Emerging lab-on-a-chip approaches for liquid biopsy in lung cancer: Status in ctcs and ctdna research and clinical validation

Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.This work was supported by FEDER funds through COMPETE (POCI-01-0145-FEDER-030831) and by Portuguese funds through Fundação para a Ciência e a Tecnologia (PTDC/BTM-TEC/30831/2017) in the framework of project TRIMARKCHIP. PCCC Beacon projects-2021 (Carmen Jeronimo & Fernando J Monteiro)

SIMBA: a web tool for managing bacterial genome assembly generated by Ion PGM sequencing technology

Background The evolution of Next-Generation Sequencing (NGS) has considerably reduced the cost per sequenced-base, allowing a significant rise of sequencing projects, mainly in prokaryotes. However, the range of available NGS platforms requires different strategies and software to correctly assemble genomes. Different strategies are necessary to properly complete an assembly project, in addition to the installation or modification of various software. This requires users to have significant expertise in these software and command line scripting experience on Unix platforms, besides possessing the basic expertise on methodologies and techniques for genome assembly. These difficulties often delay the complete genome assembly projects. Results In order to overcome this, we developed SIMBA (SImple Manager for Bacterial Assemblies), a freely available web tool that integrates several component tools for assembling and finishing bacterial genomes. SIMBA provides a friendly and intuitive user interface so bioinformaticians, even with low computational expertise, can work under a centralized administrative control system of assemblies managed by the assembly center head. SIMBA guides the users to execute assembly process through simple and interactive pages. SIMBA workflow was divided in three modules: (i) projects: allows a general vision of genome sequencing projects, in addition to data quality analysis and data format conversions; (ii) assemblies: allows de novo assemblies with the software Mira, Minia, Newbler and SPAdes, also assembly quality validations using QUAST software; and (iii) curation: presents methods to finishing assemblies through tools for scaffolding contigs and close gaps. We also presented a case study that validated the efficacy of SIMBA to manage bacterial assemblies projects sequenced using Ion Torrent PGM. Conclusion Besides to be a web tool for genome assembly, SIMBA is a complete genome assemblies project management system, which can be useful for managing of several projects in laboratories. SIMBA source code is available to download and install in local webservers at http://ufmg-simba.sourceforge.net

VIRMA-dependent N6-methyladenosine modifications regulate the expression of long non-coding RNAs CCAT1 and CCAT2 in prostate cancer

RNA methylation at position N6 in adenosine (m6A) and its associated methyltransferase complex (MTC) are involved in tumorigenesis. We aimed to explore m6A biological function for long non-coding RNAs (lncRNAs) in prostate cancer (PCa) and its clinical significance. m6A and MTC levels in PCa cells were characterized by ELISA and western blot. Putative m6A-regulated lncRNAs were identified and validated by lncRNA profiler qPCR array and bioinformatics analysis, followed by m6A/RNA co-immunoprecipitation. Impact of m6A depletion on RNA stability was assessed by Actinomycin D assay. The association of m6A-levels with PCa prognosis was examined in clinical samples. Higher m6A-levels and VIRMA overexpression were detected in metastatic castration-resistant PCa (mCRPC) cells (p < 0.05). VIRMA knockdown in PC-3 cells significantly decreased m6A-levels (p = 0.0317), attenuated malignant phenotype and suppressed the expression of oncogenic lncRNAs CCAT1 and CCAT2 (p < 0.00001). VIRMA depletion and m6A reduction decreased the stability and abundance of CCAT1/2 transcripts. Higher expression of VIRMA, CCAT1, and CCAT2 as a group variable was an independent predictor of poor prognosis (HR = 9.083, CI95% 1.911–43.183, p = 0.006). VIRMA is a critical factor sustaining m6A-levels in PCa cells. VIRMA downregulation attenuates the aggressive phenotype of PCa by overall reduction of m6A-levels decreasing stability and abundance of oncogenic lncRNAs

An Eye for Possibilities in the Development of Children with Cerebral Palsy: Neurobiology and Neuropsychology in a Cultural-Historical Dynamic Understanding

Taking children with Cerebral Palsy (CP) as an example, the article seeks an understanding ofchildren with disabilities that connects neuropsychological theories of neural development withthe situated cognition perspective and the child as an active participant in its social practices. Theearly brain lesion of CP is reconceptualised as a neurobiological constraint that exists in therelations between the neural, cognitive and social levels. Through a multi-method study of twochildren with CP, it is analysed how neurobiological constraints arise, evolve and sometimes areresolved through local matches between the child and its social practices. The result is discussedas support of a developmental science approach that includes processes at the social practice levelalong with knowledge of biological processes

The northernmost haulout site of South American sea lions and fur seals in the western South Atlantic

We present estimates of the seasonal and spatial occupation by pinnipeds of the Wildlife Refuge of Ilha dos Lobos (WRIL), based on aerial photographic censuses. Twenty aerial photographic censuses were analysed between July 2010 and November 2018. To assess monthly differences in the numbers of pinnipeds in the WRIL we used a Generalized Linear Mixed Model. Spatial analysis was carried out using Kernel density analysis of the pinnipeds on a grid plotted along the WRIL. Subadult male South American sea lions (Otaria flavescens) were the most abundant pinniped in the WRIL. Potential females of this species were also recorded during half of the census. The maximum number of pinnipeds observed in the WRIL was 304 in September 2018, including an unexpected individual southern elephant seal (Mirounga leonina), and a high number of South American fur seal yearlings (Arctocephalus australis). However, there was no statistically significant difference in counts between months. In all months analysed, pinnipeds were most often found concentrated in the northern portion of the island, with the highest abundances reported in September. This study confirms the importance of the WRIL as a haulout site for pinnipeds in Brazil, recommends that land research and recreational activities occur in months when no pinnipeds are present, and encourages a regulated marine mammal-based tourism during winter and spring months.Fil: Procksch, Natália. Universidad de Vale do Rio dos Sinos; BrasilFil: Grandi, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Ott, Paulo Henrique. Universidade Estadual Do Rio Grande Do Sul; Brasil. Grupo de Estudos de Mamíferos Aquáticos Do Rio Grande Do Sul (GEMARS); BrasilFil: Groch, Karina. Instituto Australis de Pesquisa E Monitoramento Ambiental. Projeto Baleia Franca; BrasilFil: Flores, Paulo A. C.. Centro Mamíferos Aquáticos, Currently at Área de Proteção Ambiental; BrasilFil: Zagonel, Marcelo. Universidad de Vale do Rio dos Sinos; BrasilFil: Crespo, Enrique Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Machado, Rodrigo. Grupo de Estudos de Mamíferos Aquáticos Do Rio Grande Do Sul (GEMARS); BrasilFil: Pavez, Guido. Universidad de Valparaiso; ChileFil: Guimarães, Murilo. Universidade Federal do Rio Grande do Sul; BrasilFil: Veronez, Maurício. Universidad de Vale do Rio dos Sinos; BrasilFil: de Oliveira, Larissa Rosa. Grupo de Estudos de Mamíferos Aquáticos Do Rio Grande Do Sul (GEMARS); Brasil. Universidad de Vale do Rio dos Sinos; Brasi

Validity and Reliability of the Frontotemporal Dementia Rating Scale (FTD-FRS) for the Progression and Staging of Dementia in Brazilian Patients

Introduction: Few studies on instruments for staging frontotemporal dementia (FTD) have been conducted.  Objective: The objective of this study was to analyze the factor structure, internal consistency, reliability, and convergent validity of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS).  Methods: A total of 97 individuals aged 40 years and above with >2 years’ education took part in the study, 31 patients diagnosed with behavioral variant FTD (bvFTD), 8 patients with primary progressive aphasia, 28 with Alzheimer disease, 8 with mild cognitive impairment, and a control group of 22 healthy subjects. The FTD-FRS was completed by family members or caregivers, and Neurologists completed the 8-item Clinical Dementia Rating for Frontotemporal Lobar Degeneration (CDR-FTLD) scale (6 original domains plus Language and Behavior). The Alzheimer disease and FTD patients had equivalent disease severity level.  Results: The internal consistency of the FTD-FRS, estimated by Cronbach α, was 0.975 whereas test-retest reliability was 0.977. Scree plot and exploratory factor (Varimax rotation) analyses revealed the existence of 4 factors, with eigenvalues >1, which together explained 77.13% of the total variance with values of 1.28 to 17.52. The domains of the Brazilian version of the FTD-FRS scale correlated with the domains of the CDR-FTLD.  Conclusions: The present study is the first to document the factorial structure of the FTD-FRS and its convergent validity with the CDR-FTLD. These tools are key to determine dementia severity in FTD. The Brazilian FTD-FRS demonstrated adequate psychometric properties for use in Brazil. This instrument may contribute to disease staging in FTD and may help to document intervention-related changes

Avaliação da composição corporal de jogadores de futebol sub-20 da cidade de Uberlândia, Minas Gerais

Introduction: Football depends on several variables to be performed at its highest performance, among these variables, one of the most important is body composition, as it is related to the athlete's physical capacity and sports performance, which can influence the team's results. Objective: To evaluate the body composition of young soccer athletes, in an under-20 team. Methodology: Sixteen soccer players from a sub-20 team, aged 18 to 20 years, were evaluated. Weight and height were measured; in addition, they performed the electrical bioimpedance test to assess the parameters of body composition, mainly muscle mass and fat percentage. From the muscle mass, the muscle mass index (BMI) was calculated, dividing the total muscle mass by height in meters squared. Result: Most athletes were above the ideal fat percentage (n = 12), however, most individuals had values close to the ideal, which may have been a variation of the body composition assessment method itself. We observed that 4 individuals had an adequate percentage of fat. Regarding the IMM, the average values were within the normal range (10.9 ± 0.6 kg / m2), with only 4 athletes having little muscle mass. Conclusion: Almost all athletes had muscle mass within the normal range, while the majority had values above the adequate percentage of fat. These results show that future nutritional interventions should be carried out in these athletes, focusing mainly on reducing the percentage of fat.Trabalho de Conclusão de Curso (Graduação)Introdução: O futebol depende de diversas variáveis para ser realizado no seu mais alto rendimento, entre essas variáveis, uma das mais importantes é a composição corporal, pois está relacionada com a capacidade física e desempenho esportivo do atleta, podendo influenciar nos resultados da equipe. Objetivo: Avaliar a composição corporal de jovens atletas de futebol, em uma equipe sub-20. Metodologia: Foram avaliados 16 atletas de futebol de campo de uma equipe sub-20, com idade de 18 a 20 anos. Foram mensurados peso e estatura; além disso, fizeram o exame de bioimpedância elétrica para avaliar os parâmetros de composição corporal, principalmente massa muscular e percentual de gordura. A partir da massa muscular, foi calculado o índice de massa muscular (IMM), dividindo a massa muscular total pela altura em metros ao quadrado. Resultado: A maioria dos atletas estava acima do percentual de gordura ideal (n= 12), entretanto, a maior parte dos indivíduos apresentava valores próximos ao ideal, o que pode ter sido uma variação do próprio método de avaliação da composição corporal. Observamos que 4 indivíduos apresentavam percentual de gordura adequado. Em relação ao IMM, os valores médios estavam dentro da normalidade (10,9 ± 0,6 kg/m2 ), sendo que apenas 4 atletas apresentavam pouca massa muscular. Conclusão: Quase todos os atletas apresentaram massa muscular dentro da normalidade, enquanto que a maioria apresentou valores acima do adequado de percentual de gordura. Estes resultados mostram que devem ser realizadas futuras intervenções nutricionais nestes atletas, focando principalmente na redução do percentual de gordura