1,720,982 research outputs found
Effects of Lumacaftor/Ivacaftor on physical activity and exercise tolerance in three adults with cystic fibrosis
No full textThe combination of the corrector lumacaftor with the potentiator ivacaftor has been approved for treatment of cystic fibrosis (CF) patients homozygous for the Phe508del CFTR mutation. There are no reports detailing the effect of lumacaftor–ivacaftor on physical activity (PA) and exercise tolerance. We performed incremental cardiopulmonary exercise testing (CPET) and we assessed PA pre- and post 2 years initiation of lumacaftor–ivacaftor in three CF adults. PA of mild intensity improved by +13% in patient 1, + 84% in patients 2 and + 89% in patient 3. Oxygen uptake increased both at anaerobic threshold and at peak exercise (patient 1 + 33%, patient 2 + 42% and patient 3 + 20%). Daily physical activities and exercise tolerance improved after two years of lumacaftor–ivacaftor therapy
Advantages and limits in the adoption of reproducible research and R-tools for the analysis of omic data
No full textReproducible (computational) Research is crucial to produce transparent and high quality scientific papers. First, we illustrate the benefits that scientific community can receive from the adoption of Reproducible Research standards in the analysis of high-throughput omic data. Then, we describe several tools useful to researchers to increase the reproducibility of their works. Moreover, we face the advantages and limits of reproducible research and how they could be addressed and solved. Overall, this paper should be considered as a proof of concept on how and what characteristic - in our opinion - should be considered to conduct a study in the spirit of Reproducible Research. Therefore, the scope of this paper is two-fold. The first goal consists in presenting and discussing some easy-to-use instruments for data analysts to promote reproducible research in their analyses. The second aim is to encourage developers to incorporate automatic reproducibility features in their tools
Distinct Antigen Delivery Systems Induce Dendritic Cells' Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis.
No full textVaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells’ maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells’ polarization through the induction of Il12b, Il12rb, Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis
Chromatin and Transcriptional Response to Loss of TBX1 in Early Differentiation of Mouse Cells
Full text linkThe T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and the gene is haploinsufficient in DiGeorge syndrome, a typical developmental anomaly of the pharyngeal apparatus. Despite almost two decades of research, if and how TBX1 function triggers chromatin remodeling is not known. Here, we explored genome-wide gene expression and chromatin remodeling in two independent cellular models of Tbx1 loss of function, mouse embryonic carcinoma cells P19Cl6, and mouse embryonic stem cells (mESCs). The results of our study revealed that the loss or knockdown of TBX1 caused extensive transcriptional changes, some of which were cell type-specific, some were in common between the two models. However, unexpectedly we observed only limited chromatin changes in both systems. In P19Cl6 cells, differentially accessible regions (DARs) were not enriched in T-BOX binding motifs; in contrast, in mESCs, 34% (n = 47) of all DARs included a T-BOX binding motif and almost all of them gained accessibility in Tbx1−/− cells. In conclusion, despite a clear transcriptional response of our cell models to loss of TBX1 in early cell differentiation, chromatin changes were relatively modest
A novel shiny platform for the geo-spatial analysis of large amount of patient data
Full text linkIt has been estimated that up to 80% of all data stored in health care databases may have spatial components. To fully exploit such components, there is a need of improving existing tools or developing novel spatio-temporal functionalities. Geographic information systems (GIS) as QuantumGis, SOLAP2, etc. are potential candidates to support decisional needs, but despite their capabilities, they are still scarcely employed in association within BI applications. For these reasons, we are developing a GIS user-friendly interface in R environment in order to dynamically and interactively visualize and analyze (within BI platforms) diverse informative data layers (e.g., pathology incidence data, environmental pollution, etc.). Although preliminary, we believe that this kind of tools could be suitable used for epidemiologic, environmental and economical studies by providing geographical maps and statistical data analyses of interest for different stakeholders.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Dietary Fatty Acids Contribute to Maintaining the Balance between Pro-Inflammatory and Anti-Inflammatory Responses during Pregnancy
No full textBackground: During pregnancy, the balance between pro-inflammatory and anti-inflammatory responses is essential for ensuring healthy outcomes. Dietary Fatty acids may modulate inflammation. Methods: We investigated the association between dietary fatty acids as profiled on red blood cells membranes and a few pro- and anti-inflammatory cytokines, including the adipokines leptin and adiponectin at ~38 weeks in 250 healthy women. Results: We found a number of associations, including, but not limited to those of adiponectin with C22:3/C22:4 (coeff -1.44; p = 0.008), C18:1 c13/c14 (coeff 1.4; p = 0.02); endotoxin with C20:1 (coeff -0.9; p = 0.03), C22:0 (coeff -0.4; p = 0.05); MCP-1 with C16:0 (coeff 0.8; p = 0.04); and ICAM-1 with C14:0 (coeff -86.8; p = 0.045). Several cytokines including leptin were associated with maternal body weight (coeff 0.9; p = 2.31 × 10-5), smoking habits (i.e., ICAM-1 coeff 133.3; p = 0.09), or gestational diabetes (i.e., ICAM-1 coeff 688; p = 0.06). Conclusions: In a general cohort of pregnant women, the intake of fatty acids influenced the balance between pro- and anti-inflammatory molecules together with weight gain, smoking habits, and gestational diabetes
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