bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Mutation of the AR Androgen Receptor Gene
Authors: Aljasser Abdullah Abdulruhman 
Published: May 2021

Abstract
Androgen insensitivity syndrome (AIS), formerly known as testicular feminization, is an X-linked recessive condition resulting in a failure of normal masculinization of the external genitalia in chromosomally male individuals. The basic etiology of androgen insensitivity syndrome is a loss-of-function mutation in the androgen receptor (AR) gene. Loss of AR function means that, despite normal levels of androgen synthesis, the typical postreceptor events that mediate the effects of hormones on tissues do not occur. This results in the phenotype of prenatal undervirilization of external genitalia, absence of pubic and axillary hair, lack of acne, and absence of voice changes at puberty We present This baby reffered at age of 2 months from pediatric surgery as a case of bilateral inguinal hernia and chromosomes 46xy. Phenotypically female no male structures no phallus and single opening and visible labia, both test are in the inguinal canals. HCG stimulation test shows: Testosterone: the level at (0) time: 0.8 nmol/l then 3 days: 31.4 nmol/l. DHT dihydrotetostrerone: the level at (0) time: 13 NG/L then 3 days: 485 The baby was given 3 doses of Testosterone injections 150mg but no response at the genetalia. Radiological investigations shows ultrasound both tests at the inguinal canals and no uterus Also MRI of pelvis shows absence of uterus and both test at the inguinal canals Molecular genetics analysis for Androgen receptor gene: Exon 7 c.2512 G &gt;A hem. P.Glu838lys missense, novel VUS,likely pathogenic. The segregations analysis test in the process. Her we present a novel mutation of the AR gene not reported yet in literature.
Are Current Normal Values of 11DOC Useful for Diagnosis of Non Classical Congenital Adrenal Hyperplasia Due to 11β- Hydroxylase Deficiency?
Authors: Barash Galia , Drach Lior , Naugolni Larisa , Yacoel Tamar , Bistritzer Tzvi Tzvi , Rachmiel Marianna 
Published: May 2021

Abstract
Background: A non-classic form of 11β-hydroxylase deficiency (NC 11β-OHD) has been reported to cause mild androgen excess, with a clinical presentation of precocious puberty, menstrual cycle abnormalities, or hirsutism during adolescence. Since genetic diagnosis of NC 11βOHD is yet not routinely available, the current gold standard for biochemical diagnosis is elevated 11 DOC levels after corticotropin stimulation test (ACTHstimT). However, there are no clear hormone level cutoffs. One of the accepted references for basal and stimulated levels for the pediatric population was published in 1991 by Lashansky et al1. Aim: To determine the correlation between 11DOC levels measured during ACTHstimT, clinical symptoms attributed to NC11βOHD and androgen levels at presentation, and long-term follow-up among children and adolescents with hyperandrogenism. Methods: a retrospective study including all patients who underwent ACTHstimT between 20072015, in one center, during which 11 DOC levels were routinely measured as part of the test. Clinical data was collected from the patients’ medical files and, by telephone calls for complete long-term follow-up. 11DOC levels before and after ACTHstimT were categorized as elevated according to both pre-defined cut-offs; greater than 1.5 times the 95th percentile according to Lashansky1 normal level for sex and age, and greater than 1.5 times the upper limit of the normal level of the commercial kit. Results: Data were complete at presentation for 136 patients, 92 females, and for long for 98 patients, 68 females, mean follow up duration of 3.1 years (1.37,5.09). There was no statistically significant difference in the number of cases with elevated 11DOC according to both cut-offs, among patients with precocious and early puberty, premature adrenarche nor acne. Higher baseline and stimulated 11 DOC levels were demonstrated in females who presented with mild hirsutism and regular menses. Long term data demonstrated no statistically significant difference in the number of cases with elevated 11DOC levels among patients with compromised final adult height, PCOS or hyperandrogenism. There was negative correlation between stimulated 11 DOC levels and basal levels of testosterone, androstenedione and DHEAS levels. Conclusions: This report demonstrates that the current interpretation of 11DOC levels, basal and ACTHstimulated in children, according to 1.5 times the highest range, of both, the Lashansky1 acceptable norms for children, and some of the laboratory’s kit, are not clinically applicable.1Lashansky G, Saenger P, Fishman K, Gautier T, Mayes D, Berg G and Reiter E. Normative data for adrenal steroidogenesis in a healthy pediatric population: Age- and sex-related changes after adrenocorticotropin stimulation. J. Clin. Endocrinol. Metab. 1991; 73(3): 674-686.
Food Perception and Differences in Dietary Decision-Making in Youth With Congenital Adrenal Hyperplasia
Authors: Luo Shan , Overholtzer Lloyd N , Lim Seung-Lark , Kim Elaine , Fraga Nicole , Herting Megan M , Tanawattanacharoen Veeraya K , Geffner Mitchell E , Kim Mimi S 
Published: May 2021

Abstract
Background: Youth with congenital adrenal hyperplasia (CAH) have a higher prevalence of obesity, early adiposity rebound, and increased fat mass. Unsuccessful dietary self-control could contribute to obesity, and understanding food-seeking behavior could therefore guide prevention. Dietary decision-making involves key brain regions such as the limbic system and the prefrontal cortex, which are associated with choice and reward. These regions (i.e., prefrontal cortex, amygdala, hippocampus) can be smaller in volume in CAH patients. However, little is known about dietary decision-making in CAH. We hypothesized that CAH youth would exhibit differences in dietary decision-making and aimed to study food choices in CAH youth compared to controls.
Methods: 37 CAH youth (12.2 ± 3.1 y, 60% male, BMIz 1.6 ± 0.8) and 100 controls (11.7 ± 2.4 y, 57% male, BMIz 0.9 ± 1.2) completed a behavioral computer-based food choice task. They rated 30 high- and 30 low-calorie food cues for tastiness, healthiness, and liking. Food pairs discordant for taste and health ratings were generated, and youth were asked to choose the item they wanted to eat. Cursor-trajectory analyses measured area under the curve (AUC) and maximum deviation time (MDT), with successful choice trials evident when the healthier food was chosen. Based on individual ratings for food cues, β-coefficients for ratings predicting food preference were generated.
Results: CAH youth and controls did not show differences in food ratings (P &gt; 0.30 for all) or in the percentage of successful trials of total choice trials (P = 0.16). However, CAH youth showed larger mean AUCs compared to controls [T(135) = 2.15; P = 0.03] suggesting that they may experience more conflict and exert more cognitive effort in decision-making. CAH youth also had longer mean MDTs [T(102.3) = 2.59; P = 0.01] in successful choice trials, indicating a later time at which a final decision was made. β-health and β-taste predicting food preference did not differ between groups, and β-health was correlated with successful choice trials in both CAH (r = 0.38, P = 0.02) and controls (r = 0.48, P &lt; 0.01). However, β-taste was negatively correlated with successful choice trials in controls only (r = -0.42, P &lt; 0.01; CAH r = -0.22, P = 0.18).
Conclusion: Although youth with and without CAH had similar perceptions of food, CAH youth may exert greater cognitive effort and experience more conflict in dietary decision-making. This could suggest that factors inherent to CAH such as abnormal neural pathways, or disease treatment, could affect the cognitive control of food choices in CAH youth.
Growth Hormone Therapy for Children With Duchenne Muscular Dystrophy and Glucocorticoid Induced Short Stature
Authors: Lavi Eran , Cohen Amitay , Dor Talya , Tsabari Reuven , Zangen David 
Published: May 2021

Abstract
Background: Duchenne Muscular Dystrophy (DMD) is the most common form of inherited muscle disease in childhood. DMD patients have severe growth retardation due to several reasons including chronic treatment with glucocorticoid (GC). Data regarding the efficacy and safety of Recombinant Growth Hormone (rGH) treatment in DMD patients is very limited. The aim of this study is to evaluate efficacy and safety of growth hormone treatment in 4 DMD boys with glucocorticoid induced growth failure. Methods and Results: 4 prepubertal patients with DMD on high dose of GC (Deflazecort or Prednisone) at an age range between 12-13.6 years and significantly delayed bone age (8.5-11 years) were studied. rhGH was subcutaneously administered at a dose of 0.033 mg/kg/d for a duration of 12-18 months. Pretreatment annual growth rate of the 4 patients (0, 3,2.5, 1.5 cm/yr) improved during treatment (3.8, 7.8, 7.2, 3.3 cm/yr respectively). While height SD improved in 2 patients: -2.74 and -2.96 height SD to -2.52 and -2.64 height SD on rGH therapy, In the other two patients pretreatment continuous decline in height SD was arrested. Motor function decline was similar pre-growth hormone and during treatment. Cardiopulmonary function measured by ejection fraction and forced vital capacity was unchanged during the treatment period. Conclusions: This report of growth hormone therapy in DMD patients revealed an improved prepubertal growth velocity without detrimental effects observed on neuromuscular and cardiopulmonary function. Larger randomized control studies are required to prove safety and efficacy of this treatment in DMD patients.
Gut Microbiota Assessment in Obese Children and Adolescents by Machine Learning Algorithms
Authors: d’Annunzio Giuseppe , Biassoni Roberto , Marco Eddi Di , Valle Alberto La , Piccolo Gianluca , Bonaretti Carola , Napoli Flavia , Patti Giuseppa , Minuto Nicola , Maghnie Mohamad 
Published: May 2021

Abstract
Gut microbiota has been recently established to play a contributory role in the development and progression of obesity, a multifactorial disease predisposing to several comorbidities. Our aim was to evaluate the gut microbiota composition by machine learning algorithms in 33 Italian obese children and adolescents. Patients were divided in 3 groups: simple obesity (n=10, mean age 11.6 +3.0, median 10.8), metabolic syndrome (n=16, mean age 13.3+3.0, median 13.5) or Prader Willi syndrome (n=7, mean age 8.3+5.3, median 8.7). Inclusion criteria were living in Northern Italy, born singleton birth, personal history negative for acute or chronic gastrointestinal diseases and/or antibiotic or probiotics administration in the previous month. As controls 17 healthy control (mean age 12.0+2.4 median 10.6) were analyzed using the same approach. Statistical analysis for sparse high-throughput sequencing data algorithm (metagenomeSeq) using cumulative sum scaling for data normalization was performed. False discovery rate adjusted p-value using zero-inflated Gaussian fit statistical model (indicated with q). Over all analyses Parasutterella resulted with a q=0.014424, the comparison between obese patients and controls was q=0.021194. In the overall analysis Acidaminococcus intestini showed q=0.039528 while the comparison in pairs of two between metabolic syndrome and controls was q=0.03979. Using the EdgeR algorithm Clostridium bartlettii abundance between Prader Willi patients and controls resulted in q=0.02189. In overall analysis Ruminococcus flavefaciens resulted q=6.1528E-17 (using the DESeq2 algorithm); in pairs analysis Ruminococcus flavefaciens showed significant difference in Prader Willi patients as compared to obese (q=0.013755) and metabolic syndrome ones (q=0.021898). In overall analysis Veillonellaceae showed a FDR q=0.029303. while its richness resulted more than 150 times higher in metabolic syndrome patients than in controls (q=0.039793 evaluated with DESeq2 algorithm). Among Veillonellaceae descendants, the Veillonella rogosae showed, on the contrary, the lowest abundance in metabolic syndrome patients as compared to other groups. In detail, Veillonella rogosae abundances were 13 (FDR q=0.014566), around 20 times (FDR q=0.010646) and &gt;20 (FDR q=0.0025008) less abundant in metabolic syndrome patients than obese, Prader Willi patients and controls, respectively. Significant differences in gut microbiota composition was found among patients with different degrees of obesity and controls. Further, Prader Willi patients showed a peculiar microbiota assessment.
Hormonal Replacement Therapy in Premenopausal Women With Hypogonadism: An Analysis of Prescriber Practices
Authors: Martirossian Alexandra Nicole , Williams Kelley , Silverstein Julie Martha 
Published: May 2021

Abstract
Introduction: Estrogen replacement therapy in premenopausal women with hypogonadism is important for reducing risk of osteoporosis, cardiovascular disease, and urogenital atrophy. Numerous formulations of estrogen are available and there is limited evidence to guide management. We conducted a preliminary retrospective study to determine prescribing practices of hormonal replacement therapy (HRT) in premenopausal women with hypogonadism and frequency of DEXA scan screening.
Methods: Using ICD 10 and billing codes, females ages 18-51 with a diagnosis of hypogonadism were identified. Patients with a diagnosis of prolactinoma, breast or endometrial cancer, and significant thrombotic disease as well as patients without clinical data were excluded. Information regarding etiology of hypogonadism, age of diagnosis, type/dose of estrogen and progesterone prescribed, prescriber specialty [obstetrics and gynecology (OB/GYN), endocrinology (ENDO), primary care (PCP), or other], and DEXA results was recorded. Prescriptions for estrogen and progesterone were compared in women with primary vs secondary hypogonadism and among specialties. For bone density, we analyzed the frequency of DEXA scan ordering. Statistical analysis was performed using Fisher’s Exact Test.
Results: Out of 1,306 patients identified, 150 met criteria for analysis. 99 (66%) had primary hypogonadism, 47 (31%) had secondary hypogonadism, and 4 (3%) had mixed or unknown type. OB/GYN was the most common prescriber (n=88, 59%) followed by ENDO (n=39, 26%) and PCP/other (n=23, 15%). For all patients, type of estrogen prescribed differed by specialty (p=0.041) with ENDO most commonly prescribing transdermal estradiol (47%), OB/GYN either transdermal estradiol (30%) or oral ethinyl estradiol (30%), and PCP/other oral estradiol (45%). Patients with primary, but not secondary hypogonadism, were prescribed more transdermal estradiol by ENDO as compared to OB/GYN (68% vs 27%, p=0.039). In patients with secondary hypogonadism on oral ethinyl estradiol, mean daily dose (mcg) differed among providers ((ENDO 27 ± 6, OB/GYN 35 ± 8, PCP/other 10 ± 0, p=0.04). There was no difference in dosing of other types of estrogen, prescribing practices for progesterone, or frequency of DEXA scans among providers. DEXA scans were performed at least once in 59 (39%) and more than once in 20 (13%) patients.
Conclusions: Overall, premenopausal women with hypogonadism seeing ENDO as compared to other providers were more frequently prescribed transdermal estradiol as compared to oral estradiol and/or other types of estrogen. Only dosages of oral ethinyl estradiol differed by provider. Despite an increased risk of osteoporosis, a minority of patients underwent DEXA scans. This study highlights heterogeneity in prescribing practices and underscores the need for further research to guide management of premenopausal women with hypogonadism.
Bone Morphogenetic Protein 2 Increases Human Trophoblast Invasion by Up-Regulating Integrin Beta3
Authors: Hu Cuiping , Yan Junhao 
Published: May 2021

Abstract
The adequate invasion of extravillous trophoblast cells (EVTs) is indispensable for the implantation of embryos and subsequent remodeling of uterine spiral arteries in early human gestation. Bone morphogenetic protein 2 (BMP2), which is abundantly expressed at the maternal-fetal interface, has been shown to promote the human EVT invasion process (1). Integrin switching (i.e., a switch from α6β4 to αvβ3) plays essential roles in cell-extracellular matrix adhesion and has been reported to influence EVT migration and invasion (2). Moreover, integrin β3 has been found to promote the adhesion, invasion, and migration abilities of embryonic trophoblasts (3). However, whether integrin β3 participates in BMP2 signaling and mediates BMP2-increased-human trophoblast invasion remains unknown. The purpose of our study was to explore the effects of BMP2 on integrin αvβ3 expression and the possible mediation role of integrin β3 in BMP2-regulated human trophoblast invasion. We used immortalized human trophoblast cell line (HTR8/SVneo) and primary human extravillous trophoblast cells (EVTs) isolated from first-trimester villi as study models. RT-qPCR and Western blot assay were respectively utilized to detect the messenger RNA and protein levels of intergrin αv and β3. The function of the target protein was studied by siRNA knockdown, and the trophoblast invasion ability was checked by Matrigel-coated transwell invasion assays. Our results demonstrated that the mRNA and protein levels of integrin β3, rather than integrin αv, were up-regulated after BMP2 treatment in HTR8/SVneo and primary EVT cells. Importantly, siRNA-mediated down-regulation of integrin β3 significantly inhibited basal and BMP2-induced HTR8/SVneo cell invasionas measured by transwell invasion assay. In conclusion, we findings support that BMP2 promotes human trophoblast cell invasion by up-regulating integrin β3 expression, benefiting the in-depth understanding of the pro-invasive effect of BMP2 on human trophoblasts during early pregnancy. Reference: (1) Hong-Jin Zhao et al., Cell Death Dis 2018;9:174. (2) Damsky, C.H. et al, Development 1994; 120, 3657-3666. (3) Dong-Mei He et al., Reproduction 2019;157:423-430.
Sex Differences in the Human Placenta MicroRNA Transcriptome
Authors: Flowers Amy E , Gonzalez Tania L , Eisman Laura E , Joshi Nikhil , Wu Di , Zhang Yizhou , Santiskulvong Chintda , Tang Jie , Buttle Rae , Sauro Erica , Clark Ekaterina L , Jefferies Caroline , Chan Jessica , Lin Yayu , Williams John , Pisarska Margareta Danuta 
Published: May 2021

Abstract
Maternal and fetal pregnancy outcomes vary based on fetal sex likely due to differences in placental function, reflected by sex differences in RNA expression. RNA transcripts are subject to fine-tuning control by post-transcriptional regulation including miRNAs binding to target RNAs and altering gene expression. Here we identify sexually dimorphic miRNA expression throughout gestation in the human placenta. Next-generation sequencing was used to identify human placenta miRNA expression profiles in first and third trimester uncomplicated pregnancies using discarded tissue obtained after chorionic villous sampling (n=113) and placenta (n=47). Differential expression analysis and mRNA target analysis were also examined. Sequencing identified 2,503 unique mature miRNAs expressed in each trimester. Of these, 13 significantly sexually dimorphic (FDR&lt;0.05) miRNAs were identified in the first trimester and 4 significantly sexually dimorphic miRNAs were identified in the third trimester, including one miRNA, hsa-miR-361-5p, expressed across gestation. All of these sexually dimorphic miRNAs were significantly upregulated in females compared to males. Pathways analysis with predicted targets suggests sex differences in cancer and inflammation-related pathways in the first trimester and inflammation and growth-related pathways in the third trimester. Differential expression analysis on sex-segregated data identified 613 miRNAs upregulated in female placentas and 636 miRNAs upregulated in male placentas across gestation (FDR&lt;0.05). In conclusion, fetal sex affects placental miRNA expression profiles and differentially expressed miRNAs may affect relevant downstream pathways, which may account for differences in pregnancy outcomes due to fetal sex. This work provides an expression atlas to direct functional studies investigating placental sex differences.
Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency
Authors: Chen Jingfei , Duan Jialei , Montalbano Alina , Li Boxun , Hon Gary , Mendelson Carole R 
Published: May 2021

Abstract
Single-cell RNA-seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-DeficiencyOur previous findings suggest that the fetus signals the mother when it is ready to be born through secretion of surfactant components/immune modulators, surfactant protein A (SP-A) and platelet-activating factor (PAF) by the fetal lung into amniotic fluid (AF). This occurs with increased proinflammatory cytokine expression by fetal AF macrophages (Mϕ), increased myometrial NF-κB activation and contractile (CAP) gene expression. Steroid receptor coactivator (Src)-1 and Src-2 are critical for developmental induction SP-A and PAF by the fetal lung. The finding that pregnant wild-type (WT) mice carrying Src-1 and Src-2 double-deficient fetuses (Src-1/-2d/d) manifested a marked delay (~38h) in parturition, further suggests that signals for parturition arise from the fetus and that Src-1 and Src-2 serve a critical role. Infiltrating leukocytes at the maternal-fetal interface (MFI)/decidua are known to play a central role in pregnancy maintenance and parturition timing. However, there is limited knowledge regarding gestational changes in immune cell composition toward term. To analyze gestational changes in the composition of immune cells within decidua and effects of Src-1/-2d/d, we conducted single-cell RNA-seq of ~17,000 decidual leukocytes (CD45+) from pregnant mice at 15.5 and 18.5 dpc carrying WT or Src-1/-2d/d fetuses. Unsupervised clustering identified 22 distinct decidual immune cell clusters, comprised of Mϕ, B cells, natural killer cells, neutrophils, dendritic cells and monocytes. Significant differences in cell type composition and transcriptional profiles were found across study groups (WT @ 15.5 dpc vs. 18.5 dpc; Src-1/-2d/dvs. WT @15.5 dpc and 18.5 dpc). Interestingly, in deciduas of pregnant mice carrying WT fetuses, Mϕ and B cell clusters markedly increased between 15.5 and 18.5 dpc, whereas, neutrophils declined; however, these gestational changes did not occur in pregnant mice carrying Src-1/-2d/d fetuses. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these immune cell subtypes to uncover their putative functions. These findings highlight the complexity and dynamics of the decidual immune cell landscape during the transition from myometrial quiescence to contractility, and the fetal-maternal interactions leading to parturition. Support: NIH grants R01-HL050022 (CRM) and P01-HD087150 (CRM), Burroughs Wellcome Preterm Birth Grant #1019823 (CRM).