bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-631 Quality of Life in a Pragmatic Trial of a Type 1 Diabetes Adolescent Transition Program
Authors: Leung Joseph M W S , Al-Yahyawi Naseem Y , Choi Heywood S , Stewart Laura L , Tang Tricia S , Amed Shazhan 
Published: May 2020

Abstract
Introduction: Adolescents with type 1 diabetes (T1D) experience ongoing deterioration in their glycemic control as they transition to young adulthood.1 Several trials have evaluated possible transition interventions to ameliorate the care gap between pediatric and adult services in T1D care, although it remains unclear which are the most appropriate.2,3 In this pragmatic study, we sought to determine whether the change in quality of life pre- and post-transition was different between adolescents with T1D accessing a transition program versus those who did not.
Methods: Between 2016-2018, we recruited 68 adolescents with T1D at their last pediatric diabetes clinic visit from a tertiary diabetes center without a structured transition program (control group) and 33 from a community-based outreach clinic with a transition program (intervention group) consisting of a transition coordinator, joint transition clinics, and pediatric and adult clinics located in the same building. At the time of transition and at one-year post-transition, we conducted chart reviews and administered surveys, including the SF-8 quality of life questionnaire. Analysis included descriptive statistics and linear regression models.
Results: The control and intervention groups had the following characteristics, respectively: age at transition 18.4 years vs. 20.5 years (p&lt;0.001); female 47% vs. 55% (p=0.49); average A1C at the time of transition 8.2% vs. 9.1% (p=0.0053). There was no statistically significant difference in the change in SF-8 scores for each of the eight domains (general health, physical functioning, role physical, bodily pain, vitality, social functioning, mental health, and role emotional) between the two groups. However, older age at transition was associated with an improvement in SF-8 vitality domain scores between the pre- and post-transition timepoints (p=0.034). Female sex was associated with a worsening in SF-8 vitality domain (p=0.004) and social functioning domain (p=0.015) scores between the pre- and post-transition timepoints. Finally, higher average A1C in the year prior to transition was associated with a worsening in SF-8 role physical domain scores between the pre- and post-transition timepoints (p=0.002).
Conclusions: Quality of life scores in the vitality domain improved in the first year post-transition amongst young adults with T1D who transitioned at an older age, suggesting that a later transition may benefit adolescents with T1D. Additionally, worsening quality of life scores amongst young women and in those with higher pre-transition A1Cs suggest that these populations may require more specialized care at the time of transition.
References: 1. Foster et al. Diabetes Technol Ther. 2019;21(2):66-72.
2. White et al. Lancet Child Adolesc Health. 2017;1(4):274-83.
3. Spaic et al. Diabetes Care. 2019;42(6):1018-26.
OR13-02 Treatment with Zoledronic Acid Subsequent to Denosumab Cannot Fully Prevent Bone Loss
Authors: Sølling Anne Sophie K , Harsløf Torben , Langdahl Bente Lomholt 
Published: May 2020

Abstract
Purpose: Treatment with denosumab (DMAB) decreases bone resorption and fracture risk. Following discontinuation, bone resorption increases, bone mass is lost and fractures have been reported. The aim of the study was to investigate if an infusion of zoledronic acid (ZOL) can prevent increases in bone turnover and bone loss in patients previously treated with DMAB and if the timing of the ZOL infusion is important. Methods: The study was a 2-year randomized, open label, interventional study in patients with osteopenia after DMAB treatment for an average of 4.6 years. ZOL was administrated 6 months (6M group, n=20) or 9 months (9M group, n=20) after the last DMAB injection or when bone turnover was increased (OBS group, n=20). Patients in the OBS and the 9M groups were monitored closely and if p-carboxy-terminal collagen crosslinks (CTX) increased &gt; 1.26 ug/l (50% above the range for postmenopausal women and elderly men), if BMD decreased &gt; 5% at the lumbar spine or total hip, or if a patient suffered a low energy vertebral or hip fracture, ZOL was administered. In the OBS group, ZOL was administered no later than month 6. The patients were monitored with DXA 6, 12 and 24 months after treatment. ZOL was re-administered if BMD decreased &gt; 5% at the lumbar spine or total hip or if CTX increased above 1.26 ug/l. We report the outcome 12 months after the initial ZOL infusion. The study is ongoing. Results: A total of 60 postmenopausal women and men with a mean age of 67.7 (range 51-85) years were enrolled in the study. In the OBS group 1, 2, 6, 1 and 0 patients fulfilled the CTX or BMD criteria for treatment 1, 2, 3, 4 and 5 months after baseline. The remaining 10 patients were treated at month 6. In the 9M group 2 patients fulfilled the CTX criteria for ZOL treatment at month 2. A total of 10, 5 and 5 patients in the 6M, 9M and OBS groups, respectively were re-retreated. In the 6M group CTX decreased initially, but increased rapidly thereafter, and 6 months after ZOL, CTX was 0.60±0.08 g/L (mean±SEM). CTX increased rapidly in the 9M and OBS Groups before ZOL, was suppressed by ZOL but increased again thereafter; CTX was 0.47±0.05 μg/L and 0.47±0.05 μg/L 6 months after ZOL in the 9M and the OBS groups, respectively. Mean CTX was within the premenopausal reference range 12 months after ZOL in all 3 groups. From study baseline to twelve months after ZOL BMD at the lumbar spine had decreased by 4.8±0.7%, 4.1±1.1%, and 4.7±1.2% in the 6M, 9M and OBS groups, respectively (p≤0.002 for all without differences between groups) and at the total hip by 2.6±0.5%, 3.2±0.8%, and 3.6±0.8% in the 6M, 9M and OBS groups, respectively (p≤0.001 for all without differences between groups). The decline in BMD was more pronounced in the months before ZOL in the 9M and OBS groups whereas the decline was steadier in the 6M group. Conclusion: Treatment with ZOL irrespective of the timing did not fully prevent loss of BMD in patients with osteopenia.
SUN-021 Age-Specific Multiples of the Median Level of Serum Anti-Mullerian Hormone Is a Potential Marker for Diagnosis of Polycystic Ovary Syndrome
Authors: Raymond Li Hang Wun , He Yi-Lei , Li Rong , Wong Ching Yin Grace , Sy Barre , Lam Ching Wan , S L Lam Karen , Peng Hong Mei , Mu Sha , Schooling Mary , Yeung William Shu Biu , Ho Pak Chung , Ng Ernest Hung Yu 
Published: May 2020

Abstract
Serum anti-Mullerian hormone (AMH) levels are significantly higher in women with polycystic ovary syndrome (PCOS) than in normal ovulatory women. Different diagnostic cut-off values of AMH for discriminating women with PCOS from normal controls have been proposed. This is attributed partly to the different assay methods used with different calibration, as well as the age-related changes in serum AMH levels. We propose that it may be more appropriate to use age-specific multiples of the median (MoM) of AMH value instead of a “one for all ages” cut-off as a diagnostic threshold. Hence, we conducted a retrospective study to validate the performance of age-specific MoM of AMH value in the diagnosis of PCOS. We studied on a cohort of 751 women presented to the clinic for menstrual disorders or fertility treatment, including 473 women diagnosed with polycystic ovary syndrome by the Rotterdam criteria and 278 normal ovulatory controls. Their archived serum samples, collected at the early follicular phase, were retrieved and assayed for AMH by the automated Access AMH assay. The MOM AMH of each subject was calculated based on the age-specific reference ranges recently established by our group. Our results showed that MOM AMH was significantly higher in women with PCOS compared to controls (p&lt;0.0001). When stratified into five-yearly age groups, there was no significant difference in MOM AMH (p&gt;0.05) among women with PCOS aged 21-25, 26-30 and 31-35 years, but those aged 36-40 years had significantly higher MOM AMH (p&lt;0.05) compared to the other younger age groups. Among the ovulatory controls, no significant difference was observed in MOM AMH among all the age groups (p&gt;0.05). The area under the receiver-operator characteristic curve was 0.852 (95% CI 0.825-0.877) (p&lt;0.0001) for discriminating women with PCOS from ovulatory controls by MOM AMH. The best cut-off value of MOM AMH was 1.44, and the corresponding sensitivity and specificity were 76% and 79% respectively. At the fixed specificity of 80% and the corresponding sensitivity of 73% (with positive and negative likelihood ratios of 3.8 and 0.33 respectively), the cut-off value of MOM AMH was 1.5. In conclusion, age-specific MOM AMH is a promising surrogate of antral follicle count in the diagnosis of PCOS.
MON-024 Steroid Cell Tumor, Not Otherwise Specified; A Rare Case of Hyperandrogenism
Authors: folawewo kehinde Matilda , Shanaz Fazeena , Hodge MaKenzie , Osman Nada , Zenebe Anteneh Woldetensay , Ganta Vijaya A , Odonkor Wolali Akua-Sabia , Nunlee-Bland Gail Louise 
Published: May 2020

Abstract
BACKGROUND:
Steroid cell tumor is a rare sex cord stromal tumor. There are 3 types including steroid cell tumor not otherwise specified (NOS), stromal luteoma and leydig cell tumors.
Steroid cell tumor (NOS) is the most common of all the subtypes. About 75% of the steroid cell tumor (NOS) are secretory. They can secrete androgens and estrogens. In a few cases, cortisol and renin secretion have been reported. The patient’s clinical features depend on the hormone secreted.
CASE PRESENTATION
Here, we report a case of a 22-year-old woman who was seen at an outpatient clinic for hirsutism, irregular menstrual bleeding, and progressive weight gain. Examination revealed androgenic facial hair growth, clitoromegaly and obesity.
Initial differentials on presentation were PCOS, ovarian or adrenal pathology. Initial LH, FSH values were normal. Lab investigation showed elevated testosterone, DHEAS and 17-OH progesterone levels. Baseline labs showed Androstenedione of 3345 ng/dl (41-262 ng/dl), DHEAS of 595.5 ug/dl (110- 431.7 ug/dl), 17-OH progesterone was 2394 ng/dl (follicular: 15-70 ng/dl, Luteal: 35-290 ng/dl), total and free testosterone was 558 ng/dl (premenopausal; 10-55ng/dl) and 33.0 pg/ml, (0.8-1.4pg/ml), respectively. Patient subsequently had an ACTH stimulation test which showed an increase in 17-OH progesterone from 384 ng/dl to 657 ng/dl and a repeat showed an elevation from 204 to 322 ng/dl, ruling out a late onset CAH. She was then sent for pelvic sonogram which showed the presence of a left ovarian mass 4.9x 4.8x 4.8 cm and a pelvic CT scan confirmed a left ovarian mass measuring 6.8x5.5x 5.5 cm and an unremarkable right ovary. She underwent a laparoscopic unilateral salpino-oophorectomy and histology confirmed the diagnosis of an ovarian steroid cell tumor (NOS). Post-surgery, the androgen levels returned to normal. The patient is now being followed for recurrence.
CONCLUSION
Women who present with virilism should be evaluated adequately with comprehensive history taking and physical examination along with appropriate biochemical tests and imaging studies to confirm tumor location and plan for surgery.
MON-719 The Cellular and Molecular Landscape of Hypothalamic Patterning and Differentiation
Authors: Kim Thomas 
Published: May 2020

Abstract
The hypothalamus is a central regulator of physiological homeostasis. During development, multiple transcription factors coordinate the patterning and specification of hypothalamic nuclei. However, the molecular mechanisms controlling hypothalamic patterning and cell fate specification are poorly understood. To identify genes that control these processes, we have used single-cell RNA sequencing (scRNA-Seq) to profile mouse hypothalamic gene expression across multiple developmental time points. We have further utilised scRNA-Seq to phenotype mutations in genes that play major roles in early hypothalamic patterning. To first understand hypothalamic development, hypothalami were collected at both embryonic (E10-E16, E18) and postnatal (PN4, PN8, PN14, PN45) time points. At early stages, when the bulk of hypothalamic patterning occurs (E11-E13), we observe a clear separation between mitotic progenitors and postmitotic neural precursor cells. We likewise observed clean segregation among cells expressing regional hypothalamic markers identified in previous large-scale analysis of hypothalamic development. This analysis reveals new region-specific markers and identifies candidate genes for selectively regulating patterning and cell fate specification in individual hypothalamic regions. With our rich dataset of developing mouse hypothalamus, we integrated our dataset with the Allen Brain Atlas in situ data, publicly available adult hypothalamic scRNA-Seq dataset to understand hierarchy of hypothalamic cell differentiation, as well as re-defining cell types of the hypothalamus.
We next used scRNA-Seq to phenotype multiple mutant lines, including a line that has been extensively characterised as a proof of concept (Ctnnb1 overexpression), and lines that have not been characterised (Nkx2.1, Nkx2.2, Dlx1/2 deletion). We show that this approach can rapidly and comprehensively characterize mutants that have altered hypothalamic patterning, and in doing so, have identified multiple genes that simultaneously repress posterior hypothalamic identity while promoting prethalamic identity. This result supports a modified columnar model of organization for the diencephalon, where prethalamus and hypothalamus are situated in adjacent dorsal and ventral domains of the anterior diencephalon. These data serve as a resource for further studies of hypothalamic development and dysfunction, and able to delineate transcriptional regulatory networks of hypothalamic formation.
Lastly, using our mouse hypothalamus as a guideline, we are comparing dataset of developing chicken, zebrafish and human hypothalamus, to identify evolutionarily conserved and divergent region-specific gene regulatory networks. We aim to use this knowledge and information of key molecular pathways of human hypothalamic development and produce human hypothalamus organoids.
MON-707 Improving Screening for Diabetic Retinopathy in a Resident Based Clinic
Authors: Tofil Kathrin Sandra , Jayawardena Nishanie , Khan Noor , Escobar Francisco Bonilla 
Published: May 2020

Abstract
Introduction Diabetic retinopathy is the leading cause of blindness in US Adults. In order to improve screening rates, we partnered with the Division of Ophthalmology and installed an onsite retinal camera at our primary care clinic. This led to an improvement in EMR reported screening rates from 20.5% to 44% over the first 3 months. We noticed that any fundus photo, whether gradable or not, led to an automatic annotation in EMR (EPIC) health Maintenance that screening had been completed. Abnormal or ungradable (quality too poor to interpret) retinal photos must be followed up with a complete ophthalmologic evaluation. We designed a chart audit to investigate further whether ungradable retinal photos were being followed up appropriately. Methods A retinal camera was installed in the clinic, and patients obtained DR screening during their routine visits from May through October 2018. The nursing staff received training on using the camera and ensuring image quality. These images were then sent to an Ophthalmologist and resulted within the work week. Patients with an abnormal or poor-quality retinal photo were contacted by their resident PCP. We did a retrospective chart review of patients with ungradable photos evaluating whether patients were contacted and whether they followed up with Ophthalmology in the 3 month period after the initial intervention. Results Of the 131 patients who received fundus photos in the study period, 29 (22%) had ungradable photos. Twenty-four of these patients were contacted and ophthalmology consults were placed for 22 patients. Eleven (38%) of these patients went on to complete screening with Ophthalmology within 3 months of the ungradable photo. Eighteen patients, or 62% of ungradeable photos, remained incorrectly identified as having completed retinopathy screening by EMR. Discussion Over reliance on EMR reporting features can lead to incorrect assumptions about DR screening. Based on this analysis, we need to design better interventions for following up on ungradable photos and ensuring appropriate follow up. One such intervention may be changing how EMR reports ungradable photos. EPIC is a widely used EMR in outpatient settings and other practices may be facing similar issues.
OR01-05 Long-Term Efficacy of T3 Analogue Triac in MCT8 Deficiency
Authors: Geest Ferdy S van , Groeneweg Stefan , Toor Hans van , Wal Ronald van der , Waart Monique de , van den Berg Sjoerd Adrianus Antonius , Peeters Robin Patrick , Visser W Edward 
Published: May 2020

Abstract
Background: MCT8 deficiency is a severe disorder caused by mutations in the thyroid hormone transporter MCT8. MCT8 deficiency is characterized by severe intellectual and motor disability and high serum T3 concentrations that result in thyrotoxic symptoms in peripheral tissues. This predisposes to substantial morbidity and mortality. Preclinical studies showed that the T3 analogue Triac can bypass defective MCT8 at the cellular level. Recently, we reported the results of an international multicenter trial, in which biochemical and clinical outcomes improved in patients with MCT8 deficiency who were treated with Triac for 12 months (1). However, long-term follow-up data of patients with MCT8 deficiency treated with Triac are lacking, particularly in young children. Therefore, we aimed to investigate the long-term efficacy of Triac therapy in a worldwide cohort of patients with MCT8 deficiency.
Methods: We investigated the efficacy of oral Triac treatment in pediatric (n=78) and adult (n=5) patients with MCT8 deficiency in 20 countries. Triac dose was titrated according a predefined dose-escalation scheme aiming to normalize serum T3 concentrations (target 1.4-2.5 nmol/L). Thyroid function tests and biochemical markers of thyroid hormone action in peripheral tissues (SHBG, creatine kinase, creatinine) were measured at baseline and during control visits.
Findings: In total, 83 patients with a median baseline age of 5 years (range 6 months – 66 years) were treated, including 24 patients aged 0-2.5 years and 17 patients aged 2.5-5 years. They were treated with Triac during 144 patient years, of whom the follow-up time was &gt;5 years in 9 patients and 2-5 years in 22 patients. Mean dose was 45 µg/kg/day (range 11-107 µg/kg/day). Once a stable dose was achieved, no further dose adjustments were needed.
Mean serum T3 concentrations decreased from 5.02 to 1.94 nmol/L (normal 1.4 – 2.5 nmol/L). SHBG concentrations improved from 238 to 204 nmol/L (normal 40-140 nmol/L). Mean creatine kinase and creatinine concentrations improved from 113 to 140 U/L (normal &lt;230 U/L) and from 32 to 38 µmol/L (normal 31-68 μmol/L), respectively. No drug-related severe adverse events were reported.
Interpretation: Triac is a safe treatment that results in sustainable improvements of the severe thyrotoxic state in pediatric and adult patients with MCT8 deficiency.
References: 1. Groeneweg S, Peeters RP, Moran C, Stoupa A, Auriol F, Tonduti D, et al. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(9):695-706.
MON-488 Technologies of Diffuse Optics in the Diagnosis of Thyroid Cancer
Authors: Velazquez Gloria Beatriz Aranda , Presti Giuseppe Lo , Cortese Lorenzo , Contini Davide , Mora Alberto Dalla , Halperin Irene , Hanzu Felicia Alexandra , Pifferi Antonio , Squarcia Mattia , Tosi Alberto , Durduran Turgut , Porta Mireia Mora 
Published: May 2020

Abstract
BACKGROUND:
The most common tool to test malignancy in the study of thyroid nodules (NT) is ultrasound and fine needle aspiration biopsy (FNAB). However, the sensitivity and specificity of the method and the effectiveness in thyroid cancer are limited; therefore new methods to study thyroid nodules are required. In this way our goal is to introduce hybrid diffuse optical instruments that are capable to measure and discriminate altered microvascular blood flow, blood volume and tissue scattering coefficients of TN. Near-infrared diffuse optical technologies aim to overcome the shortcomings of present techniques while screening for malignant thyroid nodules for early and fast diagnosis of cancer. This idea was based on the previous experience in breast cancers with diffuse optical techniques.
METHODS:
We have developed a device based on near-infrared diffuse correlation spectroscopy (DCS), which is a technology aimed at retrieving the microvascular flow of a certain region of tissue by mean of low power near-infrared laser light, and used in combination with a commercial ultrasound system (US). In order to combine these devices, we have developed a probe enabling multimodal data acquisition and subsequently we have analyzed the optical properties and the blood flow index in the thyroid lobes of eleven subjects who presented a thyroid nodule.
RESULTS:
Four subjects have required FNAB: P4 and P7 were reported as being malignant (Bethesda VI and IV respectively) while P6 and P8 were evaluated as being benign (Bethesda II). Surgical removal confirmed papillary thyroid carcinoma in P4, while denied the result of FNAB for P7 (Multinodular thyroid hyperplasia). We have considered the contralateral lobe as intra-subject reference to validate the feasibility of the DCS system in a very absorbing tissue as thyroid is. The difference between the blood flow index of the nodule and the contralateral lobe is maximum for subject P4, while the difference in benign subjects is lower. T-test showed no significant difference between benign nodules and contralateral lobes. Subject P7 showed a small difference as for other benign subjects despite the FNAB results indicating presence of malignancy.
CONCLUSION:
Apparently diffuse optics technologies would be able to differentiate malignant thyroid nodules from benign thyroid nodules, but more measurements require confirming our preliminary results as that diffuse optical technology can complement the current techniques such as US and FNAB.
A new measurement campaign is being scheduled with a completed, fully integrated device that was developed within the LUCA project (http://www.luca-project.eu).