Archives of Medical Research最新文献

{"title":"Genomics, Transcriptomics, and Epigenetics of Sporadic Pituitary Tumors","authors":"Daniel Marrero-Rodríguez,&nbsp;Sandra Vela-Patiño,&nbsp;Florencia Martinez-Mendoza,&nbsp;Alejandra Valenzuela-Perez,&nbsp;Eduardo Peña-Martínez,&nbsp;Amayrani Cano-Zaragoza,&nbsp;Jacobo Kerbel,&nbsp;Sergio Andonegui-Elguera,&nbsp;Shimon S. Glick-Betech,&nbsp;Karla X. Hermoso-Mier,&nbsp;Sophia Mercado-Medrez,&nbsp;Alberto Moscona-Nissan,&nbsp;Keiko Taniguchi-Ponciano,&nbsp;Moises Mercado","doi":"10.1016/j.arcmed.2023.102915","DOIUrl":"10.1016/j.arcmed.2023.102915","url":null,"abstract":"<div><p><span>Pituitary tumors<span><span> (PT) are highly heterogeneous neoplasms, comprising functioning and nonfunctioning lesions. Functioning PT include prolactinomas, causing amenorrhea-galactorrhea in women and sexual dysfunction in men; GH-secreting </span>adenomas causing acromegaly-gigantism; ACTH-secreting </span></span>corticotrophinomas<span><span> causing Cushing disease<span> (CD); and the rare TSH-secreting thyrotrophinomas that result in central hyperthyroidism. Nonfunctioning PT do not result in a hormonal hypersecretion syndrome and most of them are of gonadotrope differentiation; other non-functioning PT include </span></span>null cell adenomas<span> and silent ACTH-, GH- and PRL-adenomas. Less than 5% of PT occur in a familial or syndromic context whereby germline mutations<span> of specific genes account for their molecular pathogenesis<span>. In contrast, the more common sporadic PT do not result from a single molecular abnormality but rather emerge from several oncogenic events that culminate in an increased proliferation of pituitary cells, and in the case of functioning tumors, in a non-regulated hormonal hypersecretion. In recent years, important advances in the understanding of the molecular pathogenesis of PT have been made, including the genomic, transcriptomic<span>, epigenetic<span>, and proteomic characterization of these neoplasms. In this review, we summarize the available molecular information pertaining the oncogenesis of PT.</span></span></span></span></span></span></p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138049026","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":"Pharmacological Treatment of Cushing's Syndrome","authors":"Frederic Castinetti","doi":"10.1016/j.arcmed.2023.102908","DOIUrl":"10.1016/j.arcmed.2023.102908","url":null,"abstract":"<div><p>The 1^st<span><span><span> line treatment of </span>Cushing's syndrome<span><span> is surgery, whatever the aetiology. The role of pharmacological treatment is clear in cases where surgery fails or is impossible, in cases of metastases, or while awaiting the delayed effects of radiotherapy. However, certain situations remain controversial, in particular the possible role of pharmacological treatment as a preparation for surgery. This situation must be divided into 2 parts, severe </span>hypercortisolism<span> with immediate vital risk and non-severe hypercortisolism with diagnostic delay. The initiation and adjustment of treatment doses is also controversial, with the possibility of titration by gradual </span></span></span>dose increase based on biological markers, or a more radical “block and replace” approach in which the ultimate goal is to achieve hypocortisolism, which can then be supplemented. Each of these approaches has its advantages and drawbacks and should probably be reserved for different patient profiles depending on the severity of hypercortisolism. In this review, we will focus specifically on these 2 points, namely the potential role of preoperative pharmacological treatment and, more generally, the optimal way to initiate and monitor drug treatment to ensure that eucortisolism or hypocortisolism is achieved. We will define for each part which profiles of patients should be the most adapted to try to give advice on the optimal management of patients with hypercortisolism.</span></p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136400742","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":"Primary Pituitary Carcinoids Do Not Exist: A Reappraisal in the Era of Pituitary Neuroendocrine Tumours","authors":"Eleni Armeni ,&nbsp;Krystallenia I. Alexandraki ,&nbsp;Federico Roncaroli ,&nbsp;Ashley B. Grossman","doi":"10.1016/j.arcmed.2023.102841","DOIUrl":"10.1016/j.arcmed.2023.102841","url":null,"abstract":"<div><p>The <em>World Health Organization</em><span><span> classification of pituitary tumours<span><span><span>, published in 2022, supported a change in the terminology from “pituitary adenoma” to “pituitary neuroendocrine tumour” (PitNET). The neuroendocrine cells represent an integral part of the diffuse neuroendocrine system, including, among others, </span>thyroid C cells, the </span>parathyroid<span> chief cells, and the anterior pituitary. Normal and neoplastic adenohypophyseal neuroendocrine cells have light microscopic, ultrastructural features and an immunoprofile compatible with the neuroendocrine cells and neuroendocrine tumours from other organs. Moreover, neuroendocrine cells of pituitary origin express transcription factors which indicate their cell-lineage origin. Thus, pituitary tumours are now considered as a continuum with other neuroendocrine tumours. PitNETs may occasionally be aggressive. In this context, the term “pituitary carcinoid” has no specific meaning: it either represents a PitNET, or a metastasis to the </span></span></span>pituitary gland<span> of a neuroendocrine tumour<span> (NET). An accurate pathological evaluation, combined where necessary with functional radionuclide imaging, can define the origin of the tumour. We recommend that clinicians liaise with patient groups to understand the terminology to define primary tumours of adenohypophyseal cells. It is incumbent upon the responsible clinician to explain the use of the word “tumour” in a given clinical context.</span></span></span></p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9739170","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":"Acromegalic Cardiomyopathy: An Entity on its own? The Effects of GH and IGF-I Excess and Treatment on Cardiovascular Risk Factors","authors":"Peter Wolf ,&nbsp;Luigi Maione ,&nbsp;Peter Kamenický ,&nbsp;Philippe Chanson","doi":"10.1016/j.arcmed.2023.102921","DOIUrl":"10.1016/j.arcmed.2023.102921","url":null,"abstract":"<div><p><span>Acromegaly is a chronic disease resulting from constantly elevated concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). If not adequately treated, GH and IGF-I excess is associated with various cardiovascular risk factors. These symptoms mainly include hypertension and impaired </span>glucose metabolism<span><span>, which can be observed in approximately one-third of patients. Other comorbidities are dyslipidemia and the presence of </span>obstructive sleep apnea syndrome.</span></p><p><span>However, even in the absence of conventional cardiovascular risk factors, myocardial hypertrophy can occur, which reflects the impact of GH and IGF-I excess itself on the </span>myocardium<span><span> and is defined as acromegalic cardiomyopathy. Whereas previous echocardiography-based studies reported a high prevalence of cardiomyopathy, this prevalence is much lower in cardiac magnetic resonance imaging-based studies. Myocardial hypertrophy in acromegaly is due to a homogeneous increase in the intracellular myocardial mass and extracellular myocardial matrix and improves following successful treatment through intracellular changes. Intramyocardial water retention or ectopic </span>lipid accumulation might not be of relevant concern.</span></p><p>Successful treatment significantly improves myocardial morphology, as well as cardiovascular risk factors. In addition to GH/IGF-I-lowering therapy, the diagnosis and treatment of cardiovascular complications is crucial for the successful management of acromegaly.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138471375","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":"Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series","authors":"Ingrid Marijke Zandbergen ,&nbsp;Kristin Michelle Huntoon ,&nbsp;Timothy G. White ,&nbsp;Leontine Erica Henriëtte Bakker ,&nbsp;Marco Johanna Theodorus Verstegen ,&nbsp;Luma Mudhafar Ghalib ,&nbsp;Wouter Ralph van Furth ,&nbsp;Iris Catharina Maria Pelsma ,&nbsp;Amir R. Dehdashti ,&nbsp;Nienke Ruurdje Biermasz ,&nbsp;Daniel M. Prevedello","doi":"10.1016/j.arcmed.2023.102919","DOIUrl":"10.1016/j.arcmed.2023.102919","url":null,"abstract":"<div><h3>Background</h3><p><span>Endoscopic transsphenoidal surgery (ETSS) for </span>prolactinoma<span> is reserved for dopamine agonist<span> (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5–20%) rates highlighted that surgery might be first-line treatment.</span></span></p></div><div><h3>Aims</h3><p>To report on outcomes of ETSS in a cohort of prolactinomas.</p></div><div><h3>Methods</h3><p>Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0–55.5] months) operated between 2010–2019 with histopathological confirmation.</p></div><div><h3>Results</h3><p>Median preoperative prolactin levels were 166 (98–837 µg/L; males 996 [159–2145 µg/L] vs. females 129 [84–223 µg/L], <em>p</em><span> &lt;0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), </span><em>p</em> &lt;0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (<em>p</em> &lt;0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), <em>p</em> = 0.006. Long-term remission (i.e., DA-free prolactin level &lt;1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], <em>p</em><span> = 0.002). Transient DI (</span><em>n</em> = 29, 21.2%) was the most frequent complication.</p></div><div><h3>Conclusions</h3><p>Despite high proportions of macroprolactinoma and KNOSP 3–4, long-term remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138471377","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":"Efficacy and Safety of Pegvisomant in the Treatment of Acromegaly","authors":"Linus Haberbosch ,&nbsp;Christian J. Strasburger","doi":"10.1016/j.arcmed.2023.102884","DOIUrl":"10.1016/j.arcmed.2023.102884","url":null,"abstract":"<div><p>Pegvisomant<span>, the first and currently only clinically available growth hormone receptor<span><span> antagonist, is an effective therapeutic option for the medical treatment of acromegaly, a </span>rare disorder<span> characterized by excessive growth hormone secretion. With now over 20 years of real world experience, its safety and efficacy is well-established. However, several aspects of its clinical use are still controversially discussed.</span></span></span></p><p>The high cost of pegvisomant has limited its use in several countries, and recent studies have reported a lower efficacy than the initial clinical trials<span>. A reported increase in tumor volume under therapy varies between studies and has been attributed to either actual growth or re-expansion after cessation of somatostatin receptor ligand therapy. Furthermore, different combinations of pegvisomant and other therapeutic agents aiming at reduction of acromegaly disease activity have been proposed to increase or retain effectiveness while lowering side effects and cost.</span></p><p>This review aims to assess current clinical data on the safety and efficacy of pegvisomant while also addressing controversies surrounding its use.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10143529","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":"Obesity as a Neuroendocrine Disorder","authors":"Aldo Ferreira-Hermosillo ,&nbsp;Regina de Miguel Ibañez ,&nbsp;Enid Karina Pérez-Dionisio ,&nbsp;Karen Alexandra Villalobos-Mata","doi":"10.1016/j.arcmed.2023.102896","DOIUrl":"10.1016/j.arcmed.2023.102896","url":null,"abstract":"<div><p><span>Obesity is one of the most prevalent diseases in the world. Based on hundreds of clinical and basic investigations, its etiopathogenesis goes beyond the simple imbalance between energy intake and expenditure. The center of the regulation of appetite and satiety lies in the nuclei of the </span>hypothalamus<span> where peripheral signals derived from adipose tissue<span> (e.g., leptin), the gastrointestinal tract<span><span>, the pancreas, and other brain structures, arrive. These signals are part of the homeostatic control system (eating to survive). Additionally, a hedonic or reward system (eating for pleasure) is integrated into the regulation of appetite. This reward system consists of a dopaminergic circuit that affects eating-related behaviors influencing food preferences, food desires, gratification when eating, and impulse control to avoid compulsions. These systems are not separate. Indeed, many of the hormones that participate in the homeostatic system also participate in the regulation of the hedonic system. In addition, factors such as genetic and </span>epigenetic<span> changes, certain environmental and sociocultural elements, the microbiota, and neuronal proinflammatory effects of high-energy diets also contribute to the development of obesity. Therefore, obesity can be considered a complex neuroendocrine disease, and all of the aforementioned components should be considered for the management of obesity.</span></span></span></span></p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72016440","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":"Genetic Testing in Hereditary Pituitary Tumors","authors":"Gamze Akkuş,&nbsp;Márta Korbonits","doi":"10.1016/j.arcmed.2023.102920","DOIUrl":"10.1016/j.arcmed.2023.102920","url":null,"abstract":"<div><p>Genetic testing is becoming part of mainstream endocrinology<span><span>. An increasing number of rare and not-so-rare endocrine diseases have an identifiable genetic cause, either at the germline or at the somatic level. Here we summerise germline genetic alterations </span>in patients<span><span> with pituitary neuroendocrine tumors (pituitary adenomas). These may be disorders with isolated </span>pituitary tumors<span><span>, such as X-linked acrogigantism, or AIP-related pituitary tumors, or as part of syndromic diseases, such as multiple endocrine neoplasia type 1 or </span>Carney complex<span>. In some cases, this could be relevant for treatment choices and follow-up, as well as for family members, as cascade screening leads to early identification of affected relatives and improved clinical outcomes.</span></span></span></span></p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441817","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":"ABHD5-CPT1B: An Important Way of Regulating Placental Lipid Metabolism in Gestational Diabetes Mellitus","authors":"Yuqi Yang ,&nbsp;Yue Peng ,&nbsp;Bin Yu ,&nbsp;Huiyan Wang","doi":"10.1016/j.arcmed.2023.102925","DOIUrl":"https://doi.org/10.1016/j.arcmed.2023.102925","url":null,"abstract":"<div><h3>Background and Aim</h3><p>Gestational diabetes mellitus<span> (GDM) is one of the most common metabolic disorders in pregnancy, and a novel association of maternal lipid profile has been suggested to play an important role. However, the molecular mechanism is not clear.</span></p></div><div><h3>Methods</h3><p><span>Bio-analyzed combined with placental metabonomics and single-cell RNA-sequencing (scRNA-seq) successfully identified a potentially important molecule: α-β hydrolase domain-containing protein 5 (ABHD5). The syncytiotrophoblast (SCT) cell model was adopted as a fusion of BeWo cells in response to </span>forskolin. On this basis, the high glucose-stimulated cell experiment was carried out. 15 women with GDM and 15 normal pregnant women were recruited for validation experiments.</p></div><div><h3>Results</h3><p><span>ABHD5 was mainly expressed in the trophoblast cells, especially in </span>SCT<span><span> cells, and significantly decreased in the GDM placenta. After stimulation by high glucose, the expression of ABHD5 was downregulated in a time-dependent manner in BeWo cells treated with forskolin. At the same time, </span>lipid droplets<span> (LDs) were increased in the SCT. LD storage was also increased in the SCT with siABHD5, while it was significantly reduced in SCT cells with high ABHD5 expression. However, this effect could be attenuated by downregulated carnitine palmitoyltransferase 1B (CPT1B).</span></span></p></div><div><h3>Conclusions</h3><p>ABHD5-CPT1B is confirmed as an important regulator of placental lipid metabolism.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138472529","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":"Prolactinomas Resistant to Dopamine Agonists: Pathophysiology and Treatment","authors":"Ilan Shimon","doi":"10.1016/j.arcmed.2023.102883","DOIUrl":"10.1016/j.arcmed.2023.102883","url":null,"abstract":"<div><p><span><span><span>Prolactinomas are the most common functional </span>pituitary tumors<span>, accounting for 40% of all pituitary adenomas<span><span><span>. Medical treatment with </span>dopamine agonists (DA), mainly </span>cabergoline, is considered the primary therapy for these patients. Prolactin normalization is achieved in 80–90% of prolactinomas treated with cabergoline. Patients resistant to the standard dose can escalate the dose of cabergoline up to the maximum tolerated dose. The expression of dopamine (D2) receptors and dopamine affinity is decreased in aggressive and resistant prolactinomas. Patients with aggressive and DA-resistant adenomas or with rare PRL-secreting carcinomas can be treated off-label with </span></span></span>temozolomide (TMZ), a DNA </span>alkylating agent<span><span><span><span>. TMZ is effective in 40–50% of treated lactotroph tumors showing at least a partial response. However, patients tend to escape from the effect of TMZ after a limited time of response. Other therapeutic options include aromatase inhibitors, the </span>somatostatin receptor ligand </span>pasireotide<span>, peptide receptor<span> radionuclide therapy (PRRT), immune-checkpoint inhibitors, tyrosine-kinase inhibitors, or </span></span></span>everolimus<span>, the mammalian target of rapamycin inhibitor. These experimental treatments were effective in some patients carrying refractory prolactinomas showing usually partial tumor control. However, the number of treated patients with any of these new therapeutic options is very limited and treatment results are inconsistent, thus additional experience with more patients is required.</span></span></p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193516","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}