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Purpose: Long noncoding RNAs (lncRNAs) play an essential role in the epigenetic regulation of various key genes involved in vital cellular functions. A somatic dinucleotide mutation in the lncRNA GAS8-AS1 was reported in Chinese papillary thyroid cancer. However, GAS8-AS1 dinucleotide alteration and its impact have never been explored in differentiated thyroid cancers and other populations. Methods: We extracted genomic DNA from 265 DTCs and 97 normal healthy subjects, PCR amplified and Sanger sequenced to examine the GAS8-AS1 dinucleotide alteration. Calculated genotype/allele frequency to test Hardy-Weinberg Equilibrium (HWE) and performed a genetic model of inheritance to determine its association with DTC risk. Correlated the GAS8-AS1 dinucleotide variant distribution with clinical characteristics to find the association. Predicted GAS8-AS1 RNA secondary structure for wild type and variant using RemuRNA and RNAfold to assess the conformational changes. Results: GAS8-AS1 dinucleotide alteration (n.713A > G, rs55742939; n.714T > C, rs61118444) identified in DTCs is a germline variant not somatic. The GAS8-AS1 genotype and allele frequency significantly deviated for HWE in DTCs (χ2 = 37.954; p = 0.0001) though not associated with its risk. Dinucleotide variant distribution was remarkably associated with early-stage disease (p = 0.002), lymph node (p = 0.01), and distant metastasis (p = 0.01) in DTCs. The GAS8-AS1 bearing dinucleotide variant markedly showed conformational change compared to that of its wild type. Conclusions: These findings indicate that GAS8-AS1 is genetically deregulated and implicated in several stages of DTC tumorigenesis suggesting it could be a promising prognostic biomarker in DTCs. [ABSTRACT FROM AUTHOR]

In 2012, somatic EPAS1 pathogenic variants were found to cause a triad of pheochromocytoma/paragangliomas (PPGLs), polycythemia, and somatostatinoma. Since then, a limited number of studies on this subject have been reported, and data on the long-term outcome of metastatic disease are not available on this rare syndrome. We comprehensively reviewed EPAS1-related PPGL and describe an unusual patient who has been living with an EPAS1- related metastatic PPGL for 47 years. The results of this work show that EPAS1 pathogenic variants are rare, more in females and patients without pathogenic variants in other PPGL susceptibility genes. PPGLs are the most common manifestation followed by polycythemia and somatostatinoma. The EPAS1 pathogenic variants are often postzygotic, and the timing of their acquirement during embryonic development seems to correlate with the number and timing of development of the disease manifestations. Although recurrent and multifocal disease is common in EPAS1- related PPGL, distant metastases are uncommon and usually indolent. This is illustrated by a case of a man who was diagnosed at the age of 9 years and is currently 56 years old, alive, and well for 47 years with these metastases. He was found to have a somatic EPAS1 pathogenic variant (c.1592C>A, p.Pro531His) in bilateral pheochomocytoma and a pancreatic NET (somatostatinoma) but not in genomic DNA isolated from peripheral leukocytes. This and previous reports suggest that distant metastases are uncommon and less aggressive in EPAS1-related PPGLs compared to those found in other hereditary PPGLs. [ABSTRACT FROM AUTHOR]

Context Data on germline genetics of pituitary adenomas (PAs) using whole-exome sequencing (WES) are limited. Objective This study investigated the germline genetic variants in patients with PAs using WES. Methods We studied 134 consecutive functioning (80.6%) and nonfunctioning (19.4%) PAs in 61 female (45.5%) and 73 male patients (54.5%). Their median age was 34 years (range, 11-85 years) and 31 patients had microadenomas (23.0%) and 103 macroadenomas (77%). None of these patients had family history of PA or a known PA-associated syndrome. Peripheral blood DNA was isolated and whole-exome sequenced. We used American College of Medical Genetics and Genomics (ACMG) criteria and a number of in silico analysis tools to characterize genetic variant pathogenicity levels and focused on previously reported PA-associated genes. Results We identified 35 variants of unknown significance (VUS) in 17 PA-associated genes occurring in 40 patients (29.8%). Although designated VUS by the strict ACGM criteria, they are predicted to be pathogenic by in silico analyses and their extremely low frequencies in 1000 genome, gnomAD, and the Saudi Genome Project databases. Further analysis of these variants by the Alpha Missense analysis tool yielded 8 likely pathogenic variants in 9 patients in the following genes: AIP :c.767C>T (p.S256F), CDH23 :c.906G>C (p.E302D), CDH23 :c.1096G>A (p.A366T), DICER1 :c.620C>T (p.A207V), MLH1 :c.955G>A (p.E319K), MSH2 :c.148G>A (p.A50T), SDHA :c.869T>C (p.L290P) and USP48 (2 patients): c.2233G>A (p.V745M). Conclusion This study suggests that about 6.7% of patients with apparently sporadic PAs carry likely pathogenic variants in PA-associated genes. These findings need further studies to confirm them. [ABSTRACT FROM AUTHOR]

Five glass samples with the following chemical formation: 21.5 SiO2-58.5B2O3-(20-x) ZnO- xLa2O3, where x = 0–10 mol% were fabricated utilizing melt quenching. With an increase in La2O3, the glasses' density increased from 3.174 to 4.754 g/cm3. Experimental data were used to evaluate the mechanical characteristics, and the Makishima and Mackenzie model's semi-empirical methods were used to analyze the elastic properties. As the amount of La2O3 increases, there's a noticeable rise in the velocity of ultrasonic waves. This heightened velocity is likely linked to the strengthening or increased rigidity of the glass network. Elastic moduli values of the glasses under investigation increase with an increase La2O3 content. Employing Phy-X/PSD code, the radiation attenuation behaviour of zinc borosilicate glasses with varying La2O3 concentrations were examined. With increased energy, the enhancement LAC decreases from 2.576 to 0.0375. The ZBSL10 glasses demonstrated strong mechanical and physical characteristics as well as radiation shielding capabilities. The features of the ZBSL glasses are particularly attractive for a variety of mechanical and shielding applications. [ABSTRACT FROM AUTHOR]

This work examined the SiO2–Pb3O4–ZnO–Y2O3 glasses mechanical, structural, and radiation shielding features. X-ray diffraction is a powerful technique for investigating the structural properties of these glasses. Experimental results were used to evaluate the mechanical characteristics, and the Makishima and Mackenzie model's semi-empirical approaches were used to investigate the elastic properties. Longitudinal velocity VL increase from 4935 m/s to 5325 m/s, while transverse velocity VT increase from 2520 m/s to 2905 m/s. Hardness improved from 4.41 to 8.31 GPa. The behaviour of the elastic moduli at both theoretical and experimental levels is the same. The mass attenuation coefficients (MAC), mean free paths (MFP), tenth & half-value layers (TVL), (HVL), and energy building factors (EBF) were estimated. Overall, higher MAC values were produced by a decrease in ZnO concentration and an increase in Y2O3 content. As the concentration of Y2O3 increases, the MFP, TVL, and HVL values decrease. Better radiation shielding is provided by lower MFP, TVL, and HVL values. The MFP, TVL, and HVL values are lower in the G 5 sample with the Y2O3 contribution (5%, mole). Higher concentrations of Y2O3 in glasses with a SiO2-Pb3O4-ZnO-composition were shown to have improved radiation shielding properties. [ABSTRACT FROM AUTHOR]