bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-LB40 Adrenalectomy - A Rural Teaching Hospital Experience
Authors: Shen Alice S 
Published: May 2020

Abstract
Background: Studies characterize the surgical managements of adrenal tumors are not common in rural hospitals. Methods: A retrospective study conducted at a single rural teaching hospital with subjects including 37 patients who had laparoscopic or open adrenalectomy between 2011 and 2017. Baseline characteristics and postoperative outcomes of patients were examined using univariate and multivariate methods. Logistic regression models were used to analyze perioperative complications. Truncated negative binomial regression models was used to analyze hospital length of stay. Pathologic distribution, correlation of pre-op and pathologic diagnoses were also analyzed.Results: On average, five adrenalectomies per year were done for primary adrenal pathology. Adrenocortical adenoma and pheochromocytoma were the two most common pathologic diagnoses. Length of stay increased in patients with open surgery, RR 3.78 (1.60-8.91), and malignancy, RR 3.18 (1.43-7.06), based on multivariate analysis. Factors associated with post-operative complications in univariable analysis are tumor size odds ratio (OR) 1.02 (95% confidence interval 1.00 to 1.05), and open surgery, OR 4.29 (0.96-21.52). This significance was not present at the multivariable analysis. Conclusions: Evaluation and surgical management of adrenal tumors in a rural hospital for seven years were characterized. The results of this study will contribute to future epidemiological research on adrenal incidentalomas and surgical managements of adrenal tumors in rural hospitals.
SUN-LB127 In Experimental Peripheral Arterial Disease MIR29a Modulation Improves Perfusion Recovery and Muscle Function to a Greater Extent Than ADAM12 Augmentation in Mice With Type 2 Diabetes
Authors: Lamin Victor 
Published: May 2020

Abstract
Diabetes Mellitus (DM) is a major risk factor for developing peripheral arterial disease (PAD) and individuals with DM have worse PAD outcomes but the molecular mechanisms involved are poorly understood. We previously identified a disintegrin and metalloproteinase gene 12 (ADAM12) as a key genetic modifier of post-ischemic perfusion recovery in experimental PAD that it is regulated by miR29a through direct interaction. In ischemic hind limbs non-diabetic mice, miR29a expression is downregulated and allows ADAM12 upregulation. However, in ischemic hind limbs of type 2 DM (DM2) mice miR29a expression remains elevated and prevents ADAM12 upregulation. Hence, we hypothesized that inhibition of miR29a or augmenting ADAM12 would improve the impaired perfusion recovery typical of mice with DM2 in experimental PAD. Here, in mice with DM2 we compare the therapeutic effectiveness of miR29a inhibition (miR29aINH) to ADAM12 gene overexpression on perfusion recovery in experimental PAD.
26 - 28 weeks old C57BL/6 mice on high fat diet were randomized into 3 treatment groups: sham (saline), miR29aINH, or ADAM12 plasmid. Agents were delivered by micro-bubbles at 5 days and 1 day pre-surgery. Experimental PAD was achieved by unilateral ligation and excision of the femoral artery of the left hind limb. The right hind limb serves as non ischemic control. Peripheral blood flow is measured by Laser Speckle Contrast Imaging. Tibialis anterior contractile function was assessed using an Aurora 300B-LR. ADAM12 and miR29a expression levels were quantified using qPCR on day 3 post surgery since perfusion at this point is similar between the experimental groups. Data are expressed as means ± SEM. Statistical significance of P &lt; 0.05 as significant is performed with the independent Student’s t-test.
Gene expression analysis 3 days post ischemia showed miR29a inhibitor reduced miR29a levels (miR29aINH: 0.70±0.06, n=5, ADAM12: 0.62±0.06, n=4, p=0.3938 and Sham: 1.02±0.06, n=5, p= 0.004 for miR29aINH vs Sham) and increased ADAM12 expression to a greater extent than ADAM12 gene transfer (miR29aINH: 208.62±24.52, n=3, ADAM12: 20.71±2.98, n=4, p= 0.0003 and Sham: 11.75±4.94, n=4). 3 weeks post-surgery, there was significantly higher perfusion recovery in mice treated with miR29aINH compared to ADAM12 gene transfer (miR29aINH: 97.59±6.14, n= 10, ADAM12: 58.45±4.87, n=8, p=0.002 and Sham: 42.52±5.35, n=5). Muscle contraction in the ischemic limb was &gt;2-fold stronger in the miR29aINH treated mice compared to ADAM12 gene transfer (miR29aINH: 0.54±0.08, n=7, ADAM12: 0.26±0.06, n=7, p= 0.0170 and Sham: 0.17±0.06, n=6).
Our result reveals for the first time that inhibiting elevated microRNAs may be a more effective therapeutic approach than gene transfer to improve blood flow and muscle function in type 2 DM and PAD.
SAT-LB136 A Proteomic Approach to Identify Circulating Glucocorticoid Responsive Proteins in Humans
Authors: Inder Warrick John , Keshvari Sahar , Barclay Johanna L , Ruelcke Jayde E , Stoll Thomas , Mohamed Ahmed , Nolan Brendan J , Cesana-Nigro Nicole , Hill Michelle M 
Published: May 2020

Abstract
Glucocorticoids used in pharmacological doses for the treatment of a variety of medical conditions, and endogenous glucocorticoid excess - Cushing’s syndrome, may result in several adverse effects, but currently there is no clinically useful biomarker of glucocorticoid activity. We have applied a proteomic approach to the discovery of glucocorticoid-responsive proteins potentially measurable in human serum samples. To minimise the masking by abundant serum proteins, we conducted discovery proteomics on the secretome of ex vivo-stimulated peripheral blood mononuclear cells (PBMC) isolated from 12 volunteers. The PBMC were divided into 4 treatment groups; +/- dexamethasone 100 ng/mL (dex) for 4h, or +/- dex for 24h. In all treatment groups, media was changed to serum free for 3h before collection. Media samples were processed for proteomics, with 561 and 273 proteins analysed by label-free quantification (LFQ) for the 4h and 24h secretome, respectively. Paired statistical analysis at the 2 time points generated a shortlist of 43 candidate biomarker proteins, which was verified using a multiple reaction monitoring (MRM) assay, confirming the differential secretion of 12 proteins at both 4h and 24 h. Five proteins were selected for validation using enzyme linked immunosorbent assay (ELISA) in an independent cohort: β2 microglobulin (B2M), lysozyme C (LYZ), high-mobility group protein 2 (HMG2), nucleophosmin (NPM1) and nucleolin (NCL). Twenty new volunteers (10M and 10F) had venous blood drawn at baseline and 12h after 4 mg oral dex. Four proteins were detectable by ELISA, three of which showed statistically significant change in concentration. Serum LYZ and NPM1 significantly decreased following dex: LYZ - 101 ± 5.5 vs 67 ± 4.4 ng/mL, (P&lt;0.0001); NPM1 - 17.4 ± 1.0 vs 14.3 ± 0.9 ng/mL, (P&lt;0.01), while HMG2 significantly increased - 819 ± 34 vs 984 ± 60 pg/mL (P&lt;0.01). These results demonstrate that an ex vivo proteomic approach using PBMC in conditioned media can identify glucocorticoid-responsive proteins measurable in human serum.
MON-LB304 The Construction of the Online Health Guidance Service for Life-Style Related Diseases (Kanazawa Slim Study)
Authors: Kometani Mitsuhiro , Oka Rie , Yasugi Ayaka , Gondo Yuko , Nomura Akihiro , Aono Daisuke , Higashitani Takuya , Karashima Shigehiro , Usukura Mikiya , Furukawa Kenji D , Yoneda Takashi 
Published: May 2020

Abstract
Background: Metabolic syndrome is a cluster of metabolic disorders including elevated blood pressure, high plasma glucose, excess body fat around the waist, and abnormal cholesterol or triglyceride levels. These conditions cause serious complications such as heart disease, stroke and type 2 diabetes. In Japan, specific health checkups and specific health guidance which focused on metabolic syndrome has been performed since 2008. Those who fall under certain criteria need to receive a medical treatment guidance from doctor, public health nurse or dietitian. Those who received health guidance receives a reassessment of improvement of their life-style 3-6 months later. However, the efficacy of this approach has not been elucidated. In addition, many persons who have metabolic syndrome do not receive this instruction. Recently, the image analysis technology using the artificial intelligence (AI) progresses rapidly. The smart device application “Asken” has an AI-powered photo analysis system which analyzes the photo of the entire meal, and delivers individualized messages and dietary feedbacks. In this study, we utilized the Internet of Things (IoT) device which includes Asken app, body composition analyzer and sphygmomanometer that can connect wirelessly. Objective: Our aim is to assess the efficacy of specific health guidance adding on IoT device. This is a multicenter, unblinded, non-randomized controlled study. Results: At the end of January 2020, we recruited 219 participants including 105 participants with IoT devices. We used 48 participants (32 with IoT and 16 without IoT) who had finished a reassessment 3 to 6 months after initial guidance. Results: Age, body weight (BW), body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (T-Chol), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), non-HDL cholesterol (n-HDL), and triglyceride (TG), did not differ between IoT-use and control group. 6 months after initial guidance, the quantity of decrease of BW in IoT-use group was significantly larger than control (-2.5 ± 4.1 kg vs. 0.6±4.4, p = 0.03). In addition, the quantities of decrease of both T-Chol and n-HDL in IoT-use group were also significantly larger than control (T-Chol, -5.9 ± 32.0 vs. 14.3 ± 31.6, p = 0.02; n-HDL, -7.6 ± 29.0 vs. 9.4 ± 27.5, p = 0.01). Conclusion: Using IoT device might be useful for body weight loss and the improvement of mild hypercholesterolemia in those with metabolic syndrome.
SAT-LB43 Allgrove’s: A Syndrome for the “A”ges
Authors: Bailey Richard , Nyquist Alexandra , Broome David Tyler , Zimmerman Robert S , Makin Vinni 
Published: May 2020

Abstract
Allgrove’s syndrome is an inherited condition caused by mutations in the AAAS gene (encoding the protein ALADIN) and is inherited in an autosomal recessive pattern (1). It classically is characterized by three specific features: achalasia, Addison’s disease, and alacrima (reduced or absent ability to secrete tears). This has led to the name “Triple A syndrome”, and some have suggested a 4th ‘A’ of autonomic disturbance (2). It is important to note that the phenotype of this condition is variable, and some patients may have all three (or four) of the manifestations at initial presentation, and that other patients may develop or have worsening of the ‘As’ over time. In this clinical vignette, we present a patient with Allgrove’s syndrome who developed clinical manifestations of the third ‘A’ of Addison’s disease later in life. A 46-year-old female patient presented to our tertiary referral center for follow-up of Allgrove’s disease after having been diagnosed with genetic testing as an adolescent. Prior to presentation, she underwent esophagectomy in 1995 and additionally had confirmed alacrima with ophthalmology. She was undergoing annual surveillance testing with 8 am cortisol and ACTH stimulation testing to monitor for the development of adrenal insufficiency. Prior to consultation, her baseline cortisol was 8.7 ug/dL. At presentation and the age of 46, her ACTH stimulation test (0.25 mg cosyntropin, 3 timepoints) was positive for adrenal insufficiency with a baseline cortisol of &lt; 0.5 ug/dL (8 am), with 30-minute value of 4.4 ug/dL and 60-minute value of 6.3 ug/dL (peak). She was started on replacement dosing of hydrocortisone 20 mg at 8 am and 10 mg at 2 pm, in addition to calcium and vitamin D supplementation. Of note, her adrenal antibody (21-hydroxylase antibodies) were negative on two separate occasions. Allgrove’s syndrome is a rare condition described by the development of three, or at times four, characteristics with support of genetic testing. This case demonstrates that patients with Allgrove’s syndrome can present with two clinical manifestations of the condition (alicrima and achalasia) and develop the third (adrenal insufficiency) later in life. Therefore, regular screening for the missing clinical manifestation of this disease should be considered. References: 1. National Institute of Health: Genetic and Rare Disease Information Center. Triple A Syndrome. Genetics Home Reference. February 2010; http://ghr.nlm.nih.gov/condition/triple-a-syndrome. Accessed 2/1/2020. 2. Kimber J, McLean BN, Prevett M, Hammans SR. Allgrove or 4 “A” syndrome: an autosomal recessive syndrome causing multisystem neurological disease. J Neurol Neurosurg Psychiatry. 2003;74:654-657.
MON-LB65 Lithium: The Culprit of Multiple Endocrinopathies
Authors: Yau Alice , Bahtiyar Gul , Rodriguez Giovanna , Martinez Escudero Jose R 
Published: May 2020

Abstract
Background: Lithium, commonly used to treat various psychiatric disorders such as bipolar disorder, can cause acute toxicity that presents with nausea, vomiting and diarrhea. Lithium can also cause life-threatening endocrine abnormalities, including hypercalcemia, hypernatremia, and both hypo- and hyperthyroidism.
Clinical Case: A 61-year old female with hypothyroidism, bipolar disorder, hyperparathyroidism with two-gland parathyroidectomy on lithium for over 30 years presented with altered mental status.
Initial labs revealed elevated creatinine 1.92 mg/dL (0.8-2.00mg/dL) compared to baseline 0.82 mg/dL, sodium 154 mg/dL (135-147 mg/dL), Corrected calcium 11.7 mg/dL (8.5-10.5 mg/dL), PTH 96 pg/mL (15-65 pg/mL), and high lithium levels 1.45 mmol/L (0.60-1.20 mmol/L). Further studies showed hypotonic polyuria with no increase in urine osmolality after desmopressin, consistent with nephrogenic diabetes insipidus. Lithium was held and she was treated with aggressive intravenous hydration with dextrose 5% water.
Hypercalcemia is thought to result from increased secretion of PTH due to an increased set point at which calcium suppresses PTH release; this often resolves once lithium is stopped. Lithium can also unmask previously unrecognized mild hyperparathyroidism, and/or raise serum PTH concentrations independent of calcium levels.1 The drug interferes with the kidneys’ ability to concentrate urine in the collecting tubules by desensitizing response to antidiuretic hormone, causing diabetes insipidus. The resulting volume depletion from excessive urinary water loss in turn lead to acute kidney injury and hypernatremia.2 Hypothyroidism results from lithium-inhibited synthesis and release of thyroid hormones and decreases iodine trapping.
Conclusion: Although these are infrequent complications of lithium use, they remain pertinent clinical findings to consider due to their morbidity. In this case, our patient may have avoided multiple chronic electrolyte abnormalities leading to altered mental status if lithium toxicity had been recognized earlier.
References:1. García-Maldonado, Gerardo, and Rubén de Jesús Castro-García. “Endocrinological Disorders Related To The Medical Use Of Lithium. A Narrative Review”. Revista Colombiana De Psiquiatría (English Ed.), vol 48, no. 1, 2019, pp. 35-43. Elsevier BV, doi:10.1016/j.rcpeng.2018.12.005.
2. Tasci, E. “Lithium-Induced Nephrogenic Diabetes Insipidus Responsive To Desmopressin”. Acta Endocrinologica (Bucharest), vol 15, no. 2, 2019, pp. 270-271. ACTA Endocrinologica Foundation, doi:10.4183/aeb.2019.270.
SAT-LB134 Aging Related Changes in Sex Hormone-Binding Globulin in Men With HIV
Authors: Dias Jenny Pena , Haberlen Sabina , Dobs Adrian , Lake Jordan , Palella FranK J , Kingsley Lawrence , Basaria Shehzad Sultan , Price Jennifer C , Budoff Matt , Thio Chloe L , Brown Todd Tarquin 
Published: May 2020

Abstract
Background: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates the bioavailability of sex hormones, may directly affect glucose metabolism, and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether age-related trajectories of SHBG differ by HIV serostatus. Methods: SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (MW/oH) from the Multicenter AIDS Cohort Study (MACS) in four U.S. cities, who had ≥2 samples over a 10 year period. Outcome measure: SHBG, log2SHBG. Multivariable linear mixed-effects regression models were used to evaluate whether SHBG (log2-transformed) and its rate of change differed by HIV serostatus after adjustment for covariates: age, race, BMI, smoking, education, hepatitis C virus infection, total testosterone concentrations, time of day of blood drawn and comorbidities (history of diabetes, kidney disease, liver disease, cancer, depression, hypertension) Results: At baseline, mean age among MWH was similar to MW/oH (51±5 vs 49±6 years). However, SHBG values were higher in MWH compared to MWo/H (65.6±48.8 nmol/L vs. 45.4±22 nmol/L, p&lt;0.001). The rate of SHBG change with age was (1.021 (95% CI:1.010-1.028) or 2.1% per year in MWH and (1.014 nmol/L/year (95% CI:1.010-1.019) or 1.4% per year in MW/oH, p=0.05 for difference in slopes. Among MWH, higher SHBG levels were significantly associated with lower CD4+ T cell count (0.99 (5%CI:0.98-1.00), p&lt;0.05), fewer cumulative years on zidovudine (0.98 nmol/L (95%CI:0.96,1.00), p&lt;0.001) and greater cumulative years on non-nucleoside reverse transcriptase inhibitors drugs (1.02 (95%CI:1.00,1.04), p&lt;0.05). Conclusion: Aging-related increases in SHBG were greater in magnitude among men with HIV and were related to poorer immunologic status and antiretroviral factors. The mechanisms and consequences of these findings require further investigation.
SUN-LB135 Estrogen Receptor Beta Inhibits NFkB Signaling to Inhibit Triple Negative Breast Cancer
Authors: Aspros Kirsten , Subramaniam Malayannan , Ye Zhenqing , Sun Zhifu , Ingle James , Goetz Matthew , Hawse John 
Published: May 2020

Abstract
Triple Negative Breast Cancer (TNBC) affects approximately 15-20% of BC patients, yet accounts for a disproportionately higher rate of BC morbidity and mortality, in part due to lack of targeted therapies. We have shown that estrogen receptor beta (ERβ) is expressed in approximately 20% of TN breast tumors and that ligand-mediated activation of ERβ with estradiol (E2) or ERβ-selective agonists decreases tumor cell proliferation, invasion and migration in vitro and in vivo. Therefore, we aimed to elucidate the mechanisms by which ERβ elicits its anti-cancer effects in TNBC. RNAseq analysis of ERβ-expressing MDA-MB-231 cells demonstrated that ERβ significantly downregulates NFκB signaling in the presence of E2. ChIPseq for ERβ in these cells revealed that ERβ primarily associated with estrogen response elements, but 12% of all ERβ binding sites were located at NFκB consensus motifs. Using an NFκB reporter construct and qPCR, ERβ was shown to block TNFα-mediated induction of NFκB signaling and NFκB target gene expression. RNAseq analysis of MDA-MB-231-ERβ cells treated with TNFα or E2+TNFα revealed substantial global inhibition of TNFα regulated genes in the presence of E2. ChIPseq for NFκB demonstrated that ERβ significantly alters NFκB’s cistrome whereby it can both diminish NFκB binding and redistribute NFκB throughout the genome. ChIPseq also demonstrated that ligand-mediated activation of ERβ significantly diminished an activating histone mark (H3K27Ac) at many of these NFκB target genes while enhancing a repressive mark (H3K27Me3). The addition of H3K27Me3 at these loci was shown to occur through the recruitment of the histone methyltransferase, EZH2. Drug-mediated blockade of EZH2 activity reversed suppression of NFκB target gene expression by ERβ. Knockdown of NFκB or Mutation of ERβ’s DNA binding domain rendered ERβ incapable of associating with DNA, recruiting EZH2, methylating NFκB target gene loci, repressing NFκB target gene expression and inhibiting proliferation. Interestingly, ERβ was shown to elicit more potent anti-cancer effects in TNBC cells expression a constitutively active form of NFκB. These finding suggest that a primary mechanism by which ERβ functions as a tumor suppressor is through inhibition of NFκB pathway activity. Our studies have also revealed that ERβ functions as a molecular switch for EZH2 and repurposes it for tumor suppressive activities, as EZH2 has previously been reported to enrich NFκB signaling in TNBC. These findings could address the paradox that high EZH2 expression is associated with worse TNBC patient outcomes, while high H3K27Me3 expression is associated with improved patient outcomes. Currently, a Mayo Clinic Breast Cancer SPORE prospective phase II clinical trial is underway to investigate the efficacy of estradiol for the treatment of metastatic ERβ+TNBC and to further evaluate the cross-talk between ERβ, EZH2 and NFκB signaling.
SUN-LB81 Coexisting Malignant Struma Ovarii and Cervical Follicular Variant Papillary Thyroid Carcinoma
Authors: Rind Jubran Afzal Khan , Saeed Zeb Ijaz 
Published: May 2020

Abstract
A 44-year-old woman presented with left lower quadrant abdominal pain for 2 months. Further evaluation revealed a left adnexal mass and she underwent a TAH-BSO. A 12 cm mass arising from the left ovary was resected which on microscopy appeared to be papillary thyroid carcinoma follicular variant arising from a mature teratoma (struma ovarii). A thyroid ultrasound showed two subcentimeter right thyroid nodules without any concerning lymphadenopathy. A total thyroidectomy was then performed to allow her to receive adjuvant RAI. The cervical thyroid pathology showed a 0.6 cm follicular variant papillary thyroid carcinoma with negative margins without angioinvasion, lymphatic invasion or extrathyroidal extension. Thyroid hormone suppression with levothyroxine was started. Preoperatively, thyroglobulin was 1381 ng/ml (nl range 1.3-31.8 ng/ml). After TAH-BSO and thyroidectomy, thyroglobulin was undetectable and so was the anti-thyroglobulin antibody. With an undetectable thyroglobulin level, it was decided not to pursue adjuvant RAI and continue TSH suppression with levothyroxine. Simultaneous existence of malignant struma ovarii and cervical papillary thyroid cancer is rare and has a favorable prognosis compared to metastasis to the ovaries from primary cervical thyroid papillary carcinoma. Due to the rarity of this condition, management is not clear or well supported by evidence. Various approaches are suggested by different authors, including thyroidectomy after resection of malignant struma ovarii to facilitate adjuvant RAI, only performing surgical resection of the ovarian tumor in the absence of high risk features or performing thyroidectomy and RAI only in metastatic or recurrent disease.
References:1.Aaron Leong, Philip J. R. Roche, Miltiadis Paliouras, Louise Rochon, Mark Trifiro, Michael Tamilia, Coexistence of Malignant Struma Ovarii and Cervical Papillary Thyroid Carcinoma, The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 12, 1 December 2013, Pages 4599-46052.Synchronous malignant struma ovarii and papillary thyroid carcinoma Pablo Fernández Catalina,Antonia Rego Iraeta, Mónica Lorenzo Solar, Paula Sánchez Sobrino DOI: 10.1016/j.endoen.2016.08.006