bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Covid-19 on the Rate of Diabetic Ketoacidosis in Pediatric New-Onset Type 1 Diabetes
Authors: Bogale Kaleb T , Urban Valerie , Schaefer Eric , Krishna Kanthi Bangalore 
Published: May 2021

Abstract
Introduction: Several demographic and clinical characteristics, including age, low socioeconomic status, and misdiagnosis at initial clinical presentation were previously associated with increased risk of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in the pediatric population. However, it is unclear whether the coronavirus (COVID-19) pandemic and subsequent lockdown influenced the rate of DKA in children newly diagnosed with T1D. We undertook this study to identify the impact of the COVID-19 pandemic on the rate of DKA in children newly diagnosed with T1D in a single tertiary care referral center in central Pennsylvania. Methods: We performed an extension of a retrospective analysis of all pediatric patients (age ≤18) newly diagnosed with T1D within a tertiary care referral center between 01/01/2017-09/14/2020. Demographics, insurance coverage, and all clinical documents 30 days before their T1D diagnosis were abstracted to assess for symptoms at diagnosis (polyuria, polydipsia, nocturia, weight loss, nausea, vomiting, altered mental status, infection, vision changes, and autism spectrum disorder), lab values (blood glucose, HbA1c, venous pH, and bicarbonate), and any healthcare encounters within 30 days of their diagnosis of T1D. We performed descriptive statistics and univariate analyses [evaluating children diagnosed with T1D during the pre-COVID-19 era (diagnosed between 1/1/2017-2/28/2020) and post-COVID-19 era (diagnosed between 03/01/2020-09/14/2020) associated with the incidence of DKA], followed by logistic regression analysis (incorporating key clinical factors previously associated with DKA and the pre- or post- COVID-19 era classification). Results: 412 pediatric patients with T1D [171 F:241 M; 370 pre-COVID-19 era:42 post-COVID-19 era] were included. The percentages of DKA diagnoses at admission were very similar between the pre-COVID-19 and post-COVID-19 groups (47% vs. 48%), as were the severity (13% vs. 14% mild DKA; 33% vs. 31% moderate or severe DKA). There were no temporal associations with the rate of DKA in respect to COVID-19, however, age (0-3 and 9-13 years), misdiagnosis during a preceding healthcare encounter, presenting to the emergency department directly, elevated HbA1c (&gt;10.0%/13.4mmol/L), and altered mental status were associated with increased risk of DKA on multivariable analysis. Conclusion: There were no fluctuations in the rate of DKA among pediatric patients newly diagnosed with T1D throughout the COVID-19 pandemic in central Pennsylvania. Interestingly, some geographic locations observed an increased frequency of DKA in children newly diagnosed with T1D, while others noted a decreased rate. Regardless, our findings suggest previously described predictors of DKA in the pediatric population persist, even in the setting of the COVID-19 pandemic.
Defects in the GnRH Neuronal Migration factor, CCDC141, Lead to Self-Limited Delayed Puberty
Authors: Saengkaew Tansit , Mancini Alessandra , Ruiz-Babot Gerard , Cabrera Claudia P , Barnes Michael R , Dunkel Leo , Guasti Leonardo , Howard Sasha 
Published: May 2021

Abstract
GnRH neuronal biology has been identified as a critical element in the pathogenesis of self-limited DP, previously implicated exclusively in the pathophysiology of idiopathic hypogonadotropic hypogonadism (IHH). We hypothesise that this condition may be inherited via genetic variants discoverable through whole-exome sequencing (WES), by focusing on genes involved in GnRH neuron development and function, and genes reported in IHH. We analysed WES data from large Finnish cohort with familial self-limited DP, focusing on genes recently reported in IHH. WES data of 100 DP families have been analysed with a total of 193 individuals: 100 probands, 158 affected and 35 unaffected family members. Potentially pathogenic rare variants segregating within cohort families were identified using a virtual panel of recently reported IHH genes (n=13). This analysis identified 6 rare potentially pathogenic variants in CCDC141 in 25 individuals of 8 families which account for almost 10% of self-limited DP cases in this cohort, without variants identified in cohort control cases. Previous studies reported that homozygous or compound heterozygous mutations of CCDC141 cause Kallmann syndrome and IHH, due to impaired GnRH neuronal migration. In this study, all 6 CCDC141 variants were heterozygous missense variants predicted to be deleterious by in silico prediction tools. Most probands were male (n=7) with typical features of self-limited DP, with absence of secondary sexual characteristics, delayed bone age, and low gonadotropins and sex steroids at first presentation and spontaneous entry into puberty later than age of 14 years without treatment. The majority of pedigrees displayed good segregation of variants with the DP trait, following an autosomal dominant inheritance pattern. However, in two families, there was a complex inheritance pattern with compound heterozygosity (p.Ser55Cys and p.Asp767Asn) and possible incomplete penetrance. In vitro study showed that the overexpression of four key CCDC141 variants in HEK293 cells delayed cell migration, 72% in p.Ser55Cys (p=0.04), 66% in p.Gln507His (p=0.04), 65% in p.Asp767Asn (p=0.02), and 83% in p.Ala1073Thr (p=0.01), when compared to WT (100%). Moreover, WT-overexpressed cells increased the rate of cell migration when compared to non-transfected cells (100% vs 65%, p=0.005), reaffirming that CCDC141 has a role in cell migration. In conclusion, heterozygous deficiency of CCDC141, previously reported to cause IHH, can cause self-limited DP due to abnormal GnRH migration during foetal development.
Growth Outcome and Metabolic Profile of PWS Patients Treated With GH and Differences Between AGA and SGA Group
Authors: Yoon Ju Young , Cheon Chong Kun , Yoo Seok Dong 
Published: May 2021

Abstract
Objective: Prader-Willi syndrome (PWS) is a complex genetic disease associated with growth impairment, severe obesity and metabolic dysfunctions. High proportion of PWS patients are born small for gestational age (SGA), which also increase the risk of growth impairment and metabolic dysfunction. The aim of this study was to describe growth outcome and and metabolic profiles in GH treated PWS patients. We also investigated the differences in clinical outcomes between AGA and SGA group Methods: Data of 55 children and adults with genetically verified PWS aged more than 2 years old (32 male and 23 female, age 2-18.8 years) from single center were studied. Only patients who were treated with GH were included. The clinical characteristics and laboratory findings were reviewed retrospectively. Results: Among 55 subjects, 39 had 15q11-13 deletion and 16 had uniparental disomy (UPD). Twenty (36.3%) were born SGA. All patients received GH treatment, and 11 (20%) discontinued GH treatemnt. Mean age at GH treatment initiation was 2.5 (range 0.3-12.4) years, and mean duration of treatment was 6.3 (range 1.0-11.3) years. Current height-SDS (-0.36 vs -0.16) and BMI-SDS (1.44 vs 1.33) did not differ between AGA and SGA group. Two patients in SGA group, but none in AGA group had diabetes mellitus. Mean glucose level was also higher in SGA group (100.1 vs 114.4 mg/dL) Conclusions: Our report gives an overview of growth profile and metabolic dysfunctions recorded in GH treated PWS patients. Growth profile did not differ between AGA and SGA group. Glucose level was higher in SGA group, so more careful monitoring and prevention for DM will be required in SGA group.
Pituitary Hypoplasia Is the Best MRI Predictor of the Severity and Type of Growth Hormone Deficiency in Children With Congenital Growth Hormone Deficiency
Authors: Sharma Himanshu , Kumar Anshul , Purwar Naincy , Mathur Nitish , Sharma Balram , Mathur Sandeep Kumar 
Published: May 2021

Abstract
Background and Objectives: Congenital idiopathic growth hormone deficiency(GHD) is associated with various MRI abnormalities, including both sellar anomalies such as pituitary hypoplasia, ectopic pituitary, empty sella and abnormalities of the pituitary stalk and extrasellar abnormalities such as Arnold Chiari malformation, corpus callosum agenesis, arachnoid cyst, septum pellucidum agenesis, enlarged ventricles, vermis dysplasia, and sphenoid cyst. However, it remains contentious whether MRI brain findings could provide an additional avenue for precisely predicting the differentiation of GHD based on severity(severe or partial) and type(isolated GHD or multiple pituitary hormone deficiency MPHD). This study aimed to ascertain the abnormality that is the best predictor of severe GHD and type of GHD amongst the different MRI findings. Methods: This was an analytical cross-sectional study conducted from 2018-2020. During the study period, we included a total of 100 subjects diagnosed to have idiopathic GHD after the exclusion of syndromic causes, system illness, presence of pituitary mass, and those with h/o cranial irradiation. Patients were divided into severe GHD and partial GHD based on peak stimulated GH of &lt;5 ng/dl and ≥ 5 ng/dl respectively and into groups based on isolated GHD and MPHD. Patients were further divided into groups based on the presence of pituitary hypoplasia,extrasellar brain abnormalities (EBA), and presence of ectopic posterior pituitary and/or pituitary stalk abnormalities(EPP/PSA), respectively. Analyses were performed using SPSS version 24.0 software. Results: Amongst 100 subjects with idiopathic congenital GHD, 66 (66%) subjects had Isolated GHD while the remaining 34 (34%) had MPHD. 71 had severe GHD, and 29 had partial GHD. Amongst the MRI findings, pituitary hypoplasia was the most common finding observed in 53% of patients, while 23(23%) had EBA, and 25(25%) had EPP/PSA. Pituitary hypoplasia was observed to be the best predictor of severity of GHD with an odds ratio(OR) of 10.8 (95% CI 3.38-29.6) followed by ectopic posterior pituitary /pituitary stalk abnormalities (OR =2.8, 95% CI 1.5-9.5) while the presence of extrasellar abnormalities was the weakest predictor (OR =1.8, 95% CI 1.05-3.2). Pituitary hypoplasia was the only finding to significantly predict MPHD (OR=9.2). On ROC analysis, a Pituitary height SDS of -2.03 had a 73.2 % sensitivity and specificity of 79.3%(AUC =0.787,95% CI 0.7-0.873) for severe GHD and a sensitivity of 88.2 % and specificity of 66.7% (AUC =0.745, 95% CI 0.68-0.877) for MPHD. Conclusion: We observed Pituitary hypoplasia to be not only the most frequent MRI abnormality but also the best predictor of severe GHD and MPHD amongst various sellar and extrasellar abnormalities.
A Rare Variant of Turner Syndrome With Isodicentric X Chromosome Resulting in Trisomy: A Case Report
Authors: Chan Jacqueline T , Cabanas Ma Cristine C 
Published: May 2021

Abstract
Introduction: Turner syndrome is a genetic disorder caused by the loss of an X-chromosome affecting approximately 1 in every 2,500 females. A constitutional karyotype of 45, X accounts for nearly 50% of patients, while mosaicism and other chromosomal structural abnormalities such as deletions, duplications, ring, isodicentric chromosomes, inversions and translocations, have been reported. Isodicentric X chromosomes are formed presumably by end-to-end fusion of chromatids after a break, with subsequent loss of an acentric fragment. These chromosomes in general have phenotypes characteristic of the resultant X deletions. We present a case of a 14-year-old female diagnosed with Turner syndrome and with 2 abnormal cell lines. Case Presentation: This is a case of a 14-year-old female referred to pediatric endocrinology for concerns of short stature and delayed puberty. She denied any food intolerance, bloating and diarrhea. She is otherwise healthy with unremarkable past medical history. Her weight was normal at 15th percentile. Her height was 137cm or 0.01 percentile with a Z score of –3.6. Work up revealed hypothyroidism with TSH 16.3 mcIU/mL (0.4-4.7 mcIU/mL), positive thyroid peroxidase antibody &gt;900 IU/ml and thyroglobulin antibody 14 IU/mL (&lt; 1.8IUm/mL) and celiac disease (tissue transglutaminase IgA &gt; 100 U/mL) both without associated symptoms. Estradiol level was undetectable, and LH and FSH were 9.89 mIU/ml and 52.69 mIU/ml respectively. The rest of her labs including growth factors were normal. Bone age was normal at 13 years for chronological age of 14 years old. Chromosomal microarray revealed 2 abnormal cell lines: one with monosomy X, the other with a normal X chromosome and an isodicentric X chromosome involving the Xp11.22-q28 region resulting in trisomy of the latter cell line.
Levothyroxine was started. Plan is to start growth hormone therapy and initiate puberty after. Patient referred to necessary subspecialties for hearing evaluation as well as cardiac evaluation Conclusion
Turner syndrome usually presents as females with short stature, gonadal dysgenesis and 45,X cell line that is either singly or in combination with another
mosaic cell line. Our patient presented with short stature and absence of puberty. Initial investigation revealed hypothyroidism and highly positive celiac antibodies, but unable to attribute her short stature to both diagnoses given the lack of other symptoms. This case emphasizes the importance of checking the karyotype in females presenting with short stature and more importantly delayed puberty as part of the diagnostic algorithm. In addition, checking thyroid and celiac panel are also imperative as treatment of these are treatable etiologies of short stature.
Factors Affecting Thyroid Hormone Changes Over 1 Month After Birth in Preterm Newborns
Authors: Kim Seulki , Kim Sung Eon , Lee Na Yeong , Ahn Moon Bae , Kim Shin Hee , Cho Won Kyung , Cho Kyung Soon , Jung Min Ho , Suh Byung-Kyu 
Published: May 2021

Abstract
Purpose: To analyze factors affecting thyroid hormone changes over 1 month after birth in preterm newborns. Methods: Thyroid hormones, including free thyroxine (fT4) and thyroid stimulating hormone (TSH) of 216 preterm newborns (mean gestational age [GA] 33.6±2.6 weeks), were retrospectively reviewed at the 1st and 4th weeks after birth. Preterm newborns were classified into three groups according to the GA (&lt; 28 weeks, group A; 28-32 weeks, group B; 32-36 weeks, group C). The association between thyroid hormone changes and clinical factors was analyzed. Results: Preterm newborns with older GA had higher concentrations of fT4 (group A, 0.9±0.2 ng/dL; group B, 1.2±0.2 ng/dL; group C, 1.5±0.3 ng/dL) and TSH (group A, 2.7±3.2 mIU/L; group B, 4.5±3.3 mIU/L; group C, 6.0±3.8 mIU/L), both at the 1st week after birth. fT4 and TSH at the 1st week after birth were positively correlated with the GA (r=0.52, P=0.0001; r=0.30, P=0.0001) and Apgar score at 5 minutes (r=0.31, P=0.0001; r=0.28, P=0.0001). TSH concentration at the 1st week after birth was significantly lower in the abnormal brain sonogram group than in the normal brain sonogram group (4.4±3.7 vs 6.1±3.4 mIU/L, P=0.001); there were no differences at the 4th week after birth between these groups (4.2±2.6 vs 3.4±2.4 mIU/L, P=0.485). Multiple linear regression analysis revealed that GA was positively correlated with fT4 and TSH at the 1st week, and fT4 at 4th week after birth (B=0.08, SE=0.12, P=0.0001; B=0.34, SE=0.15, P=0.029; B=0.02, SE=0.01, P=0.013). Conclusion: Thyroid hormone levels in preterm newborns are mostly within the normal reference value of full-term newborns within 4 weeks of life, and are mainly affected by GA and brain ultrasound abnormalities.
Impact of Male Hypogonadism on Bone Mineral Density in Childhood Hemato-Oncologic Disease
Authors: Kim Sungeun , Lee Nayeong , Kim Seulki , Ahn Moon Bae , Kim Shin-Hee , Won-Kyoung Cho , Cho Kyoung Soon , Jung Min-Ho , Suh Byung-Kyu 
Published: May 2021

Abstract
Introduction: Patients with childhood hemato-oncologic diseases have many medical problems, not only due to disease itself, but also adverse effects of specific treatment that patients had. Osteoporosis, one of the most common side effects of the treatment, decreases quality of life when the disease progresses. Our study investigated the impact of male hypogonadism on secondary osteoporosis in childhood hemato-oncologic patients, using association between male sex hormone and bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA). Methods: This study collected BMD score (T-score) of 52 male subjects who were diagnosed with hemato-oncologic diseases in the past (average age of 22.3 years at DXA examination). All subjects measured serum testosterone and we divided them into two subgroups according to gonadal status. The first group, called hypogondal group, was a group of subjects with serum testosterone level less than 3.5 ng/ml. The other group was classified into eugonadal group, with serum testosterone level equal or more than 3.5 ng/ml. Mean BMD score of spine and hip were presented and compared between the two groups. Furthermore, relativity with other risk factors for osteoporosis was calculated using multiple regression analysis. Results: Overall, spine BMD in the hypogondal group did not significantly differ from the eugonadal group. However, hip BMD was significantly lower in the hypogonadal group (mean difference; 0.8, p = 0.023). Furthermore, testosterone level itself showed linear correlation with BMD score in hip (p = 0.013). When other risk factors for osteoporosis were taken into account, hemato-oncologic patients treated with total body irradiation also had significantly lower hip BMD (p = 0.007) compared with non-irradiation group. Hypogonadism still remained a significant factor for decreased bone mineral density in hip (p = 0.022). Conclusions: Hemato-oncologic patients with hypogonadism or previously treated with total body irradiation are at increased risk of decreased bone mineral density in both hips. Hypogonadism alone remains independent risk factor for osteoporosis in hip. Attention of these male patient should be paid to prevent the incidence of secondary osteoporosis.
Estrogen Supplementation Is Associated With Higher Quality of Life Scores in Women With Cystic Fibrosis
Authors: Wu Malinda , Arora Neha , Sueblinvong Viranuj , Hunt William R , Tangpricha Vin 
Published: May 2021

Abstract
Purpose: With rapid advancements in therapeutic options for patients with cystic fibrosis (CF), the median predicted survival has increased to 47 years along with the prevalence of non-pulmonary complications for patients with CF. Women with CF suffer irregular menses, sexual dysfunction and low bone mineral density. With increasing pregnancies among women with CF, they may consider contraception. Estrogen supplementation may modulate these outcomes and others. The purpose of this study was to explore the effects of supplemental estrogen use on quality of life (QOL) in CF.
Methods: Women with CF ages 16-50 years were administered a validated CF-specific QOL survey (CFQ-R) during a routine CF clinic visit through an IRB-approved cross-sectional study. The QOL domain scores of subjects taking and not taking estrogen were compared pairwise by Kruskal Wallis tests and overall by Wilcoxon signed rank test.
Results: The estrogen exposed and estrogen unexposed subjects with CF had similar age, BMI, FEV1, race, CF mutation, pancreatic insufficiency, diabetes and relationship status. The estrogen exposed subjects were taking 20-30 mcg of ethinyl estradiol in oral contraceptive pills. The estrogen exposed subjects had consistently higher QOL scores than the estrogen unexposed subjects (p=0.001). The estrogen exposed subjects had significantly higher scores in 7 of the 12 CFQ-R categories: physical, vitality, treatment burden and role domains and weight, respiratory and digestion symptom scales (p&lt;0.05). When correcting for multiple comparisons, the estrogen-supplemented women had higher role domain scores than women not taking estrogen supplement (p=0.03).
Conclusions: Estrogen supplementation was associated with improved quality of life in women with CF. This cross-sectional study highlights the need for further investigation into the potential benefits of estrogen supplementation. The dose, route, formulation and timing of estrogen therapy may modulate the beneficial effects for women with CF.
Support: This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award TL1TR002382 and UL1TR002378, and Cystic Fibrosis Foundation award WU20D0. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or CFF.
Gonadotropin Response to Insulin and Lipid Infusion Reproduces the Reprometabolic Syndrome of Obesity in Lean Women
Authors: Santoro Nanette F , Santoro Nanette F 
Published: May 2021

Abstract
Introduction: The reprometabolic syndrome of obesity is associated with reduced gonadotropins and impaired LH and FSH response to gonadotropin releasing hormone (GnRH). We sought to reproductive the reprometabolic syndrome in normal weight, eumenorrheic women by infusing a combination of insulin and lipid. Materials and Methods: 15 women, mean age 32 (IQR 26,36) and BMI 21.9 (20.2, 22.9) were recruited with intent to perform early follicular phase, 6-hour infusions of insulin (20-40mg/mU/m2/min) and lipid (Intralipid) or saline infusion (controls); 12 women completed both intended studies and an additional 3 women completed only one of the two studies. The first 4 hours of each study assessed endogenous gonadotropins; at 4hrs, a 75 ng/kg GnRH bolus was administered and sampling continued until 6hrs. Linear mixed model analysis was used to determine differences between Intralipid versus saline on endogenous LH pulse amplitude (primary outcomes), mean FSH, and area under the curve (AUC) response to GnRH (secondary outcomes). Results: LH pulse amplitude, mean FSH, and both AUC responses to GnRH were all reduced by Intralipid/insulin; mean FSH (P=0.03) and AUC for LH (P=0.05) were at or near statistical significance. LH pulse amplitude and response to GnRH were significantly reduced (P=0.04 and 0.02) when one participant with very high LH and AMH levels was excluded. Discussion: Acute infusion of insulin/lipid to eumenorrheic, normal weight women recapitulated the reprometabolic syndrome of obesity. These findings imply that specific circulating factors in obese women contribute to their sub fertility and thus may be amenable to discovery and treatment.