1,720,968 research outputs found
Patient derived cancer-associated fibroblasts from non-small cell lung cancer undergo phenotypic drift in culture
Nanostring nCounter targeted RNA Seq. data of fibroblast cells isolated from human non-cancerous lung tissue and non-small cell lung cancer tumour tissue as well as fibroblasts maintained for three passages in culture from both origins as shown in Mathieson et al. (submission) "Patient derived cancer-associated fibroblasts from non-small cell lung cancer undergo phenotypic drift in culture".
Cancer-associated fibroblasts (CAFs) are the predominant cell type in the stroma of many solid organ malignancies, including non-small cell lung cancer (NSCLC). They are widely studied and represent a diverse population of cells presenting with different phenotypes and functions. CAF research often relies on propagation and culture in vitro for functional assay and co-culture experimentation. In this study we investigated the phenotype of CAFs from NSCLC patients compared to non-cancerous lung fibroblasts by tracking changes in CAF subset marker expression levels by flow cytometry. We demonstrate that CAFs from NSCLC undergo phenotypic drift in culture, and that of the previously defined subsets there is a convergence to a phenotype predominantly upregulated in non-cancerous lung when CAFs are maintained in standard culture conditions. Together we show the phenotype, transcriptome and function of fibroblasts converge between CAFs and fibroblasts from non-cancerous lung, suggesting that standard culture conditions promote this phenotype. We highlight the need to understand and monitor the culture phenotype during functional studies with CAFs, as the heterogeneity found in the tumour microenvironment is rapidly lost in cultured cells
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
Fibroblast heterogeneity in non-small cell lung cancer and optical imaging targeting fibroblast activation protein
Cancer associated fibroblasts (CAFs) are one of the predominant cell types of non-small cell
lung cancer (NSCLC) tumour stroma. This thesis will investigate fibroblast heterogeneity in
NSCLC; defining their phenotype by expression of CAF markers, phenotypic changes in culture
and develop optical imaging probes for imaging fibroblasts in-situ.
In the first results chapter, CAFs have been isolated from NSCLC patient resections and their
phenotype characterised using known CAF markers by flow cytometry. This data led to the
identification of five CAF subsets, CAFS1-S5. By comparing CAFs isolated from tumour tissue
and fibroblasts isolated from tumour adjacent non-cancerous lung (NCL), it was identified that
two of these subsets, CAF-S2 and CAF-S3, were phenotypically similar to NCL fibroblasts,
whereas the three subsets, CAF-S1, CAF-S4 and CAF-S5, were predominant in cancerous
tissue. The presence of these subsets was then investigated by multiplex
immunofluorescence staining of a tumour microarray, which contained a cohort of 163 NSCLC
patient tumours. It was found that the presence of CAF-S1 and CAF-S5, both subsets where
CAFs expressed fibroblast activation protein (FAP) and podoplanin, with CAF-S1 also
expressing alpha-smooth muscle actin, were indicative of poorer recurrence free survival
outcome.
Then in the second results chapter, the effects on cell phenotype of culturing CAFs and NCL
fibroblasts was investigated. This revealed that when cultured by standard tissue culture
methods, fibroblast phenotype converged to a CAF-S3 phenotype, regardless of cancerous or
non-cancerous origin. To try and overcome the limitations of standard tissue culture methods,
a NSCLC tumour organoid model was then developed, which allowed for the culture of other
cell types, predominantly epithelial cells, alongside fibroblasts.
Fibroblast activation protein (FAP) was expressed on the CAF subsets present predominantly
in tumour tissue, and expression of FAP was low on NCL fibroblasts. In the final results
chapter, FAP was considered as a target for optical imaging probes. The iterative development
of a FAP probe which is specific over similar peptidases to FAP is described. These optical
imaging probes could be used to highlight the tumour stroma and allow disease-monitoring,
prognostication and potentially stratify treatment therapies. It is shown that a FAP probe can
be designed to be selective over closely related peptidases, compatible with physiological
levels of FAP expressed on primary CAFs, and the probe can be used to image NSCLC samples
on a clinically compatible fibre-based imaging system.
In conclusion, this thesis describes the CAF signatures in human NSCLC, changes over time in
culture, the development of an organoid model and an optical imaging strategy for FAP
imaging
Dispelling the Myths Behind First-author Citation Counts
We 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
We 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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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