bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-101 Costa Rican National Primary Congenital Hypothyroidism Screening Program Evaluation. Retrospective Cohort Trial Between 2015 and 2017
Authors: Cob Alejandro , Aita Fred Cavallo , Rodríguez Agnes 
Published: May 2020

Abstract
Congenital hypothyroidism (CH) is one of the leading causes of intellectual impairment worldwide in infancy. The newborn screening has been able to prevent this mental disability, by a prompt initiation of therapy. Over the last years the incidence of HC has been increasing, mainly by lowering the screening cut-off level that leads to detection of milder cases. There is conflicting evidence if children with mild CH without treatment may develop neurological impairment in the future.
Costa Rican newborn screening program in divided in three stages, measuring serum TSH concentrations from a heel prick aliquot of capillary blood dried onto a filter paper. Each test has different TSH cut-off values to determine if the newborn needs a clinical evaluation by an endocrinologist, needs another screening test or rules out hypothyroidism.
We developed an observational, descriptive, retrospective study, based on medical records, to evaluate our newborn screening program performance. The study included the total national population of screened newborns from 2015 to 2017. Descriptive analysis and analytical analysis of variables were done, and test’s sensitivity and specificity were determined.
The study analyzed 204.241 screened newborns, and 145 children referred to the Endocrinology Department of the National Children Hospital. This population represents 97% of births in these 3 years. The recall rate for a first positive test was 0.3%. Congenital hypothyroidism was confirmed in 73% of children referred to the Endocrinology Department because of a positive screening. Incidence was 1/1926 births. Detection rate was independent of birth weight nor gestational age. 45.3% of children diagnosed with CH were detected after the first screening test, 52.8% after the second screening test and 1.9% after the third screening test. Screening test analysis showed high sensitivity and specificity, with diagnostic accuracy above 90%, except for the third screening test. Free thyroxine measurements alone weren’t useful to predict CH diagnosis.
The coverage of the national neonatal screening program extends almost to the entire population. Our test specificity is within international standards. Incidence of CH in Costa Rica is similar to that reported in medical literature. With current detection cut-off level, there is no need of performing a second mandatory evaluation to preterm and low weight newborns. The third screening test has a low performance rate, does not improve detection of children with CH significantly, and delays clinical evaluation by the endocrinologist. Prognosis of treated children with CH is excellent, with no evidence of severe cognitive deficit.
SAT-208 An Adrenal Incidentaloma with Extramedullary Hematopoiesis
Authors: Zachary Tyler , Lien Lillian 
Published: May 2020

Abstract
Introduction: Adrenal adenomas are incidentally noted during nonadrenal disease imaging at a rate up to 4%. Frequency of incidentalomas increases with age, most being adrenocortical adenomas. This case highlights an uncommon etiology of such an adrenal mass finding. Case Description: A 37-year-old with a history of hypertension, hypothyroidism, and tobacco use was admitted after post-operative complication. Prior to surgery, she had been experiencing right upper quadrant pain along with 70 lb weight loss and diarrhea. She otherwise had frequent palpitations. Patient had undergone cholecystectomy and common hepatic duct injury was noted. Imaging revealed a 5.3 x 3.5 cm right adrenal mass previously unknown prior to surgery. Hormonal workup was negative for overproduction of aldosterone, cortisol, DHEA-S or metanephrines. Discussion: Patient underwent successful resection of adrenal mass, revealing adrenal adenoma with osseous metaplasia and hematopoiesis. Extramedullary hematopoiesis is a usually discovered incidentally as in this case. Typical sites are the spleen and liver. Cases of adrenal gland manifestations have been reported in the presence of hemoglobinopathies (thalassemia, hereditary spherocytosis) or myelofibrosis. At four-month follow-up, laboratory testing on this patient didn’t suggest any erythrocytic or leukocytic disorder. Conclusion: This case highlights an uncommon finding of hematopoiesis in an adrenal incidentaloma without any underlying hematologic defect or disease. References: Motta, I., Boiocchi, L., Delbini, P., Migone De Amicis, M., Cassinerio, E., Dondossola, D., Rossi, G. and Cappellini, M. D. (2016), A giant adrenal myelolipoma in a beta-thalassemia major patient: Does ineffective erythropoiesis play a role?. Am. J. Hematol., 91: 1281-1282. doi:10.1002/ajh.24446. Stewart P, Newell-Price J. (2016). The Adrenal Cortex. In Melmed S, Polonsky K, Larsen P, Kronenberg H, Williams Textbook of Endocrinology. (13th ed., pp 489-555). Philadelphia, PA: Elsevier
MON-601 Obesity Pharmacotherapy Is Effective in the United States Veterans Affairs Patient Population: A Local and Virtual Cohort Study
Authors: Pendse Jay , Vallejo-García Franco , Parziale Andrew , Griffin Megan , Callanan Mae , Tenner Craig , Diaz Jose Orlando Aleman 
Published: May 2020

Abstract
Background: Overweight and obesity are major health burdens, and the military veteran population may be disproportionately affected. Multiple new pharmacologic agents and combinations have been approved by the FDA for use in medical weight management. Using deidentified records from our local interdisciplinary weight management clinic and a national clinical data repository, we assessed obesity pharmacotherapy use and its real-world effectiveness for weight loss and improvement of comorbid metabolic parameters in this vulnerable population.
Methods: During the initial year of the local weight management clinic, we found over 50 records with monthly followup of lifestyle intervention augmented by obesity pharmacotherapy. In the national clinical data repository, we identified over 2 million records for unique individuals prescribed bupropion-naltrexone, liraglutide, lorcaserin, orlistat, or phentermine-topiramate, and metformin considered as a control prescription. We selected records with detailed documentation of weight trends from 1 year before to 1 year after first prescription date for further analysis.
Results: The most commonly prescribed medications in our local weight management clinic were metformin, liraglutide, orlistat, and combination phentermine/topiramate. On average, we observed −4.0 ± 2.1 kg weight loss over the initial 6-month intervention in records that completed at least 3 visits within this period. In the national database, over 800,000 records for an obesity or control metformin prescription provided adequate weight documentation to compare weight slopes during the year before and after the prescription start date. Records for metformin prescriptions showed −0.04 ± 0.008 kg/week difference in weight slope over one year before versus after the prescription start date. The greatest difference in weight slope was seen with phentermine-topiramate (−0.13 ± 0.03 kg/week), followed by lorcaserin, liraglutide, bupropion-naltrexone, and orlistat.
Conclusions: Our data suggests that veterans with obesity experience weight loss at 1 year follow-up when engaged with our interdisciplinary weight management clinic. Nationally, veterans with obesity experience modest weight loss when prescribed pharmacotherapy. Taken together, our two data sources provide complementary perspectives to help guide obesity pharmacotherapy in veterans with obesity.
MON-129 Analysis of Omega3 PUFAs Status Among the Female and Male Population of the Moscow Region
Authors: Vorslov Leonid , Davidyan Ovanes , Avetisyan Artur , Nizhnik Aleksander , Paramonov Sergey , Kalinchenko Svetlana Yurevna 
Published: May 2020

Abstract
INTRODUCTION:
All humans have levels of EPA+DHA that if methodologically correctly assessed in erythrocytes, are optimal more than 8%. Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest not only in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias, but also many serious health issues that can be prevented by optimal levels.
OBJECTIVE: The aim of this study was to assess in a retrospective study the omega-3 PUFAs status at Moscow region according age and sex.
SUBJECTS AND METHODS:
In this retrospective study, the records of 1349 patients who presented with various complaints in the period from 2013 to 2017 aged 1 to 91 were examined. Fatty acids within the red blood cell membranes were analyzed as methyl ethers after trans-esterification with sodium methylate using GC-MS followed by omega-3 index calculation.
RESULTS:
Deficiency of omega-3 PUFAs was found in 68.5% of patients. The most severe deficiency was noted in children and adolescents aged 0 to 17 years (in girls to a greater extent). In age groups of 18–44 and 45–59 years, the prevalence of severe (&lt;4%) and moderate (4–8%) deficiency was comparable in males and females: among 18–44-year-old men severe deficiency was noted in 5.6%, moderate – in 29.4%, at the age of 45–59 years – in 7 and 23%, respectively; among women – 6.4, 24.4, 8.4 and 20%, respectively. In the age group of 60-74 years, prevalence of severe deficiency was significantly higher in men, who had severe deficiency in 9.2% of cases, whereas in women of the same age it was found only in 4.8% of cases, the prevalence of moderate deficiency is 23 and 23.8%, respectively.
CONCLUSIONS:
Such high prevalence of severe omega-3 PUFA deficiency in girls under 17 is likely due to girls’ and their parents’ concerns about weight, diet and veganism, and requires the inclusion of omega-3 index analysis in adolescent girls’ screening. Thus, during the most important period – the period of puberty – 25% of girls have metabolic and hypoxic disorders due to deficiency of omega-3 PUFA and are at risk of not only diseases associated with metabolic disorders, but also reproductive disorders (infertility, miscarriage, fetal malformations). The obtained data is indicative of the necessity to choose dosages of omega-3 PUFAs, considering not only the patients age, but also their gender.
SAT-138 Neutrophil Elastase Promotes Proliferative Signals in Prostate Cells Through EGFR and DDR1
Authors: Xiao Zhiguang , Lerman Irina , Hammes Stephen R 
Published: May 2020

Abstract
Studies examining many different cancers have demonstrated that inflammation plays a critical role in tumor progression, in part through the release of proteases from stromal cells that function to either remodel the tumor microenvironment or to directly stimulate cancer cells to grow. One specific protease, neutrophil elastase (NE), has been shown to be a critical regulator of cancer growth in several mouse models. Accordingly, our laboratory demonstrated that NE, most likely from granulocytic myeloid-derived suppressor cells, potentially promotes prostate cancer progression in several different in-vivo and in-vitro models. To date, however, little is known regarding the mechanisms utilized by NE to promote tumor growth. It has been suggested that NE might cleave epidermal growth factor (EGF) or transforming growth factor-α from the cell surface to induce activation of EGFR/ERK signal transduction in an autocrine fashion. Alternatively, NE has been shown to enter into early endosomes to degrade insulin receptor substrate-I, ultimately resulting in phosphoinositol 3-kinase hyperactivity and subsequent tumor cell proliferation. Here we demonstrate that NE triggered proliferative signals in six prostate cell lines representing the spectrum of prostate cell differentiation, including normal prostatic epithelium, benign prostatic hypertrophy, and metastatic prostate cancer. Focusing on ERK signaling, we found that the stimulatory effect of NE on ERK phosphorylation was dose dependent and was abrogated by small interfering RNA induced EGFR knockdown, as well as by pretreatment of cells with irreversible EGFR inhibitor AG1478. Unlike EGF, however, NE-initiated EGFR phosphorylation was minimal. Thus, while EGFR appears to be critical for NE-induced ERK activation, perhaps it is not extensively activated directly by NE. Notably, discoidin domain receptor-1 (DDR1) was strongly expressed in normal prostate epithelium cells, but gradually decreased and had little expression in benign and metastatic prostate cancer cells sequentially. Nevertheless, similar to EGFR knockdown, silencing of DDR1 in all cell types inhibited NE mediated pERK upregulation, suggesting that DDR1 may also be important for NE-induced action. Together, our data suggest that NE, in concert with low level signals from the EGFR and DDR1, play an important role in promoting prostate cell proliferation both in normal and cancerous prostate epithelial cells.
OR31-06 Candidate Gene Variants in a Large Cohort of Women with Primary Ovarian Insufficiency
Authors: Gorsi Bushra , Moriwaki Mika , Moore Marvin B , Rajkovic Aleksandar , Nelson Lawrence M , Yandell Mark , Welt Corrine Kolka 
Published: May 2020

Abstract
Primary ovarian insufficiency (POI) is highly heritable. The majority of cases have no known cause. We hypothesized that mutations in previously identified genes or genes from the same pathways are the cause of POI in a recessive or dominant manner. Subjects included 294 women diagnosed with POI (amenorrhea with an elevated FSH level). All had a 46XX karyotype, and normal FMR1 repeat number. Subjects were recruited in Boston (n=95), at the NIH and Washington University (n=98), and in Pittsburgh (n=98). Controls included subjects recruited for health in old age and disorders unrelated to reproduction or cancer, and subjects from the 1000 Genomes Project (total n=587). Variants were called using the Sentieon software package (https://www.sentieon.com). Case and control samples were stratified on ethnicity, relatedness and heterozygosity. Peddy and XPAT were used to calculate quality control metrics to detect outlier samples for removal from analysis to create a homogenous dataset. The number of cases (227) and controls (458) was adjusted for downstream analysis. XPAT imposed additional quality filters and removed variants. A second filter removed variants that did not pass a Gnomad filter of &lt;0.001 allele frequency. VAAST was used to determine a composite likelihood ratio (CLR) as the test statistic to represent the aggregate burden of variants of affected individuals in each transcript relative to a set of 458 control genomes. The significance of each transcript’s VAAST CLR score was evaluated by 1 million permutations. We screened exomes for variants in previously identified genes causing POI in humans and those demonstrating infertility in a male or female mouse model. We also used the American College of Medical Genetics and Genomics standards for interpretation of pathogenicity of a variant, with priority on null variants in genes with probability of loss of function intolerance based on the observed vs. expected rate in gnomAD, in vivo or in vitro functional evidence of a damaging effect, significantly increased prevalence compared to controls, i.e. not found in any controls or in fewer than 10 in the gnomAD database if the subject had a matching race/ethnicity. Thirty-four subjects were removed for poor quality exomes and relatedness. Fifty-three subjects had at least one variant in a previously identified POI gene or one in which there was a previously identified functional model. Two subjects carried recessive variants and 30 carried at least one novel heterozygous candidate variant for follow up. Analysis of genetic causes of POI in this large cohort identified candidate causal gene variants in over half of the subjects. The data demonstrate that the genetic architecture is heterogeneous. Although recessive mutations have been identified in consanguineous families, the data suggest that a dominant or oligogenic pattern of inheritance may be important.
SAT-295 An Extremely Rare Novel Missense Variant C.912G≫A; P.M304I in SOX3 Gene Is Responsible for X-Linked GH Deficiency in a Brazilian Boy Without Mental Retardation
Authors: Benedetti Anna Flavia Figueredo , Silva Juliana M , Biscotto Isabela Peixoto , Ferreira Nathalia Pereira , Arnhold Ivo J , Mendonca Berenice Bilharinho , Carvalho Luciani Renata Silveira 
Published: May 2020

Abstract
SOX3 (SRY-related HMG-box gene 3), located in the X chromosome, spans only one exon and is expressed in the infundibulum, diencephalon and hypothalamus. Alterations in SOX3, mainly deletions or insertions in the polyalanine tract, were associated with mental retardation, isolated GH deficiency (IGHD) or combined pituitary hormone deficiencies (CPHD). Missense variants are rare and only two were reported. Our aim was to find a molecular cause in patients with pituitary hormone deficiency and determine genotype-phenotype correlation. Twenty-eight patients (15F:13M) 24 CPHD:4 IGHD were selected for the study. Whole blood DNA was extracted using the Salting Out method. Library preparation was performed following Agilent’s SureSelectXT customized gene panel protocol containing 654 genes known to cause endocrine diseases. Illumina NextSeq 500 platform was used for sequencing at SELA. Alignment to genome reference hg19 was performed using BWA-MEM. Variants were called with FreeBayes and annotated by Annovar. Allele frequency ≤1% for exonic regions was considered in 1000 Genomes, gnomAD, ABraOM and SELA populational databases for variant filtering. Family segregation was done using Sanger sequencing. RNA and protein analysis were performed using mfold and YASARA, respectively. Protein models were made by I-Tasser. SOX3 missense variant (c.912G&gt;A/p.M304I) was found in one male patient, without mental retardation, diagnosed with IGHD at the age of 7 years. After GH replacement, he reached final height at the age of 18 within family target height. Pituitary image showed an ectopic posterior pituitary, hypoplastic anterior pituitary and thin pituitary stalk. SOX3 (c.912G&gt;A/p.M304I) variant in hemizygous state was absent in populational data banks. In silico prediction algorithms SIFT, PolyPhen, and Mutation Assessor were predicted as damaging. Family segregation showed normal mother and sister carriers of the variant, while father, brother and uncle (from mother’s side), all phenotypically normal, did not harbor the variant. RNA In silico analysis pointed that the variant causes mRNA structure change. Protein stability dropped from 677.46 kcal/mol in wild type to 666.69 kcal/mol in p.M304I, making it less stable. Protein Interaction analysis with DNA binding motif (PDB 2LE4) required two times less energy in mutant (376.19 kcal/mol) than wild type protein (646.77 kcal/mol), leading to a less stable interaction. We conclude that one among 28 patients presented a rare novel variant in SOX3 associated to IGHD in a patient without mental retardation and compatible with an X-linked inheritance pattern.
OR08-05 Sex and Ethnic Differences in Advanced Lipoprotein Profiles in South Asians, African-Americans, and Caucasians
Authors: Sarcone Camila , Fosam Andin , Armiyaw Abdul-Latif , Grewal Shivraj , Bansal Rashika , Rabel Antoinette , Muniyappa Ranganath 
Published: May 2020

Abstract
Background: African-Americans (AA) and South Asians (SA) are known to have higher risk for T2D and cardiovascular disease (CVD) compared to Caucasians (CA). Advanced analysis of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy can offer insights into CVD risk and lipid metabolism beyond a standard lipid panel. Insulin resistance (IR) is known to be associated with atherogenic lipoprotein profile.
Objective: To characterize the lipoprotein profile in AA, CA, and SA men and women.
Design: A cross-sectional study of 182 healthy, non-diabetic SA, AA and CA patients was conducted at NIH. Subjects underwent an intravenous glucose tolerance test from which insulin sensitivity (Si) was derived using the Minimal Model. Lipoprotein profiles were measured by NMR with the LP4 deconvolution algorithm, which reports triglyceride-rich lipoprotein particles (TRLPs), high-density lipoprotein particles (HDLPs), and low-density lipoprotein particles (LDLPs). For group comparisons, Si was adjusted for age and fat free mass. Lipoprotein parameters were adjusted for age and body fat %.
Results: Fifty-nine non-diabetic SA (33 males, 26 females), 49 AA (26 males, 23 females), and 74 CA (29 males, 45 females) were included in the study. Ethnic differences in Si were observed in men (p=0.002) but not in women (p=0.43). SA men had a significantly lower Si than both AA and CA men (p=0.02). TG concentrations and TRL particle number were significantly higher in CA men and women when compared with AA. TRLP size was not different between the ethnic groups in either sex. LDL particle number and ApoB concentration was significantly higher in SA men and women compared to AA and CA. There were no ethnic or sex differences in LDL size. HDL concentration, HDL particle number, and ApoA-I levels were not different between the groups in both sexes. However, in SA, large HDL particle number and HDL particle size was significantly lower than CA. Cholesteryl ester transfer protein (CETP) activity was significantly higher in SA men, but not women, when compared with AA and CA. Ethnic differences in LDLP and L-HDLP number remained even after adjusting for Si.
Conclusions: In SA men and women, the lipoprotein phenotype (higher LDLP and lower L-HDLP) is independent of insulin sensitivity. Increased CETP activity may contribute to the lower large HDL particle number in this group. In AA, TG and TRLP number were lower as previously reported. Further investigation is needed to determine the factors mediating the atherogenic profile in SA.