Broken silence: 22,841 predicted deleterious synonymous variants identified in the human exome through computational analysis.

Synonymous single nucleotide variants (sSNVs) do not alter the primary structure of a protein, thus it was previously accepted that they were neutral. Recently, several studies demonstrated their significance to a range of diseases. Still, variant prioritization strategies lack focus on sSNVs. Here, we identified 22,841 deleterious synonymous variants in 125,748 human exomes using two in silico predictors (SilVA and CADD). While 98.2% of synonymous variants are classified as neutral, 1.8% are predicted to be deleterious, yielding an average of 9.82 neutral and 0.18 deleterious sSNVs per exome. Further investigation of prediction features via Heterogeneous Ensemble Feature Selection revealed that impact on amino acid sequence and conservation carry the most weight for a deleterious prediction. Thirty nine detrimental sSNVs are not rare and are located on disease associated genes. Ten distinct putatively non-deleterious sSNVs are likely to be under positive selection in the North-Western European and East Asian populations. Taken together our analysis gives voice to the so-called silent mutations as we propose a robust framework for evaluating the deleteriousness of sSNVs in variant prioritization studies.

Nyssorhynchus darlingi genome-wide studies related to microgeographic dispersion and blood-seeking behavior.

BACKGROUND: In Brazil, malaria is concentrated in the Amazon Basin, where more than 99% of the annual cases are reported. The main goal of this study was to investigate the population structure and genetic association of the biting behavior of Nyssorhynchus (also known as Anopheles) darlingi, the major malaria vector in the Amazon region of Brazil, using low-coverage genomic sequencing data. METHODS: Samples were collected in the municipality of Mâncio Lima, Acre state, Brazil between 2016 and 2017. Different approaches using genotype imputation and no gene imputation for data treatment and low-coverage sequencing genotyping were performed. After the samples were genotyped, population stratification analysis was performed. RESULTS: Weak but statistically significant stratification signatures were identified between subpopulations separated by distances of approximately 2-3 km. Genome-wide association studies (GWAS) were performed to compare indoor/outdoor biting behavior and blood-seeking at dusk/dawn. A statistically significant association was observed between biting behavior and single nucleotide polymorphism (SNP) markers adjacent to the gene associated with cytochrome P450 (CYP) 4H14, which is associated with insecticide resistance. A statistically significant association between blood-seeking periodicity and SNP markers adjacent to genes associated with the circadian cycle was also observed. CONCLUSION: The data presented here suggest that low-coverage whole-genome sequencing with adequate processing is a powerful tool to genetically characterize vector populations at a microgeographic scale in malaria transmission areas, as well as for use in GWAS. Female mosquitoes entering houses to take a blood meal may be related to a specific CYP4H14 allele, and female timing of blood-seeking is related to circadian rhythm genes.

Meaning-making in occupational therapy interventions: a scoping review / A construção de sentidos nas intervenções em terapia ocupacional: uma revisão de escopo

Abstract Introduction Meaning-making is an experience-centred process. It is an essential element for understanding the impact of occupational therapy interventions focused on fostering processes of becoming, one of the four integrated dimensions of meaningful occupation (along with doing, being, and belonging). Objective This paper aims to explore further some of the aspects that are essential for meaning-making in occupational therapy interventions. Method A scoping review guided by Arksey and O'Malley's methodological framework was conducted. In the initial search, 528 articles were retrieved from three databases; 16 met the criteria for inclusion: articles in English, peer-reviewed, published between January 2008 and December 2017, that addressed some type of occupational therapy intervention, with data related to the meanings of the participants of the studies. Results The articles address a multiplicity of populations, services, and fields of practice, in qualitative studies, with methodologies that prioritise reflection on the lived experience. Thematic analysis highlights the interconnection between being, doing, and belonging to foster meaning-making; implications of professional actions; and meaning-making triggered by reflective processes. Conclusion Meaning-making demands reflection on the lived experience, and is influenced by human and physical environments. Both conditions/limitations and new skills/abilities enhance processes of meaning-making. Implications for future research are considered.

Resumo Introdução A construção de sentidos é um processo centrado na experiência, essencial para a compreensão do impacto das intervenções em terapia ocupacional voltadas para a promoção de processos de transformação/becoming, uma das quatro dimensões integradas da ocupação significativa (juntamente com o fazer/doing, ser/being e pertencer/belonging). Objetivo Este artigo tem como objetivo identificar aspectos essenciais para a construção de sentido em intervenções de terapia ocupacional. Método Foi realizada uma revisão de escopo. Na busca inicial, 528 artigos foram recuperados de três bases de dados; 16 atenderam aos critérios de inclusão: artigos em inglês, revisados por pares, publicados entre janeiro de 2008 e dezembro de 2017, que abordassem algum tipo de intervenção de terapia ocupacional, com dados referentes aos sentidos construídos pelos participantes dos estudos. Resultados Os artigos abordam múltiplas populações, serviços e campos de prática, em estudos qualitativos, com metodologias que priorizam a reflexão sobre a experiência vivida. A análise temática destaca a interconexão entre ser, fazer e pertencer para promover a construção de sentido; implicações para ações profissionais; e construção de sentido desencadeada por processos reflexivos. Conclusão A construção de sentidos demanda reflexão sobre a experiência vivida, é influenciada pelos ambientes humanos e físicos. Tanto as condições limitantes como as novas habilidades adquiridas desencadeiam processos de construção de sentido. Implicações para pesquisas futuras são indicadas.

Diálogos com Benetton e Latour: possibilidades de compreensão da inserção social / Dialogues with Benetton and Latour: possibilities for an understanding of social insertion

Resumo Este ensaio busca tecer reflexões em torno da temática da inserção social, caminhando pela construção de conhecimento em terapia ocupacional, em sua lida com sujeitos imersos em problemáticas ligadas à exclusão social. Tais reflexões sustentam-se no trabalho desenvolvido por Bruno Latour, sociólogo francês, em especial em seu trabalho metodológico sobre a Teoria Ator-Rede, que busca desvelar a ação de seres humanos e não humanos que leva outros a agirem no mundo; e nas proposições do Método Terapia Ocupacional Dinâmica, desenvolvido por Jô Benetton, terapeuta ocupacional brasileira, em seu arcabouço metodológico para ajudar pessoas a agirem no mundo. Assim, este ensaio busca desvelar pontos nos quais essas duas propostas teórico-metodológicas se aproximam e podem oferecer novas possibilidades para compreender a inserção social em construção, no movimento dinâmico, fluido e instável do social, em processos que favoreçam a participação dos sujeitos na construção do coletivo, com base em seu modo de ser, de fazer e de se relacionar.

Abstract This essay aims to weave reflections around the theme of social insertion, walking through the construction of knowledge in occupational therapy, in its deal with persons immersed in issues related to social exclusion. These reflections are based on the Bruno Latour's work, a French sociologist, in particular his Actor-Network Theory, which seeks to unveil the action of human and non-human beings that leads others to act in the world; and on the propositions of the Dynamic Occupational Therapy Method, developed by Jô Benetton, a Brazilian occupational therapist, in her methodological framework to help people to act in the world. This essay aims to reveal points in which these two theoretical-methodological proposals approach and can offer new possibilities to understand social insertion in construction, in the dynamic, fluid and unstable movement of the social, in processes that favor people´s participation in the construction of the collective, based on their way of being, doing and relating.

Machine Learning Supports Long Noncoding RNAs as Expression Markers for Endometrial Carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is the second most common type of gynecological tumor. Several research studies have recently shown the potential of different ncRNAs as biomarkers for prognostics and diagnosis in different types of cancers, including UCEC. Thus, we hypothesized that long noncoding RNAs (lncRNAs) could serve as efficient factors to discriminate solid primary (TP) and normal adjacent (NT) tissues in UCEC with high accuracy. We performed an in silico differential expression analysis comparing TP and NT from a set of samples downloaded from the Cancer Genome Atlas (TCGA) database, targeting highly differentially expressed lncRNAs that could potentially serve as gene expression markers. All analyses were performed in R software. The receiver operator characteristics (ROC) analyses and both supervised and unsupervised machine learning indicated a set of 14 lncRNAs that may serve as biomarkers for UCEC. Functions and putative pathways were assessed through a coexpression network and target enrichment analysis.

A construção de sentidos sobre o que é significativo: diálogos com Wilcock e Benetton / The meaning making of what is meaningful: dialogues with Wilcock and Benetton

Resumo Este ensaio buscou tecer relações em torno da construção de sentidos sobre o que é significativo como elemento relevante para o conhecimento e a prática da terapia ocupacional, por meio do diálogo com duas autoras, Ann Wilcock, com sua Perspectiva da Natureza Ocupacional da Saúde, sustentada na perspectiva paradigmática da ocupação como promotora de bem-estar e saúde, e Jô Benetton, com seu Método Terapia Ocupacional Dinâmica, apoiada na perspectiva paradigmática da terapia ocupacional, do tratar por meio de ocupações/atividades. O que é significativo pode ser considerado atrelado ao conceito de saúde que cada uma propõe: Wilcock e sua ênfase na ocupação significativa, em oposição a uma disfunção ocupacional; e Benetton, com foco na saúde qualificada pelo sujeito-alvo das intervenções em terapia ocupacional como o que lhe traz bem-estar e o ajuda a agir no mundo. Esperamos contribuir para o debate em torno dos conceitos que sustentam intervenções em terapia ocupacional, em uma reflexão sobre o processo de construção de sentidos nas intervenções de terapia ocupacional.

Abstract This essay sought to weave a dialogue around the meaning of what is meaningful as a relevant element for Occupational Therapy knowledge and practice, through the dialogue with two authors, Ann Wilcock, in her Perspective of the Occupational Nature of Health, sustained in an occupation paradigmatic perspective, in which the occupation promotes well-being and health, and Jô Benetton, with her Dynamic Occupational Therapy Method, supported in occupational therapy paradigmatic perspective, as a treatment by occupations/activities. What is meaningful can be considered linked to the concept of health that each one proposes: Wilcock and her emphasis on meaningful occupation, as opposed to an occupational dysfunction; and Benetton, focusing on what the target person of occupational therapy interventions qualifies as healthy and helps him/her to act in the world. We hope to contribute to the debate around the concepts that support interventions in occupational therapy, reflecting on the process of meaning making in occupational therapy interventions.

Comunidade de prática de terapeutas ocupacionais iniciantes: o início da prática em saúde mental / Comunidad de práctica de terapeutas ocupacionales principiantes: inicio de la práctica en salud mental / Community of practice of newly occupational therapists: the mental health practice beginning

O início da prática é um período de intensa socialização profissional e de vivências dilemáticas e estressantes. Este artigo apresenta parte dos resultados de uma pesquisa-ação que objetivou compreender aspectos do desenvolvimento profissional em terapia ocupacional, e contou com participação de seis terapeutas ocupacionais iniciantes, da pesquisadora e de dois terapeutas ocupacionais experientes em uma comunidade de prática, com encontros presenciais gravados e transcritos, e atividades virtuais ­ dados analisados tematicamente. A temática dos dilemas vividos na prática iniciante e a construção de sentidos sobre eles organizaram-se em quatro subtemas: O não-saber como alimento para o desenvolvimento profissional; Ser terapeuta na saúde mental; O uso de atividades em saúde mental e o que é específico em terapia ocupacional; Aprender a encontrar o foco em atendimentos de curto tempo. Esperamos que este artigo possa ampliar reflexões sobre a formação inicial e continuada em terapia ocupacional, além de indicar novas possibilidades de pesquisa na temática.

El inicio de la práctica profesional es un período de intensa socialización y vivencias de dilemas y estrés. Este artículo presenta parte de los resultados de una investigación-acción con el objetivo de comprender algunos aspectos del desarrollo profesional en terapia ocupacional; participan seis terapeutas ocupacionales que inician su trabajo , la investigadora y dos terapeutas ocupacionales con experiencia, en una comunidad de práctica. Los encuentros presenciales fueron grabados y transcritos, además de actividades virtuales y los datos fueron analizados por tema. La temática de los dilemas vividos en la práctica inicial y la construcción de significados de éstos se organizaron en cuatro subtemas: La falta de conocimiento para el desarrollo profesional; ser terapeuta en la salud mental; el uso de actividades específicas de TO en salud mental y qué es para terapia ocupacional; aprender a encontrar el foco de la intervención de corto tiempo. Esperamos que este artículo pueda ampliar reflexiones sobre la formación inicial y continuada en terapia ocupacional, e indicar nuevas posibilidades de investigación en la temática.

The beginning of practice has been considered an intense professional period of socialization and high level of stress. This article presents some results from an Action Research which included the participation of six beginners occupational therapists, the researcher and two experienced occupational therapists in a community of practice. The meetings were recording and transcribing beside virtual activities. All data were thematically analyzed. The theme of dilemmas in the beginning of practice and the construction of meaning were organized in four themes: Non-knowing nurturing professional development; being a therapist in mental health; use of activities and occupational therapy specificity; learning to find the focus of the intervention on short-term care. We hope this study could expand reflections on initial and continuing training in occupational therapy, and to indicate new possibilities for research in the subject.

Analysis of the Cancer Genome Atlas Data Reveals Novel Putative ncRNAs Targets in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the prevalent type of primary liver malignancy. Different noncoding RNAs (ncRNAs) that negatively regulate gene expression, such as the microRNAs and the long ncRNAs (lncRNAs), have been associated with cell invasiveness and cell dissemination, tumor recurrence, and metastasis in HCC. To evaluate which regulatory ncRNAs might be good candidates to disrupt HCC proliferation pathways, we performed both unsupervised and supervised analyses of HCC expression data, comparing samples of solid tumor tissue (TP) and adjacent tissue (NT) of a set of patients, focusing on ncRNAs and searching for common mechanisms that may shed light in future therapeutic options. All analyses were performed using the R software. Differential expression (total RNA and miRNA) and enrichment analyses (Gene Ontology + Pathways) were performed using the package TCGABiolinks. As a result, we improved the set of lncRNAs that could be the target of future studies in HCC, highlighting the potential of FAM170B-AS1 and TTN-AS1.