bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell Function
Authors: Ezeh Uche , Chen Ida Y-D , Chen Yen-Hao , Azziz Ricardo 
Published: May 2020

Abstract

Context
Impaired sensitivity to the antilipolytic action of insulin in adipose tissue (AT) may play a role in determining metabolic dysfunction in polycystic ovary syndrome (PCOS).

Objectives
To test the hypothesis that insulin resistance (IR) in AT is associated with whole-body insulin sensitivity and β-cell function in PCOS.

Research Design and Setting
Prospective cross-sectional study.

Methods
Eighteen participants with PCOS and 18-matched control participants underwent a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT); subgroups underwent single-slice computed tomography scans determining AT distribution and adipocyte glucose transporter type 4 (GLUT-4) expression.

Main Outcome Measures
IR in AT in basal (by the adipose insulin resistance index [Adipo-IR]) and dynamic (mFSIVGTT-derived indices of insulin-mediated nonesterified fatty acids [NEFA] suppression [NEFAnadir, TIMEnadir, and %NEFAsupp]) states; whole-body insulin-mediated glucose uptake and insulin secretion in basal (by homeostatic model assessment [HOMA]-IR and HOMA-β%) and dynamic (mFSIVGTT-derived insulin sensitivity index [Si], acute insulin response to glucose [AIRg], and disposition index [Di]) states.

Results
Participants with PCOS had higher HOMA-IR and HOMA-β%, lower Si and Di, higher longer TIMEnadir, higher Adipo-IR and NEFAnadir, and a trend toward lower GLUT-4, than the control group participants. Adipo-IR was associated with dynamic state IR in AT (NEFAnadir TIMEnadir, and %NEFAsupp), but only in PCOS, and with HOMA-IR and HOMA-β% in both groups. NEFAnadir and TIMEnadir were negatively and %NEFAsupp positively associated with Si only in PCOS, but not with AIRg and Di, or GLUT-4 expression.

Conclusion
Women with PCOS demonstrated increased IR in AT, which is closely associated with whole-body IR but not with dynamic state β-cell function or adipocyte GLUT-4 gene expression.
Racial-Ethnic Inequity in Young Adults With Type 1 Diabetes
Authors: Agarwal Shivani , Kanapka Lauren G , Raymond Jennifer K , Walker Ashby , Gerard-Gonzalez Andrea , Kruger Davida , Redondo Maria J , Rickels Michael R , Shah Viral N , Butler Ashley , Gonzalez Jeffrey , Verdejo Alandra S , Gal Robin L , Willi Steven , Long Judith A 
Published: May 2020

AbstractContextMinority young adults (YA) currently represent the largest growing population with type 1 diabetes (T1D) and experience very poor outcomes. Modifiable drivers of disparities need to be identified, but are not well-studied.ObjectiveTo describe racial-ethnic disparities among YA with T1D and identify drivers of glycemic disparity other than socioeconomic status (SES).DesignCross-sectional multicenter collection of patient and chart-reported variables, including SES, social determinants of health, and diabetes-specific factors, with comparison between non-Hispanic White, non-Hispanic Black, and Hispanic YA and multilevel modeling to identify variables that account for glycemic disparity apart from SES.SettingSix diabetes centers across the United States.ParticipantsA total of 300 YA with T1D (18-28 years: 33% non-Hispanic White, 32% non-Hispanic Black, and 34% Hispanic).Main OutcomeRacial-ethnic disparity in HbA1c levels.ResultsNon-Hispanic Black and Hispanic YA had lower SES, higher HbA1c levels, and much lower diabetes technology use than non-Hispanic White YA (P &lt; 0.001). Non-Hispanic Black YA differed from Hispanic, reporting higher diabetes distress and lower self-management (P &lt; 0.001). After accounting for SES, differences in HbA1c levels disappeared between non-Hispanic White and Hispanic YA, whereas they remained for non-Hispanic Black YA (+ 2.26% [24 mmol/mol], P &lt; 0.001). Diabetes technology use, diabetes distress, and disease self-management accounted for a significant portion of the remaining non-Hispanic Black–White glycemic disparity.ConclusionThis study demonstrated large racial-ethnic inequity in YA with T1D, especially among non-Hispanic Black participants. Our findings reveal key opportunities for clinicians to potentially mitigate glycemic disparity in minority YA by promoting diabetes technology use, connecting with social programs, and tailoring support for disease self-management and diabetes distress to account for social contextual factors.
Cellular Heterogeneity of the Luteinizing Hormone Receptor and Its Significance for Cyclic GMP Signaling in Mouse Preovulatory Follicles
Authors: Baena Valentina , Owen Corie M , Uliasz Tracy F , Lowther Katie M , Yee Siu-Pok , Terasaki Mark , Egbert Jeremy R , Jaffe Laurinda A 
Published: May 2020

Abstract
Meiotic arrest and resumption in mammalian oocytes are regulated by 2 opposing signaling proteins in the cells of the surrounding follicle: the guanylyl cyclase natriuretic peptide receptor 2 (NPR2), and the luteinizing hormone receptor (LHR). NPR2 maintains a meiosis-inhibitory level of cyclic guanosine 5′-monophosphate (cGMP) until LHR signaling causes dephosphorylation of NPR2, reducing NPR2 activity, lowering cGMP to a level that releases meiotic arrest. However, the signaling pathway between LHR activation and NPR2 dephosphorylation remains incompletely understood, due in part to imprecise information about the cellular localization of these 2 proteins. To investigate their localization, we generated mouse lines in which hemagglutinin epitope tags were added to the endogenous LHR and NPR2 proteins, and used immunofluorescence and immunogold microscopy to localize these proteins with high resolution. The results showed that the LHR protein is absent from the cumulus cells and inner mural granulosa cells, and is present in only 13% to 48% of the outer mural granulosa cells. In contrast, NPR2 is present throughout the follicle, and is more concentrated in the cumulus cells. Less than 20% of the NPR2 is in the same cells that express the LHR. These results suggest that to account for the LH-induced inactivation of NPR2, LHR-expressing cells send a signal that inactivates NPR2 in neighboring cells that do not express the LHR. An inhibitor of gap junction permeability attenuates the LH-induced cGMP decrease in the outer mural granulosa cells, consistent with this mechanism contributing to how NPR2 is inactivated in cells that do not express the LHR.
SAT-131 Asymptomatic Severe Hypoglycemia with Lactic Acidosis in a Case of Non-Hodgkin’s Lymphoma - an Unusual Phenomenon of Hyper-Warburgism
Authors: Goyal Itivrita , Karadsheh Oday , Pandey Manu Raj , Sharma Rajeev , Chaudhuri Ajay 
Published: May 2020

Abstract
INTRODUCTION
Hypoglycemia in malignancy is well known with several etiologies; impaired liver function, insulin receptor autoantibodies, production of insulin-like substance by malignant cells or large tumor burden. Another possible mechanism is the Warburg effect where metabolism shifts towards glycolytic pathways over oxidative phosphorylation even under aerobic conditions leading to excess lactate production. This leads to glucose consumption due to shunting of glucose away from normal cells to cancer cells. Very few cases of lactic acidosis and severe hypoglycemia in Non-Hodgkin’s Lymphoma have been described in the literature. We report such an unusual case here.
CASE DISCUSSION
A 52-year-old, African-American male was admitted for severe malnutrition with 80 lb. weight loss, severe hypoglycemia and progressively increasing right chest wall mass. On arrival, he had no classic symptoms of hypoglycemia. Physical exam revealed persistent tachycardia, white patches on oral mucosa and posterior tongue, and an indurated mass on right chest wall with extensive swelling of right upper limb. Lab work was significant for blood glucose (BG) of 41 mg/dL (60–100), lactate 16 mmol/L (0.5 to 2), anion gap 26 mEq/L (3–10), albumin 2.3 g/dL (3.4 to 5.4) and normal renal and liver function tests. Fingerstick sugar readings were persistently in the 20s with no response to multiple boluses of dextrose and glucagon. He was started on dextrose 5% (D5) drip and intravenous solumedrol. Solumedrol was weaned off and D5 titrated down to investigate causes of hypoglycemia. BG dropped to 39 and corresponding labs showed insulin level of &lt; 2 mcUnit/mL (2–20), C-peptide of 0.2 ng/mL (0.8–6.0) and ketone level of 0.2 mmol/L (&lt;0.4). IGF-1 and IGF-2 were both low at 26 ng/mL (61–200) and 113 ng/mL (333–967) respectively. A CT torso with contrast showed bilateral pleural effusions, moderate pericardial effusions and a large ill-defined heterogeneous mass along anterior chest wall. He underwent ultrasound guided biopsy of the chest wall mass and diagnosed with diffuse large B-cell lymphoma. He also tested positive for HIV/AIDS and Hepatitis C. PET scan showed diffuse FDG (fluorodeoxyglucose) uptake consistent with advanced disease. He was started on chemotherapy and lactate and BG normalized soon after 1st cycle.
CONCLUSION
In our case; suppressed insulin, low C-peptide and IGF-2 levels indicate non-insulin mediated hypoglycemia due to rapid glucose utilization by cancer cells. Severe hypoglycemia with lack of neuroglycopenic symptoms suggests use of lactate (rather than glucose) as an alternative metabolic fuel for brain, thus preserving its function. Our patient presented with an exaggerated Warburg effect (hyper-Warburgism) as evident by extreme glucose consumption, severe lactic acidosis and large tumor burden on FDG/PET. Chemotherapy must be instituted timely to correct these abnormalities.
SAT-427 Quality of Life Following Treatment for Graves’ Disease: A Comparison of Radioactive Iodine Ablation and Surgery
Authors: Rowe Christopher W , Blefari Nicholas D , Rutherford Natalie , Bendinelli Cino , O’Neill Chris 
Published: May 2020

Abstract
Introduction: Quality of Life (QoL) is reduced in patients with Graves’ disease, however the impact of treatment modality is unclear, with conflicting evidence from recent studies (1–3). We hypothesized that surgery would have a greater impact than radioiodine on QoL in Graves’ disease, especially with regard to the physical-symptom subdomain.
Methods: Patients treated with thyroid surgery for benign disease (n=425) or radioactive iodine for hyperthyroidism (n=1637) at a single tertiary institution between 2000 and 2017 were invited to complete a validated thyroid-specific QoL instrument (City of Hope), reporting scores 0–10, where higher scores are associated with greater QoL. Responses were received from 307 patients, of whom 114 (37%) had Graves’ disease, treated with total thyroidectomy (n=23) or doses of 15mCi (550MBq) radioiodine (n=91, including 19 patients receiving 2 or more doses). The results of patients with Graves’ disease are reported here. Medians [interquartile ranges] are compared with the Mann-Whitney test (alpha 0.05).
Results: 85% of respondents were female, with no difference in gender between groups (p=0.11). Thyroidectomy patients were more likely to be younger (36 [31–49] vs 50 [39–59] years, p=0.004); and have a shorter duration between treatment and survey (5.9 [2.4–9.6] vs 7.6 [4.9–11.6] years, p=0.04). No overall QoL deficit was seen in patients treated with surgery compared to radioiodine (6.8 [5.2–7.3] vs 7.0 [5.8–8.1], p=0.08). However, patients treated with surgery reported reduce QoL in psychological (6.6 [4.7–7.5] vs 7.0 [5.9–8.2] p=0.05) and social (7.9 [6.4 – 8.9] vs 8.9 [7.4–9.8] p=0.01) subdomains compared to radioiodine-only treated patients. Within the social subdomain, the QoL detriment was driven by lower scores relating to questions regarding impact on personal and family relationships, support, and isolation (p&lt;0.001), and not by impact on activities of daily living or employment concerns. Interestingly, there was no between group difference in the physical symptom subdomain (p=0.16). QoL differences between treatment modalities were preserved when patients receiving multiple doses of radioiodine were excluded.
Discussion In this non-randomised cross-sectional study from a tertiary-hospital population in Australia, a QoL deficit was demonstrable in subdomain scores for patients with Graves’ disease treated with surgery compared to radioiodine, although the overall result was not significantly different. Better understanding of patient experiences is required to guide treatment strategies and appropriately counsel patients.
References (1) Torring et al. Thyroid. 2019;29(3):322–31. (2) Abraham-Nordling et al. Thyroid. 2005;15(11):1279–86. (3) Ljunggren et al. Thyroid. 1998;8(8):653–9.
SAT-379 Giant Parathyroid Adenoma
Authors: Saberi Sima , Wasco Matthew J , Behjatnia Ramin , Kimball Beth 
Published: May 2020

Abstract
Giant parathyroid adenoma
Background: Primary hyperparathyroidism is the most common cause of hypercalcemia. On ultrasound PTH adenomas are typically homogenous, hypoechoic, oval or bean-shaped with peripheral vascularity.
Clinical Case: A 60 year old woman with a history of calcium oxalate nephrolithiasis presented with fatigue, worsening depression, body aches of 3 months duration. Labs showed a serum calcium 11.1 mg/dl (normal range 8.5–10.1 mg/dl), PTH 114.3 pg/ml (normal range 12–88 pg/ml), 25 OH Vitamin D 11 ng/ml (normal range above 29 ng/ml), alkaline phosphatase 137IU/L (normal range 27–120 IU/L), spot urine calcium 34.8 mg/dl, spot urine creatinine 92.1 mg/dl (estimated 24 hour urine calcium 415 mg/dl). She was started on Vitamin D 1000 IU daily. A PTH scan with SPECT/CT showed a right parathyroid adenoma and possible thyroid nodules. A neck ultrasound demonstrated a left 1.5 cm thyroid nodule and a right 3cm lesion. She underwent FNA of the left thyroid nodule and pathology was suggestive of a benign follicular nodule. She underwent parathyroid gland exploration with resection of the right lesion which was a 3.5 x 2.5 x 1.4 cm right superior 5.68 gm PTH adenoma. Postoperatively her serum calcium normalized to 10.1 mg/dl, PTH was 8.4 pg/ml, 25 OH vitamin D was 15 ng/ml. Her Vitamin D dose was increased.
Clinical Lessons: A normal parathyroid gland typically weighs 30–60 mg and is 3–4 mm in size. The differential diagnosis for large parathyroid lesions is parathyroid carcinoma vs giant parathyroid adenoma. Although there is not a definitive size cutoff to define giant parathyroid adenomas, a size greater than 3.5 gm has been used (1). On ultrasound giant parathyroid adenomas are homogenous with smooth borders whereas parathyroid carcinomas are large lobulated heterogeneous hypoechoic lesions (2). A depth/width ratio on ultrasound may be the ultrasound parameter with greatest discriminatory capacity as a depth/width ratio greater than or equal to 1 had 94% sensitivity and 95% specificity for parathyroid carcinoma (2). Whether vitamin D deficiency is a risk factor for the development of large parathyroid glands is controversial as there has been conflicting data on this (1,3). Because there is no serum calcium level that distinguishes parathyroid carcinoma from a parathyroid adenoma neck ultrasound may be a helpful tool in evaluating these patients.
References:
1. Spanhemier PM, Stoltze AJ, Howe JR, et al. Do giant PTH adenomas represent a distinct clinical entity? Surgery. 2013 Oct; 154(4):714–719.
2. Hara H, Igarashi A, Yano Y, et al. Ultrasonagraphic features of PTH carcinoma. Endocr J. 2001 April 48(2):213–217.
3. Rao DS, Honasoge M, Divine GW, et al. Effect of vitamin D nutrition on PTH adenoma weight: pathogenetic and clinical implications. J Clin Endocrinol Metab. 2000 Mar 85(3): 1054–1058.
OR29-03 The Effects of Hormone Therapy on Premature Ovarian Failure Following Allogenic Hematopoietic Stem Cell Transplantation: A Single-Center Experience
Authors: Ha Jeonghoon , Han Je-Ho , Kang Moo-Il 
Published: May 2020

Abstract
Background: With increasing survival rates after hematopoietic stem cell transplantation (HSCT), it has become important to evaluate methods of improving patients’ quality of life. Most female patients of childbearing age experience premature ovarian failure after transplantation, which results in decreased quality of life and an increase in fracture risk due to rapid bone loss. We analyzed the effects of hormone therapy (HT) on serum follicle stimulating hormone (FSH), serum estradiol, and bone mineral density (BMD) in young female HSCT recipients. Methods: This retrospective cohort study included 234 female patients who underwent allogenic HSCT between April 2009 and April 2018 at our center. The maximum age at the time of transplantation was 40 years, and patients were followed up for at least 3 years. Of the 734 patients who were initially screened, 360 patients aged &lt;18 years and 8 who were transferred to another institution after transplantation were excluded from the study. There were 93 patients who died within 3 years of transplantation, while 30 were lost to follow-up, and 9 were followed-up for less than 3 years. Changes in hormone levels and BMD, according to HT regimen, were evaluated in 234 patients. Results: The mean age at transplantation was 30.47 ± 6.55 years. Out of 234 patients, 170 (72.6%) patients received HT, starting treatment at a mean of 15.1 ± 8.2 months after transplantation. A significant increase in estradiol level was observed in patients receiving HT (p &lt; 0.001); no difference was observed between the 3 different types of HT regimen (p = 0.534). After 2 years of HT, BMD was significantly increased at all measurement sites: lumbar spine 5.8 ± 6.26% (p &lt; 0.001), femoral neck 3.4 ± 17.78% (p = 0.037), total hip 2.1 ± 7.15% (p = 0.001). Again, there was no difference in changes between the HT regimens (p = 0.646 for lumbar spine, p = 0.840 for femoral neck, and p = 0.855 for total hip). These changes were significant even in patients with graft versus host disease (GVHD) or steroid exposure. Conclusion: In patients with premature ovarian failure following allogenic HSCT, HT effectively lowered serum FSH and increased serum estradiol levels. HT significantly increased BMD regardless of the history of GVHD or steroid exposure. These changes in hormones and BMD were independent of the HT regimen.
OR02-01 Gene Dosage Changes in RBFOX-2 Can Affect Upper and Lower Tract Genitourinary Development
Authors: O’Neill Marisol A , White Jeffrey T , Lamb Dolores J 
Published: May 2020

Abstract
Searching for genetic and genomic alterations in patients with genitourinary (GU) birth defects can aid in the identification of genes that are important for normal GU development. Using data in DECIPHER, RBFOX-2, located at 22q12 was identified as one such candidate gene and the effect of haploinsufficiency in humans and a mouse model (Rbfox-2α/+) assessed. RBFOX2 is an RNA-binding protein regulating alternative splicing. It also impacts steroid receptor transcriptional activity. RBFOX family members are thought to affect different developmental programs via isoform-specific localization and splicing activities. RBFOX-2 plays a vital role in multiple developmental processes including heart, brain, muscle and testis development. “Non-syndromic” patients with congenital GU anomalies were more likely to harbor RBFOX-2 CNVs (2.4%; hypospadias, 21% cryptorchidism, 29% vesicoureteral reflux and 29% ureteropelvic junction obstruction) relative to the general population (0.11%) indicating that 22q12 is a hotspot genetic locus for GU anomalies. CNVs (microdeletions and microduplications) spanning RBFOX-2 were identified in twenty-seven humans with a wide range of birth defects(intellectual disability, CNS, cardiac, genitourinary, facial, hearing, vision, growth and stature anomalies) and the phenotype of the haploinsufficient Rbfox-2α/+mouse model closely correlated with the human phenotype, although Rbfox-2α/+ andRbfox-2α/α are neonatal lethal. By E18.5 day of development 100% of the Rbfox-2α/+ and null fetuses exhibited hypospadias, megacystis (50%) and bilateral hydroureteronephrosis. RNA Seq was performed on genital tubercles from three Rbfox2fl/fl, Gdf9 icre+ and three Rbfox2fl/fl P1 males. 377 genes were differentially expressed between the two groups including 212 genes which were upregulated and 165 genes which were downregulated. Hallmark gene set analysis revealed downregulation of Wnt/β-catenin signaling and hedgehog signaling, both pathways which are well defined in genital development. Gene ontology (GO) analysis further defined downregulation of pathways (fibroblast growth factor, retinoic, androgen, estrogen and G-protein receptor signaling) including those involving negative regulation of embryonic development, epithelial development, morphogenesis of epithelial tube, renal, ureter, limb and several other developmental pathways. These results support the hypothesis that loss of Rbfox2 during development leads to hypospadias through impaired development of the urethral epithelium.
OR24-03 GRK2 Mediates Beta-Adrenergic Receptor Crosstalk to Enhanced Adrenocortical AngII-Dependent Aldosterone Production
Authors: Lymperopoulos Anastasios , Pollard Celina M , Pereyra Janelle M , Desimine Victoria L , Wertz Shelby L , Perez Arianna , Ferraino Krysten E , Cora Natalie 
Published: May 2020

Abstract
Aldosterone is produced by adrenocortical zona glomerulosa (AZG) cells in response to hyperkalemia or angiotensin II (AngII) acting through its type I receptors (AT1Rs). AT1R is a G protein-coupled receptor (GPCR) that induces aldosterone synthesis and secretion via both G proteins and the GPCR adapter proteins βarrestins. AZG cells express all three subtypes of β-adrenergic receptor (AR) and respond to catecholamines by producing aldosterone. Being GPCRs, both activated βARs and AT1Rs are phosphorylated by GPCR-kinases (GRKs), followed by βarrestin binding to initiate G protein-independent signaling. Herein, we investigated whether the major adrenal GRKs, GRK2 and GRK5, are involved in catecholaminergic regulation of AngII-dependent aldosterone production. We used the human AZG cell line H295R, in which we measured aldosterone secretion via ELISA and synthesis via real-time PCR for steroidogenic acute regulatory (StAR) protein and CYP11B2 (aldosterone synthase) mRNA levels. Isoproterenol (Iso, a βAR full agonist) treatment significantly augmented AngII-dependent aldosterone synthesis (2.2+0.8-fold CYP11B2 & 1.6+0.5-fold StAR mRNA inductions over AngII alone; p&lt;0.05, n=4), as well as secretion (2.3+0.8-fold of vehicle with Iso; 3.2+1.1-fold of vehicle with AngII; 7.4+1.1-fold of vehicle with Iso+AngII, p&lt;0.05 vs. either agent alone; n=5) in H295R cells. Importantly, GRK2, but not the other major GRK isoform expressed in human adrenals GRK5, was indispensable for the catecholamine-mediated enhancement of aldosterone production in response to AngII in H295R cells. Specifically, GRK2 inhibition with the small molecule Cmpd101 abolished Iso effects on AngII-induced aldosterone synthesis and secretion (Iso+AngII-induced aldosterone secretion: 8.1+2.3-fold of vehicle without Cmpd101; 2.8+0.8-fold of vehicle with Cmpd101; p&lt;0.05, n=5). In contrast, GRK5 knockout via CRISPR/Cas9 did not affect the synergism between isoproterenol and AngII in stimulating aldosterone production. Mechanistically, βAR-activated GRK2, but not GRK5, phosphorylated and activated the Ca2+-activated chloride channel anoctamine-1 (ANO1), also known as transmembrane member (TMEM)16A, ultimately increasing aldosterone production in H295R cells (Iso+10–6 M [Ca2+]-induced ANO1 activity of Cmpd101-pretreated cells: 55+15 % of non-Cmpd101-pretreated cells; p&lt;0.05, n=5). AngII alone failed to stimulate GRK2 in H295R cells. In conclusion, GRK2 mediates a βAR-AT1R signaling crosstalk at the level of ANO1 activation, which results in enhanced aldosterone production in H295R cells. This finding suggests that adrenal GRK2 may be a molecular link connecting the sympathetic nervous and renin-angiotensin systems in the adrenal cortex and that GRK2 inhibition might be therapeutically advantageous for aldosterone suppression.