bluuebunny/crossref_metadata_2025_split huggingface dataset:
7345 Study on the correlation between the levels of myokines and metabolic abnormality in obese children
Authors: Ouyang L , Li M , Yang F 
Published: October 2024

Abstract
Disclosure: L. Ouyang: None. M. Li: None. F. Yang: None.
Objective: There are limited drug options to treat childhood obesity. Studies have found that myokines play an important role in the mechanism of exercise in the treatment of obesity. However, the correlation between myokines and metabolic abnormalities in obese children is still unclear. The purpose of this study is to analyze the correlation between the levels of myokines and metabolic abnormalities in obese children to provide the basis for the future application of myokines in childhood obesity. Methods: 41 obese children who visited the pediatric clinic of our hospital from March to October 2022 were enrolled, and 11 healthy non-obese children who had a regular physical examination in the pediatric clinic during the same period were enrolled. Basic information, anthropological indicators and biochemical indicators were collected. Human myokine magnetic bead panel was used to detect serum myokine levels including irisin, FGF21, BDNF, LIF, MSTN, IL 6, and IL 15. Difference analysis, rank sum test and Spearman analysis were used to conduct the correlation between the levels of myokines and metabolic abnormalities in obese children. Results: We found that the BMI-SDS and body fat rate of obese children with abnormal metabolism was higher than those with normal metabolism status(p&lt;0.05). Children with abnormal glucose metabolism had an increased risk of abnormal lipid metabolism and hyperuricemia(p &lt; 0.05), and children with abnormal lipid metabolism had an increased risk of hyperuricemia and hypertension(p&lt;0.05). The obese children with abnormal glucose and lipid metabolism had an increased risk of abnormal purine metabolism. The levels of leukemia inhibitory factor and brain-derived neurotrophic factor in obese children were significantly higher than those in non-obese children (p&lt;0.05), and the level of fibroblast growth factor 21 in obese children with abnormal metabolism was significantly higher than that in children with normal metabolism (p&lt;0.05), respectively. There was a significant positive correlation between BMI-SDS and the levels of irisin, leukemia inhibitory factor and brain-derived neurotrophic factor (r=0.361, 0.368, 0.343, p=0.009, 0.007, 0.013, respectively). There was a significant positive correlation between irisin, BDNF, LIF, MSTN and IL 6, and between FGF21 and irisin, MSTN, IL 6 in children (p &lt; 0.05). Conclusions: With the increase in BMI, the risk of metabolic abnormalities in obese children increases. Obese children with one kind of metabolic abnormality are prone to merge with other metabolic abnormalities. The levels of leukemia inhibitory factor, fibroblast growth factor 21, irisin, brain-derived neurotrophic factor, and other myokine in obese children and obese children with abnormal metabolism are different from those in non-obese children and obese children with normal metabolism respectively, and there is interaction between myokines.
Presentation: 6/1/2024
7237 Targeting IGF-I to Growth Plate Cartilage Augments Therapeutic Effects on Skeletal Growth and Reduces Hypoglycemic Effects in Mice
Authors: Tailor Krishma , Stowe Tim , van Ree Janine , Ventura Brit , van Deursen Jan , O’Brien Robert , Baron Jeffrey , Lui Julian 
Published: October 2024

Abstract
Disclosure: K. Tailor: None. T. Stowe: None. J. Ree: None. B. Ventura: None. J. Deursen: None. R. O'Brien: None. J. Baron: None. J. Lui: None.
Recombinant human growth hormone (GH) is commonly used to treat short stature in children but has limited efficacy in severe, non-GH-deficient conditions, such as skeletal dysplasias, and has adverse off-target effects. Because short stature is the result of reduced growth plate chondrogenesis, we hypothesized that targeting chondrogenic growth factors specifically to the growth plate might augment the therapeutic skeletal effect while diminishing adverse effects on non-target tissues. Toward this end, we previously developed fusion proteins conjugating insulin-like growth factor-1 (IGF-1) with a single-chain human monoclonal antibody fragment (ScFv) targeting matrillin-3 (1), a protein specifically expressed in cartilage matrix, and demonstrated increased on-target therapeutic efficacy at the growth plate and decreased off-target effects in a GH-deficient (lit) mouse model (2). In the current study, we established a second GH-deficiency model by administration of a GH antagonist, pegvisomant (PEG), in C57BL/6 wild-type male mice. Alternate-day injection of pegvisomant at 40 mg/kg for 7 days reduced body weight, serum IGF-1 levels, and growth plate height in mice. Using this model, we found that once-daily SQ administration of cartilage-targeted IGF-I (named CV1574-1) for five days increased body weight and growth plate height greater than an equimolar dose of IGF-I itself administered twice daily. Hypoglycemia is an adverse effect of recombinant IGF-1 treatment. Therefore, we also monitored blood glucose levels after a single SQ injection of CV1574-1 and found that this fusion protein showed a reduced hypoglycemic effect compared to injection of IGF-I itself. Lastly, to gain mechanistic insight into the role of matrillin-3 targeting on therapeutic efficacy, we assessed the ability of CV1574-1 to induce pAKT signaling in vitro. Transient exposure to CV1574-1 caused more prolonged induction of pAKT signal in wild-type rat chondrosarcoma (RCS) cells compared to matrillin-3-knockout RCS cells, suggesting that matrillin-3 targeting extends the duration of IGF-1 receptor activation. To summarize, the current findings demonstrate that CV1574-1, a fusion protein that targets IGF-1 to cartilage, improves efficacy at the growth plate, reduces hypoglycemic effects, and, in vitro, prolongs receptor activation. Our study provides further evidence that cartilage-targeted therapy has the potential to provide new pharmacological approaches for the treatment of childhood linear growth disorders, including skeletal dysplasias and growth failure due to systemic disease. Reference:(1) Cheung et al. Pharma Res 2015, 32(7):2439-49.(2) Lui et al. Molecular Therapy 2019, 27(3):673-680
Presentation: 6/3/2024
7338 Temporal Trend of Age at Menarche in Korean Adolescents: A Population-based Study
Authors: Kim Hwa Young , Kim Jaehyun 
Published: October 2024

Abstract
Disclosure: H.Y. Kim: None. J. Kim: None.
Background: The age at menarche has been decreasing worldwide. Previous studies in Korean adolescents also reported a downward trend of age at menarche. We investigated the current trends of age at menarche in Korean adolescents using nationally representative data. Methods: Data from the Korea National Health and Nutrition Examination Survey 2007-2021 were used in this study. A total of 50,730 females born between 1927 and 2004 with information on age at menarche were included in this study. The trend of age at menarche was analyzed according to 12 birth-year groups (with 5-year interval) using quantile regression analysis. Results: The mean age at menarche decreased over time, from 16.58±0.02 years for females born before 1950 to 12.45±0.04 years for females born between 2000 and 2004 (P &lt;0.001). According to the percentiles group of age at menarche, the menarche age decreased by 0.073 years per year (95% confidence intervals [CIs], 0.072-0.074) in the 50th percentile group, 0.088 years per year (95% CI, 0.085-0.091) in the 97th percentile group, and 0.050 years per year (95% CI, 0.048-0.052) in the 3rd percentile group (P &lt;0.001 for all). A decreasing trend of age at menarche was more prominent in the obese group (0.080 years per year, 95% CI, 0.078-0.082) compared to the non-obese group (0.069 years per year, 95% CI, 0.068-0.071) (P &lt;0.001 for both). Conclusion: Ongoing downward trend in age at menarche was observed in Korean adolescents born until 2004, decreasing by 0.73 years per decade. A downward trend was faster in individuals in the higher percentile of age at menarche and in those with obesity.
Presentation: 6/1/2024
8764 A Unique Case of Infertility in a Patient with NCCAH
Authors: Paravastu Mounika , Patel Ruchita 
Published: October 2024

Abstract
Disclosure: M. Paravastu: None. R. Patel: None.
Background: Non-Classic Congenital Adrenal Hyperplasia (NCCAH) in women often presents with hirsutism, acne, menstrual dysfunction, or infertility. Subfertility in patients with NCCAH can be attributed to menstrual disorders including oligomenorrhea or secondary amenorrhea. We report a unique case in which a patient with NCCAH with consistently normal menstrual cycles is experiencing infertility. Case Description: A 31 y/o female with no PMH was referred to our Endocrinology Clinic for evaluation of Infertility and elevated 17-Hydroxyprogesterone levels (17OHP). Patient has been having trouble conceiving for the past 2 years, no prior successful pregnancies. She started menstrual cycles at age 17, she reports having regular menstrual cycles. Prior to our evaluation, she was seen in Reproductive Endocrinology who completed hormonal and imaging evaluation. Elevated 17OHP: 286ng/dL. Rest of hormonal workup within normal range. Normal Pelvic Ultrasound. Hormonal workup was repeated in our clinic. 17OHP is elevated at 617.01ng/dL. Rest of lab work returned normal with DHEAS:218.9mcg/dL, TSH: 2.826mcUnits/mL, Free Testosterone: 5.4pg/mL, Prolactin:11.7ng/mL, Beta HCG: negative, LH: 13.5mUnits/mL, FSH: 5.3mUnits/mL, Estradiol 79pg/mL. Cosyntropin stimulation test was completed. Baseline AM 17OHP:469.78ng/dL, Baseline Cortisol: 17.9mcg/dL. 17OHP 30 minutes-post:1216.4ng/dL, Cortisol 30 minutes-post: 18.5mcg/dL. 17OHP 60 min-post: 1051ng/dL, Cortisol 60 minutes post:16.4 mcg/dL. Given Inconclusive Cosyntropin stimulation test results, Genetic Testing was recommended. Genetic testing returned positive for NCCAH, patient’s husband is not a carrier of this gene. She was started on Hydrocortisone therapy for treatment of infertility. Shortly after she started on hydrocortisone therapy, patient did successfully conceive, however the pregnancy later resulted in a miscarriage. Conclusion: Subfertility in patients in NCCAH is thought to be due to menstrual irregularities including oligomenorrhea or secondary amenorrhea. We report the first case of a woman with diagnosis of NCCAH who is experiencing infertility despite having normal menstrual cycles.
Presentation: 6/1/2024
6681 Age and Sex Disparity in NASH and the Potential Role of Estradiol Treatment for NASH
Authors: Tripathi Madhulika , Sakthivel Suganya , Suzuki Ayako , Singh Brijesh K , Yen Paul M 
Published: October 2024

Abstract
Disclosure: M. Tripathi: None. S. Sakthivel: None. A. Suzuki: None. B.K. Singh: None. P.M. Yen: None.
Introduction: NAFLD (nonalcoholic fatty liver disease) and its more severe form, NASH (nonalcoholic steatohepatitis) are sexually dimorphic conditions that exhibit higher prevalence in men than women during reproductive ages but have similar prevalence after menopause. Reproductive age women are protected from hepatic fibrosis relative to men, although they lose this protection after menopause. These sex differences in NASH have been attributed, at least partly, to different circulating estrogen levels. However, the underlying mechanism(s) is not fully understood. We thus conducted animal experiments to investigate: 1) sex differences in the histologic severity of NASH, necroinflammatory and fibrogenic activities, and other relevant pathways in young and old male and female mice and 2) the effects of estradiol administration on these parameters in old male and female mice to evaluate the therapeutic potential of estradiol in NASH. Methodology: Young/reproductive age (12-weeks old) and old/post-reproductive age female and male (48∼50-weeks weeks old) C57BL/6J mice were fed control chow diet (NCD) or high-fat methionine/choline-deficient (MCD) diet for six weeks to induce NASH. The old mice were administered 200nM 17β-estradiol (physiological) in drinking water. We analyzed serum and hepatic NASH parameters, ER stress, and lysosome-autophagy defects. Results and Conclusion: Among reproductive age mice with NASH, females developed less severe histologic inflammation and fibrosis and decreased gene expression of Il1b, Il6, Tgfb, Col1a1, Ccl2, and Ccl5, and lower hepatic collagen than males. Females with NASH also had less inhibition of hepatic autophagy and lysosomal protein expression than males with NASH. Among old mice, post-reproductive age females fed NCD or MCD exhibited more severe hepatic inflammation and fibrosis and had higher gene expression of inflammatory and fibrogenic markers with comparable autophagic inhibition and lysosomal defects as similar age males. Physiological doses of estradiol significantly reduced hepatic gene expression of inflammatory and fibrogenic markers, ER stress and lysosomal-autophagic defects in post-reproductive age females. In conclusion, similar to clinical NASH, we observed marked sex and age-related differences in the severity of NASH. Furthermore, physiological doses of estradiol treatment improved the hepatic histology, lysosome-autophagy, inflammation, and fibrosis in post-reproductive age female mice with NASH and suggests that estradiol supplementation may decrease or reverse NASH progression in post-menopausal women with NASH.
Presentation: 6/2/2024
7299 An Eucaloric High-Fat Diet Suppresses Urinary Estrogen and Progesterone Metabolites, Mimicking Reprometabolic Syndrome in Normal Weight Women
Authors: Kuhn Katherine , Bradford Andrew P , Duffy Katelyn , Britton Olivia , Santoro Nanette F 
Published: October 2024

Abstract
Disclosure: K. Kuhn: None. A.P. Bradford: Consulting Fee; Self; Amazon. N.F. Santoro: Advisory Board Member; Self; Menogenix, Astellas, Que Oncology, Amazon. Consulting Fee; Self; Ansh.
Introduction: Reprometabolic syndrome is associated with relative hypogonadotropic hypogonadism, reduced fecundability, and increased pregnancy loss in women with obesity. We employed a eucaloric, high-fat diet (HFD) to attempt to reproduce the decreased urinary estrogen and progesterone metabolites, characteristic of this phenotype, in healthy women of normal BMI. Materials and Methods: 18 women with normal BMI (18-24.9kg/m²), mean age 29.1±6.3, were recruited for a four-month study including a prescribed 30-day, eucaloric, high-fat, dietary intervention (48% calories from fat). Women collected daily morning urine for 4 menstrual cycles. Daily urinary estrone conjugate (E1c) and pregnanediol-3-glucuronide (Pdg) levels were measured by immunoassay before, during and after the HFD. Paired t tests were used to compare average urinary E1c and Pdg levels and area under the curve (AUC) to determine the impact of the HFD. Cycles were aligned by LH peak (day 0). Results: Participants were weight stable throughout the 4 month study period with no change in BMI (pre-diet BMI 21.46±1.95 kg/m2 and post-diet BMI 21.35±1.81 kg/m2). Average mid cycle E1c peak was significantly lower during (32.4 ng/mg creatinine) and after the HFD (26.5 ng/mg creatinine), compared to pre-diet levels (43.2 ng/mg creatinine; p&lt; 0.001). Post-diet urinary Pdg (AUC) was also significantly lower than pre-diet (p&lt; 0.01). Follicular (days -14 to 0) and luteal phase (days 2-14) E1c AUC was significantly decreased post HFD (p&lt; 0.05). Follicular and luteal phase Pdg levels were also significantly decreased post HFD (p&lt;0.001, both). No significant changes in menstrual cycle length were observed throughout the study. Conclusion: Consumption of a high-fat diet for one month was sufficient to induce a significant reduction in E1c and Pdg, characteristic of Reprometabolic Syndrome of obesity, in normal weight, eumenorrheic women. This finding provides important insights regarding the mechanisms underlying reproductive dysfunction in obesity and indicates that a dietary intervention may be an effective strategy to mitigate sub-optimal reproductive hormone levels in women with obesity-related subfertility.
Presentation: 6/1/2024
7609 Androgen Receptor Positive DCIS in a Transmasculine Individual on Testosterone Therapy
Authors: Kelly J , Cohen B 
Published: October 2024

Abstract
Disclosure: J. Kelly: None. B. Cohen: None.
Introduction: The rate of breast cancer in transgender men is lower than in cisgender women, perhaps due to lower estrogen levels in the setting of suppression from exogenous testosterone, lack of clear guidelines on screening after top surgery, and increase in mastectomies. However, the impact of testosterone therapy on existing breast cancer is not known. Concerns regarding use of testosterone in patients with breast cancer include the potential for conversion of testosterone to estradiol, as well as direct androgen receptor (AR) stimulation. However, for some patients, hormone therapy is lifesaving and stopping gender affirming hormone therapy (GAHT) will negatively impact patient well-being. This creates a challenging clinical scenario when transgender patients on testosterone are diagnosed with breast cancer.Case Presentation: We present a case of a 29-year-old self-identified transmasculine nonbinary individual (assigned female at birth) who underwent chest reconstruction surgery after several months on daily transdermal testosterone therapy. A 4 cm DCIS ER+/AR+ with possible micro invasion was incidentally noted on pathology. They had no family history of breast cancer. The patient underwent chest MRI which was negative for persistent disease. The treating oncologist did not recommend Tamoxifen. The patient chose to discontinue testosterone therapy due to uncertainty regarding future breast cancer risk. However, due to worsening depression and fatigue, the patient chose to resume GAHT after receiving counseling of possible risk, though likely low, of cancer recurrence. Given that they had undergone bilateral mastectomy which, unlike chest reconstruction surgery where some breast tissue is left for contouring, all breast tissue was removed and given that chest MRI was negative for disease, cancer recurrence was felt to be low. Furthermore, though AR positivity was noted, the clinical implications are unclear and it is not known whether testosterone would stimulate tumor growth or potentially have antagonistic effects on ER signaling. Additionally, any stimulatory effects of AR signaling may be balanced by androgen suppression of gonadotroph production and reduction in estrogen production; this is more clearly associated with stimulatory effects on cancer growth. And finally, the potential risks of therapy must be weighed against the benefits provided to the patient’s well-being and mental health. Ultimately, the patient resumed testosterone therapy and has been doing well.Teaching Point: This case illustrates the uncertainties regarding the management of gender affirming testosterone therapy in patients with DCIS or breast cancer. It also highlights the need for a patient centered approach to decisions regarding changes to GAHT, to appropriately weigh the risks and benefits of continuing therapy.
Presentation: 6/2/2024
7641 Antimüllerian Hormone Levels by Phenotypes in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Authors: Schwenck-Carvalho Patricia , Simoes Ricardo , Maffaziolli Giovana , Soares-Jr José Maria , Baracat Edmund C , Maciel Gustavo Arantes 
Published: October 2024

Abstract
Disclosure: P. Schwenck-Carvalho: None. R. Simoes: None. G. Maffaziolli: None. J. Soares-Jr: None. E.C. Baracat: None. G.A. Maciel: None.
Objective: This study aims to comprehensively evaluate the levels of antimüllerian hormone (AMH) across the different phenotypes (A, B, C, D) of Polycystic Ovary Syndrome (PCOS) according to Rotterdam diagnostic criteria. Methods: In this systematic review and meta-analysis, two independent reviewers following PRISMA guidelines conducted a comprehensive search of PubMed, Embase, and Web of Science databases for studies published from inception up to December 2023. Studies reporting the AMH levels by PCOS phenotypes were considered for inclusion. The quality of studies was assessed using the ROBINS-E tool. The primary outcome of interest was the mean level of AMH among the PCOS phenotypes regardless of AMH assay used (tAMH). In a secondary analysis, AMH levels were converted into AMH Beckman Coulter Gen II assay (bcAMH). Secondary outcomes included age and BMI by phenotype. Random-effects models were applied to assess mean levels and SMD (standardized mean differences) with 95% confidence intervals (CI 95%). Results: Forty-nine studies were included in this review involving a total of 15 535 subjects. The meta-analysis showed that AMH levels vary according to the PCOS phenotype, being higher into the A phenotype followed by D, C and B: PCOS A tAMH=9.87ng/mL (SMD 2.97 CI 95% 9.29-10.48) bcAMH=11.49ng/mL (SMD 3.06 CI 95% 10.47-12.61), PCOS B tAMH 5.71ng/mL (SMD 0.98, CI 95% 4.96-6.57) bcAMH=6.25ng/mL (sd 1.36 CI 95% 5.20-7.51), PCOS C tAMH 6.91ng/mL (SMD 1.42 CI 95% 6.30-7.57) bcAMH=7.98ng/mL (SMD 1.52 CI 95% 7.16-8.90), PCOS D tAMH 7.80ng/mL (sd 2.27, CI 95% 7.20-8.45) bcAMH=8.97ng/mL (SMD 2.44 CI 95% 8.04-10.00). There were no significant differences between age and BMI through phenotypes - PCOS A age=26.17 years (SMD 4.02 CI 95% 24.29-28.30), BMI=26.11kg/m² (SMD 3.82 CI 95% 25.31-26.94); PCOS B age=27.22 years (SMD 3.75 CI 95% 26.16-26.95), BMI=25.89kg/m² (SMD 3.07 CI 95% 24.86-26.95); PCOS C age=27.46 years (SMD 4.12 CI 95% 26.49-28.46), BMI=25.19kg/m² (SMD 3.44 CI 95% 24.42-25.98); PCOS D age=27.57 years (SMD 4.01 CI 95% 26.68-28.49), BMI=24.78kg/m² (SMD 3.90 CI 95% 24.06-25.53). The heterogeneity among the studies was high, indicating that factors beyond phenotypic categories may be influencing AMH in PCOS. Conclusions: Our findings emphasize the need for phenotype-specific considerations in PCOS management and suggest that AMH levels could enhance the characterization of PCOS subtypes. Additionally, the variability observed in AMH assays across different studies highlights the future need for a universal standardization of AMH measurement techniques.
Presentation: 6/3/2024