bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU581 Possible Markers For Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I
Authors: Yamamoto Yukichika , Otsuka Yuki , Tokumasu Kazuki , Sunada Naruhiko , Nakano Yasuhiro , Honda Hiroyuki , Sakurada Yasue , Hasegawa Toru , Hagiya Hideharu , Otsuka Fumio 
Published: October 2023

Abstract
Disclosure: Y. Yamamoto: None. Y. Otsuka: None. K. Tokumasu: None. N. Sunada: None. Y. Nakano: None. H. Honda: None. Y. Sakurada: None. T. Hasegawa: None. H. Hagiya: None. F. Otsuka: None.
Almost three years have passed since coronavirus disease 2019 (COVID-19) pandemic broke out, and along with the number of acute COVID-19 patients, the number of patients suffering from chronic prolonged symptoms after COVID-19, long COVID, or post COVID-19 condition, has also increased. We establised an outpatient clinic specialized for COVID-19 after care (CAC) in Okayama University Hospital in Japan in February 2021. Our recent study has revealed that the most common symptom is “fatigue”, a part of which potentially may develop into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, the pathogenesis and specific prognosticator have yet to be elucidated. The aim of this study was to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. This retrospective observational study investigated the patients who visited our CAC outpatient clinic between February 2021 and March 2022. Of the 234 patients, 139 (59.4%) had fatigue symptoms, of whom 50 (21.4%) met the criteria for ME/CFS (ME/CFS group), while other 89 did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients’ backgrounds were not significantly different among the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and Self-Rating Depression Scale (SDS). Of note, serum ferritin levels, which were correlated to FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/mL; interquartile range (IQR), 58.8-353.8) than those of non-ME/CFS (98.2 μg/mL; 40.4-251.5) and no-fatigue (86.7 μg/mL; 37.5-209.0) groups, and this trend was prominent in the female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in the serum, and that insulin-like growth factor (IGF)-I levels were inversely correlated with ferritin levels (R = -0.328, p &lt; 0.05). Collectively, we revealed that serum ferritin levels could be a possible predictor for developing ME/CFS related to long COVID, especially in female patients. Earlier studies have suggested that hyperferritinemia is a clinical feature in the patients of long COVID, in which hepcidin-like effects could also be involved. Our present study also uncovered a relationship between hyperferrinemia and endocrine disorders among patients developing ME/CFS after COVID-19, although further investigations are necessary to understand the characteristics of ferritin metabolism.
Presentation: Thursday, June 15, 2023
OR0302 Regulation Of Human Melanocortin-5 Receptor By Isoforms Of Melanocortin-2 Receptor Accessory Proteins
Authors: Jiang Shanshan , Tao Ya-Xiong 
Published: October 2023

Abstract
Disclosure: S. Jiang: None. Y. Tao: None.
Melanocortin-5 receptor (MC5R) is ubiquitously expressed in central nervous system and peripheral tissues, has unique pharmacological properties, and physiological functions. Melanocortin-2 receptor accessory proteins (MRAPs) are regulators of melanocortin receptor family. To investigate the effects of MRAPs on trafficking, ligand binding and signaling properties of human (h) MC5R, HEK293T cells were transiently co-transfected with plasmids encoding MC5R and different isoforms of MRAPs (hMRAP1a, hMRAP1b, hMRAP2a, hMRAP2b, and hMRAP2c). The results showed that hMRAP1a and hMRAP2a increased the cell surface expression of hMC5R. All MRAPs have no effect on affinity to the superpotent analog of α-melanocyte stimulating hormone (α-MSH), NDP-MSH, while hMRAP2c significantly increased maximal binding. Additionally, α-MSH induced ERK1/2 activation. A higher basal level of ERK1/2 phosphorylation was observed when co-transfected with some MRAPs. All MRAPs had no effect on α-MSH-stimulated cAMP production (Gs-cAMP pathway). In summary, the two MRAP1s and three MRAP2s had differential effects on MC5R trafficking, binding, and signaling. These findings led to a better understanding of the regulation of MC5R by MRAP1s and MRAP2s.
Presentation: Thursday, June 15, 2023
SAT025 Characterization Of The Melatonin Type 1 Receptor / Cannabinoid Type 1 Receptor (MT1/CB1) Heteromers
Authors: Cui Yuanxu , Cherdoud Hakima , Marsicano Giovanni , Bellocchio Luigi , Jockers Ralf , Lahuna Olivier 
Published: October 2023

Abstract
Disclosure: Y. Cui: None. H. Cherdoud: None. G. Marsicano: None. L. Bellocchio: None. R. Jockers: None. O. Lahuna: None.
Membrane receptors belonging to the G proteins coupled receptors (GPCRs), the largest family of proteins in the human genome with more than 800 members. GPCR functions were initially thought to take place at the plasma membrane upon binding of single monomeric receptor unit by their cognate ligand. This scheme was complexified after identification of cross-talks between GPCRs upon heteromerization and identification of functional GPCRs within intracellular organelles as nucleus or endosomes. Among a few others receptors, functional melatonin receptor type 1 (MT1) and cannabinoid receptor type 1 (CB1) were found in neuronal mitochondria, suggesting a cross-talk between them. Here, we are identifying and characterizing MT1/CB1 heteromers as a new GPCR heteromer. Previously we showed that coexpression of the MT1 and CB1 receptors induced the constitutive formation of MT1/CB1 heteromers using coimmunoprecipitation experiments on transiently transfected HEK293 cells. Using simultaneous PLA (Proximity Ligation Assay) and immunofluorescence experiments, we described the existence of intracellular MT1/CB1 heteromers associated with the mitochondrial network. Since then, we have further characterized the properties of MT1/CB1 heteromers. Coimmunoprecipitation experiments performed on cerebellum from wild-type, MT1 or CB1 knock-out mice enabled us to identify MT1/CB1 heteromers in vivo. We established stable monoclonal HEK293 cell lines expressing both receptors. Transmission Electronic Microscopy (TEM) and PLA experiments showed the presence of MT1/CB1 complexes not only intracellularly but also at the cell surface. Using PLA experiments we identified a penetrating interfering peptide that specifically dissociate the MT1/CB1 complex and thus open the door to experiments targeting specifically the complex. We were able to follow the melatonin-dependent internalization and trafficking of the MT1/CB1 complex from the plasma membrane to the late endosomes using a combination of Nanoluciferase complementation experiments and bystander BRET (Bioluminescence Resonance Energy Transfer). Costimulation of HE293 cells expressing both receptors with melatonin and the selective CB1 agonist ACEA (Arachidonyl-2'-chloroethylamide), a derivative of the endocannabinoid AEA (Arachidonylethanolamide or anandamide) resulted in a potentiation of the melatonin-dependent cAMP inhibition. Use of the identified interfering peptide will enable us to identify actions on signaling pathways resulting from a direct cross-talk between MT1 or CB1 subunits.
Presentation: Saturday, June 17, 2023
THU138 The Association Between Irisin And Anthropometric And Metabolic Parameters In Obese Children And Adolescents
Authors: Kim Sung Eun , Kim Shin-Hee , Park Su Jin , Sim Soo Yeun , Kim Seulki , Ahn Moon Bae , Won-kyoung Cho , Soon Cho Kyoung , Jung Min-Ho , Suh Byung-Kyu 
Published: October 2023

Abstract
Disclosure: S. Kim: None. S. Kim: None. S. Park: None. S. Sim: None. S. Kim: None. M. Ahn: None. C. Won-kyoung: None. C. Kyoung Soon: None. M. Jung: None. B. Suh: None.
Background: Irisin is a myokine secreted from skeletal muscle that plays an important role in the regulation of adipokine secretion and the differentiation of osteoblast and osteoclasts. Irisin has been shown to increase browning of adipose tissue, thermogenesis, energy expenditure, and insulin sensitivity. The aim of this study was to evaluate the relation of serum irisin level with metabolic, anthropometric parameters and bone mineral density in children and adolescents. Methods: This study included 103 Korean children and adolescents in a single center: 49 (47.6 %) obese participants with a body mass index (BMI) ≥95th percentile and 54 (52.4%) healthy control with BMI 15-85th percentile. Fasting serum irisin was quantitatively assayed by ELISA. Lipid profile, fasting blood glucose, fasting insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), Tryglyceride and glucose (TyG) index, osteocalcin and 25-hydroxyvitamin D3 were measured as metabolic parameters. Bone mineral density (BMD) was performed by dual energy X-ray absorptiometry (DXA) in 33 healthy subjects. Results: Serum irsin was significantly higher in obese group than in control group (mean 18.1 ± 3.5 vs 16.2 ± 2.0ng/mL; P = 0.002). There was no significant difference in serum irisin levels between prepubertal and pubertal subjects. In the all participants, irisin level was positively correlated with height SDS (r = 0.24; P = 0.02), BMI SDS (r = 0.37; P &lt;0.001), HOMA-IR(r = 0.21; P = 0.04) and osteocalcin (r = 0.27; P = 0.006). Serum irisin level was negatively correlated with HDL cholesterol (r = -0.29; P = 0.005) and positively correlated with total body less head (TBLH) Z-score (r = 0.40, P = 0.03). Conclusions: This study showed the association between irisin levels with BMI standard deviation score, HOMA-IR and HDL cholesterol. Our data showed a positive correlation between irisin levels and BMD in healthy subjects. Further studies are needed to clarify the mechanisms by which irisin could affect glucose/lipid metabolism and bone metabolism.
Presentation: Thursday, June 15, 2023
THU222 Malignancy Risk In Nodules Classified As Atypia Of Undetermined Significance In A Predominantly Hispanic Free-standing Children’s Hospital
Authors: Baboun Daniela , Solano Natalia , Sanchez Andrea Martinez , Brathwaite Carole , Restrepo Ricardo , Alkhoury Fuad , Carrillo-Iregui Adriana 
Published: October 2023

Abstract
Disclosure: D. Baboun: None. N. Solano: None. A. Martinez Sanchez: None. C. Brathwaite: None. R. Restrepo: None. F. Alkhoury: None. A. Carrillo-Iregui: None.
Background: During the last 3 decades, there has been an increase in pediatric thyroid cancer. Ultrasound-guided fine needle aspiration (US-FNA) of thyroid nodules continues to be the main modality for histopathological evaluation. Thyroid nodules reported as atypia of undetermined significance (AUS) present a challenge to clinicians in deciding on surgical intervention versus observation (1). Objective: The purpose of this study is to determine the rate of malignancy in cases classified as AUS in the predominantly Hispanic population treated at a free-standing children’s hospital. Methods: Upon Institutional Review Board approval, we performed a retrospective chart review from 2012-2022 of 211 patients who underwent US-FNAs of thyroid nodules. We analyzed demographics and histopathological diagnoses. Results: The majority of our population identified as Hispanic (80.10%). There were 167 (79.10%) females and 44 (20.90%) males, and the age range was 4-21 years. Two hundred eleven patients underwent a total of 232 US-FNAs. The Bethesda distribution is as follows: 29 (12.50%) nondiagnostic, 98 (42.24%) benign, 45 (19.40%) AUS, 21 (9.05%) follicular neoplasm, 9 (3.88%) suspicious, and 30 (12.93%) malignant. Of the AUS group, 33 of the 43 patients underwent surgery. Of the surgical specimens, 16 (48.48%) were malignant, and 17 (51.52%) were benign. Of the 10 patients who did not undergo surgery, 2 underwent a repeat US-FNA with benign results, 5 were monitored, and 3 did not return for a follow-up. Conclusions: In our experience, patients with US-FNAs classified as AUS have a rate of malignancy of 48.48%, which is consistent with the published rate of higher incidence in the pediatric population than in the adult population. Thus, our results support the current recommendation of surgical intervention rather than observation in these pediatric patients. Molecular markers are a useful tool for determining management of thyroid nodules in adults; however, further research in the pediatric population is needed to have standardized recommendations.
Reference: (1) Rossi, E.D. et al., Cancer Cytopathology. 2017 Aug 125:594-603.
Presentation: Thursday, June 15, 2023
THU240 A Study Of 21 Cases Of Graves Disease In Childhood Presenting At Our Hospital For The First Time
Authors: Kashima Takemoto , Ujita Nagisa , Konno Hiroaki , Fujioka Akiko , Miyagi Hajime , Igarashi Mizuho , Doi Hibiki , Yoshii Keisuke , Naiki Yasuhiro , Horikawa Reiko , Noordin Mazidah 
Published: October 2023

Abstract
Disclosure: T. Kashima: None. N. Ujita: None. H. Konno: None. A. Fujioka: None. H. Miyagi: None. M. Igarashi: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. M. Noordin: None.
Although Graves disease is most common among women in their 20s and childhood-onset cases account for less than 5% of all cases of Graves disease, they account for the majority of hyperthyroidism in children. We report here a retrospective review of data on pediatric patients with Graves' disease who visited our hospital for the first time at the time of their initial examination. Methods We analyzed 21 pediatric patients with Graves disease who visited our hospital between November 2004 and January 2022. The electronic medical records of 21 patients were retrospectively reviewed for sex, age, height SD score, weight SD score, underlying disease, blood test results, and treatment initiation. Results There were 17 girls and 4 boys. The median age was 11 years and 5 months. Symptoms such as fever, feverishness, palpitations, weight loss, hyperactivity, and irritability were observed in 5 of the patients. Four patients had symptoms related to academic performance, such as low grades and poor concentration. Median physical findings were height SD score 0.62 (N=21), weight SD score 0.06 (N=21), and body mass index -4.4%. Two patients had bronchial asthma and atopic dermatitis, and one had myasthenia gravis and trisomy21 as underlying diseases. One patient was considered to have attention deficit hyperactivity disorder and was receiving antipsychotic medication. The median blood test values at the first visit were ALP 857 U/L (N=19), total cholesterol level 122 mg/dL (N=19), fT3 14.31 pg/mL (N=21), fT4 4.60 ng/dL (N=21), thyroid stimulating antibody 668 % (N=7), TSH receptor antibody 16.6 IU/L (N=20 TSH was less than sensitive in all cases. Nineteen patients received thiamazole. Fourteen patients received propranolol. Five patients received inorganic iodine. Five patients received inorganic iodine, starting at a median of 0.926 mg/kg/day of body weight. Discussion As with adults, females were more common. The symptoms were similar to those of attention deficit hyperactivity disorder, and thus warranted attention. Symptoms related to poor academic performance were also considered important. Anti-thyroglobulin antibodies and anti-TPO antibodies were also detected, suggesting that we should be careful about the possibility of the disease progressing to Hashimoto's disease.
Presentation: Thursday, June 15, 2023
FRI593 Ergocalciferol And Pancreatic β-Cell Function In New-onset Type 1 Diabetes: A Randomized Controlled Trial
Authors: Nwosu Benjamin Udoka , Parajuli Sadichchha , Sharma Rohit , Barton Bruce Alan , Lee Austin F 
Published: October 2023

Abstract
Disclosure: B.U. Nwosu: None. S. Parajuli: None. R. Sharma: None. B.A. Barton: None. A.F. Lee: None.
Background: The impact of high-dose vitamin D (ergocalciferol) on pancreatic β-cell function in youth with newly diagnosed type 1 diabetes (T1D) is unclear. Objective: To determine the effect of ergocalciferol on residual pancreatic β-cell function (RBCF) in youth with newly diagnosed T1D. Hypothesis: Ergocalciferol supplementation increases RBCF and prolongs the partial clinical remission (PR) phase of T1D. Design, Setting, and Participants: This 12-month randomized, double-blind, placebo-controlled trial of youth aged 10-21 years with newly diagnosed T1D of &lt;3mo was conducted at a single center in the US between October 19, 2017 through April 20, 2021. Interventions: Participants were randomized 1:1 to once weekly dose of 50,000 IU of ergocalciferol for 2 months, and then once every 2 weeks for 10 months, versus placebo. Main outcomes and measures: The primary outcome was the percentage change from baseline in the area under the curve (AUC) of stimulated C-peptide over 12 months. Results: Thirty-six subjects were randomized to either the ergocalciferol arm: n=18, mean age 13.3±SD2.8 years, with 10 male and 8 female subjects; or to the placebo arm: n=18, mean age 14.3±2.9 years, with 14 male and 4 female subjects. Ergocalciferol significantly reduced the temporal trends in both the A1c (p=0.04) and the insulin-dose adjusted A1c (IDAA1c) (p=0.02), and the overall group means for IDAA1c versus placebo (p=0.02). A random intercept model, adjusted for age, sex, and race, showed that the percentage change in AUC C-peptide from baseline through the 12-month study period declined in both arms of the study. Specifically, by 28.4 ± 6.2 (p&lt;.0001) in the ergocalciferol arm and by 41.5 ± 5.9 (p&lt;.0001) in the placebo arm, with the decline in the ergocalciferol arm being significantly slower than that in the placebo arm, p=0.029 for the difference in the slopes of the trends between the two arms. There were no adverse events. Conclusion: High-dose ergocalciferol significantly slowed the rate of decline in C-peptide compared to placebo in children and adolescents with T1D.
Presentation: Friday, June 16, 2023
FRI594 Results Of A New Transition Of Care Process From Pediatric To Adult Diabetes Services
Authors: Cooper Felicia Ilyssa , Vyas Neha , Pierce Jessica , Kulasingham Alicia Yavani 
Published: October 2023

Abstract
Disclosure: F.I. Cooper: None. N. Vyas: None. J. Pierce: None. A. Kulasingham: None.
Adolescence is a challenging time in a child’s life and can be even more stressful for those living with diabetes. It has been shown that glycemic levels worsen in young adulthood due to factors such as increasing insulin resistance and gaps in care during the transitioning from pediatric to adult diabetes care. Data suggest that beginning transition preparation in early adolescence is associated with better outcomes. Our aim was to create a transition of care program for youth in our diabetes clinic following the Got Transition Core Elements and assess its effectiveness.
First, we established a clinic transition policy and corresponding informational letter, which we distributed to youth ages 12-16. Then, we adopted a Diabetes Summary Form to track and monitor transition progress. Next, we implemented transition readiness screening to youth ages 14-16 using the Readiness Assessment of Emerging Adults with Diabetes Diagnosed in Youth (READDY) tool. Last, we distributed GotTransition.org surveys to youth and their caregivers to assess satisfaction with our clinic’s transition process and perceived readiness to move to an adult provider. The transition letter distribution rate had a mean of 56% and the READDY completion rate had a mean of 40%. Although we did not achieve our distribution target goal of 80%, 90% of those who did complete the READDY indicated they were somewhat or very ready to transition to adult care. The satisfaction survey revealed that many youths still need assistance with insurance (32%) and finding an adult provider (45%). Overall, our initial efforts to establish a healthcare transition program were successful. We will continue our work on 1) improving letter distribution and readiness screening rates, 2) designing a curriculum centered around adolescent-specific issues, including insurance needs and 3) increasing our connections with adult endocrinologists to facilitate seamless transitions. We hope other pediatric diabetes clinics can learn from our experience, as well expanding to other subspecialty clinics in our children’s hospital.
Presentation: Friday, June 16, 2023
FRI166 Characterization of Aldosterone-producing Cell Cluster (APCC) At Single-cell Resolution
Authors: Iwahashi Norifusa , Umakoshi Hironobu , Seki Tsugio , Gomez-Sanchez Celso , Mukai Kuniaki , Suematsu Makoto , Umezawa Yuta , Oya Mototsugu , Kosaka Takeo , Seki Masahide , Suzuki Yutaka , Horiuchi Yutaka , Nishimoto Koshiro , Ogawa Yoshihiro 
Published: October 2023

Abstract
Disclosure: N. Iwahashi: None. H. Umakoshi: None. T. Seki: None. C. Gomez-Sanchez: None. K. Mukai: None. M. Suematsu: None. Y. Umezawa: None. M. Oya: None. T. Kosaka: None. M. Seki: None. Y. Suzuki: None. Y. Horiuchi: None. K. Nishimoto: None. Y. Ogawa: None.
Context: The adrenal cortex consists of zona glomerulosa (ZG), fasciculata (ZF), and reticularis. Aldosterone-producing cell clusters (APCCs) that express aldosterone synthase (CYP11B2) strongly can be frequently found in adult adrenals and harbor somatic mutations that are also present in aldosterone-producing adenomas (APAs). Primary aldosteronism is mainly caused by APAs or idiopathic hyperaldosteronism (IHA). We presume that APCCs are causing IHA and are precursors of APAs. However, the gene expression characteristics and especially the development of APCCs are not well understood. Objective: This study aimed to analyze the transcriptome of APCCs at single-cell resolution and infer the developmental trajectory. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on two adult adrenals. Results: Immunohistochemical analyses confirmed the presence of APCCs in the two adrenals. scRNA-seq data of 6770 adrenal cells were obtained and 2928 high-quality cells were selected after quality control procedures. Unsupervised clustering and marker gene expressions such as CYP11A1 and NR5A1 identified 1765 adrenocortical cells, which were further divided into six clusters (B1-6). Using the list of APCC/ZG upregulated genes from our previously reported DNA microarray study, three clusters (B1, B3, and B6, totaling 923 cells) were identified as APCC/ZG cells. By further subclustering, the APCC/ZG cells were divided into 3 clusters (C1, C2, and C3). The APCC cluster (C3, 64 cells) and ZG cluster (C1, 447 cells) were identified. Cluster C2 seemed to be ZG-to-ZF transitional cells. RNA velocity analysis, which aimed to infer the direction of differentiation, inferred a direction of development from ZG cells to APCCs. Conclusion: Our results revealed the gene expression characteristics of APCC at single-cell resolution and show that some ZG cells remodel into APCCs.
Presentation: Friday, June 16, 2023