Presumed TP53 mosaicism: variants detected using a NGS hereditary cancer multigene panel

Aims/Context: NGS multigene panels are routinely used to identify germline pathogenic variants in cancer susceptibility genes. In addition, NGS allows the identification of low-level mosaicism events that may not be detectable by conventional Sanger sequencing. We describe two cases of presumed TP53 mosaic variants detected by NGS on blood-derived DNA, and confirmed by ARMS-PCR and Sanger sequencing. Case 1: female, 87 years old, colon cancer at 83 and metachronous breast cancer at 86, no history of familial cancer. Case 2: female, 75 years old, ovarian cancer at 71, local relapse at 74. Methods: NGS using TruSight® Cancer Sequencing Panel and TruSight® Rapid Capture kit (Illumina) and paired-end sequencing on MiSeq® platform (Illumina). Bioinformatic analysis with MiSeq Reporter, Enrichment, VariantStudio, VEP, Alamut Visual, VarAFT, VarSome and IGV. ARMS-PCR and Sanger sequencing were used to confirm the TP53 variants. Results and Conclusions: Two cases of presumed TP53 mosaic variants were studied. Case 1: the missense alteration TP53: c.764T>G, p.(Ile255Ser) was detected with a variant allele frequency (VAF) of 26% (39/150 reads). This variant is described in ClinVar as a somatic alteration, classified as likely pathogenic. It is not reported in gnomAD and VarSome software classified it as a variant of uncertain significance. Case 2: missense variant TP53: c.524G>A, p.(Arg175His) detected with a VAF of 15% (10/58 reads). This variant is described as pathogenic in HGMD Professional, LOVD and ClinVar, in association with Li-Fraumeni syndrome. These two cases seem to represent TP53 mosaicism, supported by: i) VAF lower than 30%, ii) detection at the sensitivity limit of Sanger sequencing and iii) confirmation by ARMS-PCR. Confirming this hypothesis by studying tumor and other tissue samples and offspring analysis (underway in both cases), is essential for disease diagnosis, assessing recurrence risk and genetic counseling. The hypothesis of acquired aberrant clonal expansion limited to the hematologic compartment, versus a germline variant should be considered in similar cases, and confirmatory methodologies are mandatory.info:eu-repo/semantics/publishedVersio

A brief overview of current drug repurposing approaches for COVID-19 management

This brief overview is intended to shed light on the current drug repositioning (also called drug repurposing) in the therapeutics of the novel coronavirus disease which emerged in 2019 (COVID-19). In this sense, the repositioning drugs for new indications can offer a better risk-versus-reward trade-off when compared to other drug development strategies, given that it makes use of drugs whose safety profile are already understood. Nonetheless, this approach allows healthcare professionals to promptly tackle the disease by investigating readily available drugs against it

Анализ на поведението при решения на топ треньори от висша лига преди и след спортното състезание

Submitted article is thorough study of top coaches behavioral responses during the competition. A detailed analysis of the literature /from the last 15 years / is made, focusing on various determinants of sporting success which determine the role of the coach to shine and not be underestimated. It stressed the need to examine current trends, that elucidate the process complexity / behavioral and cognitive / in coaching job.Представената статия е задълбочено проучване на поведенчески реакции на топ треньори по време на състезание. Подробен анализ на литературата / от последните 15 години / е направен, фокусиран върху различните детерминанти на спортния успех, който да подчертае ролята на треньора. Обръща се внимание на необходимостта, да се разгледат съвременните тенденции, които осветляват сложността на процеса /поведенческа и когнитивна/ в треньорската работа.info:eu-repo/semantics/publishedVersio

Pisco-de-peito-ruivo : uma das aves nativas mais recentes nos Açores

A secção Biologia é coordenada pelo Professor Universitário Armindo Rodrigues.[…]. No âmbito destes estudos, foi recentemente publicado um artigo científico na revista internacional Journal of Ornitology (Jornal de Ornitologia) sobre a filogeografia e diversidade genética do pisco-de-peito-ruivo nos Açores (Phylogeography and genetic diversity of the Robin (Erithacus rubecula) in the Azores islands: evidence of a recent colonisation), que com base em estudos moleculares e biométricos, concluiu que o pisco-de-peito-ruivo, também conhecido nos Açores como santantoninho, papinho ou caixinha, e com o nome científico de Erithacus rubecula, é uma das espécies nativas de aves mais recentes na região, tendo a colonização ocorrido durante os últimos 80.000 anos, e que a rota de colonização mais provável para as ilhas do Atlântico tenha sido uma primeira dispersão da Europa para as ilhas Canárias e/ou para a ilha da Madeira e daí para os Açores, onde rapidamente se expandiram para todas as ilhas do arquipélago, excepto para as ilhas do grupo ocidental (Flores e Corvo). […].info:eu-repo/semantics/publishedVersio