Unraveling the relevance of arl gtpases in cutaneous melanoma prognosis through integrated bioinformatics analysis

Funding Information: Funding: This research was funded by iNOVA4Health—UIDB/04462/2020, a program financially supported by the Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência. M.P. was funded by the Liga Portuguesa Contra o Cancro ‒ Núcleo Regional do Sul (LPCC‐NRS). D.B. was funded by the FCT Investigator Program (IF/00501/2014/CP1252/CT0001). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Cutaneous melanoma (CM) is the deadliest skin cancer, whose molecular pathways underlying its malignancy remain unclear. Therefore, new information to guide evidence‐based clinical decisions is required. Adenosine diphosphate (ADP)‐ribosylation factor‐like (ARL) proteins are membrane trafficking regulators whose biological relevance in CM is undetermined. Here, we investigated ARL expression and its impact on CM prognosis and immune microenvironment through integrated bioinformatics analysis. Our study found that all 22 ARLs are differentially expressed in CM. Specifically, ARL1 and ARL11 are upregulated and ARL15 is downregulated regardless of mutational frequency or copy number variations. According to TCGA data, ARL1 and ARL15 represent independent prognostic factors in CM as well as ARL11 based on GEPIA and OncoLnc. To investigate the mechanisms by which ARL1 and ARL11 increase patient survival while ARL15 reduces it, we evaluated their correlation with the immune microenvironment. CD4+ T cells and neutrophil infiltrates are significantly increased by ARL1 expression. Furthermore, ARL11 expression was correlated with 17 out of 21 immune infiltrates, including CD8+ T cells and M2 macrophages, described as having anti‐tumoral activity. Likewise, ARL11 is interconnected with ZAP70, ADAM17, and P2RX7, which are implicated in immune cell activation. Collectively, this study provides the first evidence that ARL1, ARL11, and ARL15 may influence CM progression, prognosis, and immune microenvironment remodeling.publishersversionpublishe

Pre-match Warm-Up Dynamics and Workload in Elite Futsal

Warming up prior to competition is a widely accepted strategy to increase players’ readiness and achieve high performances. However, pre-match routines are commonly based on empirical knowledge and strongly influenced by models emerging from elite team practices. The aim of the present study was to identify and analyze current pre-match warm-up practices in elite futsal. Forty-three elite players were analyzed during their pre-match warm-up routines during the Portuguese Futsal Cup Final 8. Warm-up tasks were classified according to duration, type of activity, sequence, and structure. External load variables included the total distance covered, total distance covered per minute, running distance per minute, sprinting distance per minute, number of accelerations per minute, and number of decelerations per minute. Results highlighted that warm-up routines lasted for 27.5 ± 9.2 min and included nine major different tasks. Open-skill activities were prioritized by coaches; competitive and non-competitive futsal-specific tasks were included in 90% of the total warm-up routines, with a higher focus on non-competitive tasks (68% of total time). The intensity progressively increased during warm-ups, mainly because of the higher number of accelerations and decelerations per minute. Pre-match warm-up routines strongly endorse futsal-specific and representative tasks in order to establish pre-match settings able to prepare players for the upcoming game. When designing pre-match warm-up routines, coaches should be aware that duration, sequence, and type of tasks may affect players’ acute performance and readiness

Evidence of validity for the online version of the assessment of adherence to antiretroviral therapy questionnaire

A Patient-Reported Outcome (PRO) measure titled Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral (acronym CEAT-VIH) is currently available in paper-and-pencil and digital (online assessment) formats. Due to the advantages of online assessment, the main objective of this work was to evaluate psychometric properties of the online version, in an international sample, to accumulate evidence of its validity and provide score norms for the questionnaire. A psychometric study was performed with an international sample of 1,470 participants, from 30 countries, to accumulate evidence of CEAT-VIH validity regarding internal structure and related external criterion (e.g., viral load, number of pills, and AIDSrelated symptoms). Descriptive statistics and normative data for scores are also presented. The majority of participants were men (72.4%), aged 15 to 78 years old (M = 39.3, SD = 12.6). A unidimensional model with five facets occurred as the observed variables converged, which presented a good model fit (comparative fit index [CFI] = 1.000; Tucker–Lewis index [TLI] = 0.999; standardized root mean square residual [SRMR] = 0.027; and root mean square error of approximation [RMSEA] [90% confidence interval, CI] = 0.009 [0.000, 0.038], p = .995). There was a weak invariance for the CEAT-VIH structure for language versions and countries. Cronbach’s alpha values for the instrument (17 items) were acceptable across language versions (.88-.96). Evidence of validity related to external criteria was achieved by associations (e.g., Spearman and Mann–Whitney) between CEAT-VIH scores and relevant clinical (e.g., CD4+ cells, viral load, number of pills, and AIDSrelated symptoms) and sociodemographic (e.g., gender, age, employment status, education level, place of residence, and participation at local AIDS association) variables. In conclusion, the overall data on the evaluated psychometric properties allow recommendation of the use of this instrument in research and applied settings

Apropriação das Tecnologias da Informação e Comunicação no ensino de ciências: uma revisão sistemática da última década (2007-2016)

Este trabalho tem como propósito analisar o objetivo das pesquisasenvolvendo as Tecnologias da Informação e Comunicação (TIC) no Ensino de Ciências. Para isso, realizou-se uma revisão sistemática em 11 revistas da área de Ensino no período de 2007-2016. Nesse sentido, a partir de três critérios pré-estabelecidos investigamos nos artigos a intencionalidade da pesquisa em analisar as estratégias de uso das TIC, as contribuições e limitações do uso das TIC e o interesse na aplicação/utilização das TIC. Os resultados mostram que dos 291 artigos analisados, 47% são direcionados para a utilização de algum material suportado pelas TIC, sem a preocupação de quem (o professor) irá utilizar ou como (a estratégia) será essa utilização. Além disso, identificamos a necessidade de pesquisas voltadas à elaboração de estratégias para o uso adequado das TIC

The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp-) deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations

A MEDIAÇÃO FAMILIAR E O FIM DO RELACIONAMENTO CONJUGAL: O PROBLEMA DO ACESSO À JUSTIÇA E A EXPERIÊNCIA DAS OFICINAS DE PARENTALIDADE.

O presente artigo objetiva discorrer sobre as mudanças sociais relacionadas à família, verificando o surgimento do conflito na ausência de diálogo na família. Examinar a importância da mediação na melhoria do diálogo no fim do relacionamento conjugal, já que a ruptura na relação familiar ocasiona o sofrimento em todos os envolvidos no litígio. Contextualizar o aumento da demanda judicial com o problema do acesso à justiça. Apresentar a experiência pioneira das oficinas de parentalidade, que utilizam técnicas da mediação de conflitos, para auxiliar no diálogo em divórcios conturbados, baseando o estudo em pesquisa de campo, bibliografia e dados governamentais