RESUMO
The analysis of curated genomic, metagenomic and proteomic data is of paramount importance in the fields of biology, medicine, education, and bioinformatics. Although this type of data is usually hosted in raw format on free international repositories, the full access requires lots of computing power and large storage disk space for the domestic user. The purpose of the study is to offer a comprehensive set of microbial genomic and proteomic reference databases in an accessible and easy-to-use form to the scientific community and demonstrate its advantages and usefulness. Also, we present a case study on the applicability of the sketched data, for the determination of overall genomic coherence between two members of the Brucellacea family, which suggests they belong to the same genomospecies that remain as discrete ecotypes. A representative set of genomes, proteomes (from type material), and metagenomes were directly collected from the NCBI Assembly database and Genome Taxonomy Database (GTDB), associated with the major groups of Bacteria, Archaea, Virus, and Fungi. Sketched databases were subsequently created and stored on handy reduced representations by using the MinHash algorithm implemented in Mash software. The obtained dataset contains more than 133 GB of space disk reduced to 883.25 MB and represents 125,110 genomics/proteomic records from eight informative contexts, which have been prefiltered to make them accessible, usable, and user-friendly with limited computational resources. Potential uses of these sketched databases are discussed, including but not limited to microbial species delimitation, estimation of genomic distances and genomic novelties, paired comparisons between proteomes, genomes, and metagenomes; phylogenetic neighbor's exploration and selection, among others.
A análise de dados genômicos, metagenômicos e proteômicos com curadoria é de suma importância nos campos da biologia, medicina, educação e bioinformática. Embora esse tipo de dados geralmente seja hospedado em formato bruto em repositórios internacionais gratuitos, o acesso total requer muita capacidade de computação e grande espaço em disco de armazenamento para o usuário doméstico. Os objetivos do estudo são oferecer um conjunto abrangente de bancos de dados de referência genômica e proteômica microbiana de forma acessível e fácil de usar para a comunidade científica e demonstrar suas vantagens e utilidade. Além disso, apresentamos um estudo de caso sobre a aplicabilidade dos dados esboçados para a determinação da coerência genômica geral entre dois membros da família Brucellacea, o que sugere que eles pertencem às mesmas genomoespécies que permanecem como ecótipos discretos. Um conjunto representativo de genomas, proteomas (de material tipo) e metagenomas foi coletado diretamente do banco de dados NCBI Assembly e do banco de dados de taxonomia do genoma (GTDB), associada aos principais grupos de bactérias, Archaea, vírus e fungos. Bancos de dados esboçados foram subsequentemente criados e armazenados em representações reduzidas práticas usando o algoritmo MinHash implementado no software Mash. O conjunto de dados obtido contém mais de 133 GB de espaço em disco reduzido para 883,25 MB e representa 125,110 registros genômicos/proteômicos de oito contextos informativos, que foram pré-filtrados para torná-los acessíveis, utilizáveis ââe amigáveis ââcom recursos computacionais limitados. Os usos potenciais desses bancos de dados esboçados são discutidos, incluindo, mas não se limitando, a delimitação de espécies microbianas, estimativa de distâncias genômicas e novidades genômicas, comparações emparelhadas entre proteomas, genomas e metagenomas, exploração e seleção filogenética de vizinhos, entre outros.
Assuntos
Classificação , Genoma , Genes MicrobianosRESUMO
The analysis of curated genomic, metagenomic and proteomic data is of paramount importance in the fields of biology, medicine, education, and bioinformatics. Although this type of data is usually hosted in raw format on free international repositories, the full access requires lots of computing power and large storage disk space for the domestic user. The purpose of the study is to offer a comprehensive set of microbial genomic and proteomic reference databases in an accessible and easy-to-use form to the scientific community and demonstrate its advantages and usefulness. Also, we present a case study on the applicability of the sketched data, for the determination of overall genomic coherence between two members of the Brucellacea family, which suggests they belong to the same genomospecies that remain as discrete ecotypes. A representative set of genomes, proteomes (from type material), and metagenomes were directly collected from the NCBI Assembly database and Genome Taxonomy Database (GTDB), associated with the major groups of Bacteria, Archaea, Virus, and Fungi. Sketched databases were subsequently created and stored on handy reduced representations by using the MinHash algorithm implemented in Mash software. The obtained dataset contains more than 133 GB of space disk reduced to 883.25 MB and represents 125,110 genomics/proteomic records from eight informative contexts, which have been prefiltered to make them accessible, usable, and user-friendly with limited computational resources. Potential uses of these sketched databases are discussed, including but not limited to microbial species delimitation, estimation of genomic distances and genomic novelties, paired comparisons between proteomes, genomes, and metagenomes; phylogenetic neighbor's exploration and selection, among others.
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Proteoma , Proteômica , Filogenia , Genômica , Biologia ComputacionalRESUMO
Resumen La diabetes mellitus gestacional se define como cualquier intolerancia a los carbohidratos diagnosticada durante el embarazo. La prevalencia de esta enfermedad es aproximadamente de 2 a 5% de los embarazos normales y depende de la prevalencia de la población a la diabetes mellitus tipo 2. Se asocia con resultados adversos para la madre, el feto, el recién nacido, el niño y los hijos adultos de madre diabética. La detección de la diabetes mellitus gestacional está en el cribado, realizado como sea necesario a través de medidas de diagnóstico. La poroyección puede ser selectiva, basada en la estratificación del riesgo o ser universal. Las pruebas oportunas permiten al médico obstetra evaluar la tolerancia de la glucosa relacionada con el estado resistente a la insulina del embarazo y permite iniciar el tratamiento antes de que ocurra el crecimiento fetal excesivo. Una vez que se estableció el diagnóstico de diabetes mellitus gestacional se justifica la estrecha vigilancia perinatal. El objetivo del tratamiento es reducir la morbilidad y mortalidad materno-fetal relacionadas con la enfermedad. Los valores exactos necesarios de glucosa todavía no están demostrados de manera absoluta. La decisión de inducir el parto y cuándo depende de la edad gestacional, el peso fetal estimado, el control de la glucemia materna y la puntuación obispo. Se necesitan investigaciones futuras en materia de prevención de diabetes mellitus gestacional, los objetivos del tratamiento y eficacia de las intervenciones, las directrices en la atención del embarazo y la prevención de las secuelas metabólicas a largo plazo para el niño y la madre.
Abstract Gestational diabetes mellitus is defined as any carbohydrate intolerance first diagnosed during pregnancy. The prevalence of gestational diabetes mellitus is about 2-5% of normal pregnancies and depends of the prevalence of same population to diabetes mellitus type 2. It is associated with adverse outcome for the mother, the fetus, neonate, child and adult offspring of the diabetic mother. Detection of gestational diabetes mellitus lies on screening, followed as necessary by diagnostic measures. Screening can either be selective, based upon risk stratification or universal. Timely testing enables the obstetrician to assess glucose tolerance in the presence of the insulin-resistant state of pregnancy and permits treatment to begin before excessive fetal growth has occurred. Once a diagnosis of gestational diabetes mellitus was made close perinatal surveillance is warranted. The goal of treatment is reducing fetal-maternal morbidity and mortality related with gestational diabetes mellitus. The exact glucose values needed are still not absolutely proved. The decision whether and when to induce delivery depends on gestational age, estimated fetal weight, maternal glycemic control and bishop score. Future research is needed regarding prevention of gestational diabetes mellitus, treatment goals and effectiveness of interventions, guidelines for pregnancy care and prevention of long term metabolic sequel for both the infant and the mother.
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PURPOSE: We assessed therapeutic outcomes of reirradiation with helical tomotherapy (HT) for locoregional recurrent nasopharyngeal carcinoma (LRNPC) patients. METHODS AND MATERIALS: Treatment outcomes were evaluated retrospectively in 17 consecutive LRNPC patients receiving HT between 2006 and 2012. Median age was 57 years and most patients (n = 13) were male. Simultaneous systemic therapy was applied in 5 patients. Initial treatment covered the gross tumor volume with a median dose of 70 Gy (60-81.6 Gy). Reirradiation was confined to the local relapse region with a median dose of 63 Gy (50-70.2 Gy), resulting in a median cumulative dose of 134 Gy (122-148.2 Gy). The median time interval between initial and subsequent treatment was 42 months (11-126). RESULTS: The median follow-up for the entire cohort was 23 and 35 months for survivors. Three patients (18 %) developed both local and distant recurrences and only one patient (6 %) suffered from isolated local recurrence. Two-year actuarial DFS and LC rates were 74 and 82 %, respectively. Two-year OS rate was 79 %. Acute and late grade 2 toxicities were observed in 8 patients (47 %). No patient experienced late grade ≥3 toxicity. Late toxicity included fibrosis of skin, hypoacusia, dysphagia, and xerostomia. Patients with higher Karnofsky performance status scores associated with a lower risk of mortality (HR 0.85, p = 0.015). CONCLUSION: Reirradiation with HT in patients with LRNPC is feasible and yields encouraging results in terms of local control and overall survival with acceptable toxicity.
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Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Carcinoma , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos RetrospectivosRESUMO
PURPOSE: The objective of this study is to evaluate the tolerability and outcome of craniospinal irradiation (CSI) with helical tomotherapy (HT) in the treatment of medulloblastoma. METHODS: We evaluated 19 consecutive patients with primary medulloblastoma who were treated with HT from 2007 through 2010. HT regimens to the neuroaxis included: 23.4 Gy at 1.8 Gy/fraction (N = 10), 36 Gy at 1.8 Gy/fraction (N = 7), and 39 Gy bid at 1.3 Gy/fraction (N = 2). The tumor bed received 54-60 Gy. Potential associations between patient, treatment, and toxicity factors and overall survival (OS) were assessed in univariate analyses using the Cox proportional hazards model. Spearman's rank correlation coefficient was used to correlate potential risk factors with the grade of acute toxicity. RESULTS: The median age at diagnosis was 5 years (range 2-14) and the median follow-up for alive patients (N = 14) 40 months (range 10-62). Two- and three-year overall survival was 75 and 68 %, respectively. The most common acute toxicity was hematological (79 %), being grade 2 and grade 3 in 4 (21 %) and 11 (58 %) cases, respectively. No grade ≥2 late toxicities were observed. Higher grades of acute body toxicity were found in older children (P = 0.004). Longer time between diagnosis and radiation therapy was correlated with shorter OS (P = 0.03). In addition, higher grades of acute thrombocytopenia were associated with shorter OS (P = 0.03). CONCLUSIONS: CSI delivered with HT for medulloblastoma is well tolerated with low rates of severe acute toxicity. Further research is necessary to assess late toxicity with a longer follow-up.
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Neoplasias Cerebelares/radioterapia , Radiação Cranioespinal/métodos , Meduloblastoma/radioterapia , Radioterapia de Intensidade Modulada , Adolescente , Criança , Pré-Escolar , Radiação Cranioespinal/efeitos adversos , Feminino , Humanos , Masculino , Radioterapia de Intensidade Modulada/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. RESULTS: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.
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Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/cirurgia , Neoplasias/cirurgia , Radiocirurgia , Radioterapia de Intensidade Modulada , Cirurgia Assistida por Computador , Adolescente , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: High-dose-rate brachytherapy (HDR-BT) is an accepted part of treatment for endometrial carcinoma and is usually performed in 1-2 fractions per week using different total doses and doses per fraction. To reduce the overall treatment time, HDR-BT was administered with a 3-4 days/week schedule. PATIENTS AND METHODS: From June 2003 to December 2008, 164 patients with stage I-IIIc endometrial carcinoma were treated with HDR-BT (4-5 Gy per fraction). The patients were divided into two groups; Group 1 (40/164 patients) was treated with HDR-BT alone (6 fractions; 4 fractions/week) and Group 2 (124/164 patients) was treated with both (External Beam Radiotherapy [EBRT] + HDR-BT: 3 fractions/week). Complications were analyzed using RTOG scores for rectum and bladder and the objective scores of LENT-SOMA for vaginal complications. RESULTS: The mean followup was 48 months. In Group 1, 35 % of patients underwent treatment in ≤10 days and 65 % in >10 days. In Group 2, 53.2 % received treatment in ≤5 days and in 46.8 % in >5 days. Vaginal relapse was observed in only two patients (1.2 %), both having received adjuvant EBRT + HDR-BT. Acute vaginal toxicity appeared in 8.5 % and late vaginal toxicity in 20.7 % of patients with 13.4 % being G1, 6.7 % G2 and only 0.6 % being G4. No statistically significant differences were found in complications in either brachytherapy group regardless of the overall time. CONCLUSION: In our series, three fractions given in 3-5/days after EBRT or six fractions in 10 days, is a safe regimen in terms of complications and local control.
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Braquiterapia/efeitos adversos , Neoplasias do Endométrio/radioterapia , Recidiva Local de Neoplasia/prevenção & controle , Vagina/efeitos da radiação , Neoplasias Vaginais/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Vagina/patologia , Neoplasias Vaginais/patologiaRESUMO
Genotoxicity caused by tobacco smoke was assessed in peripheral blood lymphocytes of smokers living in Mexico City by determining sister chromatid exchange (SCE), cell proliferation kinetics (CPK), replication index (RI) and mitotic index (MI). Nicotine levels, and its major metabolite cotinine, were also estimated in urine samples using gas-chromatography-mass spectrometry to quantify smoking intensity. The outcome of the analysis and the comparison of the 77-smoker group with a non-smoking control group showed that moderate and heavy smokers exhibited significant differences (P < 0.001 and P < 0.05, respectively) in CPK, with an underlying delay in the cellular cycle; similarly, RI was significantly different in these groups (P < 0.001 and P < 0.0001, respectively). There were significant correlations (P < 0.05) between age and number of years the subject had been smoking, as well as between RI and nicotine and cotinine levels and between CPK (M1, M2 and M3) and nicotine and cotinine levels. Smokers were classified for the analysis according to the nicotine levels (it is in relation to number of cigarettes smoked per day) found in urine (ng/mL) as: light (10-250), moderate (251-850) and heavy (851-4110). Significant differences in CPK were found (P < 0.05) between moderate and heavy smokers and non-smokers. Significant differences in RI were found between moderate (P < 0.001) and heavy smokers (P < 0.0001) and non-smokers, but not for the light smoking group. MI was determined in 57 of the smokers, whereas SCE frequency was only recorded in 34 smokers. Both parameters yielded no significant differences, nor correlations with any of the assessed variables. In conclusion, cytokinetic and cytostatic effects were mainly detected in heavy and moderate smokers. Cell cycle delay and RI decrease were found in all ;healthy' smokers. The nicotine and cotinine exposure (causing oxidative damage to DNA) may have implications in the decrease in cell replication due to direct damage to DNA and/or a decrease in the DNA repair mechanisms. Alternatively, nicotine and cotinine may possibly induce apoptosis.