Alterações induzidas pelo treino de pré-época no futebol

info:eu-repo/semantics/publishedVersio

Alterações induzidas pelo treino de pré-época no futebol

info:eu-repo/semantics/publishedVersio

MON-LB48 The Genomic Landscape of Sporadic Thyrotrophinomas

Abstract Background: Thyrotrophinoma (TSHoma) is rare and knowledge on the genomic landscape of this tumour type is very limited. Aim: To perform whole-exome sequencing (WES) in a population of TSHomas to identify recurrent somatic genetic events Method: WES was performed on paired tumour and germline DNA of 7 patients with TSHomas. Three tissue samples were formalin-fixed paraffin-embedded and 4 fresh frozen tumour samples. Fresh blood samples were also collected from each patient. The average of mean depth of coverage amongst all samples was 129X, and 97% of target bases were covered ≥20X. Results:Four (57%) of the seven patients were male and median age at diagnosis was 52 years. (IQR 46, 60) Six patients (86%) had macroadenomas. Four patients (57%) had central thyrotoxicosis at diagnosis and three patients’ tumour stained positive for TSH on histology examination. Two patients (29%) had growth hormone co-secreting tumours. In total, 69 somatic variants were identified to be of potential interest, averaging 1.4 variants per million base-pair of DNA read. No variants were observed in more than one individual. According to the GTEx database, 9 of 69 genes (DRC3, HDAC5, KDM1A, POLR21, TCF25, THAP7, TTC13, UNC5D, UNC13A) were highly expressed in the pituitary (top 10%). Four of these genes appear to contribute to tumour development via epigenetic pathway. Specifically, three of these genes (HDAC5, KDM1A, THAP7) either interact with or form part of histone deacetylases whilst POLR21 encodes a subunit of RNA polymerase II which is responsible for mRNA synthesis. On the other hand, TCF25 gene is thought to act as transcriptional repressor and UNC5D plays a role in cell-cell adhesion. Large scale copy number variations involving gain or loss of whole chromosome or chromosome (chr) arm were observed in six (86%) tumour samples. Chr 5, 9, 13 and 19 were most commonly affected by chromosomal gains. Deletion of chr 1p was seen in two cases and mutations in KDM1A (p.Glu161fs/c.482_491delAGGAAGAAAA) and ADGRB2 gene (p.Leu1565Gln/c.4694T>A) were found in each of the remaining single copy of chr 1p. ADGRB2 gene is thought to be involved in cell adhesion and angiogenesis inhibition. Copy neutral loss-of-heterozygosity were present in two (29%) of the tumour samples (chr 2 and 12q). However, no somatic mutation was found in these regions. Gene level copy number analysis identified a potential deletion in TTI2 gene which encodes for a regulator in DNA damaging response as well as telomere length regulation. ConclusionOverall, the rate of somatic variant mutations in TSHomas is low, consistent with the relative benign nature of this tumour type. No classical driver mutations were identified by this study however, chromosomal anomalies and epigenetics may play an important part in TSHoma development

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour's molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

Fuzzy model to estimate the number of hospitalizations for asthma and pneumonia under the effects of air pollution

OBJECTIVE Predict the number of hospitalizations for asthma and pneumonia associated with exposure to air pollutants in the city of São José dos Campos, São Paulo State. METHODS This is a computational model using fuzzy logic based on Mamdani’s inference method. For the fuzzification of the input variables of particulate matter, ozone, sulfur dioxide and apparent temperature, we considered two relevancy functions for each variable with the linguistic approach: good and bad. For the output variable number of hospitalizations for asthma and pneumonia, we considered five relevancy functions: very low, low, medium, high and very high. DATASUS was our source for the number of hospitalizations in the year 2007 and the result provided by the model was correlated with the actual data of hospitalization with lag from zero to two days. The accuracy of the model was estimated by the ROC curve for each pollutant and in those lags. RESULTS In the year of 2007, 1,710 hospitalizations by pneumonia and asthma were recorded in São José dos Campos, State of São Paulo, with a daily average of 4.9 hospitalizations (SD = 2.9). The model output data showed positive and significant correlation (r = 0.38) with the actual data; the accuracies evaluated for the model were higher for sulfur dioxide in lag 0 and 2 and for particulate matter in lag 1. CONCLUSIONS Fuzzy modeling proved accurate for the pollutant exposure effects and hospitalization for pneumonia and asthma approach.OBJETIVO Prever o número de internações por asma e pneumonia associadas à exposição a poluentes do ar no município em São José dos Campos, estado de São Paulo. MÉTODOS Trata-se de um modelo computacional que utiliza a lógica fuzzy baseado na técnica de inferência de Mamdani. Para a fuzzificação das variáveis de entrada material particulado, ozônio, dióxido de enxofre e temperatura aparente foram consideradas duas funções de pertinência para cada variável com abordagem linguísticas: bom e ruim. Para a variável de saída número internações por asma e pneumonia, foram consideradas cinco funções de pertinências: muito baixo, baixo, médio, alto e muito alto. O número de internações no ano de 2007 foi obtido do Datasus e o resultado fornecido pelo modelo foi correlacionado com os dados reais de internação com defasagem (lag) de zero a dois dias. A acurácia do modelo foi estimada pela curva ROC para cada poluente e nestas defasagens. RESULTADOS No ano de 2007 foram registradas 1.710 internações por pneumonia e asma em São José dos Campos, SP, com média diária de 4,9 internações (dp = 2,9). Os dados de saída do modelo mostraram correlação positiva e significativa (r = 0,38) com os dados reais; as acurácias avaliadas para o modelo foram maiores para o dióxido de enxofre nos lag 0 e 2 e para o material particulado no lag 1. CONCLUSÕES Modelagem fuzzy se mostrou acurada para a abordagem de efeitos da exposição aos poluentes e internação por pneumonia e asma

Development and validation of a targeted gene sequencing panel for application to disparate cancers

© 2019, The Author(s). Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy