bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-LB115 Metformin-Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes Mellitus: The Sydney Memory and Ageing Study
Authors: Samaras Katherine , Makkar Steve , Crawford John D , Kochan Nicole A , Wen Wei , Brian Draper , Trollor Julia N , Brodaty Henry , Sachdev Perminder S 
Published: May 2020

Abstract
Background Metformin use in diabetes has been associated with both increased and decreased dementia rates in observational studies of people with diabetes.
Objective: To examine changes in global cognition and specific cognitive domains over 6 years in older adults with diabetes treated with metformin, compared to other glucose lowering medications, and to people without diabetes.
Methods Data were examined from the Sydney Memory and Ageing Study, a prospective observational study of 6 years duration of 1037 non-demented community-dwelling elderly aged 70-90 at baseline, derived from a compulsory electoral roll. Neuropsychological testing was performed every 2 years with domain measures of memory, executive function, language, visuospatial function, attention and processing speed and a composite of global cognition. Data were analysed by linear mixed modelling, including age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking and apolipoprotein E ε4 carriage as covariates.
Results: At baseline, 123 participants had diabetes (DM) with 67 receiving metformin (DM+MF) who were similar in demographics to those not receiving metformin (DM-noMF) and those without diabetes (no-DM). Participants with diabetes had higher BMI, lower HDL- and LDL-cholesterol and more prevalent heart disease, hypertension and smoking, compared to no-DM.
Over 6-years, DM+MF participants had significantly slower rates of decline in global cognition and executive function, compared to DM-noMF, adjusted for covariates. The rate of decline for each cognitive domain was similar between DM+MF and controls. No impact was found in analyses examining interactions with sex, ApoEε4 carriage or hyperlipidemia. No difference was found in the rate of decline in brain volumes between the groups over 2 years.
Incident dementia was significantly higher in DM-noMF, compared to DM+MF (adjusted OR 5.29 [95% CI 1.17-23.88], p,0.05), whereas risk of incident dementia was similar between DM+MF and participants without diabetes.
Conclusions: In older people with diabetes receiving metformin, rates of cognitive decline and dementia were similar to that found in people without diabetes and significantly less than that found in people with diabetes not receiving metformin. Large randomized studies in people with and without diabetes are required to determine whether these associations can be attributed to metformin alone or if other factors explain these observations. Future studies will clarify if this cheap and safe medication can be repurposed for prevention of cognitive decline in older people.
SUN-LB102 Development of a Conceptual Model to Present the Impacts of Obesity on Physical Functioning
Authors: Poon Jiat Ling , Marshall Chris , Johnson Chloe , Pegram Hannah , Hunter Maile , Kan Hongjun , Ahmad Nadia 
Published: May 2020

Abstract
Background. Obesity is a chronic disease with a significant negative impact on health-related quality of life (HRQoL) and specifically, physical functioning, including the ability to complete activities of daily living (ADLs). Weight loss based on lifestyle management (e.g. diet, exercise), surgery, and pharmacotherapy can improve physical functioning; however, there is a need for further qualitative research to support the content validity of patient-reported outcome (PRO) measures for use in clinical studies of obesity and thus inform regulatory decision-making. Objective. To explore the impacts of obesity on physical functioning and develop a conceptual model (a visual representation of the concepts of importance and relevance to the experience of living with obesity) to ultimately support the content validity of PRO measures.Methods. Qualitative semi-structured interviews were conducted in the United States with individuals who have overweight and obesity (Body Mass Index [BMI] ≥ 27.0 kg/m2) with a history of at least one unsuccessful dietary effort to lose body weight. Recruitment quotas targeted a sample with diverse demographic and clinical characteristics, including participants with and without diabetes. Experienced qualitative interviewers used open-ended questions to elicit spontaneous reports of the impact of obesity on individuals’ daily lives, and specific probing questions to explore impacts on physical functioning. Interviews were audio-recorded, transcribed and analyzed using thematic techniques. Results. A total of 33 participants were interviewed (mean BMI of 37.6 kg/m2 [27.4 kg/m2 to 56.6 kg/m2]; mean age of 45 years [19 to 81 years]). The sample included a mix of races (Caucasian: n=12, 36%), education completed (high school: n=17, 51%) and split of gender (female: n=16, 48%). During development of the conceptual model, two separate domains were identified to group the reported impacts on physical functioning: ‘Mobility/Movement’ and ‘ADLs’. The most frequently reported impacts related to Mobility/Movement were ‘running’ (n=31/33, 94%), ‘bending’ (n=27/33, 82%), ‘walking’ (n=26/33, 79%), ‘difficulty standing for prolonged periods’ (n=22/33, 67%), and ‘lifting’ (n=19/33, 58%). All participants reported effects on some aspect of physical functioning, which were often characterized in terms of their direct impact on ADLs such as ‘household chores’ (n=21/33, 64%). Conclusions. The conceptual model will serve as a basis to identify fit-for-purpose PRO measures with strong content validity to evaluate the impact of anti-obesity therapies on physical functioning in future clinical studies. Obesity has a consistent and significant impact on physical functioning, leading to limitations in various aspects of mobility and affecting an individual’s ability to carry out specific daily activities.
MON-LB017 The Effectiveness of Computed Assessment Using GP and TW3 Hybrid System
Authors: Chung Lindsey Yoojin , Lee Kyu-chong , Ahn Kyung-Sik , Lee Jae Jun , Kang Chang Ho , Lee Kee-Hyoung 
Published: May 2020

Abstract
Background: Bone age assessments (BAAs) is an important clinical modality to investigate endocrine, genetic and growth disorders in children. It is generally performed by radiological examination of the left hand by using either the Greulich-Pyle (GP) or the Tanner-Whitehouse (TW) method. However, both clinical procedures show several limitations, from significant intra- and inter-operator variability to examination effort of clinicians. To address these problems, several automated approaches have been proposed; nevertheless, some disparity still exists between automated BAAs and manual BAAs to be employed in clinical practice. To overcome this disparity, deep learning-based bone age assess software using GP and TW3 hybrid method has been developed. In this study, we evaluate the accuracy and efficiency of the new automated hybrid software system for bone age assessment and validate its feasibility in clinical practice. Materials and Methods: Greulich-Pyle (GP) and Tanner-Whitehouse (TW3) hybrid method-based deep-learning technique was used to develop the automated software system for bone age assessment. Total 102 radiographs from children with the chronological age of 4.9-17.0 years (mean age 10.9±2.3, 51 cases for females and 51 cases for males) were selected and bone age was estimated with this software. For validation of the automated software system, three human experts have manually performed BAAs at expert’s discretion based on GP method for accuracy estimation and one naïve radiologist performed BAAs with automated software system assist and BAAs reading time was recorded in each session for efficiency evaluation. The performance of automated software system was assessed by comparing mean absolute difference (MAD) between the system estimates and the experts manual BAAs.Results: The results of bone age assessment by human experts and automated software system showed no significant difference between the two groups. Each assessed average of bone age were 11.39 ± 2.74 and 11.35 ± 2.76, respectively. MAD was 0.39 years between automated software system BAAs and experts manual BAAs. The 95% confidence interval of the MAD was 0.33 years and 0.45 years. BAAs reading time was reduced from 56.81 sec (95% confidence interval 52.81 - 60.81 sec) in naïve manual BAAs to 31.72 sec (95% confidence interval 29.74 - 33.69 sec) in automated software system assisted BAAs and statistically significant (p &lt; 0.001). MAD showed 0.42 years between naïve manual BAAs and the software-assisted BAAs (95% confidence interval 0.31-0.47 years).Conclusion: The newly developed GP and TW3 hybrid automated software system were reliable for bone age assessments with equivalent accuracy to human experts. Also, the automated system appeared to enhance efficiency by reducing reading times without compromising diagnostic accuracy.
SUN-LB58 Repeated Once-Daily Administration of the Non-Hormonal Neurokinin 1,3 Receptor Antagonist NT-814 Reduces LH, Estradiol and Progesterone in Healthy Women
Authors: Dhillo Waljit Singh , Ballantyne Elizabeth , Donaldson Kirsteen , Kerr Mary , Trower Mike , Pawsey Steve 
Published: May 2020

Abstract
Introduction: Uterine fibroids (UF) affect up to 25% of women and endometriosis (EM) 10% of women worldwide. An ideal therapy would lower estradiol concentrations to reduce hormonal drive to the endometrium and myometrium, but not to the levels which cause the hot flashes and bone loss associated with current treatments. A target estradiol range of 110-180 pmol/L has been proposed1. GnRH secretion is modulated by neurokinin B (NKB) acting at the NK3 receptor via hypothalamic neurons expressing kisspeptin, NKB & dynorphin (KNDy neurons). In addition, Substance P acting at the NK1 receptor may also stimulate reproductive hormone release. We hypothesised that NT-814, a dual NK1,3 receptor antagonist, would reduce GnRH release and hence LH, estradiol and progesterone levels in women. This preliminary clinical study in healthy pre-menopausal women evaluated this hypothesis.
Methods: We undertook a randomized, single-blind, placebo-controlled study. 32 healthy women attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3/4, 9/10, 15/16 and 21/22 to measure serum sex hormone concentrations. No treatment was given in cycle 1 (baseline). During cycle 2, participants received placebo or one of three doses of NT-814 once per day; 40mg, 80mg or 120mg (n=8 per group) for up to 21 days.
Results: Compared to placebo, NT-814 reduced LH, estradiol and progesterone concentrations in a dose-related manner. The median changes in average LH (IU/L) during cycle 2 compared to cycle 1 were: placebo, 0.16; 40mg, -0.13; 80mg, -0.46; 120mg, -0.58. Median change in average estradiol (pmol/L) in cycle 2 was: placebo, -16.5; 40mg, -9.3; 80mg, -92.1; 120mg, -141.4. The median changes in progesterone (nmol/L) on day 21/22 in cycle 2 compared to cycle 1 were: placebo, 3.2; 40mg, 8.0; 80mg, -5.7; 120mg, -19.4. The reductions in estradiol and progesterone with 120 mg NT-814 were significant (p=0.038 & p=0.046, respectively). There were no clear changes in FSH concentrations. Of note, in women treated with 120mg NT-814, the average estradiol level reduced from 310.8 pmol/L in cycle 1 to 179.8 pmol/L in cycle 2. Cycle length was extended by at least 6 days in 5 of 8 women receiving the 120 mg dose. NT-814 was well tolerated; no participant experienced hot flashes during treatment.
Conclusions: Once-daily administration of the non-hormonal NK1,3 receptor antagonist NT-814 reduced serum LH, estradiol and progesterone in healthy women in a dose-related manner without causing vasomotor symptoms. The 120 mg dose of NT-814 lowered estradiol levels to potentially ideal levels for UF and EM treatment. These preliminary data support further studies with NT-814 to establish its efficacy and safety in treating patients with these hormone driven disorders.
References: 1Barbieri RL Am J Obstet Gynaecol 1992 166 740-5.
SUN-LB136 A Comparison of Androgen Receptor Splice Variant, AR-V7, and Glucocorticoid Receptor Activity in Prostate Cancer
Authors: Dash Amit K , Paul Basil , Robertson Matthew J , Nagandla Harika , Rajapakshe Kimal Isira , Coarfa Cristian , Weigel Nancy Lynn 
Published: May 2020

Abstract
Prostate Cancer (PCa) is an androgen dependent disease and patients with metastatic PCa are treated with androgen deprivation therapy (ADT). Although most tumors respond initially, tumors become resistant and are termed castration resistant prostate cancer (CRPC). There is compelling evidence that most of these tumors retain androgen receptor (AR) dependence and some data to suggest that, in some cases, the glucocorticoid receptor (GR) substitutes for AR. AR, itself, is re-activated through a variety of mechanisms including the expression of constitutively active AR splice variants that lack the ligand binding domain (LBD) of AR. Expression of one variant, AR-V7, which contains the amino-terminal domain and DNA binding domain of AR and 16 unique amino-acids, has been correlated with resistance to second line ADT. Although there has been some debate regarding the role of AR-V7, whether it is only a partial substitute for AR or has unique activities, our studies of engineered cell lines treated to express levels of AR-V7 equivalent to AR, clearly show that while the AR isoforms have common targets, they each also have unique targets. Consistent with this, the cistromes of the two show many unique sites as well as common sites. AR-V7 binding is enriched near the transcription start site (TSS) and we have identified a novel de novo binding motif. These findings suggest the possibility of developing a gene signature unique to AR-V7.Because GR activity in PCa has also been suggested as an escape mechanism in response to ADT, and GR binds to the same consensus response elements, we sought to identify a GR signature in PCa, to compare it with the AR and AR-V7 signatures, and to ask whether the AR-V7 and/or GR signatures are enriched in CRPC. Because much of the gene signatures are cell line dependent, we sought to compare GR and AR-V7 action in cells that express both. LN-95 cells express both AR-V7 and GR. MDA-PCa-2b cells, a cell line derived from an African American patient, expresses GR, but not AR-V7. The parental line was infected with a lentivirus that expresses AR-V7 in response to doxycycline. Transcriptomes were determined for AR, GR, and AR-V7 in these lines using RNA-Seq. Overall the magnitude of regulation of gene expression was generally lower than in the LNCaP AR-V7 and VCaP-AR-V7 lines, but there was good overlap of the MDA-PCa-2b AR-V7 regulated with the LNCaP AR-V7 regulated genes. Genes induced by GR overlapped with AR and isoform common genes, but did not overlap with AR-V7 specific genes. A comparison of AR-V7 specific genes common to the LNCaP and VCaP models as well as to publicly available data sets for LN-95 and 22RV1 AR-V7 signatures, show a strong correlation with CRPC compared to primary tumors when analyzed in the Grasso data set.
SAT-LB113 Psychosocial Benefits of Using Basal-IQ® Predictive Low Glucose Suspend Technology in a Real-World Setting: Results From Pediatric Patients With Type 1 Diabetes
Authors: Singh Harsimran , Manning Michelle , McElwee-Malloy Molly , Habif Steph 
Published: May 2020

Abstract
Recent literature has highlighted remarkable clinical benefits of the Basal-IQ PredictiveLow Glucose Suspend (PLGS) technology for both pediatric and adult patients with type 1diabetes (PwT1D). Although less frequently acknowledged in the literature, psychosocial benefits and other patient-reported outcomes (PROs) related to this technology, are critical to its sustained and satisfactory use. For purposes of this study, we analyzed pediatric PwT1Ds (n=123) who had recently started using the t:slim X2 insulin pump with Basal-IQ technology (Tandem Diabetes Care). These pediatric users were part of a larger recruited sample that also included adults with T1D (not described here). Amongst other clinical and demographic measures, pediatric PwT1Ds completed the Diabetes Impact and Device Satisfaction (DIDS) scale at baseline and then again at 6 months post-assessment(PA). The DIDS is a brief, reliable, and validated measure to ascertain device-specific satisfaction as well as impact of diabetes management in PwT1D. Pre-Post differences on DIDS were analyzed using repeated measures analysis of variance. Mean age of the pediatric sample was 12.25 years, female=45%, mean HbA1c=7.62%. At baseline, 91%used CGM, 27% used multiple daily injections, and 73% used insulin pumps as their therapy method. Parents/caregivers completed the DIDS on behalf of their child in most cases (92%). At PA, pediatric PwT1Ds, demonstrated significant changes on both subscales of the DIDS. Significant improvements were observed for device-related satisfaction (DS) (p&lt;.001) whereas significant reduction was noted for diabetes-related impact (DI) (p&lt;.01) indicating reduced burden of diabetes on daily life. These findings were noted regardless of patients’ baseline insulin delivery methods (MDI or insulin pump). For DS, at PA, patients reported the most improvement on items relating to“satisfaction with insulin delivery device” (29% increase, p&lt;.001) and “hassle to use” (58%decrease, p&lt;.001). For DI, items indicating the most reduction of diabetes impact were“worry about going low” (36% decrease, p&lt;.001) and “wake up at night to treat low BG”(27% decrease, p&lt;.001). These findings highlighted robust real-world evidence for psychosocial benefits of Basal-IQ technology for pediatric patients and their parents/caregivers. Using psychosocial PROs while evaluating medical devices and technologies is critical as they improve our understanding of patients’ experiences with these systems and their impact on quality of life. These aspects may not always be reflected in patients’ clinical outcomes but are essential for determining long term use and acceptance of new treatments and management regimens.
SAT-LB67 Pseudohypoparathyroidism 1B Presenting in a Woman Aborting With Multiple Cerebral Calcifications
Authors: Garate Dioni , Villarreal Adriana , Chiu Erika , Salsavilca Elizabeth 
Published: May 2020

Abstract
Background. Pseudohypoparathyroidism is a heterogeneous condition characterized by hypocalcaemia and hyperphosphatemia as a result of the resistance of the target organ to parathyroid hormone (PTH) 1. It is classified into several different entities (1A, 1B, 1C AND 2) according to molecular and clinical causes. PHP1B has resistance to PTH, normal levels of Gsα activity and has no clear signs of hereditary Albright osteodystrophy (AHO) or other hormonal resistance. 2 Clinical case. A 26-year-old woman was admitted to the emergency service due to an abortion and severe hypocalcemia. Background: generalized tonic-clonic seizures and hypocalcemia for nine years without treatment. The physical exam showed Chvostek and Trousseau, and round face. Its height is 148 cm, weight 60 kg, BMI of 27 kg/m2, without clinical features of AHO. Analytics reported Calcium 4.6 mg / dl (8.5-10.5), βHCG 1795 mIU / ml (&lt;10), PTH 206 pg / ml (15-65), phosphorus 7.35 mg / dl (2.5-4.9) Creatinine 0.57 mg / dl, magnesium 2.02 mg / dl, 25-OH-D3 29ng/ml (&gt;30), TSH 4.2uUI /ml (0.27-4.20), Hb 10.6 mg/dl. A brain CT scan showed calcifications in the basal ganglia (thick annular), subcortical area (crescent) and cerebellar hemispheres. Renal and thyroid ultrasound without alterations. Radiographs of four limbs and skull found no radiological signs of AHO. Ophthalmologic evaluation revealed bilateral cataract.During hospitalization she underwent curettage, was treated with calcium gluconate, then calcium and calcitriol supplements. At follow-up, serum and urine calcium levels were monitored for optimal treatment. Conclusions. We report a patient with typical biochemical findings of PHP and in the absence of AHO it would be classified as 1B. The importance of early recognition and a mandatory multidisciplinary approach offer a better prognosis avoiding extensive brain calcifications, seizures and obstetric complications. The long-term treatment of hypocalcemia associated with resistance to PTH is similar but generally more aggressive than that of primary hypoparathyroidism. 1. Linglart A, Levine M, Juppner H. Pseudohypoparathyroidism. Endocrinol Metab Clin North Am 2018; 47: 865-888. 2. Mantovani G, Bastepe M, et al. Diagnosis and treatment of pseudohypoparathyroidism and related disorders: first declaration of international consensus. Nat Rev Endocrinol. 2018; 14 (8): 476-500.
SUN-LB85 Short-Term Outcomes of Radiofrequency Ablation of a Toxic and a Non-Toxic Benign Thyroid Nodule
Authors: Segkos Konstantinos , Gkeli Myrsini G 
Published: May 2020

Abstract
Background: Radiofrequency ablation (RFA) of benign thyroid nodules has been shown to be a safe and effective minimally invasive treatment for benign thyroid nodules, based on many years of international experience. Thyroid specific devices have recently become available in the US. Here, we present representative examples of our early experience with RFA for both non-toxic and toxic thyroid nodules in our outpatient center.
Clinical Cases: Case 1: A 39 year-old woman presented with subclinical hyperthyroidism, with a TSH of 0.013 uIU/mL (0.45-4.5 uIU/mL). Evaluation showed bilateral autonomously functioning thyroid nodules. Both nodules were predominantly solid with no suspicious features and grade 3 Doppler flow, and were benign (Bethesda II) on UG-FNA. She declined treatment with total thyroidectomy, radioactive iodine, or long-term thionamides, and decided to proceed with RFA, after pre-treatment with methimazole. We decided to target the right lobe nodule first, as it was larger, with a volume of 2.63 ml. The danger triange and vagus nerve were identified, and then we injected local anesthetic using the pericapsular lidocaine technique. We then performed ultrasound-guided RFA of this nodule, using an RF generator with an internally cooled 18-gauge electrode, with a length of 7 cm and an active tip of 7 mm. Power was set at 25 Watts. The trans-isthmic approach and moving shot technique were used. Total energy delivery was 3078 WS. At the end of the procedure, we visualized a transient hyperechoic zone and there was absence of Doppler flow throughout the nodule. She tolerated the procedure well without complications. Methimazole was stopped after the procedure. At the 3-month follow-up, the nodule had decreased in volume by 72.5% and had no internal Doppler flow; TSH normalized (1.37 uIU/mL), so we decided not to proceed with RFA of the left superior toxic adenoma. Case 2: A 49 year-old woman presented with a large right lobe thyroid nodule with a volume of 6.13 ml, which was causing dysphagia and dysphonia. It was predominantly solid with no suspicious features and grade 3 Doppler flow. TSH was normal. It was benign (Bethesda II) on UG-FNA on 2 occasions. She declined surgical therapy, and decided to proceed with RFA. We performed local anesthesia and then RFA in a similar fashion to case 1, with a power of 20-40 Watts. Total energy delivery was 11,491 WS. There were no complications. At the 3-month follow-up, TSH remained normal, and the volume of the ablated nodule had decreased by 59.9%. There was no intranodular Doppler flow. Her compressive symptoms completely resolved.
Conclusion: These cases are representative of our early experience with thyroid RFA in the USA, and showcase its safety, efficacy and feasibility in the outpatient setting, for patients with toxic or non-toxic symptomatic thyroid nodules.