bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-123 Nuclear Receptor 4A1 (NR4A1) Acts as a Tumor Suppressor in Anaplastic Thyroid Cancer
Authors: Guan Hongyu , Li Hai , Xu lijuan , Li Yanbing 
Published: May 2020

Abstract
The nuclear orphan receptor NR4A1 has been demonstrated to play important roles in development and progression of various cancers. However, the biological roles and its underlying mechanisms of NR4A1 in anaplastic thyroid cancer (ATC) are largely unknown. Here, we showed that the expression level of NR4A1 was robustly down-regulated in ATC cell lines and human ATC tissues as compared to Nthy-ori 3-1 cells and normal thyroid tissues, respectively, using in silico analysis, qRT-PCR and immunohistochemistry analyses. Gain-of-function experiments were carried out to understand the NR4A1’s responsiveness to apoptotic inducers. The results showed that ectopic over-expression of NR4A1 reduced cell viability and promoted cell apoptotic rate induced by UV irradiation or Adriamycin. Moreover, the activities of caspase-3 and PARP were elevated in NR4A1 overexpression cells in response to apoptotic inducers. Furthermore, we found that down-regulation of XIPA was involved in the pro-apoptotic role of NR4A1 in ATC cells. Collectively, these findings suggest that the nuclear orphan receptor NR4A1 acts as a tumor suppressor in ATC via regulating XIPA, providing a potential therapeutic target against ATC.
MON-603 GPR142 Expression Levels Were Correlated with Plasma Ghrelin Levels and Heights in Morbidly Obese Patients
Authors: Ueda Yoko , Iwakura Hiroshi , Doi Asako , Matsutani Norihiko , Morita Shuhei , Inaba Hidefumi , Ariyasu Hiroyuki , Fukuda Naoki , Hayata Keiji , Ojima Toshiyasu , Nishi Masahiro , Yamaue Hiroki , Akamizu Takashi 
Published: May 2020

Abstract
Recently, aromatic amino acids, especially tryptophan were discovered to be the strongest ligands for GPR142, which was previously known as an orphan GPCR. GPR142 is expressed in the digestive tract and pancreas in mice and human. Previously we found that GPR142 is highly expressed in the ghrelin-producing cell line, MGN3-1 cells, and that tryptophan strongly stimulated ghrelin secretion in vitro.
In this study, we measured the mRNA expression levels of GPR142 in the gastric samples of 6 morbid obese patients undergone laparoscopic sleeve gastrectomy and compared its level with their clinical parameters. GPR142 expression levels were negatively correlated with plasma desacyl ghrelin levels (p=0.011) and positively correlated with heights (p=0.08).
The current results that GPR142 expression levels were correlated with plasma desacyl ghrelin levels may confirm the link between GPR142 signal and regulation of ghrelin secretion demonstrated in our in vitro study. Regarding to the correlation with heights, there are some reports that plasma ghrelin levels were inversely correlated with heights in children[1-3], although, as far as we know, there are no reports demonstrating the relationship between plasma ghrelin levels and heights in adults. Considering that ghrelin strongly stimulates growth hormone secretion, GPR142 signaling may have influence on height through regulating ghrelin-growth hormone axis.
Conclusion
GPR142 mRNA expression levels were negatively and positively correlated with plasma desacyl ghrelin levels and heights in morbid obese adults undergone bariatric surgery. Current results may help understanding the pathophysiological role of GPR142 in the regulation of ghrelin secretion and heights.
References
1. MO Camurdan, et al. Endocrine Journal 2006, 53 (4), 479–484
2. HS Park, et al. Metabolism Clinical and Experimental 2005, 54, 925–929
3. Joy C. Bunt,et al. J Clin Endocrinol Metab 2003, 88(8): 3756-3761
MON-592 The Impact of Bariatric Surgery on the Risk of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients
Authors: Borges-Canha Marta , Neves João Sérgio , Mendonça Fernando , Silva Maria Manuel , Costa Cláudia , Cabral Pedro M , Gonçalves Vanessa Guerreiro , Lourenço Rita , Patrícia Meira , Salazar Cristina Daniela , Maria Ferreira João Silva , Pedro Jorge Pires , Belo Sandra , Lau Eva , Sande Ana , Viana Sara , Freitas Paula , Carvalho Davide M ,   AMTCO group
Published: May 2020

Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, and the prevalence of both diseases is increasing notably. The lack of effective treatment options for NAFLD is leading to a great consideration towards the identification of new approaches.
Aim: We aimed to evaluate the change one year after bariatric surgery of parameters of hepatic function and in the hepatic scores, Fatty Liver Index (FLI, predictor of hepatic steatosis), and BARD, BMI, AST/ALT ratio and DM, (predictor of hepatic fibrosis).
Methods: Observational retrospective cohort study in morbidly obese patients that underwent bariatric surgery between January 2010 and July 2018. We excluded patients missing hepatic function parameters before or one year after the surgical procedure. We used two linear regression models: 1) unadjusted; 2) adjusted for surgery type (gastric sleeve, gastric band and gastric bypass), sex, age, body mass index, diabetes and dyslipidaemia.
Results: The included population (n=1955) had an average age of 43.1±10 years and 85.8% were female. We observed a relevant decrease in transaminases (pre-operative AST and ALT, 24.8±12.4 and 29.5±19.5U/L, vs 22.4 ± 11.1 and 22.2±14.7 post-operatively, respectively, p&lt;0.01) and gamma-glutamyltransferase (36.9±35.4 vs 21.4±22.0U/L, p&lt;0.01), and an increase in alkaline phosphatase (77.8±23.5 vs 80.8±25.4U/L, p&lt;0.01) and total bilirubin (0.56±0.23 vs 0.68±0.24mg/dL, p&lt;0.01). Both FLI and BARD markedly decrease one year after surgery (p&lt;0.01). Comparing the surgical procedures, gastric sleeve was associated with a greater reduction of hepatic enzymes and of both FLI and BARD comparing with gastric band. Comparing with gastric bypass, sleeve was associated with a greater reduction of transaminases and alkaline phosphatase, but a smaller reduction of FLI and BARD.
Conclusion: Bariatric surgery is associated with a reduction of the hepatic enzymes and an improvement of FLI and BARD. Bariatric surgery may represent an effective therapeutic approach to NAFLD.
MON-110 Utilization of GluCEST, a Novel Neuroimaging Technique, to Characterize the Brain Phenotype in Hyperinsulinism/Hyperammonemia Syndrome
Authors: Rosenfeld Elizabeth , Nanga Ravi P R , Reddy Ravinder , Revell Andy , Roalf David R , Davis Kathryn A , De Leon Diva D 
Published: May 2020

Abstract
BACKGROUND: Hyperinsulinism/Hyperammonemia (HI/HA) syndrome is the second most common form of congenital hyperinsulinism. It is caused by gain-of-function mutations in glutamate dehydrogenase (GDH), a mitochondrial enzyme expressed in pancreatic β-cells, liver, kidney, and brain, and is responsible for metabolizing glutamate into α-ketoglutarate and ammonia. In addition to hyperinsulinemic hypoglycemia due to abnormal GDH activity in pancreatic β-cells, ~80% of patients have developmental delays, learning, or behavioral disorders and &gt;60% have atypical absence seizures (Bahi-Buisson, 2008). These neurologic symptoms are not fully explained by hypoglycemia and are hypothesized to result from central nervous system (CNS) glutamate imbalance due to CNS GDH overactivity. Newer magnetic resonance imaging (MRI) techniques have allowed for sensitive estimation of CNS glutamate using Glutamate Chemical Exchange Saturation Transfer (GluCEST). We aimed to comprehensively characterize the biochemical and clinical neurologic phenotype of HI/HA leveraging GluCEST MRI.
Methods: Subjects with confirmed HI/HA diagnosis and without contraindication to MRI had electroencephalogram (EEG), serum ammonia, and the following validated neurodevelopmental assessments: ABAS-3, BRIEF, and ASEBA CBCL (if &lt;18 years) or ASR (if &gt;18 years) completed. GluCEST MRI axial hippocampal and midsagittal slices were acquired on a 7.0T Siemens scanner and reported as GluCEST % contrast. Healthy control GluCEST % contrast data were obtained from a separate study using the same neuroimaging protocol.
Results: 8 HI/HA subjects (4 female; mean age 28 years [range 16-56] years) participated to date. Median serum ammonia was 58 umol/L (IQR 39-89). 50% self-reported learning impairments and 37.5% self-reported prior ADHD diagnosis. Marked unilateral increase in hippocampal GluCEST % contrast was observed in 3/6 subjects (2 L&gt;R; 1 R&gt;L). Overall, median peak GluCEST % contrast level was significantly higher in HI/HA subjects than controls (10.3% [IQR 8.9-11.3] v. 8.0% [IQR 7.8-8.4], p=0.0013, n=6).
Conclusions: This is the first study to evaluate CNS glutamate via GluCEST in HI/HA. Hippocampal glutamate, measured by GluCEST % contrast, was significantly higher in HI/HA subjects than healthy controls. Laterality in hippocampal glutamate was observed in half of subjects. These findings are remarkable given the known role of abnormal glutamate signaling in the development of epilepsy and neurocognitive impairment. Next steps are to complete midsagittal GluCEST image processing, EEG and neurodevelopmental assessment interpretations to explore correlations between CNS phenotype and brain glutamate pattern. GluCEST holds promise for elucidating the pathophysiology of CNS manifestations in HI/HA syndrome.
SUN-311 Adrenal Reserve Testing with the Glucagon Stimulation Test (GST) and Cosyntropin Stimulation Test (CST) in Deployed Veterans with Mild Traumatic Brain Injury
Authors: Nagireddi Rama Priyanka , Win Htet Htet , Wagstaff Sarah , Neal Moira , Friedman Kathryn , Anderson Robert J 
Published: May 2020

Abstract
Introduction: Mild Traumatic Brain Injury (mTBI) is associated with anterior pituitary hormone dysfunction. The potential long-term effect of this injury on pituitary function in Veterans is not clear. We reviewed the utility of the fixed dose Glucagon Stimulation Test (GST) compared with the high dose Cosyntropin Stimulation test (CST) for hypothalamic-pituitary-adrenal (HPA) reserve over time in these patients with mTBI.
Methods: We present an interim report of our 4-year longitudinal prospective pilot study of pituitary function in Veterans diagnosed with mTBI. Of the 34 mTBI Veterans enrolled, we have tested 28 of them (4 female, 24 male; age and BMI, 31.5±7.0 years and 30.4±6.2, mean±SD, respectively) for baseline pituitary hormone levels and cortisol response to the CST. In 22 subjects growth hormone and cortisol responses to GST were tested at baseline (Year 0). Follow-up testing was done for 18 mTBI subjects in Year 1, 13 subjects in Year 2, 10 subjects in Year 3 and 5 subjects in Year 4. The same baseline data were obtained for 14 age-, sex-, deployment- and BMI-matched control subjects without mTBI (2 female,12 male; age and BMI 34.4±6.8 years and 30.5±4.9, mean±SD, respectively). Cortisol cutoffs of &lt;18 mcg/dL with the CST and &lt;9.0 mcg/dL with the GST were used for the diagnosis of adrenal insufficiency.
Results: Secondary adrenal insufficiency (AI), likely partial, was identified during this study on 6 occasions: 3/22 subjects at Year 0, 1/18 at Year 1, 0/13 at Year 2, 1/10 at Year 3 and 1/5 at Year 4. Two baseline subjects with AI reverted to normal in Years 1-3, one relapsed in Year 4 and a third had no further testing. Correlations of the cortisol levels from GST vs the 60-minute cortisol from CST were significant at Year 0 (n=22, r=0.553, p=0.008) and at Year 1 (n=18, r=0.802, p&lt;0.0001). Due to decreased numbers, there were no significant correlations at Years 2 through 4. Similar correlations were obtained using the 30-minute CST values. However, the CST cortisol value predicted the low GST value in only 2/6 subjects. The mean GST cortisol levels and 60-minute CST cortisol levels for subjects at each year were not significantly different over Years 0 through 4 based on ANOVA analyses (CST: F=1.519, p= 0.206; GST: F= 0.796, p=0.532).
Conclusions: Secondary adrenal insufficiency, likely partial, related to mTBI was detected by GST on 6 occasions (twice in one patient) over 4 years of observation. GST can provide useful information about HPA axis reserve, and appears to be more reliable than CST. Identification of potential secondary adrenal insufficiency using the GST in Veterans with mTBI can provide a beneficial combined test for these patients when other testing is not feasible.
SUN-175 Repeat Unstimulated AVS with Aid of Plasma Metanephrines Identifies Unilateral Primary Aldosteronism When Initial AVS and Metomidate PET-CT Fails To
Authors: Tan Ying Tse Sarah , Zhang Meifen , Gani Linsey , Khoo Joan , Tan Colin , Ng Keng Sin , Puar Troy H 
Published: May 2020

Abstract
Introduction
Adrenal venous sampling (AVS) is the reference test for identifying unilateral primary aldosteronism (PA). However, in patients with corticol co-secreting adrenal nodules, elevated cortisol levels may affect the interpretation of aldosterone-cortisol (AC) ratios. ACTH-stimulation may further confound results. In such patients, the use of plasma metanephrines instead of cortisol as a correcting factor may be helpful.
Case Summary
A 54 year old lady presented with 8 years of hypertension and hypokalaemia (nadir 2.2mmol/L) while on amlodipine 10mg and valsartan 80mg daily. PA was confirmed by a post-saline infusion aldosterone 1075pmol/L. CT identified a 2.4cm right lipid rich adrenal adenoma. Serum cortisol post 1mg overnight dexa-suppression test was unsuppressed at 63mmol/L.
First AVS was done sequentially under ACTH stimulation and suggested lateralization to the right, with lateralization ratio (LR) 3.4. However, this was &lt;4, and there were bilaterally low AC ratios compared to peripheral vein. Metomidate PET-CT scan then showed increased uptake over the nodule, but lower than the contralateral gland. In view of these findings, repeat AVS was done simultaneously without ACTH stimulation. Given the possibility of a co-secreting adenoma, plasma metanephrines were also measured. Second AVS showed right-sided lateralization (LR 11.8). Using metanephrines as a correction factor, the LR was even more elevated at 22.3, with contralateral suppression.
She underwent right adrenalectomy and was cured of hypertension and hypokalaemia at 6 months post surgery. Aldosterone renin ratio has normalized: aldosterone &lt;4ng/dL, plasma renin activity 0.6ng/ml/hr.
Clinical Lessons
While ACTH stimulation helps to improve success rates of cannulation by increasing cortisol gradients, most studies show that it lowers LR. Furthermore, this would be concerning in patients with cortisol co-secreting adenomas. In this case, repeat AVS without ACTH demonstrated improved lateralization to the right. The use of metanephrine as a correcting factor appears to be a better indicator of right sided disease. However, while plasma metanephrines have been shown to be useful to indicate correct catheter placement, it has not been adopted as a correction factor for dilution yet. Finally, in addition to affecting AVS results, cortisol-cosecreting tumors may also affect 11C-Metomidate PET-CT imaging.
Conclusion
In patients with suspected cortisol co-secreting adenomas, unstimulated AVS and use of plasma metanephrines may help to identify unilateral PA even when conventional AVS and metomidate scans fail to. Further studies on using metanephrines as a correcting factor for lateralisation would be helpful.
SUN-066 Prenatal Sex Steroid Serum Concentrations in Relation to Sex-Typical Play Behavior at 4 Years of Age
Authors: Sethuram Swathi , Swan Shanna , Wang Christina C L , Barrett Emily , Nguyen Ruby , Raymond Samantha , Evans Sarah , Sathyanarayana Sheela 
Published: May 2020

Abstract
INTRODUCTION: Sex differences in play behavior have been seen in rodents, primates and humans with literature showing some associations with maternal sex steroids. The PreSchool Activities Inventory (PSAI) is a validated tool to assess sexually-dimorphic play behavior. We assessed the associations between prenatal maternal estradiol (E2), free testosterone (fT) and total testosterone (T) and children’s PSAI scores at age 4.
METHODS: Data were collected in The Infant Development and the Environment Study (TIDES), a US-based multi-center pregnancy cohort. The analysis included 399 pregnant women with complete data on sex steroids, PSAI and covariates. Early pregnancy E2 and T were analyzed by liquid chromatography tandem mass spectrometry and fT by equilibrium dialysis using labeled testosterone. PSAI scores (masculine, feminine and composite) were calculated from questionnaires completed by mothers when child was approximately 4 years old. Covariates included: maternal age and education, child age at questionnaire completion, number of older brothers and sisters, infant race and parental attitudes towards sex-atypical play behavior. After demonstrating nonlinear associations between PSAI scores and sex steroids, we used multivariable sex-stratified quadratic regression to model these relationships.
RESULTS: The analysis included 192 boys and 207 girls (mean age: 4.5 years). Sex steroids in serum collected at 6-20 weeks’ gestation (mean: 11 weeks) were similar in mothers of boys and girls. In girls, E2 showed a quadratic relationship with the masculine score (beta (E2) = 0.003, p = 0.002, beta (E22) = -7.3E-7, p &lt;0.001). Masculine scores were lower among girls whose mothers had E2 above the 75th percentile (2160 pg/ml). In boys, we observed a positive linear association of borderline significance (beta (fT) = 9.11, p = 0.06) and a significant negative association for the quadratic term (beta (fT2) = -7.44, p = 0.04). PSAI measures were not associated with E2 in mothers of boys, fT in mothers of girls, or T in either sex.
DISCUSSION: This study did not replicate previously reported associations between T and masculine scores in girls. However, we found that, while most maternal E2 levels were not associated with play behavior in either sex, levels above the 75th percentile were associated with reduced masculine scores in girls at age 4. Our data also suggest a somewhat reduced feminine scores in boys born to mothers with fT above the 75th percentile. These results, based on a small sample using a maternal assessment of play behavior, should be examined in a larger sample using an objective measure of play.
SAT-412 Genetic Susceptibility to Graves’ Disease Conferred by HLA-DQβ1 Position 57
Authors: Badenhoop Klaus , Bee Sarah , med cand , Penna-Martinez Marissa 
Published: May 2020

Abstract
Introduction: Human leukocyte antigen (HLA) locus is the major genetic risk factor for autoimmune endocrine diseases. The amino acid variability at the HLA-DQβ1 position 57 encoded by both DQB1 alleles was identified as critical risk residue for type 1 diabetes. We therefore investigated this amino acid residue at HLA-DQβ1 position 57 in Graves’ disease (GD). Subjects and methods: DNA samples were obtained from 572 healthy controls (HC, 262 females/310 males) and 299 patients with GD (255 females/44 males) and genotyped for HLA-DQB1 using a sequence specific primer (SSP, 13 primer pairs) approach. The PCR amplified products were analyzed by gel electrophoresis. The HLA-DQB1 alleles were defined with their corresponding amino acid residues at the DQß chain positon 57 as follows: Ala57 (DQB1*0201,*0302), Asp57 (DQB1*0301,*0303,*0401,*0402,*0503,*0601,*0602*,0603) Val57 (DQB1*0501,*0604) and Ser57 (DQB1*0502). Finally, the frequencies for amino acid variabilities and their combinations (Ala/Ala, Ala/non-Ala and non-Ala/non-Ala) were calculated and compared by Pearson-Mantel-Haenszel Chi-squared test. Results: The presence of Ala57 was significantly more frequent in patients with GD compared to HC (25% vs. 39%, OR: 1.77; p=7x10-4), whereas Val57 was less frequent (19% vs. 12%, OR: 0.59; p=0.04). In contrast, no difference in the distribution between GD and HC concerning the amino acids Asp57 and Ser57 was observable. Similar results were found in female (Ala57 23% vs. 38%, OR:2.01; p=1.2x10-3 and Val57 19% vs. 13%, OR:0.35; p=1.2x10-4) but not in males (p &gt;0.5). Furthermore, homozygous HLA-DQB1 Ala (8% vs. 15%, OR:1.98; p=5x10-3) as well as heterozygous HLA-DQB1 Ala/non-Ala (34% vs. 45%, OR:1.58; pc=5x10-3) were significantly more prevalent, while non-Ala/non-Ala (58% vs. 40%, OR:0.49 pc=3x5x10-6) was found to be less frequent in patients than in HC. By gender stratification there was a significant difference between female patients with GD and female HC in the distribution of the mentioned amino acid combinations (Ala p=4.5x10-3, Ala/non-Ala pc=0.02, non-Ala/non-Ala p=1x10-5). Conclusion: We identify a strongly predisposing role for HLA-DQβ1 Ala5 7to GD, particularly in women, highlighting the gender specific disease risk. Immunogenetic testing may pave the way towards personalized treatment.
SUN-362 Bone Involvement in Adult Patients Affected with Ehlers-Danlos Syndromes
Authors: Eller-Vainicher Cristina , Grassi Giorgia , Chiodini Iacopo , Cairoli Elisa , Palmieri Serena , Franchetti Sara , Marinelli Barbara , Castronovo Paola , Arosio Maura , Bassotti Alessandra 
Published: May 2020

Abstract
INTRODUCTION: The Ehlers-Danlos syndrome (EDS) is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility, bone involvement is an emerging manifestation. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of clinical fractures and morphometric vertebral fractures (mVFx) in a large group of adult EDS patients. METHODS: Two-hundred and sixty-six consecutive Caucasian patients, aged ≥18 years (38.3±11.8) (190 females, 76 males) 58% with classical, 34.9% with hypermobility, 4.5% with vascular and 4.8% undefined EDS were enrolled. We had genetic information of 117 patients (74 patients showed no mutations, 2 COL2 mutations, 8 COL3 mutation, 28 COL5 mutations and 5 other genes mutations). In all subjects’ calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and radius and TBS by dual-energy X-ray absorptiometry were assessed. Moreover, we evaluated the history of clinical fragility and the mVFx presence by spine radiograph. RESULTS: The 20.6% of patients showed a Z-score BMD ≤-2.0, the 29.8% ≥1 mVFx and the 24.5% ≥1 clinical fractures. Male patients showed a higher prevalence of reduced BMD (31.9 vs 15.6%; p=0.007) and mVFx (41.4% vs 24.8%; p=0.026). Patients with ≥1 mVFx were older (43.2±12 vs 35.6±12; p=0.0001), showed a lower TBS z-score (-1.4±1.7 vs -0.8±1.2; p=0.013) and lower phosphate levels (3.3±0.6 vs 3.5±0.5; p=0.032) with an higher prevalence of hypophosphatemia (24.5% vs 8.8%; p=0.014). No difference was found in prevalence of EDS subtypes or gene mutations. In EDS patients, the VFx presence was significantly associated with TBS and age, even after adjusting for sex and hypophosphatemia. CONCLUSIONS: EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of clinical and mVFx associated with age and TBS.