bluuebunny/crossref_metadata_2025_split huggingface dataset:
8450 Accelerometer-based Sedentary Time and Physical Activity with the Risk of Severe Liver Steatosis and Liver Cirrhosis in 2684 Children: A 13-Year Longitudinal and Mediation Study
Authors: Agbaje A O 
Published: October 2024

Abstract
Disclosure: A.O. Agbaje: None.
Background: Non-alcoholic fatty liver diseases have been associated with physical inactivity in adults. However, long-term evidence on the prospective relationship of accelerometer-measured sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) with liver steatosis and fibrosis and changes in liver enzymes in a large paediatric population is scarce. Hypothesis: It was hypothesized that increased ST from childhood through young adulthood would increase the risk of severe liver steatosis and cirrhosis and worsen liver enzymes, whereas engaging in LPA and MVPA would reduce the risk. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-point accelerometer-measured ST, LPA, and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography (FibroScan 502 Touch) and categorized as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Results: Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), ST increased from 6 hours/day in childhood to 9 hours/day in young adulthood, while LPA decreased from 6 hours/day to 3 hours/day and MVPA was relatively stable at 50 minutes/day. The prevalence of liver cirrhosis [F4, ≥11·7 kPa] and severe liver steatosis [S3, controlled attenuation parameter value ≥280 dB/m] is 0.3 and 10%, respectively. Cumulative 1-minute/day increase in ST from ages 11-24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002 - 1.005] p&lt;0.001) and severe liver steatosis (1.001 [1.001 - 1.002] p=0.002) at age 24 years. Increased ST from childhood was directly associated with increased ALT, AST, and GGT from ages 17 - 24 years. Cumulative 1-minute/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990 - 0.991] p&lt;0.001) and severe liver steatosis (0.999 [0.998 - 0.999] p&lt;0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-minute/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994 - 0.998] p&lt;0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. Conclusions: Increasing LPA, sustaining MVPA, and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and cirrhosis by young adulthood.
Presentation: 6/1/2024
6703 Age-Related Reference Intervals for 11-Oxygenated Androgens in Children
Authors: IJsselstijn L , Zellerer R , Oude Engberink R , van Zelst B , van den Berg S A 
Published: October 2024

Abstract
Disclosure: L. IJsselstijn: None. R. Zellerer: None. R. Oude Engberink: None. B. van Zelst: None. S.A. van den Berg: None.
Context: 11-Oxygenated androgens have emerged as major components of several disorders of androgen excess. Levels of 11-keto androstenedione (11KA4), 11β-hydroxy androstenedione (11OHA4), 11-keto testosterone (11KT) and 11β-hydroxy testosterone (11OHT) have been mainly studied in adults and in relation to various disorders. Although it is known that 11-oxygenated androgens are pivotal in adrenarche and pubarche, well established reference intervals for children are lacking. Objective: To establish age-related reference intervals for 11-oxygenated androgens in children. Methods: Serum samples were collected from apparently healthy children with ages ranged 0-18 years (n=186, 108 boys and 78 girls). Concentrations of 11KA4, 11OHA4, 11KT and 11OHT were determined by isotope dilution mass spectrometry. Before measurement the serum was deproteinized and purified by solid-phase extraction. The lower limit of quantitation for 11KA4, 11KT and 11OHT were 3.0 ng/dL (0.10 nmol/L), and for 11OHA4 9.1 ng/dL (0.30 nmol/L). Results: For 11KA4 a difference between boys and girls was observed until the age of 6. In girls 11KA4 was undetectable where in boys concentration up to 9.61 ng/dL (0.32 nmol/L) were measured. From the age of 6 an increase of 11KA4 was observed with increasing age. From the age of 13 concentrations stabilized at 4.21-28.5 ng/dL (0.14-0.95 nmol/L) without a difference between boys and girls. 11OHA4 was detectable at all ages and showed no differences between boys and girls, except for an apparently slightly higher concentration for boys until the age of 4. The concentration 11OHA4 increased with age in an almost linear way. At the age of 18 concentrations were observed of 60.5- 296.4 ng/dL (2.00-9.80 nmol/L). For 11KT a similar relation between the concentration and age was observed until the age of 14. At the age of 14 a plateau seems to be reached at concentrations of 14.5-74.4 ng/dL (0.48-2.46 nmol/L), which slightly decreased from the age of 17. 11OHT was undetectable in both boys and girls up to the age of 9 years. After the age of 9 the concentration range increased by age up to 30.4 ng/dL (1.00 nmol/L). From the age of 12 11OHT was detectable in all girl samples, where as in boys samples with undetectable concentrations were present at all ages. Conclusions: Age-related reference ranges were established for 11KA4, 11OHA4, 11KT and 11OHT. Overall no differences were observed between boys and girls, except for 11KA4 at a young age. The concentrations measured at the age of 18 correspond to the adult values known from literature for all 4 11-oxygenated androgens.
Presentation: 6/1/2024
8400 An Unusual Case of Brittle Bone Disease
Authors: Middleton Sydney Michelle , Mogri Muniza 
Published: October 2024

Abstract
Disclosure: S.M. Middleton: None. M. Mogri: None.
Introduction: We present the case of a now 21-month-old F with prenatally suspected skeletal dysplasia; subsequent evaluation revealed concern for a form of brittle bone disease that has not been previously described. Clinical Case: The patient was delivered at 37.0 weeks gestational age via C-section. There had been prior prenatal concerns for a possible skeletal dysplasia. A skeletal survey done on day-of-life 2 noted generalized demineralization of her bones, shortening/bowing of the long bones, an acute right proximal ulnar fracture, and evidence of multiple discontinuous healed rib fractures. A repeat skeletal survey done at day-of-life 19 demonstrated worsening skeletal findings with a very poorly mineralized skull, shortening of the clavicles and extremities, progressive fractures in all extremities and further bowing of the limbs, progressive rib fractures with callus formation, and multiple vertebral bodies with stature loss concerning for compression fractures. Directed genetic testing for osteogenesis imperfecta was negative, so whole exome sequencing was pursued and identified variants of unknown significance in the KAT6B and WDR35 genes not previously described, noting that the patient was heterozygous for both. She was suspected to be a carrier for the WDR35 mutation as it is inherited in an autosomal recessive fashion, and parental genetic testing revealed that the patient’s father carried the same KAT6B mutation and was phenotypically normal. Mutations in these genes have been described in disorders associated with bone abnormalities (such as genitopatellar syndrome and cranioectodermal dysplasia 2), but with different clinical presentations. During the course of her care, she was also identified to have hypophosphatemia shortly after birth and concerns for phosphate wasting; she was noted to have a high fractional excretion of phosphate in the setting of low serum phosphorus despite enteral phosphorus supplementation. She additionally was found to have an elevated FGF23 level at the same time the suspected renal phosphate wasting was identified. Her total calcium has remained normal with normal PTH values; her 25-OH vitamin D has also been normal. She has subsequently been successfully managed on sodium phosphate and calcitriol supplementation, as well as regular zolendronate infusions, without recurrence of fractures, and is clinically doing well with improvements in her respiratory status and overall development. Conclusion: This patient illustrates a severe case of brittle bone disease that presently does not have a clear etiology, though could represent a novel genetic mutation that has not been described and could subsequently be identified with continued review of her genetic testing in the future. Reporting her case could be beneficial to other patients with similar skeletal disease in helping to identify an underlying cause.
Presentation: 6/3/2024
7350 Association between thyroid function and insulin resistance indices in Korean adolescents: Findings from the 2014-2015 KNHANES
Authors: Mun Eunji , Lee Hye Ah , Choi Jung Eun , Lee Rosie , Kim Kyung Hee , Kim Hae Soon 
Published: October 2024

Abstract
Disclosure: E. Mun: None. H. Lee: None. J. Choi: None. R. Lee: None. K. Kim: None. H. Kim: None.
Purpose: Obesity and diabetes are rising concerns among adolescents. There are several studies regarding to the association between thyroid function and IR. However, there are limited studies focus on adolescents. Furthermore, there is a lack of studies evaluating various IR indices. We investigated the association between thyroid function and insulin resistance indices in adolescents with normal thyroid function. Methods: This cross-sectional study included 465 adolescents (aged 12-18, 255 boys, 210 girls) based on data from the Korea National Health and Nutritional Examination Survey2014-2015. Thyroid function was assessed using serum thyrotropin (TSH) and free thyroxine (fT4), while IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), glucose/insulin ratio (GIR), TyG (triglyceride-glucose index), and TG/HDL. Multiple linear regression analyzed the relationship between thyroid function and IR, stratified by sex. Nonlinearity was assessed through a restricted cubic spline model. Results: The mean TSH (uIU/mL) and fT4 (ng/dL) were 2.70 and 1.29, respectively. Boys had higher TSH (2.86 vs. 2.52, p = 0.013) and fT4 (1.33 vs. 1.24, p &lt; 0.001) than girls, with significant gender differences. In girls, fT4 negatively correlated with HOMA-IR and positively with GIR. No significant relationship was found between thyroid function and IR in boys. When analyzed stratified by level of obesity, the association between IR and thyroid function was clear in the overweight/obese group in both sexes. Overweight and obese groups showed relationships between fT4 and HOMA-IR (β = 0.08, p = 0.04 in boys; β = -0.12, p &lt; 0.01 in girls) and QUICKI (β = -4.14, p = 0.03 in boys; β = 6.60, p &lt; 0.01 in girls). TSH correlated with TyG (β = 1.01, p = 0.04 in boys; β = 1.38, p = 0.01 in girls). In girls, fT4 was also related to TG/HDL (β = -0.06, p &lt; 0.05) and GIR (β = 0.14, p &lt; 0.01). Nonlinear analysis found no significant relationship between thyroid function and IR. Conclusion: The relationship between thyroid function and IR was more pronounced in the overweight and obese groups. Our study suggests that the correlation between thyroid function and insulin resistance in adolescents may vary based on gender and IR indices.
Presentation: 6/1/2024
6615 Clinical features and genetic etiology of primary ovarian insufficiency in 46,XX children
Authors: Wang F , Yin X , Lan X , Zang S , Li P 
Published: October 2024

Abstract
Disclosure: F. Wang: None. X. Yin: None. X. Lan: None. P. Li: None.
Purpose: The clinical features of primary ovarian insufficiency in 46,XX children were analyzed, the pathogenic genes of POI were screened, and the genetic etiology of primary ovarian insufficiency in children 46,XX was clarified. Method: The clinical data of 46,XX POI patients were collected, including uterine and ovarian ultrasound, serum follicle-stimulating hormone (FSH), estrogen, anti-mullerian hormone (AMH), chromosomal karyotype analysis, adrenal and thyroid function, and immune function. Whole exome sequencing (WES) and CNV were used to screen POI candidate genes. Novel mutations such as MCM8 gene were used to verify cell function. HE staining, immunohistochemistry, cell fluorescence, and Tunnel method were used to observe the changes in ovarian tissue structure. Construction overexpression plasmids of Mutant MCM8 gene in Hela cells. Result: 1. Clinical features of 46,XX POI: The age of onset of the children was 11.9∼16.1 years old. In addition to POI, the clinical phenotype showed height growth retardation. Among them, 4 cases were short stature, 3 cases were growth hormone deficiency, and 5 cases were backward in bone age. All of them showed elevated FSH (&gt;25 IU/L), and 7 cases had low serum AMH (&lt;0.5 ng/ml). 2.The Screening of POI candidate genes and pathogenicity analysis: 5 of the 10 children carried the mutations of the pathogenic genes with POI, that is, 2 cases (sisters of the same family) carried two novel heterozygous mutations of MCM8 gene, one infant carried two novel heterozygous mutations of CYP19A1 gene, and one case with delayed puberty carried one homozygous mutation of ZSW1M7 gene. 3.The MCM8 mutant were functionally validated: The sisters carried two novel mutations, namely p.C242R and p.S445*. The elder sister (the proband) showed POI, short stature and tumor susceptibility, while the younger sister showed a trend of gradual increase in FSH level and ovarian decline. The follicles of the proband disappeared and fibrous tissue proliferation, the MCM8 expression was lower, and the positive rate of cell apoptosis was higher than normal control. The downregulation of Bax and Capase3 expression in mutant MCM8 of Hela cell was delayed compared with wild type, indicating the persistence of apoptosis. Conclusion: 1. The clinical characteristics of 46,XX POI in children are ovarian hypoplasia, often combined with height growth retardation, biochemical manifestations of hypergonadotropic hypogonadism, decreased serum AMH, and karyotype 46,XX. 2.46,XX POI genetic etiology analysis found that five known POI-related pathogenic genes, namely CYP19A1, MCM8, and ZSW1M7, in which five novel mutations were identified.3.Mutant MCM8 promotes ovarian apoptosis by activating the Bcl-2/Bax/Caspase 3 pathway. Keywords: Primary ovarian insufficiency, short stature, apoptosis
Presentation: 6/3/2024
6860 Cognitive Capacity in Children with Growth Hormone Deficiency
Authors: Leal V , Alvarez V , Awadalla S S 
Published: October 2024

Abstract
Disclosure: V. leal: None. V. Alvarez: None. S.S. Awadalla: None.
Growth hormone (GH) is necessary for longitudinal growth and also has multiple other functions including neurologic development. Cognitive function in children with idiopathic isolated growth hormone deficiency (IGHD) has been poorly studied. This study aims to prospectively investigate cognitive capacity in children with IGHD.Cognitive function of 10 children with IGHD (peak GH &lt;10 μg/L) was studied using Wechsler Intelligence Scales for Children IV: Intelligence Quotient, Verbal Comprehension Index, Perceptual Reasoning Index, and Working Memory and Processing Speed Indices.6 females and 4 males were included , Age was 10.04 ±2.01 years (M± DS) , height SDS was -1.86 ±0.19 . The IQ was 100.6 ±8.5, Verbal Comprehension was 99.3 ±8.5, Perceptual Reasoning was 102.5 ±9.1, Working Memory was 99.9 ±9.8, and Processing Speed was 98.9 ±13.1. Using Spearman correlation test ; a moderate positive correlation was observed between the GH peak and the intellectual coefficient IQ and peak GH: r=0.45, p=0.18, Perceptual reasoning and GH: r=0.43, p=0.2 without a statistical significance probably because of the sample size. In conclusion; The overall IQ score fell within the normal range, with lower scores in processing speed and working memory. These findings underscore the importance of considering not only the impact on linear growth but also on cognitive development when addressing growth hormone deficiency in the pediatric population
Presentation: 6/3/2024
6941 Congenital Generalized Lipodystrophy - An Undiagnosed Case in an Underserved Border Community
Authors: Evans D , Gutierrez A , Echetebu S , Zerah M 
Published: October 2024

Abstract
Disclosure: D. Evans: None. A. Gutierrez: None. S. Echetebu: None. M. Zerah: None.
Introduction: Congenital Generalized Lipodystrophy (Berardinelli-Seip Syndrome) is estimated to occur 1-10/10 million people1. Patients may present with specific clinical features and/or hormonal imbalances such as hyperinsulinemia and hypertriglyceridemia. Complications of CGL result in a decreased average life expectancy of 51.2 years2. Here we present a case of a female from a medically underserved city in Mexico who was not diagnosed until the age of 16, three years after immigration to the United States. Case Presentation: The patient lived in Mexico and had little medical care. After she immigrated, she was referred to Pediatric Endocrinology due to an elevated hemoglobin A1c, hypertriglyceridemia, and elevated liver enzymes. At birth and in adolescence, the patient did not resemble any of her five fully biological siblings, had little adipose tissue, and had well-defined musculature. Physical exam findings included generalized absence of adipose tissue and prominent musculature, large hands and feet, acromegaloid features, acanthosis nigricans, hirsutism, and phlebomegaly. Breast development was Tanner Stage IV, and genitalia was Tanner Stage V, without clitoromegaly. Patient is currently being treated by psychiatry for Major Depressive Disorder and suicidal ideation. Results: She was diagnosed with diabetes mellitus due to elevated glucose on OGGT and hypertriglyceridemia. She was then started on a low carbohydrate diet, Metformin, and Atorvastatin. After treatment a significant improvement in labs were observed. Triglyceride levels decreased from 1112 mg/dL to 392 mg/dL(35-150 mg/dL), A1c from 8.5% to 5.8%(&lt;5.8%), AST from 36 U/L to 16 U/L(12-32U/L), and ALT from 51 U/L to 20 U/L(5-32U/L). OGGT levels measured after treatment began were as follows: fasting: 95 mg/dL (70-100mg/dL), 1 hour: 242 mg/dL (130-140 mg/dL), and 2 hours: 229 mg/dL(&lt;155 mg/dL). A liver ultrasound was normal. Genetic testing, Echocardiogram, EKG, and Leptin levels are all pending. Discussion/Conclusion: This case of an adolescent with CGL, who was not diagnosed until 16 years of age, demonstrates not only the health disparities and challenges faced by patients in border communities, but it also demonstrates the lack of knowledge of CGL in healthcare. By presenting this case, we hope to increase awareness of CGL within the medical community at large, and to improve the quality of life of our patients. References: 1. Garg, A. N Engl J Med 2004;350:1220-34 2.Akinci, B. et al., J Clin Endocrinol Metab 88:5433-5437, 2003
Presentation: 6/2/2024
9205 Copy Number Variation (CNV) in Self-Limited Delayed Puberty (SLDP)
Authors: Al-Sayed Yasmin , Ishida Miho , Hall Charlotte Louise , Howard Sasha R 
Published: October 2024

Abstract
Disclosure: Y. Al-Sayed: None. M. Ishida: None. C.L. Hall: None. S.R. Howard: None.
SLDP is where the onset of puberty is more than 2-2.5 standard deviations later than the population mean age and is often familial with strong genetic determinants. The reproductive axis is regulated by gonadotropin-releasing hormone (GnRH), which plays a crucial role in initiating puberty and maintaining fertility through its pulsatile secretion. Disruption in GnRH neuron development or hypothalamic function can lead to DP. UK Biobank data has identified negative health outcomes associated with SLDP including early menopause/andropause and cognitive and psychosocial disabilities. Consequently, there has been extensive research to investigate genes affecting the hypothalamic-pituitary-gonadal (HPG) axis that might be implicated in the pathogenesis of DP by our group and others which has identified sequence variation contributing to the aetiology of SLDP. However, factors beyond nucleotide variations, such as epigenetic changes and CNVs can also lead to pubertal timing disorders. Moreover, CNVs are seen in multiple individuals (n=92) from the Deciphering Developmental Disorders study (https://www.deciphergenomics.org) with a phenotype including DP (HP:0000823). We performed whole genome sequencing on 49 probands with SLDP and subsequently, analysed the data for CNV. The data was initially called, annotated, filtered then partitioned for classification of CNVs using a command-line tool that implements the ACMG guidelines to evaluate the pathogenicity of germline duplications and deletions. Using an unbiased candidate gene approach, we identified several deletions that affected 60 known/predicted dosage sensitive genes and combines with functional enrichment analysis; This approach revealed potential molecular pathways and biological processes involved in the pathogenesis of SLDP, including histone acetylation, and neural plate development. To refine our findings, we applied additional filters, including known HPG axis genes, GWAS loci associated with pubertal timing, decipher CNV tracks, and DP gene panels, to narrow down large number of rare predicted damaging CNVs and prioritize those with potential relevance to DP. Our study highlights the potential role of CNVs in DP and expands our understanding of the molecular pathways and biological processes involved in this condition, shedding light on the complex mechanisms underlying DP.
Presentation: 6/2/2024