1,721,130 research outputs found
The Membrane-Associated Adaptor Protein DOK5 Is Upregulated in Systemic Sclerosis and Associated with IGFBP-5-Induced Fibrosis
Full text linkSystemic sclerosis (SSc) is characterized by excessive fibrosis of the skin and internal organs due to fibroblast proliferation and excessive production of extracellular matrix (ECM). We have shown that insulin-like growth factor binding protein (IGFBP)-5 plays an important role in the development of fibrosis in vitro, ex vivo, and in vivo. We identified a membrane-associated adaptor protein, downstream of tyrosine kinase/docking protein (DOK)5, as an IGFBP-5-regulated target gene using gene expression profiling of primary fibroblasts expressing IGFBP-5. DOK5 is a tyrosine kinase substrate associated with intracellular signaling. Our objective was to determine the role of DOK5 in the pathogenesis of SSc and specifically in IGFBP-5-induced fibrosis. DOK5 mRNA and protein levels were increased in vitro by endogenous and exogenous IGFBP-5 in primary human fibroblasts. DOK5 upregulation required activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Further, IGFBP-5 triggered nuclear translocation of DOK5. DOK5 protein levels were also increased in vivo in mouse skin and lung by IGFBP-5. To determine the effect of DOK5 on fibrosis, DOK5 was expressed ex vivo in human skin in organ culture. Expression of DOK5 in human skin resulted in a significant increase in dermal thickness. Lastly, levels of DOK5 were compared in primary fibroblasts and lung tissues of patients with SSc and healthy donors. Both DOK5 mRNA and protein levels were significantly increased in fibroblasts and skin tissues of patients with SSc compared with those of healthy controls, as well as in lung tissues of SSc patients. Our findings suggest that IGFBP-5 induces its pro-fibrotic effects, at least in part, via DOK5. Furthermore, IGFBP-5 and DOK5 are both increased in SSc fibroblasts and tissues and may thus be acting in concert to promote fibrosis
Physical activity assessment in patients with axial spondyloarthritis compared to healthy controls: a technology-based approach.
No full textIntroductionTraditionally, assessment in axial Spondyloarthritis (aSpA) includes the evaluation of the capacity to execute tasks, conceptualized as physical function. The role of physical activity, defined as movement-related energy expenditure, is largely unknown and almost exclusively studied using patient-reported outcome measures. The aims of this observational cross-sectional study are to compare physical activity between patients with aSpA and healthy controls (HC) and to evaluate the contribution of disease activity to physical activity differences between groups.MethodsForty patients with aSpA were matched by age, gender, period of data acquisition in terms of days and season to 40 HC. Physical activity was measured during five consecutive days (three weekdays and two weekend days) using ambulatory monitoring (SenseWear Armband). Self-reported disease activity was measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Differences in physical activity between patients with aSpA and HC were examined with Wilcoxon signed-rank tests and a mixed linear model. Difference scores between patients and HC were correlated with disease activity.ResultsAverage weekly physical activity level (Med(IQR); HC:1.54(1.41-1.73); aSpA:1.45(1.31-1.67),MET) and energy expenditure (HC:36.40(33.43-41.01); aSpA:34.55(31.08-39.41),MET.hrs/day) were significantly lower in patients with aSpA. Analyses across intensity levels revealed no significant differences between groups for inactivity and time spent at light or moderate physical activities. In contrast, weekly averages of vigorous (HC:4.02(1.20-12.60); aSpA:0.00(0.00-1.20),min/d), very vigorous physical activities (HC0.00(0.00-1.08); aSpA:0.00(0.00-0.00),mind/d) and moderate/(very)vigorous combined (HC2.41(1.62-3.48); aSpA:1.63(1.20-2.82),hrs/d) were significantly lower in patients with aSpA. Disease activity did not interact with differences in physical activity between patients with aSpA and HC, evidenced by non-significant and very low correlations (range: -0.06-0.17) between BASDAI and HC-aSpA patients' difference scores.ConclusionsPatients with aSpA exhibit lower physical activity compared to HC and these differences are independent of self-reported disease activity. Further research on PA in patients with aSpA should be prioritized
Systemic Sclerosis Associated Interstitial Lung Disease: A Conceptual Framework for Subclinical, Clinical, and Progressive Disease
No full textAbstract
Objectives
Establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD).
Methods
A conceptual framework for subclinical, clinical, and progressive ILD was provided to eighty-three experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least 4 experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥ 75% of experts agreed. Experts provided information on which items were important in determining classification.
Results
Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%), and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT (HRCT)); risk of progression was influenced primarily by disease duration.
Conclusions
Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression, and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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