Prevalence of dengue, Zika and chikungunya viruses in Aedes (Stegomyia) aegypti (Diptera: Culicidae) in a medium-sized city, Amazon, Brazil

Aedes aegypti is associated with epidemic diseases in Brazil, such as urban yellow fever, dengue, and more recently, chikungunya and Zika viruses infections. More information about Ae. aegypti infestation is fundamental to virological surveillance in order to ensure the effectiveness of control measures in use. Thus, the present study aims to identify and compare infestation and infectivity of Ae. aegypti females in Macapa city, Amapa State (Amazon region), Brazil, between the epidemiological weeks 2017/02 and 2018/20. A total number of 303 Ae. aegypti females were collected at 21 fixed collection points, 171 at the 10 collection points in the Marabaixo neighborhood and 132 at the 11 collection points in the Central neighborhood. Among the collected samples, only two were positive for dengue virus, with a 2.08% (2/96 pools) infectivity rate for Marabaixo. The difference between the medians of Ae. aegypti females captured in Central and Marabaixo sites was not statistically significant. The findings indicate similar mosquito infestation levels between the neighborhoods, and a low-level of mosquito infectivity, although dengue virus was found only in Marabaixo. Virological surveillance of Ae. aegypti was important to identify sites of infection and determine possible routes of transmission to enable health surveillance teams to adopt preventive strategies where infected mosquitoes are present and act faster

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Viral genomic analysis of human adenovirus F (HAdV-F) and putative novel human adenovirus C (HAdV-C) recombinant through next-generation sequencing and bioinformatics.

A gastroenterite aguda em crianças ainda é uma das causas mais comuns de hospitalização e importante problema de saúde pública no Brasil. Geralmente, é causada por agentes virais, incluindo rotavírus (RVA), adenovírus humano entérico (HAdV) e norovírus (NoV). Os sorotipos 40 e 41, únicos membros da espécie F (HAdV-F 40/41), são os mais comumente associados à infecção gastrointestinal. Existem poucos dados disponíveis do HAdV-F 40/41 em relação a sua incidência e caracterização molecular. Brasil é um país com dimensões continentais e, portanto, espera-se encontrar uma diversidade genética viral elevada no país. Uma vigilância multirregional contínua é vital para estabelecer um quadro epidemiológico-molecular mais completo sobre o HAdV-F40/41 no Brasil. O objetivo do presente estudo foi investigar a frequência e diversidade genética de cepas de HAdV-F 40/41 em áreas rurais e urbanas de baixa renda no norte do Brasil usando técnicas de sequenciamento de nova geração (NGS), com foco na aquisição de sequências genômicas completas. Também foi realizada análise filogenética visando obter mais informações sobre a relação genética entre cepas brasileiras e mundiais de HAdV-F 40/41. Um total de 251 amostras de fezes coletadas de 2010 a 2016 nos estados do Pará e Tocantins foram rastreadas para o HAdV-F usando metagenômica. A infecção pelo HAdV-F foi detectada em 57,8% (145/251) das amostras. Um total de 137 amostras positivas pertenciam ao HAdV-F41 e 7 amostras ao HAdV-F40. Foi encontrada uma infecção dupla de HAdV-F40/41 em uma amostra. Foram detectadas infecções únicas pelo HAdV-F em 21,9% (55/251) das amostras e infecções mistas em 37,4% (94/251), sendo o RVA/HAdV-F a associação mais frequente (21,5%; 54/251). A análise molecular indicou que as cepas brasileiras de HAdV-F são geneticamente relacionadas às demais cepas de HAdV-F circulando mundialmente. A vigilância de vírus entéricos por NGS proposta no presente estudo também permitiu a identificação e caracterização genômica de uma nova cepa recombinante de HAdV-C (HAdV-C BR-211). A análise de recombinação revelou que a cepa HAdV-C BR- 211 é uma quimera na qual as regiões variáveis do gene Hexon combinam sequências de HAdV-C1 e HAdV-C89. Portanto, a cepa HAdV-C BR-211 possui um esqueleto genômico do tipo HAdV-C89 e uma inserção única de HAdV-C1 na sequência do gene Hexon. Além da cepa recombinante HAdV-C BR-211, a presente investigação também descreveu o genoma completo de uma cepa de HAdV-C tipo 1 (HAdV-C BR-245). Este é o primeiro estudo de HAdV-F utilizando sequenciamento de larga escala realizado no Brasil, onde os dados de genoma completo e análises de sequências foram usados para caracterizar as cepas de HAdV-F 40/41. A expansão do banco de dados de genoma viral pode contribuir significativamente para o melhoramento do sucesso da genotipagem de HAdV-F. Ainda, o aumento no conjunto de genomas anotados de HAdV-F poderá auxiliar o NCBI/GenBank a padronizar os registros de genoma dos HAdV.Acute gastroenteritis in children remains a principal cause of hospitalization and an important public health problem in Brazil. Usually, it is caused by viral agents including rotaviruses (RVA), human enteric adenoviruses (HAdV) and noroviruses (NoV). Serotypes 40 and 41 (HAdV-F40/41) are commonly associated with gastrointestinal infection and are the only members of F species. There are few available data about HAdV-F40/41 regarding its incidence and molecular characterization. Brazil is a country with continental dimensions where continuous multiregional surveillance is vital to establish a more complete picture of the epidemiology of HAdV-F. The aim of the current study was to investigate the genetic diversity and frequency of HAdV-F in rural and low-income urban areas in northern Brazil using sequencing techniques in order to obtain full-genome data. Phylogenetic analysis was also carried out with the aim to obtain more information on the genetic comparison between Brazilian and global HAdV-F strains. A total of 251 stool samples collected between 2010 and 2016 from patients with acute gastroenteritis were screened for HAdV-F using next-generation sequencing techniques. HAdV-F infection was detected in 57.8 % (145/251) of samples. A total of 137 positive samples belonged to HAdV-F41 and 7 to HAdV-F40. HAdV-F40/41 dual infection was found in one sample. Single HAdV-F infections were detected in 21.9 % (55/251) of samples and mixed infections in 37.4 % (94/251), with RVA/HAdV-F being the most frequent association (21.5 %; 54/251). Genetic analysis indicated that the HAdV-F strains circulating in Brazil were closely related to worldwide strains. Surveillance of enteric viruses by NGS proposed in this study also allowed the identification and genomic characterization of a new recombinant strain of HAdV-C (HAdV-C BR-211). Recombination analysis revealed that strain HAdV-C BR-211 is a chimera in which the variable regions of Hexon gene combined HAdV-C1 and HAdV-C89 sequences. Therefore, HAdV-C BR-211strain possesses a genomic backbone of type HAdV-C89 and a unique insertion of HAdV-C1 in the Hexon sequence. In addition to the recombinant strain HAdV-C BR-211, the present investigation also described the full-length genome of a HAdV-C strain type 1 (HAdV-C BR-245). This was the first large-scale HAdV-F study in Brazil in which whole-genome data and DNA sequence analyses were used to characterize HAdV-F strains. Expanding the viral genome database could improve overall genotyping success and assist the National Center for Biotechnology Information (NCBI)/GenBank in standardizing the HAdV genome records by providing a large set of annotated HAdV-F genomes

Mathematical modeling of human skin simulator to analyze the force applied by the needle

Dissertação (mestrado)—Universidade de Brasília, Faculdade Gama, Programa de Pós-Graduação em Engenharia Biomédica, 2014.Um dos grandes desafios da ciência atualmente é traduzir em termos e relações matemáticas o funcionamento de fenômenos e sistemas que compõem o universo. Deseja-se desenvolver e usar esse conhecimento de como os fatores de um sistema se relacionam para adequar e melhorar os processos que interagem com tal sistema. Sob o enfoque da Bioengenharia, é inserido este trabalho, que apresenta o processo de modelagem matemática da pele humana com intuito de melhorar os processos de perfuração com agulhas na região abdominal. A pele sofre uma distribuição da pressão e força de elasticidade ao ser perfurada pela agulha. Existe a necessidade de mensurar as propriedades mecânicas da pele humana por uma representação matemática capaz de simular as deformações que nela ocorrem durante os movimentos do corpo e os processos de perfuração com agulhas, visto que a pele apresenta propriedades mecânicas não lineares, anisotrópica e viscoelástica que variam. Diante disso, é proposta a utilização da teoria de Bond Graph para modelagem matemática de sistemas fisiológicos complexos para a geração de parâmetros que podem ser mais eficazes. A teoria de Bond Graph é uma representação unificada de sistemas dinâmicos, nos quais os elementos interagem entre si por meio de portas, alocados dentro do sistema, onde ocorrerá a troca de energia. Esta dissertação apresenta dois objetivos: modelagem matemática usando a técnica de modelagem pela física do processo e modelagem utilizando Bond Graph; e uma análise dinâmica desse sistema é apresentada com uma comparação dos dois métodos. O sistema modelado apresentou estabilidade, o que é um aspecto positivo e que condiz com o fato de o sistema tender a se estabilizar no decorrer do procedimento de perfuração por agulha após o primeiro contato com a pele.A major challenge now is to translate science and mathematical relationships in terms of the operating systems and phenomena that make up the universe. We intend to develop and use this knowledge as factors of a system relate to adapt and improve processes that interact with such a system. Under the focus of this work is inserted Bioengineering, which presents the process of mathematical modeling of the human skin with the aim of improving the processes of drilling needles in the abdominal region. The skin undergoes a pressure distribution of elasticity and strength to be pierced by the needle. There is a need to measure the mechanical properties of human skin by a mathematical representation capable of simulating the deformation that occurs therein during movement of the body and drilling processes with needles, since the skin has non-linear viscoelastic and anisotropic mechanical properties ranging. Therefore, we propose the use of Bond Graph theory for mathematical modeling of complex physiological systems to generate parameters that can be most effective. Bond Graph theory is a unified representation of dynamic systems in which elements interact with each other through ports allocated within the system, where the exchange of energy occurs. This work has two objectives: mathematical modeling using the technique of modeling the physics of the process and modeling using Bond Graph; and a dynamic analysis of such systems is presented with a comparison of two methods. The modeled system was stable, which is positive and which is consistent with the fact that the system tends to stabilize during the needle drilling procedure after the first contact with the skin

New Variants of Squash Mosaic Viruses Detected in Human Fecal Samples

Squash mosaic virus (SqMV) is a phytovirus that infects great diversity of plants worldwide. In Brazil, the SqMV has been identified in the states of Ceará, Maranhão, Piauí, Rio Grande do Norte, and Tocantins. The presence of non-pathogenic viruses in animals, such as phytoviruses, may not be completely risk-free. Similarities in gene repertories between these viruses and viruses that affect animal species have been reported. The present study describes the fully sequenced genomes of SqMV found in human feces, collected in Tocantins, and analyzes the viral profile by metagenomics in the context of diarrhea symptomatology. The complete SqMV genome was obtained in 39 of 253 analyzed samples (15.5%); 97.4% of them belonged to children under 5 years old. There was no evidence that the observed symptoms were related to the presence of SqMV. Of the different virus species detected in these fecal samples, at least 4 (rotavirus, sapovirus, norovirus, parechovirus) are widely known to cause gastrointestinal symptoms. The presence of SqMV nucleic acid in fecal samples is likely due to recent dietary consumption and it is not evidence of viral replication in the human intestinal cells. Identifying the presence of SqMV in human feces and characterization of its genome is a relevant precursor to determining whether and how plant viruses interact with host cells or microorganisms in the human gastrointestinal tract

Genomic Analyses of Potential Novel Recombinant Human Adenovirus C in Brazil

Human Adenovirus species C (HAdV-C) is the most common etiologic agent of respiratory disease. In the present study, we characterized the nearly full-length genome of one potential new HAdV-C recombinant strain constituted by Penton and Fiber proteins belonging to type 89 and a chimeric Hexon protein of types 1 and 89. By using viral metagenomics techniques, we screened out, in the states of Tocantins and Pará, Northern and North regions of Brazil, from 2010 to 2016, 251 fecal samples of children between 0.5 to 2.5 years old. These children were presenting acute diarrhea not associated with common pathogens (i.e., rotavirus, norovirus). We identified two HAdV-C strains in two distinct patients. Phylogenetic analysis performed using all complete genomes available at GenBank database indicated that one strain (HAdV-C BR-245) belonged to type 1. The phylogenetic analysis also indicated that the second strain (HAdV-C BR-211) was located at the base of the clade formed by the newly HAdV-C strains type 89. Recombination analysis revealed that strain HAdV-C BR-211 is a chimera in which the variable regions of Hexon gene combined HAdV-C1 and HAdV-C89 sequences. Therefore, HAdV-C BR-211 strain possesses a genomic backbone of type HAdV-C89 and a unique insertion of HAdV-C1 in the Hexon sequence. Recombination may play an important driving force in HAdV-C diversity and evolution. Studies employing complete genomic sequencing on circulating HAdV-C strains in Brazil are needed to understand the clinical significance of the presented data