Expert Review of Endocrinology & Metabolism最新文献

{"title":"Knowing when to discontinue Temozolomide therapy in responding aggressive pituitary tumors and carcinomas: a systematic review and Padua (Italy) case series.","authors":"Marta Padovan,&nbsp;Giulia Cerretti,&nbsp;Mario Caccese,&nbsp;Mattia Barbot,&nbsp;Eleonora Bergo,&nbsp;Gianluca Occhi,&nbsp;Carla Scaroni,&nbsp;Giuseppe Lombardi,&nbsp;Filippo Ceccato","doi":"10.1080/17446651.2023.2185221","DOIUrl":"https://doi.org/10.1080/17446651.2023.2185221","url":null,"abstract":"<p><strong>Introduction: </strong>Pituitary adenomas can show a tendency to grow, despite multimodal treatment. Temozolomide (TMZ) has been used in the last 15 years in patients with aggressive pituitary tumors. TMZ requires a careful balance of different expertise, especially for selection criteria.</p><p><strong>Areas covered: </strong>We conducted: (1) a systematic review of the published literature from 2006 to 2022, collecting only cases with a complete description of patient follow-up after TMZ discontinuation; (2) a description of all patients with aggressive pituitary adenoma or carcinoma treated in Padua (Italy).</p><p><strong>Expert opinion: </strong>There is considerable heterogeneity in the literature: TMZ cycles duration ranged from 3 to 47 months; the follow-up time after TMZ discontinuation ranged from 4 to 91 months (mean 24 months, median 18 months), at least a stable disease has been reported in 75% of patients after a mean 13 months (range 3-47 months, median 10 months). The Padua (Italy) cohort reflects the literature. Future directions to explore are to understand the pathophysiological mechanism of TMZ resistance escape, to develop predicting factors to TMZ treatment (especially through the delineation of the underlying transformation processes), and to further expand the therapeutic applications of TMZ (as neoadjuvant, combined with radiotherapy).</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 2","pages":"181-198"},"PeriodicalIF":3.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9285523","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":"Functional characterization of all missense variants in <i>LEPR, PCSK1</i>, and <i>POMC</i> genes arising from single-nucleotide variants.","authors":"Bhavik P Shah,&nbsp;Patrick M Sleiman,&nbsp;Jessica Mc Donald,&nbsp;Ida H Moeller,&nbsp;Patrick Kleyn","doi":"10.1080/17446651.2023.2179985","DOIUrl":"https://doi.org/10.1080/17446651.2023.2179985","url":null,"abstract":"<p><strong>Objective: </strong>Hyperphagia and early-onset, severe obesity are clinical characteristics of rare melanocortin-4 receptor (MC4R) pathway diseases due to loss-of-function (LOF) variants in genes comprising the MC4R pathway. In vitro functional characterization of 12,879 possible exonic missense variants from single-nucleotide variants (SNVs) of <i>LEPR, POMC</i>, and <i>PCSK1</i> was performed to determine the impact of these variants on protein function.</p><p><strong>Methods: </strong>SNVs of the three genes were transiently transfected into cell lines, and each variant was subsequently classified according to functional impact. We validated three assays by comparing classifications against functional characterization of 29 previously published variants.</p><p><strong>Results: </strong>Our results significantly correlated with previously published pathogenic categories (r = 0.623; <i>P</i> = 3.03 × 10^-4) of all potential missense variants arising from SNVs. Of all observed variants identified through available databases and a tested cohort of 16,061 patients with obesity, 8.6% of <i>LEPR</i>, 63.2% of <i>PCSK1</i>, and 10.6% of <i>POMC</i> variants exhibited LOF, including variants currently classified as a variant of uncertain significance (VUS).</p><p><strong>Conclusions: </strong>The functional data provided here can assist in the reclassification of several VUS in <i>LEPR, PCSK1</i>, and <i>POMC</i> and highlight their impact in MC4R pathway diseases.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 2","pages":"209-219"},"PeriodicalIF":3.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9292341","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":"An update on tirzepatide for the management of type 2 diabetes: a focus on the phase 3 clinical development program.","authors":"Juan Pablo Frías","doi":"10.1080/17446651.2023.2184796","DOIUrl":"https://doi.org/10.1080/17446651.2023.2184796","url":null,"abstract":"<p><strong>Introduction: </strong>Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), received regulatory approval from the U.S. Food and Drug Administration (13 May 2022) and marketing authorization from the European Commission (25 September 2022) for the improvement of glycemic control in adults with type 2 diabetes (T2D). In the phase 3 clinical development program (SURPASS), tirzepatide demonstrated superior glycemic and body weight control compared with placebo and active comparators across a spectrum of patients with T2D.</p><p><strong>Areas covered: </strong>This review summarizes efficacy and safety results of the tirzepatide T2D phase 3 clinical trials that supported regulatory approvals. Additionally, it discusses a meta-analysis assessing tirzepatide cardiovascular (CV) safety, and provides a brief overview of ongoing late-stage clinical trials in patients with T2D. Information in this review was acquired from peer-reviewed published trials, ClinicalTrials.gov, and the manufacturer's website.</p><p><strong>Expert opinion: </strong>Based on phase 3 clinical trial data, tirzepatide is the most potent glucose and body weight lowering agent available for the management of T2D. The potential for tirzepatide to improve CV outcomes is currently being assessed in a CV outcomes trial (SURPASS CVOT). Results of this trial are highly anticipated and expected in 2024.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 2","pages":"111-130"},"PeriodicalIF":3.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9345336","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":"Effects of hypoglycaemic therapy on frailty: a multi-dimensional perspective.","authors":"Ahmed H Abdelhafiz","doi":"10.1080/17446651.2023.2168644","DOIUrl":"https://doi.org/10.1080/17446651.2023.2168644","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of diabetes is increasing in older people. With increasing age, frailty emerges as a new complication leading to disability. Frailty does not only include physical dysfunction but also involves negative impact on cognition and mood. Triad of impairments (TOI) is a new concept that includes physical frailty, dementia and depression to reflect the wider spectrum of frailty.</p><p><strong>Areas covered: </strong>Little is known about effects of hypoglycaemic agents on frailty syndrome. A literature search was performed on studies, which reported effects of hypoglycaemic agents on the component of the TOI.</p><p><strong>Expert opinion: </strong>It appears that most hypoglycaemic agents have some effects on frailty, although the results of clinical studies are inconsistent. Metformin seems to have a consistent and a positive effect on physical frailty. Its effects on cognitive function, however, are inconclusive but tend to be positive. Metformin appeared to improve depressive symptoms. Other agents such as incretins, thiazolidinediones, and sodium glucose transporter-2 inhibitors have some positive effects on cognition and depression. Sulfonylureas, glinides, or insulin have either negative or neutral effects on TOI components. The negative effects of insulin could be partially explained by the negative psychological factors and the frequent episodes of hypoglycemia associated with such therapy.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 1","pages":"53-65"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10711488","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":"The unique pathophysiological features of diabetes mellitus secondary to total pancreatectomy: proposal for a new classification distinct from diabetes of the exocrine pancreas.","authors":"Marco Infante,&nbsp;Camillo Ricordi","doi":"10.1080/17446651.2023.2168645","DOIUrl":"https://doi.org/10.1080/17446651.2023.2168645","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes of the exocrine pancreas (DEP; a.k.a. pancreatic diabetes or pancreatogenic diabetes or type 3c diabetes mellitus or T3cDM) refers to different diabetes types resulting from disorders of the exocrine pancreas. DEP is characterized by the structural and functional loss of glucose-normalizing insulin secretion in the context of exocrine pancreatic dysfunction. Among these forms, new-onset diabetes mellitus secondary to total pancreatectomy (TP) has unique pathophysiological and clinical features, for which we propose a new nomenclature such as post-total pancreatectomy diabetes mellitus (PTPDM).</p><p><strong>Areas covered: </strong>TP results in the complete loss of pancreatic parenchyma, with subsequent absolute insulinopenia and lifelong need for exogenous insulin therapy. Patients with PTPDM also exhibit deficiency of glucagon, amylin and pancreatic polypeptide. These endocrine abnormalities, coupled with increased peripheral insulin sensitivity, deficiency of pancreatic enzymes and TP-related modifications of gastrointestinal anatomy, can lead to marked glucose variability and increased risk of iatrogenic (insulin-induced) severe hypoglycemic episodes ('brittle diabetes').</p><p><strong>Expert opinion: </strong>We believe that diabetes mellitus secondary to TP should not be included in the DEP spectrum in light of its peculiar pathophysiological and clinical features. Therefore, we propose a new classification for this entity, that would likely provide more accurate prognosis and treatment strategies.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 1","pages":"19-32"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266494","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":"Efficacy and safety of intensive versus conventional glucose targets in people with type 2 diabetes: a systematic review and meta-analysis.","authors":"Rami Aldafas,&nbsp;Thomas Crabtree,&nbsp;Yana Vinogradova,&nbsp;Jason P Gordon,&nbsp;Iskandar Idris","doi":"10.1080/17446651.2023.2166489","DOIUrl":"https://doi.org/10.1080/17446651.2023.2166489","url":null,"abstract":"<p><strong>Objective: </strong>The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D.</p><p><strong>Methods: </strong>We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbA_1clevels. Subgroup analysis was also performed to account for the inclusion of glucose only versus multi-factorial intervention trials. Results are reported as risk ratio (RR) and 95% confidence interval (CI).</p><p><strong>Results: </strong>Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5--0.87), microalbuminuria (0.67, 0.52-0.85), major amputation (0.6, 0.38-0.96), retinopathy (0.75 ,0.63-0.9), and nephropathy (0.78, 0.63-0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34-3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57-0.95).</p><p><strong>Conclusion: </strong>Targeting HbA_1c levels should be individualized based on the clinical status, balancing risks and benefits and potential risk for developing these complications among people with T2D.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 1","pages":"95-110"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10772315","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":"The role of progesterone and the progesterone receptor in cancer: progress in the last 5 years.","authors":"Jerome H Check,&nbsp;Diane L Check","doi":"10.1080/17446651.2023.2166487","DOIUrl":"https://doi.org/10.1080/17446651.2023.2166487","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with various advanced cancers devoid of nuclear progesterone receptors (nPR) have demonstrated increased quality and length of life when treated with the PR modulator mifepristone, which likely works by interacting with membrane PRs (mPR).</p><p><strong>Areas covered: </strong>Two immunomodulatory proteins are discussed that seem to play a role in cancers that proliferate whether the malignant tumor is positive or negative for the nPR. These two proteins are the progesterone receptor membrane component-1 (PGRMC-1) and the progesterone-induced blocking factor (PIBF). Both PGRMC-1 and the parent form of PIBF foster increased tumor aggressiveness, whereas splice variants of the 90 kDa form of PIBF inhibit immune response against cancer cells.</p><p><strong>Expert opinion: </strong>The marked clinical improvement following 200-300 mg of mifepristone is likely related to blocking PIBF. In the low dosage used, mifepristone likely acts as an agonist for PGRMC-1 protein. Mifepristone may be less effective for cancers positive for the nPR because the nPR may be protective and blocking it may have detrimental effects. Based on this hypothetical model, the development of other potential treatment options to provide even greater efficacy for treating cancer are discussed.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 1","pages":"5-18"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266033","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":"Why is pituitary carcinoma so rare?","authors":"Daniel Marrero-Rodríguez,&nbsp;Keiko Taniguchi-Ponciano,&nbsp;Moises Mercado","doi":"10.1080/17446651.2023.2167710","DOIUrl":"https://doi.org/10.1080/17446651.2023.2167710","url":null,"abstract":"Pituitary adenomas (PA) are rather frequent, they constitute up to 25% of all intracranial tumors, with a prevalence varying from 70 to 115 cases per 100,000 persons and an incidence of 4 to 6 per 100,000 persons per year [1]. The prevalence among autopsy and radiological studies varies between 10% and 20%. Pituitary carcinomas (PC), on the other hand, are among the least frequent malignancies known to man, barely reaching 0.2–0.4% of all pituitary tumors [2]. In fact, most practicing endocrinologists worldwide do not get to see a single case of PC during their professional lifetime. Published information regarding PC mostly consists of isolated case reports, very few series, and a handful of reviews [3–5]. Over 70% of PC are functioning, usually ACTHor PRL-secreting tumors that arise from apparently benign, but usually invasive macroadenomas, with a latency period from adenoma to carcinoma that varies from 6 months to over 10 years [3–5]. Features associated with malignancy such as hypercellularity, nuclear pleomorphism, increased mitotic activity, dural, bone and vascular invasion, extracellular matrix degradation, neoangiogenesis, a high Ki-67 proliferative index, and p53 immunostaining are not always present in PC and can occasionally be found in nonmalignant pituitary tumors [4]. Thus, the documentation of craniospinal or distant metastasis (bone, lymph nodes, liver, and lung, being the most frequently reported sites) is a sine qua non criteria to establish the diagnosis [2–5]. Lying between PA and PC in the pathological spectrum of pituitary neoplasms, we found what used to be called ‘atypical pituitary adenomas’ and that are currently known as aggressive pituitary tumors (APT). According to the European Society of Endocrinology (ESE) 2018 guidelines, APT are defined as tumors with radiological evidence of invasiveness, particularly cavernous sinus invasion, with an unusually rapid growth rate and that is persistent despite multimodal therapy (surgery, radiation, pharmacological treatment) [6,7]. It is important to emphasize, however, that while an aggressive tumor is almost always invasive, an invasive lesion does not always behave aggressively. The latter is illustrated by some giant prolactinomas that may be quite sensitive to pharmacological treatment with dopamine agonists. Interestingly, the conversion of a nonfunctioning into a functioning tumor, or more specifically, of a silent corticotrope adenoma into a Cushing diseasecausing tumor is associated with an aggressive biological behavior and should warn us of the possibility of an eventual malignant transformation [8]. In an attempt to summarize the complex cellular and subcellular events that underlie malignant transformation, Hanahan and Weinberg published back in 2000 their seminal article ‘The Hallmarks of Cancer’ [9]. The original review is based on six biological processes that characterize carcinogenesis, namely, 1) self-sufficiency in growth signals, 2) insensitivity to anti-","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 1","pages":"1-3"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266031","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":"Obesity and diabetes: the final frontier.","authors":"Marc S Rendell","doi":"10.1080/17446651.2023.2168643","DOIUrl":"https://doi.org/10.1080/17446651.2023.2168643","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity is a key target in the treatment and prevention of diabetes and independently to reduce the burden of cardiovascular disease. We reviewed the options now available and anticipated to deal with obesity.</p><p><strong>Areas covered: </strong>We considered the epidemiology, genetics, and causation of obesity and the relationship to diabetes, and the dietary, pharmaceutical, and surgical management of the condition. The literature search covered both popular media via Google Search and the academic literature as indexed on PubMed with search terms including obesity, childhood obesity, adipocytes, insulin resistance, mechanisms of satiety, bariatric surgery, GLP-1 receptor agonists, and SGLT2 inhibitors.</p><p><strong>Expert opinion: </strong>Although bariatric surgery has been the primary approach to treating obese individuals, the emergence of agents impacting the brain satiety centers now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. The GLP-1 receptor agonists have assumed the primary role in treating obesity with significant weight loss. Long-term results with semaglutide and tirzepatide are now approaching the success seen with bariatric surgery. Future agents combining the benefits of satiety control and thermogenesis to dissipate caloric excess are under investigation.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 1","pages":"81-94"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10772305","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":"Non-thionamide antithyroid drug options in Graves' hyperthyroidism.","authors":"Aliya Ruslan,&nbsp;Onyebuchi E Okosieme","doi":"10.1080/17446651.2023.2167709","DOIUrl":"https://doi.org/10.1080/17446651.2023.2167709","url":null,"abstract":"<p><strong>Introduction: </strong>The thionamide anti-thyroid drugs namely carbimazole, methimazole, and propylthiouracil, have been the predominant therapy modality for Graves' hyperthyroidism for over 60 years. Although these agents have proven efficacy and favorable side-effect profiles, non-thionamide alternatives are occasionally indicated in patients who are intolerant or unresponsive to thionamides alone. This review examines the available non-thionamide drug options for the control of Graves' hyperthyroidism and summarizes their clinical utility, efficacy, and limitations.</p><p><strong>Areas covered: </strong>We reviewed existing literature on mechanisms, therapeutic utility, and side-effect profiles of non-thionamide anti-thyroid drugs. Established non-thionamide agents act on various phases of the synthesis, release, and metabolism of thyroid hormones and comprise historical agents such as iodine compounds and potassium perchlorate as well as drug repurposing candidates like lithium, glucocorticoids, beta-blockers, and cholestyramine. Novel experimental agents in development target key players in Graves' disease pathogenesis including B-cell depletors (Rituximab), CD40 blockers (Iscalimab), TSH-receptor antagonists, blocking antibodies, and immune-modifying peptides.</p><p><strong>Expert opinion: </strong>Non-thionamide anti-thyroid drugs are useful alternatives in Graves' hyperthyroidism and more clinical trials are needed to establish their safety and long-term efficacy in hyperthyroidism control. Ultimately, the promise for a cure will lie in novel approaches that target the well-established immunopathogenesis of Graves' disease.</p>","PeriodicalId":12107,"journal":{"name":"Expert Review of Endocrinology & Metabolism","volume":"18 1","pages":"67-79"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10772811","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}