bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB113 A Continuous Remote Care Intervention Utilizing Carbohydrate Restriction Including Nutritional Ketosis Improves Markers of Metabolic Risk and Reduces Diabetes Medication Use in Patients With Type 2 Diabetes Over 3.5 Years
Authors: McKenzie Amy , Athinarayanan Shaminie , Adams Rebecca , Volek Jeff , Phinney Stephen , Hallberg Sarah 
Published: May 2020

Abstract
Novel lifestyle, pharmaceutical, and/or surgical therapies for type 2 diabetes (T2D) are under study to assess lasting impact on metabolic risk. Among them, carbohydrate restriction including nutritional ketosis (CR) has emerged as a safe and effective nutrition therapy for reducing hyperglycemia in patients with T2D1, yet longer term effects are unknown. At the conclusion of a 2-year study assessing a continuous remote care intervention utilizing CR (CCI) among patients who selected this therapy, intervention participants were offered the opportunity to consent to participate in a 3-year extension assessing outcomes at 3.5- and 5-y following initial enrollment. 143 of 169 extension-consented participants provided data at 3.5-y follow up. Among 3.5-y completers, linear mixed effects models were used to assess change over time in diabetes-related outcomes and McNemar’s tests were used to assess for a difference in the proportion of participants meeting certain criteria at baseline compared to follow-up. At enrollment, 3.5-y completers were (mean±SE) 55±1 y of age, 40.8±0.7 kg/m2, and 8±1 y since diagnosis. Following treatment with the CCI for 3.5 y, significant improvements compared to baseline were observed in HbA1c (-0.6±0.1 from 7.4±0.1%; P = 1.9x10-5), weight (-10.9±1.1 from 117.4 kg; P = 6.9x10-17), nonHDL-C (-10±4 from 139±3 mg/dL; P = 0.005), triglycerides (-41±11 from 189±10 mg/dl; P = 2.1x10-4), and HDL-C (+9±1 from 43±1 mg/dl; P = 3.0x10-11); total cholesterol and LDL-C were statistically unchanged. The percentage of participants prescribed diabetes medication decreased from 84.6 to 67.1% (P = 5.0x10-6), while 50.2% of diabetes medications and 71.4% of diabetes medications other than metformin were discontinued. The percentage of participants treated with no pharmaceuticals or monotherapy increased from 52.5 to 81.9% (P = 1.3x10-8). 45.5% (65/143) of participants achieved HbA1c &lt;6.5% with either no medication (34/65, 52%) or only metformin (31/65, 48%) at 3.5 y; 37.8% of participants maintained this status from 1 through 3.5 y of treatment. 22% of participants achieved diabetes remission at 3.5 y, and 17.5% of participants maintained remission status from 2 through 3.5 y of treatment. This demonstrates that clinically meaningful improvements across multiple markers of metabolic risk can be sustained in patients with T2D who selected treatment with this CCI for 3.5 y. Improvements in metabolic risk markers reduced the need for diabetes medication, allowing some patients to achieve and sustain diabetes remission. This ongoing trial will assess 5-y effects.
1. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2020; 43(Supplement 1): S48-S65. 2. Athinarayanan SJ, et al. Front Endocrinol. 2019; 10:348.
SUN-LB42 The Sexually Dimorphic Response of the Mouse Adrenal Inner Cortex to Thyroid Hormone Treatment
Authors: Zheng Huifei Sophia , Lyu Qiongxia , Huang Chen-Che Jeff 
Published: May 2020

Abstract
The gender bias in adrenal diseases has been noticed for a long time. Mouse studies have shown that the adrenal gland is sexually dimorphic at different levels, such as transcriptome, histology, and cell renewal. However, the mechanism behind this sexual dimorphism is not fully understood. Here, we used RNA-seq to demonstrate how male and female adrenals respond differently to the same external cue, the thyroid hormone (T3) treatment, which directly elicits its function on the adrenal inner cortex by changing the cell fate of this population. Through the comparison of the adrenal gland transcriptomes from males and females with T3 or saline treatment, we found that more genes in female adrenals were responsive to the T3 treatment, whereas the fold change of the gene expressions was greater in male adrenals. Statistical analysis identified 104 sexually dimorphic T3-responsive genes. Immunostaining results showed that many of these genes were expressed in the adrenal gland inner cortex, which contains a unique cell population called X-zone (20-alpha-HSD positive). Previous studies showed that T3 treatment leads to the expansion of the 20αHSD-positive zone both in males and in females. Here we found that the top sexually dimorphic T3-responsive gene was expressed in the adrenal inner cortex partially colocalized with X-zone. Under T3 treatment, this unique cell population that surrounds the 20-alpha-HSD positive X-zone became obvious only in females but not in males. Our findings not only identified several novel marker genes for the adrenal inner cortex but also highlighted the sex-specific response of thyroid hormone action in the mouse adrenal gland.
MON-LB103 Hyperactivation of Reward and Cognitive Control Brain Regions in Response to Food Images in Women Compared to Men With Obesity
Authors: Getachew Ethiopia D , Plessow Franziska , Van De Water Avery , Pulumo Reitumetse L , Hauser Kristine , Asanza Elisa , Kerem Liya , Harshman Stephanie G , Holsen Laura , Lawson Elizabeth A 
Published: May 2020

Abstract
Background: Obesity is a major public health concern with an estimated two thirds of the population being overweight or obese. Women have a higher rate of obesity than men (40% vs. 35%), twice the rate of class 3 obesity (10% vs. 5% with BMI&gt;40), and greater increases in obesity prevalence from 2005-2014. While emerging evidence highlights the role of food motivation circuitry in eating behavior and obesity risk, sex-specific neurobiological mechanisms have not been well defined in this population but are important to guide individual treatment strategies. Using a well-established food motivation functional magnetic resonance (fMRI) paradigm, we ran a preliminary set of analyses to investigate whether sex modulates the brain response to visual presentations of food items. We hypothesized that in a fasted state, women would demonstrate greater blood-oxygen-level-dependent (BOLD) activation in response to food images in reward-related brain regions compared to men.
Methods: Twenty-nine adults with obesity (16 female, age (mean±SD): 31.2±4.9 years, and BMI=36.5±4.1 kg/m2) completed fMRI imaging in a 3T scanner while viewing images of food (high-calorie vs. low-calorie), non-food items, and fixation stimuli following a 10-hour overnight fast. Functional MRI data were analyzed using SPM12. Regions of interest included the nucleus accumbens (NAcc), amygdala, caudate, anterior insula (aINS), hypothalamus, putamen, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), dorsal anterior cingulate cortex (dACC), and supplementary motor area (SMA). Statistical significance of p&lt;0.05 is reported at the whole brain level given the small sample size.
Results: Women with obesity exhibited greater activation than men in response to food (vs. non-food) stimuli in NAcc (t=2.44, p[uncorrected]=0.011), caudate (t=2.9, p[uncorrected]=0.004), DLPFC (t=3.32, p[uncorrected]=0.001), and dACC (t=3.17, p[uncorrected]=0.002) in a fasted state. There were no regions in which men exhibited greater activation than women.
Conclusion: Our preliminary results show that during a fasting state, women with obesity (vs. men) show greater activation in brain regions processing reward (NAcc) and control over behavior (DLPFC, dACC) in response to food (vs. non-food) stimuli. Future studies with larger sample sizes are needed to investigate the link between the highlighted sex differences in neural responses to food in the context of obesity and eating behavior and weight to further inform whether men and women would benefit from different approaches in the treatment of obesity.
SAT-LB12 Once-Weekly Somapacitan vs Daily Growth Hormone in Growth Hormone Deficiency: 2-Year Safety Results From Real 3, a Randomized Phase 2 Trial
Authors: Savendahl Lars S , Rasmussen Michael Højby 
Published: May 2020

Abstract
Growth hormone (GH) replacement therapy currently requires daily injections. Somapacitan is a long-acting GH-derivative being developed for once-weekly (OW) use in children and adults with GH deficiency (GHD). A phase 2, multinational, randomized, open-label, controlled trial (ClinicalTrials.gov: NCT02616562) investigated the efficacy and safety of OW somapacitan compared with daily GH (Norditropin® FlexPro®). GH-treatment-naïve prepubertal children with GH deficiency received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/wk (n=14) subcutaneous (sc) OW somapacitan, or sc GH 0.034 mg/kg/day (0.24 mg/kg/wk; n=14) for 52 wks, followed by a 104-wk safety extension with all patients on somapacitan receiving 0.16 mg/kg/wk while GH dose was unaltered. Safety endpoints included frequency of adverse events (AEs), including injection-site reactions, and occurrence of anti-somapacitan/anti-human growth hormone (hGH) antibodies. The 52-wk efficacy and safety results have been reported. We report here safety results at 104 wks’ total treatment. Number of AEs (% of patients) was as follows: OW somapacitan 0.04/0.16 mg/kg/wk, 51 (75%); 0.08/0.16 mg/kg/wk, 89 (80%); 0.16/0.16 mg/kg/wk, 89 (100%); and for daily GH, 82 (100%). Nasopharyngitis, influenza, allergic rhinitis and gastroenteritis were the most common AEs across all treatment groups. Pyrexia was more common in the OW somapacitan 0.04/0.16 mg/kg/wk (43.8%) and 0.08/0.16 mg/kg/wk (26.7%) groups vs the higher-dose OW somapacitan and daily GH groups (7.1% each). Most AEs were mild to moderate and unlikely related to treatment. Ten serious AEs were reported in five (8.5%) children and unlikely related to treatment, except two AEs of moderate severity during the first 26 wks: generalized edema and vomiting in one child on 0.16 mg/kg/wk OW somapacitan, rated as probably related to treatment although she was also given intravenous antibiotics for suspected infection. Injection-site reactions were reported in the 0.04/0.16 mg/kg/wk (n=2) and 0.16/0.16 mg/kg/wk (n=1) OW somapacitan groups and in the daily GH group (n=1). Four children (0.04/0.16 mg/kg/wk) and one child (0.16/0.16 mg/kg/wk) had transient anti-somapacitan antibodies; one child (0.16/0.16 mg/kg/wk) had low-titer anti-somapacitan antibodies at two consecutive visits; in one child (daily GH group) with persistent low-titer anti-hGH antibodies, treatment was discontinued at wk 52. All antibodies were non-neutralizing. In conclusion, OW somapacitan was well tolerated at all doses, with no new safety or tolerability issues identified after up to 104 wks of treatment. The frequency, severity and type of AEs were similar in the OW somapacitan and daily GH treatment groups except for pyrexia, which was unlikely related to treatment and more frequently reported in the lowest dose somapacitan group.
SAT-LB87 Golimumab Induced Thyroiditis
Authors: Mai Mo M , Karam Jocelyne G , Lynn Nyein , Singh Gurbaj , Singer Elizabeth Sedlis 
Published: May 2020

Abstract
Background:
Subacute thyroiditis is caused by an inflammation and a destruction of the thyroid cells, leading to hyperthyroidism due to leakage of thyroid hormones, followed by possible hypothyroidism and/or full recovery of thyroid function. This is a case report describing a rare occurrence of drug-induced thyroiditis secondary to golimumab.
Clinical Case:
A 79-year-old female with HTN, hyperlipidemia, dementia and rheumatoid arthritis was brought to the ER for abnormal behavior including visual hallucinating and insomnia.Initial ER evaluation showed UTI for which antibiotic therapy was initiated. Dementia workup was performed including a negative head CT, nonreactive RPR, and borderline low vitamin B12 level. TFT obtained showed low TSH of 0.2mlU/L, elevated serum FT4 of 1.72ng/ml (n=0.58-1.64ng/ml) and elevated serum FT3 4.38pg/ml (n=2.5-3.9pg/ml), suggestive of hyperthyroidism. The patient reported no heat intolerance, hyperdefecation, or weight changes, but had intermittent palpitations. She denied any history of thyroid problem and did not take thyroid medication, amiodarone, biotin, or any new drug. She reported no fever or URI symptoms within the few weeks prior to admission. In addition to prednisone and methotrexate, she was taking golimumab 50mg every 30 days for the last 22 months for RA. The patient had a family history of hypothyroidism of two daughters and sister. She denied smoking, alcohol, or any other recreational drug use. Her home medications included prednisone 5mg daily, methotrexate, folic acid, lisinopril, simvastatin, and golimumab. On physical examination, she did not appear thyrotoxic and had no exophthalmos, thyroid tenderness, thyroid enlargement or thyroid nodules. Her HR range was 80bpm.Further analysis revealed normal TSI, TPO, and TgAb levels. The thyroglobulin level was very high at 2505ng/ml (n=1.6-59.9ng/ml). Her thyroid sonogram revealed bilateral thyroid nodules, largest at 1.9cm in the right mid pole. A 24-hr RAIU scan showed very low uptake (1.8%) consistent with thyroiditis (hyperthyroid phase).Endocrinology team did not recommend any antithyroid medications. In addition, she did not warrant NSAIDs or beta blockers as she was not symptomatic or tachycardic. In the absence of an autoimmune or an obvious viral process, her subacute thyroiditis was thought to be induced by golimumab.
Conclusion:
TNFɑ inhibitors used to treat chronic inflammatory diseases, have been rarely associated with subacute thyroiditis as described in case reports with adalimumab and etanercept use. We report the first subacute thyroiditis associated with golimumab use. We suggest that drug-induced subacute thyroiditis should be one of the differential diagnoses of thyroid dysfunction in patients treated with golimumab.
MON-LB001 Ovulation Induction Results in Altered Growth and Metabolic Dysfunction in Mice Offspring
Authors: Harner Royce , Albarran Saul Lira , Chalas Celine , Donjacour Annemarie , Liu Xiaowei , Rinaudo Paolo 
Published: May 2020

Abstract
Nearly 15% of couples are affected by infertility and a large proportion of individuals will need to use ovulation induction (OI) or assisted reproductive technologies (ARTs) to conceive. Previous studies have shown that offspring conceived by ARTs are predisposed towards increased insulin resistance and glucose intolerance. However, the long-term effects of OI alone on offspring health have not been studied. This rodent study was designed to elucidate the effects of maternal superovulation on offspring growth and development.
C57Bl/6 females were either naturally mated (control= C) or super-ovulated (5 IU PMSG; 5IU hCG, OI group) and mated to C57Bl/6 males with one Agouti viable yellow (Avy) allelic mutation. The Avy allele contains an intracisternal A particle whose methylation levels determine expression of the agouti protein which alters coat color and can be used as a phenotypic readout for global methylation. Offspring (n= 108 control and n = 69 OI) were followed through 13 weeks of age to measure birth parameters, growth rate, fasting glucose, GTT, and body composition (EchoMRI). Parametric and non-parametric tests were used as indicated. Only results with p&lt;0.05 are reported.
Results: Surprisingly, while litter size was not different (C = 7, OI = 6), superovulated mothers had fewer surviving pups (C=6.5 pups, OI=5 pups). No major differences in coat color frequencies were observed between the two groups, suggesting no changes in DNA methylation. All OI pups had decreased anogenital distance (males C = 2.1mm, OI = 1.7mm; females C = 1.74mm, OI = 1.48mm), while OI female had lower birthweights (C = 1.38g and OI = 1.23g). Starting at four weeks of age, OI male had lower weight compared to control males. As early as 3 weeks, significant differences in fasting glucose levels were noted (C = 162 mg/dL, OI = 149.5mg/dL). Additionally, superovulated males had lower lean mass at 8 weeks of age (tested by EchoMRI: C = 23.6g, OI = 19.3g) and higher insulin levels at 13 weeks (120 min post injection, C = 339 mg/dL, OI = 213 mg/dL).In summary, we found that the process of OI alone has profound effects on offspring development in a sexual dimorphic fashion. Additional studies will be performed up to 30 weeks of age. Funding: R01 HD092267-01to P
SAT-LB131 Examination of Hepatic Gene Expression Following Developmental Exposure to Dieldrin in Trachemys Scripta and Discovery of a Novel Hepacivirus
Authors: O’Brien Mara H , Callard Ian P 
Published: May 2020

Abstract
The Massachusetts Military Reservation (MMR) is a Superfund site where ground water has been contaminated by a mixture of pollutants. Exposure to these chemicals is a public health concern and reproductive impairments have been observed in a population of turtles (Chrysemys picta) endemic to this site. We hypothesize that developmental exposure to endocrine disrupting compounds originating from the MMR might lead to abnormalities seen in adult animals. Upon examination of egg yolk from turtles at the impacted site, we found the presence of dieldrin and p,p’-DDE. Turtles from a reference site were also found to have p,p’-DDE present in the yolk. In order to investigate these chemicals in the laboratory we used a closely related turtle (Trachemys scripta) and applied vehicle, dieldrin, or p,p’-DDE to the eggshells. Absorption of p,p’-DDE through the eggshell was limited. Although there were variations in absorbance, we were able to achieve levels of dieldrin in the yolk similar to what was seen in animals from the impacted site. Following in ovo exposure to dieldrin, we used RNAseq to examine hepatic gene expression in neonates and found that several transcripts were repressed at least 1.5-fold in the dieldrin-treated animals. QPCR was carried out to confirm differences in gene expression. We found that hepatic gene expression (fold ± SEM) of Gamma-Butyrobetaine Hydroxylase 1 (Bbox1) was higher in vehicle-treated animals (1 ± 0.60) compared to dieldrin-treated animals (0.29 ± 0.12). Bbox1 catalyzes the last step in the L-carnitine biosynthetic pathway, which is necessary for mitochondrial beta-oxidation. Dieldrin-induced reduction in L-carnitine production may be a critical factor in adult reproductive function. Further, Protein-L-Isoaspartate (D-Aspartate) O-Methyltransferase Domain Containing Protein 1 (Pcmtd1) was higher (1± 0.76) in vehicle-treated animals compared to dieldrin-treated animals (0.13 ± 0.044), and DENN Domain Containing 5B (Dennd5b) was also found to be higher in vehicle-treated (1 ± 0.39) compared to dieldrin-treated (0.28 ± 0.10) turtles. We found that dieldrin exposure did not alter gene expression of Cytochrome p450 1a (Cyp1a) a marker of aryl hydrocarbon receptor signaling, or Vitellogenin 2 (Vtg2) a marker of estrogen signaling. In our RNAseq analysis we unexpectedly discovered a hepacivirus infecting T. scripta. In the dieldrin-treated group, we used QPCR to examine gene expression of potential markers of hepacivirus infection. Neither Interleukin 1 Beta (Il-1β), SMAD Family Member 6 (Smad6), C-C Motif Chemokine Ligand 5 (Ccl5), or TNF Receptor Superfamily Member 9 (Tnfrsf9) was found to differ in turtles carrying the virus, compared to non-infected animals. In conclusion, we found that developmental dieldrin exposure of T. scripta slightly reduces neonatal expression of several gene transcripts which may be correlated to adult reproductive fitness.
SAT-LB26 A Dual Role for IGF-1R in Mammary Tumorigenesis
Authors: Obr Alison , Maingrette Krystopher , Chang Yun-juan , Bulatowicz Joseph , Wood Terri L 
Published: May 2020

Abstract
The insulin-like growth factor type 1 receptor (IGF-1R) is now thought to have a dual function in breast cancer. Several studies have shown overexpression of the IGF-1R pathway results in increased tumor cell proliferation and survival. Recent loss-of-function models have shown decreased mammary tumorigenesis latency and increased metastasis. These recent studies correlate with analyses of human patient datasets identifying worse overall survival with low IGF-1R expression. Similarly, inhibition of IGF-1R in the clinic has had no affect or has led to worse outcomes supporting the hypothesis that the IGF-1R may have tumor suppressive properties. Our prior published studies revealed loss of IGF-1R function results in heightened tumor epithelial stress, which alters the tumor microenvironment to be permissive for metastasis. Therefore, we asked does the loss of IGF-1R inherently change the tumor epithelium or is it simply the alterations of the microenvironment that lead to a metastatic primary tumor? We first analyzed cell invasion of primary tumor epithelial cells from a mouse tumor model driven by the Wnt1 oncogene (MMTV-Wnt1) and with reduced IGF-1R signaling by expression of a dominant-negative transgene (MMTV-dnIGF-1R). Epithelial cells from the MMTV-Wnt1/dnIGF-1R (bigenic) tumors invaded at the same rate as MMTV-Wnt1 tumor epithelial cells by tail vein injection suggesting invasive capacity is unchanged with reduced IGF-1R signaling. Interestingly, size of lung micrometastases from tail vein injected bigenic tumor epithelial cells was significantly reduced and the number also decreased over time in part due to a proliferative defect determined by immunostaining for pH3. Similarly, bigenic primary tumor epithelial cells injected into the mammary gland fat pad failed to form tumors suggesting alterations in cell adhesion. Consistent with this observation, E-cadherin gene and protein expression were decreased in the bigenic tumor epithelium compared to MMTV-Wnt1 tumors. In vitro analysis of cell adhesion in MMTV-Wnt1 primary epithelial cells resulted in both K8+ (luminal) and K14+ (basal) tumor epithelial cells adherence, while only K14+ cells from bigenic tumors adhered to collagen. Similarly, the lung micrometastases from tail vein injections exhibited predominantly K14+ cells. Analysis of MMTV-Wnt1 and bigenic primary tumors using single cell RNAseq revealed alterations in both stromal and epithelial populations that may contribute to bigenic primary tumor growth and metastasis. These data support the conclusion that inhibiting IGF-1R signaling results in both alterations to the tumor epithelium (partial EMT) and microenvironment that result in metastasis, but also, that the IGF-1R deficient metastatic cells need a niche or paracine signaling to proliferate.