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Investigation of Injectable Therapeutics to Treat Right Ventricular Heart Failure
No full textCongenital heart defects are the leading cause of right ventricular heart failure (RVHF) in pediatric patients. In particular, hypoplastic left heart syndrome is a condition in which infants are born with an underdeveloped left side of the heart and must undergo three corrective open-heart surgeries to make their right ventricle their main systemic pump. Due to the increased afterload on the RV due to systemic circulation, the RV undergoes a cascade of negative remodeling characterized myocardial apoptosis, maladaptive hypertrophy, vessel rarefaction, metabolic shifts from lipid oxidation to glucose metabolism, inflammation, fibrosis, ischemia from mismatched oxygen supply/demand, and oxidative stress that cannot be corrected by standard treatments that only alleviate the underlying symptoms. Regenerative therapies such as c-kit cardiac progenitor cells (CPCs) and decellularized myocardial matrix (MM) hydrogels are promising therapeutics that mitigate negative remodeling in the RV and promote repair and improve overall cardiac function. CPCs, however, are limited due to their low survival and engraftment rates while MM hydrogels have yet to be investigated in models of RVHF. Furthermore, MM hydrogels that have been investigated are derived from the porcine left ventricle (LV) and have only been investigated in models of left ventricular heart failure, neglecting the fact that the LV and RV are two distinct tissues that arise separately during cardiac development. Thus, leading to a need to evaluate RV derived MM hydrogels to treat RVHF. Here we fabricate and characterize a new RV MM hydrogel and compare it to its predecessor, evaluate the effect of both MM on CPC behavior in vitro, compare CPC alone therapy with MM and CPC combined therapy in vivo, and investigate the mechanisms action of LV MM and RV MM and their effects on negative RV remodeling and function in a small animal model of RVHF. We have developed a new RV MM hydrogel, that while it is physically and mechanically similar to LV MM, it is distinctly different based on proteomic makeup. We further showed that both MM enhance the survival of CPCs against common implant hazards such as needle forces and reactive oxygen species as well as enhance their angiogenic paracrine signaling in vitro. Qualitative assessment showed the benefit of delivering CPCs with either MM to improve CPC retention in vivo while echocardiography demonstrated improvements to cardiac function only when comparing the combinatorial therapies to themselves at the baseline indicating a limited repair timeframe. CPCs alone however showed no functional improvement in echo or MRI when compared to the other treatment groups. CPCs also demonstrated detrimental differentially expressed genes when compared to saline and the MM group suggesting the adult cells hold no therapeutic benefit. Finally, we show proof-of-concept of intramyocardial injections of MM in a rat pulmonary artery banded model of RVHF. Animals injected with either LV MM or RV MM demonstrated significant improvements in tricuspid annular plane systolic excursion, RV end-diastolic volume, RV end-systolic volume, and RV free wall thickness. Both MM also affected pathways related to neovascularization, cardiac contractility, and cardiac development at 1 week post injection. RV MM, however, induced overexpression of pro-inflammatory and pro-fibrotic gene expression, suggesting it may induce a prolonged inflammatory response. Despite this, both MM didn’t affect macrophage, capillary, or myofibroblast density at the 1-week timepoint but did induce significant arteriole growth when compared to saline. Both MM further mitigated negative remodeling pathways by reducing hypertrophy, fibrosis and myofibroblast density and by increasing arteriole density when compared to saline. This study shows proof-of-concept of MM hydrogel therapies, tissue specific or otherwise, to not only mitigate pediatric RVHF with implications of being translated into other cases of RVHF
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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