6),\u0000metabolic syndrome (58.5%; 95% CI, 54.6-62.5); and hypertriglyceridemia (25.3%;\u000095% CI, 21.9-28.7). Despite being newly diagnosed, 7.6% (95% CI, 5.4-9.8) had\u0000microalbuminuria, and 10.3% (95% CI, 8.0-12.6) cardiovascular disease. The main\u0000unhealthy lifestyles were: low physical activity (52%; 95% CI, 48.1-55.9), alcohol\u0000consumption (47.7%; 95% CI, 44.0-51.5) and smoking (19.2%; 95% CI, 16.2-22.3).\u0000Compared with men, women had more morbid obesity (9.7% vs 4.6%, p=.014), worse\u0000lipid profile (total cholesterol: 184 (IQR, 158-207) vs. 165 (IQR, 144-192), p<.01), less\u0000treatment with metformin (74.8% vs. 84.4%, p<.01) and antiplatelet agents (8.1%\u0000vs.18.6%, p<.01), but women had fewer comorbidities. Patients with a high educational\u0000level (OR= 1.90, 95% CI, 1.28-2.81) ) and those >60 years (OR= 1.49; 95% CI, 1.01-\u00002.21) were more adherent to the Mediterranean diet, and the older ones did less\u0000intense exercise (OR= 0.34, 95% CI, 0.16-0.75). Normal blood pressure was\u0000associated with Mediterranean diet (OR= 1.52; 95% CI, 1.05-2.21) and high physical\u0000activity (OR= 4.03; 95% CI, 1.69-9.61); and body mass index was inversely associated\u0000with physical activity (OR= 0.92; 95% CI, 0.85-0.99).\u0000Conclusions\u0000Patients newly diagnosed with diabetes mellitus have crucial cardiovascular risk\u0000factors and comorbidities at the onset of the disease. These can be modified through a\u0000healthy lifestyle.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183870","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":"Establishing a Core Outcome Set for Creatine Transporter Deficiency and Guanidinoacetate Methyltransferase Deficiency","authors":"Zahra Nasseri Moghaddam, Emily K Reinhardt, Audrey Thurm, Beth K Potter, Maureen Smith, Celeste Graham, Beth H Tiller, Steven A Baker, Deborah A Bilder, Regina Bogar, Jacobus Britz, Rachel Cafferty, Daniel P Coller, Ton J DeGrauw, Vicky Hall, Gerald S Lipshutz, Nicola Longo, Saadet Mercimek-Andrews, Judith S Miller, Marzia Pasquali, Gajja S Salomons, Andreas Schulze, Celine P Wheaton, Kayla F Williams, Sarah P Young, Jasmine Li, Sofia Balog, Theresa Selucky, Sylvia Stockler-Ipsiroglu, Heidi Wallis","doi":"10.1101/2024.09.06.24313213","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313213","url":null,"abstract":"Creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies are rare inborn errors of creatine metabolism, resulting in cerebral creatine deficiency. Patients commonly exhibit intellectual and developmental disabilities, often accompanied by behavior problems, delayed speech, seizures, and motor impairments. There is currently no efficacious treatment for CTD, while the current management for GAMT requires lifelong treatment with a protein restricted diet and intake of high amounts of oral supplements. Efforts to develop effective, sustainable treatments for these disorders are limited by the lack of clinical and patient-derived meaningful outcomes. A core outcome set (COS) can facilitate consensus about outcomes for inclusion in studies. Unfortunately, patient and caregiver perspectives have historically been overlooked in the COS development process, thus limiting their input into the outcome selection. We partnered with caregivers and health professionals to establish the first COS for CTD and GAMT. The COS developed includes seven outcomes (Adaptive Functioning, Cognitive Functioning, Emotional Dysregulation, MRS Brain Creatine, Seizure/Convulsions, Expressive Communication, and Fine Motor Functions) for both CTD and GAMT, and an additional outcome for GAMT (Serum/Plasma Guanidinoacetate) that are important to stakeholders and consequently should be considered for measurement in every clinical trial. Caregivers were valued partners throughout the COS development process, which increased community engagement and facilitated caregiver empowerment. We expect this COS will ensure a patient-centered approach for accelerating drug development for CTD and GAMT, make clinical trial results comparable, minimize bias in clinical trial outcome selection, and promote efficient use of resources.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183871","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":"Primary aldosteronism results in a decline estimated glomerular filtration rate independent of blood pressure: evidence from a case-control and mendelian randomization study","authors":"mingjie xu, Boteng Yan, Mingli Li, Yushuang Wei, Xihui Jin, Xiaoyou Mai, Hui Liang, Haiyun Lan, Wenchao Xie, Tianjiao Pang, Qiang Lin, Yifeng Chen, Zeguang Zhou, Yongxian Wu, Xinyang Long, Shengzhu Huang, Chaoyan Tang, Zengnan Mo","doi":"10.1101/2024.09.08.24313278","DOIUrl":"https://doi.org/10.1101/2024.09.08.24313278","url":null,"abstract":"ABSTRACT\u0000Background: Primary aldosteronism (PA) is the predominant cause of secondary hypertension, leading to cardiovascular and renal damage via mechanisms such as oxidative stress and fibrosis. However, current epidemiology findings on the association between PA and estimated glomerular filtration rate (eGFR) remain inconsistent.\u0000Methods: A 1:1 sex- and age-matched case-control study was conducted among participants with PA, essential hypertension (EH), and normotension, with 204 participants in each group. Multiple linear regression was used to explore the correlations of PA, plasma aldosterone concentration (PAC), plasma renin concentration (PRC), and the aldosterone-to-renin ratio (ARR) with eGFR. Additionally, we performed a bidirectional two-sample mendelian randomization (MR) analysis to assess the causal relationship between PA and eGFR based on public genome wide association study (GWAS) databases, and established a multivariable MR (MVMR) analysis to further explore whether the causal effect of PA on eGFR decline independent of systolic (SBP) or diastolic blood pressure (DBP).\u0000Results: Multiple linear regression model showed that PA was associated with a decline eGFR (β = -0.234, [95% CI, -0.099, -0.039], P<0.001) after adjusted potential confounders. When stratified the PA patients into three groups according to the levels of PAC, PRC and ARR, patients in the highest PAC groups (β = -0.146 [95% CI, -0.093, -0.008], P =0.021), the lowest PRC group (β = -0.127 [95% CI, -0.084, -0.004], P =0.033), and the highest ARR group (β = -0.147 [95% CI, -0.092, -0.009], P =0.017) had much lower eGFR compared to the EH group. The inverse associations mentioned above remained significant even further adjusted for SBP or DBP, respectively. Besides, MR results indicated that genetically predicted PA was causally associated with a decline eGFR (β =-6.671×10-4[95% CI,-1.291×10-4,-4.328×10-5], P = 0.036), consistent effects were further detected in SBP (β =-1.121×10-3 [95% CI,-2.132×10-3,-1.110×10-4], P = 0.029) or DBP (β =-1.542×10-3,[95% CI,-2.693×10-3,-3.912×10-4], P = 0.008) adjusted model using MVMR analysis.\u0000Conclusion: Our study indicates that PA is causally associated with lower eGFR independent of blood pressure, and the adverse effects might be greater than negative controls or EH patients.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183872","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":"Sex-Specific Skeletal Muscle Gene Expression Responses to Exercise Reveal Novel Direct Mediators of Insulin Sensitivity Change","authors":"S Ma, MC Morris, MJ Hubal, LM Ross, KM Huffman, CG Vann, N Moore, ER Hauser, A Bareja, R Jiang, E Kummerfeld, MD Barberio, JA Houmard, WB Bennett, JL Johnson, JA Timmons, G Broderick, VB Kraus, CF Aliferis, WE Kraus","doi":"10.1101/2024.09.07.24313236","DOIUrl":"https://doi.org/10.1101/2024.09.07.24313236","url":null,"abstract":"<strong>BACKGROUND</strong> Understanding the causal pathways, systems, and mechanisms through which exercise impacts human health is complex. This study explores molecular signaling related to whole-body insulin sensitivity (Si) by examining changes in skeletal muscle gene expression. The analysis considers differences by biological sex, exercise amount, and exercise intensity to identify potential molecular targets for developing pharmacologic agents that replicate the health benefits of exercise.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183662","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":"Lifestyle Profiling Using Wearables and Prediction of Glucose Metabolism in Individuals with Normoglycemia or Prediabetes","authors":"Heyjun Park, Ahmed A. Metwally, Alireza Delfarah, Yue Wu, Dalia Perelman, Majid Rodgar, Caleb Mayer, Alessandra Celli, Tracey McLaughlin, Emmanuel Mignot, Michael Snyder","doi":"10.1101/2024.09.05.24312545","DOIUrl":"https://doi.org/10.1101/2024.09.05.24312545","url":null,"abstract":"This study examined the relationship between lifestyles (diet, sleep, and physical activity) and glucose responses at a personal level. 36 healthy adults in the Bay Area were monitored for their lifestyles and glucose levels using wearables and continuous glucose monitoring (NCT03919877). Gold-standard metabolic tests were conducted to phenotype metabolic characteristics. Through the lifestyle data (2,307 meals, 1,809 nights, and 2,447 days) and 231,206 CGM readings from metabolically-phenotyped individuals with normoglycemia or prediabetes, we found: 1) eating timing was associated with hyperglycemia, muscle insulin resistance (IR), and incretin dysfunction, whereas nutrient intakes were not; 2) timing of increased activity in muscle IS and IR participants was associated with differential benefits of glucose control; 3) Integrated ML models using lifestyle factors predicted distinct metabolic characteristics (muscle, adipose IR or incretin dysfunction). Our data indicate the differential impact of lifestyles on glucose regulation among individuals with different metabolic phenotypes, highlighting the value of personalized lifestyle modifications.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183875","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":"Association of the rs738409 polymorphism in PNPLA3 with development and severity of non-alcoholic fatty liver disease in ethnic Bengali population of West Bengal","authors":"Mousumi Das, Arindam Biswas, Soumik Goswami, Rajat Deb, Sukdeb Das, Debes Ray","doi":"10.1101/2024.09.02.24312965","DOIUrl":"https://doi.org/10.1101/2024.09.02.24312965","url":null,"abstract":"<strong>Background and Objectives</strong> Non-alcoholic Fatty Liver Disease (NAFLD) is a common disorder with a complex etiology. Polymorphic variant rs738409 (Ile148Met) in the <em>PNPLA3</em> gene has been reported to be associated with NAFLD among several ethnic populations. The present study aims to identify the potential association of this PNPLA3 gene variant with NAFLD among the ethnic Bengali population of West Bengal and correlate it with disease severity and biochemical parameters.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183873","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":"Precision medicine in Type 2 Diabetes: Targeting SGLT2-inhibitor Treatment For Kidney Protection","authors":"Thijs T Jansz, Katherine G Young, Rhian Hopkins, Andrew P McGovern, Beverley M Shields, Andrew T Hattersley, Angus G Jones, Ewan R Pearson, Richard A Oram, John M Dennis, MASTERMIND Consortium","doi":"10.1101/2024.09.01.24312905","DOIUrl":"https://doi.org/10.1101/2024.09.01.24312905","url":null,"abstract":"<strong>Background</strong> Current guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) for kidney protection to a broad range of people with type 2 diabetes (T2D), but many were not represented in key kidney outcome trials and have unclear benefit. We aimed to identify which of these people are likely to benefit.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183877","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":"SNP Genes Effect on Thyroid Disorders in a Chinese Demographic","authors":"Iris Fan, Fenglan Zhou","doi":"10.1101/2024.08.29.24312609","DOIUrl":"https://doi.org/10.1101/2024.08.29.24312609","url":null,"abstract":"Thyroid disorders, particularly hypothyroidism, are prevalent in the Chinese population and have been linked to specific genetic variations. This study investigates the associations between single nucleotide polymorphisms (SNPs) and thyroid disorders in a cohort of Chinese individuals. It aims to explore a novel aspect of thyroid disorders, precisely the effect of different SNPs on the prevalence of developing these disorders, autoimmune diseases, or cancer. It focuses on four SNPs: rs965513, rs179247, rs3087243, and rs231779. The analysis revealed significant associations between these SNPs and thyroid disorders, with the ‘A’ allele of rs179247 showing a higher risk.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183876","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}