bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-662 Diabetes Risk for Non-Obese Subjects in a Japanese Population
Authors: Tatsukawa Yoshimi , Kitamura Hiroko , Yamada Michiko , Ohishi Waka , Hida Ayumi , Yoneda Masayasu 
Published: May 2020

Abstract
[Background] Obesity is a major risk factor of developing diabetes and cardiovascular diseases, though not all obese people develop these conditions and diseases. Because Asian populations have a lower frequency of obesity in comparison with populations in the United States and Europe, it is important to detect risk factors for developing diabetes in non-obese Japanese populations. [Objectives] To examine risk factors for diabetes, and to consider countermeasures against diabetes development in Japanese populations, especially non-obese individuals. [Methods] This study examined 1,794 individuals (514 males and 1,280 females) who participated in both Adult Health Study health examinations on A-bomb survivors and their controls in Hiroshima and Nagasaki between 1994–1996 (baseline) and 2008–2011. They were aged 48–79 years and had not been diagnosed with diabetes at baseline or cancer. Obesity was defined as a BMI of 23 kg/m2 or greater based on the WHO recommendation for Asians. In accordance with AHA/NHLBI criteria for diagnosis of metabolic syndrome, we defined a diagnosis of metabolic abnormality as having at least two of the criteria other than abdominal obesity. The diagnostic criteria for diabetes were a fasting blood glucose ≥126 mg/dL, a non-fasting blood glucose ≥200mg/dL, a self-report of a diabetes diagnosis, or the initiation of medical treatment for diabetes during the follow-up period. We compared presences of fatty liver and metabolic abnormality, BMI at baseline, and changes of body weight from baseline between the group that developed diabetes and the group did not over a 15-year follow-up. [Results] During the follow-up period until 2001, 66 (7.0%) individuals and 127 individuals (14.8%) from the non-obese and obese groups, respectively, developed diabetes. BMI at baseline and presences of fatty liver and metabolic abnormality were associated with developing diabetes in both non-obese and obese groups. Changes in body weight from baseline were not a significant risk factor of diabetes in this study. Furthermore, we analyzed the association between diabetes risk and appendicular lean mass/height2 (ALM/H2) and handgrip strength based on the diagnostic criteria for sarcopenia among 676 subjects with information of these measurements at baseline. Occurrences of low ALM/H2 were associated with developing diabetes, but an association between low handgrip strength and developing diabetes was not observed. [Conclusion] Regardless of whether obesity was observed or not, presences of metabolic abnormality and fatty liver were significant risk factors. Increased risk of developing diabetes was observed among non-obese individuals with suspected sarcopenia. This study suggests that maintenance of muscle mass may be an effective countermeasure to reduce the risk of developing diabetes.
OR30-06 Assessment of Dulaglutide Safety in Older Patient Populations in Rewind
Authors: Konig Manige , Gerstein Hertzel C , Lakshmanan Mark C , Xavier Denis , Atisso Charles , Allen Sheryl , Cushman William C , Leiter Lawrence A , Raubenheimer Peter J , Franek Edward M 
Published: May 2020

Abstract
Background: Dulaglutide (DU) was superior to placebo (PL) in reducing the incidence of Major Adverse Cardiovascular Events in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND Study) broad patient population. The safety of DU treatment is also of interest to health care providers who treat an older patient population (≥65 years of age).
Aims: The primary objective of this post-hoc analysis was to evaluate DU safety in the REWIND patient subgroup populations categorized by age (≥ 65 and &lt; 65 years) with regards to the occurrence of the composite safety outcome of overall mortality and severe hypoglycemia. One of the key secondary objectives was first occurrence of severe hypoglycemia.
Methods: Patients were grouped into two age groups: ≥65 and &lt;65 years. Time-to-event for the composite safety endpoint as well as individual variables were analyzed using Cox proportional hazards regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for between group treatment differences were also calculated.
Results: Of the 9,901 patients randomized in REWIND, a total of 5,256 (DU, 2,619; PL, 2,637) were aged ≥65 years. The incidence of the composite safety outcome for patients aged ≥65 years was 399 of 2619 (15.2%) for DU-treated patients and 425 of 2,637 (16.1%) for PL-treated patients. The incidence of the composite safety outcome for those aged &lt;65 years was 188 of 2,330 (8.1%) for DU-treated patients and 224 of 2,315 (9.7%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.94 (0.82, 1.08) for patients ≥65 years of age and 0.82 (0.68, 1.00) for patients &lt;65 years of age; interaction p-value = 0.277. The incidence of the secondary outcome of first occurrence of severe hypoglycemia for patients aged ≥65 years was 46 of 2619 (1.8%) for DU-treated patients and 49 of 2,637 (1.9%) for PL-treated patients. The incidence of this outcome for patients &lt;65 years was 18 of 2,330 (0.8%) for DU-treated patients and 25 of 2,315 (1.1%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.95 (0.63, 1.42) for patients ≥65 years of age and 0.71 (0.39, 1.31) for patients &lt;65 years of age; interaction p-value = 0.443. The safety profile of DU was reviewed based upon the results of subgroup analysis of treatment emergent adverse events and serious adverse events by preferred terms for comparing PL and DU for age subgroups (≥65 years of age versus &lt;65 years). None of the results indicated that DU has a different safety profile across the age subgroups evaluated in this post-hoc analysis.
Conclusions: Treatment with DU demonstrated similar safety in REWIND patients aged ≥65 years and those aged &lt;65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.
MON-437 False Positive I-131 Uptake
Authors: Yadav Pavan Rajendra , Idea Raul J 
Published: May 2020

Abstract
Background
Iodine has high specificity for thyroid tissue hence it plays very important role is management for differentiated thyroid cancer. Despite its high specificity and sensitivity, false-positive I-131 uptake could be seen on whole body scan (WBS).
We are presenting a case of false positive intense uptake in lung due to bronchiectasis.
Clinical case
Patient is a 78-year-old Asian female who initially present with left sided 5.8 cm thyroid nodule. The fine needle aspiration was performed, and the cytology came back as Bethesda category III. Per our institute protocol a molecular mutation panel was sent, which came back with NRAS mutation.
She underwent total thyroidectomy and the histology showed 6.2 cm Follicular carcinoma with extensive angioinvasion, oncocyte type. She received adjuvant 165.2 mci of RAI. Per protocol she had a one-week I-131whole body scan.
There was intense abnormal uptake in left mid and upper chest. The stimulate thyroglobulin with a TSH of &gt;100mcIU/ml was only 0.17 ng/dl with Tab negative.
Patient subsequently had a PET CT which showed a faint diffuse FDG activity noted in the cystic bronchiectasis predominantly in the left apex, lingula, and right middle lobe. Patient informed us that she has history of pulmonary tuberculosis in 1970’s for which she was successfully treated in her home country. We had 10-year-old chest X-ray which showed stable cystic bronchiectasis lesion in the region of intense uptake.
Discussion
Although I131 whole body scan has high specificity and sensitivity but physician should be aware of potential false positive uptake to avoid unnecessary intervention. In a retrospective evaluation i the most common non-thyroid conditions included were bronchiectasis, lung infection, subcutaneous injection into gluteal fatty tissue, aortic calcification, benign bone cyst, vertebral hemangioma, recent nonthyroidal surgical procedure site, rotator cuff injury, mature cystic teratoma and ovarian follicle cyst). The accumulation of the bronchial secretion is the proposed mechanism of the high false positive uptake in bronchiectasis.
Endnotes
i Mol Imaging Radionucl Ther 2018; 27:99–106 DOI:10.4274/mirt.37450
MON-391 Implementation of an Osteoporosis Risk Assessment Instrument (ORAI) to Increase Referral Rates for DEXA Scanning in the Primary Care Setting
Authors: Saatciler Eda , Gillooly Diane , Toro Bernard , Lontai Peter 
Published: May 2020

Abstract
Abstract
Background/Purpose: Osteoporosis (OP)was first identified and named by healthcare professionals in the 18th century. Today, OP is still the source of fractures which impair mobility, leading to sub-acute stays at rehabilitation centers. A major obstacle is that primary care providers (PCPs) fail to identify warning signs of OP, and inform patients that Dual Energy X-Ray Absorptiometry (DEXA) scans that are one of the best procedures to assess bone health. This project addressed the issue of low rate of referrals for DEXA scans. Theoretical Framework: The Knowledge-to-Action (KTA) model was used to guide this study. Intervention: Implementation of osteoporosis risk assessment instrument. Methods (Design, Sample, Setting, Measures, Analysis): This includes pre-implementation phase, patients’ charts were reviewed; post-implementation phase, the number of people referred to have DEXA scans were analyzed; the evaluation phase, results compared to the previous data. The project focus exclusively on women and men ages 50 to 89 years in two primary care offices in New Jersey. Descriptive analyses concentrated on whether or not ORAI was the tool to increase DEXA scans. Results: The data analysis reflected that the baseline referral rates increased from 1.3 % to 42 % and patients who scored high on the risk assessment instrument have been referred more often than not. Moreover, patients who are at risk and younger than 65 years of age, risk assessment tools led to a positive referral for a DEXA scan. Those who are older than 65 years, risk assessment tools like ORAI should be given with fracture risk assessment tools. This is especially the case when dealing with men, a demographic group often overlooked in the fight against OP. Conclusions Implications: If this project is to be applied at other clinics, more and more patients would be referred, raising awareness of the medical benefits of early detection. Reasonably, covering a broader section of patients, earlier in their lives, will increase clinical income, bringing more patients to primary care offices.
SAT-584 Uc.336-As Inhibits White Adipocyte Differentiation and Promotes White to Brown Conversion
Authors: Li Yanbing , Guan Hongyu , Li Hai 
Published: May 2020

Abstract
Brown adipose tissue (BAT) has gained its popularity since it shows great potential in counteracting obesity and metabolic diseases development. Transcribed ultraconserved regions (T-UCRs), a novel class of long non-coding RNA (lncRNAs), have been implicated in regulating diverse biological processes, including the process of white fat browning. However, the functional and mechanistic details of T-UCRs in the browning process are poorly understood. Here, we identified that a T-UCR, uc.336-as, played an important role during the browning process. uc.336-as was significantly elevated during browning process induced by exendin-4 or β3-adrenergic agonist (CL316,243). Moreover, we found that uc.336-as promoted browning process and inhibited adipogenesis. Finally, we identified that uc.336-as promoted the expression of browning-related genes via influencing the p38 mitogen-activated protein kinase (p38 MAPK) signaling, an essential signal pathway in metabolism. Taken together, our data show that uc.336-as acts as a negative regulator in white adipocyte differentiation and promotes the browning process, suggesting a potential therapeutic role for uc.336-as in controlling obesity.
SUN-003 Very Restricted Carbohydrate (Ketogenic) Diet: A Rare Cause of a Recurrent Hypoglycemic-Euglycemic Diabetic Ketoacidosis in the Pregnancy
Authors: Yaron Marianna , Shalit Roy , Kreiser Doron , Cukierman-Yaffe Tali , Israel Eduardo , Yoeli Rakefet 
Published: May 2020

Abstract
Introduction: Although potential risk of DKA, ketogenic diet became popular among T1DM patients as proven to reduce the incidence of hypoglycemia, glycemic variability, and HbA1c (1).
Severe carbohydrate restriction had not been included among DKA precipitating factors in pregnancy since a minimum consumption of 175 g of carbohydrates a day is recommended for pregnant women by the IOM and ADA.
Proband: A 35-year-old pregnant woman (G2P1 at 29 weeks’ gestation) was admitted to the ICU because of a 12-hour history of severe nausea, 4 vomiting episodes (stomach contain), weakness, and metabolic acidosis accompanied by low normal BG values for pregnancy. She had a history of bulimia nervosa since 15 years of age that was well-controlled by severe carbohydrate restriction prior to pregnancy, and T1DM since 19 years of age. Her pre-pregnancy carbohydrate daily intake was ~ 20–30 g and BMI 24.1 kg/m2. Good glycemic control was established before conception and continued until delivery.
Upon admission, she was tachypneic and suffering from diffuse abdominal pain. Fetal monitoring and abdominal ultrasonography showed no significant changes, and the sonographic fetal weight was appropriate for gestational age.
The laboratory results revealed metabolic acidosis pH 7.23, bicarbonate 11.7 mmol/L, anion gap 22.5, and BG 78 mg/dL. Lactate and salicylate blood levels were normal. The blood β-hydroxybutyrate was highly positive and the patient was diagnosed with euglycemic DKA. She was managed with a continuous intravenous insulin infusion and fluid and electrolytes repletion.
The patient was discharged after three days of hospitalization only to return four days later because of the similar complaints with findings of blood β-hydroxybutyrate 7.7 mmol/L and BG levels of 61–65 mg/dL. Because of persistent ketonemia with low normal BG levels, patient was questioning about her dietary habits and revealed to maintain severe carbohydrate-restricted pre-conception eating manners. After repeated consultations by specialists for eating disorder, patient agreed to increase her carbohydrate intake to 120 gr per day.
Fetal brain MRI, fetal heart and brain ultrasound were performed to evaluate potential negative effects of ketones, and all were found normal. No major malformations were observed in the newborn, and a normal growth pattern was observed at 5 months of age.
Conclusion: This is the first report of a pregnant T1DM patient with long lasting bulimia nervosa excellently controlled by severe carbohydrate restriction prior pregnancy and occultly continued against medical advice through the pregnancy, causing repeatedly hypoglycemic-euglycemic DKA.
References: 1. Schmidt S, Christensen MB, Serifovski N, et al. Low versus high carbohydrate diet in type 1 diabetes: A 12-week randomized open-label crossover study. Diabetes Obes Metab 2019; 21:1680- 1688
SUN-260 Dual Role of Carboxypeptidase E in Prohormone Processing and a Novel Neurotrophic Factor Mediating Neuroprotection and Cognitive Functions in Hippocampal CA3 Neurons in Mice
Authors: Xiao Lan , Sharma Vinay , Toulabi Leila , Yang Xuyu , Lee Cheol , Abebe Daniel , Peltekian Areg , Arnaoutova Irina , Loh Yoke Peng 
Published: May 2020

Abstract
Stress causes release of glucocorticoids from the adrenals which then circulate to the brain. High concentrations glucocorticoid from chronic severe stress results in pathophysiology in the brain, including neuronal degeneration, cell death and cognitive dysfunction, leading to diseases such as Alzheimer Disease and Major Depressive Disorders. Neurotrophic/growth factors such as BDNF, NGF and NT3 have been linked to these pathological conditions. Carboxypeptidase E (CPE), a proneuropeptide/prohormone processing enzyme, also named neurotrophic factor-α1(NFα1) is highly expressed in the stress-vulnerable hippocampal CA3 neurons, and was shown to have neuroprotective activity from in vitro studies. Here we investigated if CPE-NFα1 functions in vivo, independent of its enzymatic activity, and the mechanism underlying its action. We generated knock-in mice expressing a non-enzymatic form of CPE, CPE-E342Q, but not wild-type CPE. The CPE-E342Q mice showed significantly decreased neuropeptide content and exhibited obesity, diabetes and infertility due to lack of prohormone processing activity, similar to CPE-KO mice. However, they showed no hippocampal CA3 degeneration, exhibited neurogenesis in the dentate gyrus, and displayed normal spatial learning and memory, similar to CPE wild-type mice, after weaning stress; unlike CPE-KO mice which showed hippocampal CA3 neuronal degeneration and cognitive deficits. Binding studies showed that radiolabeled CPE bound hippocampal cell membrane specifically, in a saturable manner. Binding of CPE and CPE-E342Q to hippocampal neurons activated Erk signaling and pre-treatment with either of these proteins protected neurons against H2O2- or glutamate-induced neurotoxcity by increasing BCL2 expression. In vitro and in vivo inhibitor studies demonstrated that this neuroprotective effect was independent of tyrosine kinase receptor signaling. Taken together, the data provide evidence that CPE-NFα1 is a unique neurotrophic factor which acts through a non-tyrosine kinase receptor to activate Erk-BCL2 signaling to protect hippocampal CA3 neurons against stress-induced neurodegeneration and maintaining normal cognitive functions in mice.
SAT-441 Transcriptome Analysis Under Differential Thyroid Hormone Treatment During Mouse Cerebellar Development
Authors: Yajima Hiroyuki , Sumiyasu Ishii , Miyazaki Wataru , Koibuchi Noriyuki 
Published: May 2020

Abstract
Background: Thyroid hormone (TH) plays essential roles in the development of the cerebellum by regulating transcription of target genes. TH binds to TH receptor (TR) located in the cell nucleus and stimulates transcription through TH response element (TRE). The expression of many genes is temporary and spatially regulated by TH during cerebellar development. However, the mode of transcription by TR may vary among target genes. In the liver, different duration of TH exposure resulted in distinct gene expression profiles. To examine the mechanisms of transcriptional regulation by TH in cerebellar development, gene expression profile induced by various TH exposure duration was studied. Methods: Anti-thyroid drug propylthiouracil (250 ppm in drinking water) was administered to C57BL/6J mice from the gestational day 14 to postnatal day (P) 7 to generate perinatal hypothyroid mice. To study the effect of continuous TH exposure, TH was subcutaneously administered to hypothyroid pups from P2 to P7 (6 days group). To study the effect of single TH administration, TH was injected on P7 and mice were sacrificed either 6 (6 hours group) or 24 hours (24 hours group) after injection. Cerebellar samples were collected to extract RNA and subject to microarray analysis. Microarray results were confirmed by RT-qPCR. Results: In microarray result, compared with mRNA levels of hypothyroid mice, 6 days group induced upregulation in 1007 genes and downregulation in 1009 genes, 6 hours group induced upregulation in 355 genes and downregulation in 977 genes, and 24 hours group induced upregulation in 365 genes and downregulation in 1121 genes. Only 7.6% of the genes were overlapped in three groups among positively regulated genes. In contrast, 57.2% of the genes were common in the negatively regulated genes. In RT-qPCR result, among genes known to harbor TRE, Hairless, Pcp2, and Nrgn, showed differential upregulation patterns. Hairless was upregulated in all groups, whereas Pcp2 was upregulated only in 5 days group and Nrgn was not upregulated in all groups. These results suggest that different mode of transcriptional regulation occurred in an exposure time-dependent manner of TH. Conclusion: We identified gene groups whose expression were modified by TH during cerebellar development. TH distinctively regulates transcription of target genes depending on the exposure schedule in mouse developing cerebellum.
SUN-244 Role of Activin, Follistatin, and Inhibin in the Regulation of KISS-1 Gene Expression in Hypothalamic Cell Models
Authors: Oride Aki , Kanasaki Haruhiko , Tumurgan Zolzaya , Tumurbaatar Tuvshintugs , Kyo Satoru 
Published: May 2020

Abstract
Kisspeptin (encoded by the Kiss-1 gene) in the arcuate nucleus (ARC) of the hypothalamus governs the hypothalamic-pituitary-gonadal (HPG) axis by regulating pulsatile release of gonadotropin-releasing hormone (GnRH). Meanwhile, kisspeptin in the anteroventral periventricular nucleus (AVPV) region has been implicated in estradiol (E2)-induced GnRH surges. Kiss-1-expressing cell model mHypoA-55 exhibits characteristics of Kiss-1 neurons in the ARC region. On the other hand, Kiss-1 expressing mHypoA-50 cells originate from the AVPV region. In the mHypoA-55 ARC cells, activin significantly increased Kiss-1 gene expression. Follistatin alone reduced Kiss-1 expression within these cells. Interestingly, activin-induced Kiss-1 gene expression was completely abolished by follistatin. Inhibin A, but not inhibin B reduced Kiss-1 expression. Activin-increased Kiss-1 expression was also abolished by inhibin A. Pretreatment of the cells with follistatin or inhibin A significantly inhibited kisspeptin- or GnRH-induced Kiss-1 gene expression in mHypoA-55 cells. In contrast, in the mHypoA-50 AVPV cell model, activin, follistatin, and inhibin A did not modulate Kiss-1 gene expression. The subunits that compose activin and inhibin, as well as follistatin were expressed in both mHypoA-55 and mHypoA-50 cells. Expression of inhibin βA and βB subunits and follistatin was much higher in mHypoA-55 ARC cells. Furthermore, we found that expression of the inhibin αsubunit and follistatin genes was modulated in the presence of E2 in mHypoA-55 ARC cells. The results of this study suggest that activin, follistatin, and inhibin A within the ARC region participate in the regulation of the HPG axis under the influence of E2.