1,720,962 research outputs found
Mitochondrial-DAMPs released after lung transplantation promote primary graft dysfunction
Full text linkLung transplantation (LTx) often results in primary graft dysfunction (PGD), a form of acute lung injury (ALI) that is responsible for poor short and long-term outcomes. Although the underlying mechanisms that promote PGD are undefined recent evidence has pointed to the involvement of danger associated molecular patterns (DAMPs). Mitochondrial DAMPs (Mt-DAMPS) share the potent immunostimulatory qualities of bacterial pathogen-associated molecular patterns (PAMPs) since they can activate the necrotactic formyl peptide receptor 1 (FPR1) regulating neutrophil migration to injured areas. However, the contribution of the Mt-DAMPs-FPR1 axis to organ transplant injury remains unclear.
In a murine orthotopic LTx model of PGD, we detected the release of donor-derived Mt-DAMPs into the injured airways. We also demonstrate that FPR1 expression in the recipient regulates neutrophil intragraft distribution by promoting airways neutrophilia. This effect seems to be specifically associated with the activation of the Mt-DAMPs-FPR1 axis which leads to neutrophil upregulation of adhesion molecules and increased extravascular neutrophil cluster stability. As a consequence of FPR1 expression, we demonstrated prolonged neutrophil retention into the injured airways and exacerbation of the ALI. In a prospective study of 62 human lung recipients, circulating Mt-DAMPs, in the form of mitochondria DNA (Mt-DNA), were increased after LTx and the higher perioperative levels were predictive of severe late PGD.
In conclusion, this thesis proposes that the early release of graft-derived Mt-DAMPs after LTx contributes to exacerbating ALI through an FPR1 dependent regulation of neutrophil intragraft trafficking and activation. Moreover, higher perioperative circulating levels of Mt- DNA in human LTx recipients appear to be a possible biomarker for the early detection of severe PGD
Radiological evaluation of biomarkers for renal cell carcinoma
Full text linkRole of MRI DWI sequences in the evaluation of early response to neo- angiogenesis inhibitors in metastatic renal cell carcinoma
Purpose: Angiogenesis inhibitors have a potential role in treating metastatic renal cell carcinoma, but it is still not clear why some patients don't respond. Our objective was to look for DWI parameters able to identify patients with metastatic renal cell carcinoma who would not benefit from target therapy. RECIST1.1 was considered as Reference Standard.
Methods & Materials: We prospectively enrolled 43 patients candidate to start angiogenesis inhibitors with at least one target lesion and who underwent 1,5T MRI examination with multiple bvalues DWI sequences (0,40,200,300,600): one week before (t0), 2 weeks after (t2) and 8 weeks (t8) after treatment beginning. ADC value was calculated drawing ROIs on 3 different planes.
33 patients with 38 lesions had suitable data for comparative evaluation.
Results: At T8 follow-up 9 patients had partial response (PR), 20 table disease (SD), 4 progression disease (PD); average progression free survival was 272 days. PD group, as compared to DC or to PR showed significantly lower ADC values at b40 at t0 (p<0.05): we can assess that more vascularised lesions are more responsive to treatment. PD group have significantly lower ADC values then both other groups, at t0, t2 and t8, for all b-values (p<0.05).
PFS and OS correlates well with ADC, in particular OS with ADC b40 at t0 (r=0,69).
Coclusions: Results show that PD group has significantly lower ADC values than PR or DC everytime (t0, t2, t8)
At t0 there is a better correlation between PFS or OS & ADC than PFS & dimensional criteria.
ADC at t0 may help selecting patients with promising good response to angiogenesis inhibitors.
Moreover at t0 and at t2 ADC has the potential to select patients who wouldn't benefit from angiogenesis inhibitors
Nowadays, in the era of target therapy, it is crucial to select patients potentially responders. We have to look at cost/benefit ratio and at increasing costs of treatment options.
DWI has the potential role to identify patients whose's tumor wouldn't benefit from target therapy, adding a value (ADC) to other imaging (e.g. DCE-MRI, texture imaging) and clinical parameters (e.g. miRNA) in a hypothetic multiparametric analysis.CT Texture Analysis in Clear Cell Renal Cell Carcinoma: a Radiogenomics Prospective
Purpose: The aim of this study was to investigate whether quantitative parameters obtained from CT Texture Analysis (CTTA) correlate with expression of miRNA in clear cell Renal Cell Carcinoma (ccRCC).
Methods and Materials: In a retrospective single centre study, multiphasic CT examination (with arterial, portal, equilibrium and urographic phases) was performed on 20 patients with clear cell renal carcinomas (14 men and 6 women; mean age 65 years ± 13). Measures of heterogeneity were obtained in post-processing by placing a ROI on the entire tumour and CTTA parameters such as entropy, kurtosis, skewness, mean, mean of positive pixels, and SD of pixel distribution histogram were measured using multiple filter settings. Quantitative data were correlated with the expression of miRNAs obtained from the same cohort of patients: 8 fresh frozen samples and 12 formalin-fixed paraffin-embedded samples (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both evaluations (miRNAs and CTTA) were performed on tumour tissues as well as on normal cortico-medullar tissues. Analysis of Variance with linear multiple regression model methods were obtained with SPSS statistic software. For all comparisons, statistical significance was assumed p<0.05
Results: We evidenced that CTTA has robust parameters (e.g. entropy, mean, sd) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression (R2 =0,25) was evidenced in tumour tissues as compared to normal tissues (R2 =0,15).
Interestingly, excluding four patients with extreme over-expression of miR-21-5p, excellent relation between entropy and miR21-5p levels was found specifically in tumour samples (R2= 0,64; p<0.05).
Conclusion: Entropy and miRNA-21-5p show promising correlation in ccRCC; in addiction CTTA features, in particular mean and entropy show a statistically significant increase in ccRCC as compared with normal renal parenchyma
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
Residual clonable host cell detection for predicting engraftment of T cell depleted BMTs.
No full textRejection of T-depleted BMTs is predominantly mediated by alloreactive host T cells. A low but significant number of radiochemoresistant clonable T cells can be detected following a conventional cytoreductive protocol given prior to T-depleted BMT. Elimination of these cells increases the engraftment rate. We found no clonable T cells at the end of the conditioning regimen in 100 ml of peripheral blood from 47 patients who received an HLA-identical T-depleted BMT. None rejected the graft and none displayed mixed chimerism. In addition, although no clonable T cells were detected in nine patients who received a mismatched BMT, two rejected their graft. However, in three mismatched patients, who for clinical reasons received a modified pre-BMT schedule, the presence of host clonable T cells was associated with immunological rejection. These findings suggest that the detection of clonable T cells should prove a valuable indicator for optimising immunosuppression prior to T-depleted BMT
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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