1,720,997 research outputs found
Horizon of the pre-implantation kidney biopsy for allocation: multidisciplinarity, methodology and innovation
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Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury
Background!#!Endothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg5 activation in murine EPCs, utilized for AKI therapy.!##!Methods!#!Ischemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected post-ischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 h and 6 weeks later.!##!Results!#!Both, native and transfected EPCs (EPCs!##!Conclusions!#!Constitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined
Bone morphogenetic protein-5 and early endothelial outgrowth cells (eEOCs) in acute ischemic kidney injury (AKI) and 5/6-chronic kidney disease
Early endothelial outgrowth cells (eEOCs) reproducibly have been shown to act protectively in acute ischemic kidney injury (AKI) and chronic kidney injury. Bone morphogenetic protein-5 (BMP-5) acted antifibrotically in human hypertensive nephropathy. The aim of the curent study was to analyze effects of BMP-5 treatment in an eEOC-based therapy of murine AKI and 5/6-nephrectomy. Male C57/Bl6N mice were either subjected to unilateral renal artery clamping postuninephrectomy or to 5/6-nephrectomy. Untreated or BMP-5-pretreated murine eEOCs were injected into recipient animals at the time of reperfusion (AKI) or at 2 and 5 days after 5/6-nephrectomy. Analysis of renal function and morphology was performed at 48 h and at 6 wk (AKI) or at 8 wk (5/6 model). Cellular consequences of eEOC treatment were evaluated using different in vitro assays. AKI was mitigated significantly by injecting BMP-5-pretreated eEOCs. Renal function was improved at 48 h and at 6 wk after cell therapy. In 5/6-nephrectomy, the cells failed to protect renal function, but proteinuria was reduced after administering untreated eEOCs. BMP-5 pretreatment resulted in aggravated proteinuria and renal fibrosis. In 5/6-nephrectomized animals, percentages of anti-smooth muscle actin +/CD31+ cells increased, indicating endothelial-mesenchymal transition (EnMT). In vitro analysis revealed increased cell migration and reduced cell apoptosis/necrosis. Paracrinic activity remained unaffected. BMP-5 acts as a potent eEOC agonist in murine AKI in the short and mid to long term. Cell effects in 5/6-nephrectomy are heterogenous, but untreated cells act antiproteinurically and antifibrotically without any impact on EnMT.Else Kroner-Fresenius-Stiftun
Angiopoietin-2 modulates eEOC-mediated renoprotection in AKI in a dose-dependent manner
Background: Early endothelial outgrowth cells (eEOCs) significantly protect mice from acute kidney injury (AKI). Angiopoietin-2 (Ang-2) has been shown to be critically involved in vascular repair and homeostasis. The aim of this study was to investigate consequences of Ang-2 treatment of syngeneic murine eEOCs in a cell-based therapeutic approach for AKI. Methods: Male 8- to 12-week-old C57/Bl6N mice, subjected to unilateral renal ischemia (40 minutes) postuninephrectomy were systemically injected with 0.5 x 10(6) untreated or Ang-2-pretreated syngeneic murine eEOCs. Renal function and morphology were analyzed 48 hours later. Cellular consequences of eEOC treatment with Ang-2 were evaluated using different in vitro assays (direct and indirect migration, apoptosis/necrosis, ELISA studies). Results: Administration of untreated eEOCs did not protect mice from AKI. Ang-2 dose-dependently modulated cell effects in AKI. While incubating the cells at a concentration of 200 ng/mL (1 hour) did not have any effect on renal function, doubling the concentration (400 ng/mL) resulted in significant renoprotection of cell-injected mice. With 800 ng/mL, cell injection dramatically worsened renal function of treated animals. In vitro analysis showed significantly accelerated migration of cultured mature endothelial cells after incubation with supernatant from Ang-2-treated eEOCs (200 and 400 ng/mL). These effects were most pronounced with 400 mg/mL. In addition, Ang-2 promoted survival of eEOCs. Cellular releases of VEGF and IL-6 were decreased by Ang-2, while TGF-beta levels in the medium of Ang-2-stimulated eEOCs were not different from those in untreated cells. Conclusion: Ang-2 acts as modulator of eEOCs in AKI. The migration analysis indicates that the Ang-2 significantly alters indirect (paracrine) activity of eEOCs, thus promoting renoprotection in a dose-dependent manner.Else Kroner-Fresenius-Stiftun
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
Permutation-Invariant Cascaded Attentional Set Operator for Computational Nephropathology
Key PointsPermutation-invariant cascaded attentional set operator (PICASO) is a versatile set operator that uses Transformers to dynamically aggregate histopathologic features from a set of glomerular crops.For detecting active crescent in patients with IgA nephropathy on internal and external validation sets, PICASO achieved an area under the receiver-operating characteristic curve of 0.99 and 0.96, respectively.In the case-level classification of antibody-mediated rejection in kidney transplants, PICASO performed well, with an area under the receiver-operating characteristic curves of 0.97.BackgroundThe advent of digital nephropathology offers the potential to integrate deep learning algorithms into the diagnostic workflow. We introduce permutation-invariant cascaded attentional set operator (PICASO), a novel permutation-invariant set operator to dynamically aggregate histopathologic features from instances. We applied PICASO to two nephropathology scenarios: detecting active crescent lesions in sets of glomerular crops with IgA nephropathy (IgAN) and case-level classification for antibody-mediated rejection (AMR) in kidney transplant.MethodsPICASO is a Transformer-based set operator that aggregates features from sets of instances to make predictions. It uses initial histopathologic vectors as a static memory component and continuously updates them on the basis of input embeddings. For active crescent detection in patients with IgAN, we obtained 6206 periodic acid-Schiff-stained glomerular crops (5792 no active crescent, 414 active crescent) from three different health institutes. For the AMR classification, we have 1655 periodic acid-Schiff-stained glomerular crops (769 AMR and 886 non-AMR images) from 89 biopsies. The performance of PICASO as a set operator was compared with other set operators, such as DeepSet, Set Transformer, DeepSet++, and Set Transformer++, using metrics including area under the receiver-operating characteristic curve (AUROC), area under the precision-recall curves, recall, and accuracy.ResultsPICASO achieved superior performance in detecting active crescent in patients with IgAN, with an AUROC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) on internal validation and 0.96 (95% CI, 0.95 to 0.98) on external validation, significantly outperforming other set operators (P < 0.001). It also attained the highest AUROC of 0.97 (95% CI, 0.90 to 1.0, P = 0.02) for case-level AMR classification. The area under the precision-recall curve, recall, and accuracy scores were also higher when using PICASO, and it significantly outperformed baselines (P < 0.001).ConclusionsPICASO can potentially advance nephropathology by improving performance through dynamic feature aggregation. © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology
GNCnn: A QuPath extension for glomerulosclerosis and glomerulonephritis characterization based on deep learning
The digitalization of traditional glass slide microscopy into whole slide images has opened up new opportunities for pathology, such as the application of artificial intelligence techniques. Specialized software is necessary to visualize and analyze these images. One of these applications is QuPath, a popular bioimage analysis tool. This study proposes GNCnn, the first open-source QuPath extension specifically designed for nephropathology. It integrates deep learning models to provide nephropathologists with an accessible, automatic detector and classifier of glomeruli, the basic filtering units of the kidneys. The aim is to offer nephropathologists a freely available application to measure and analyze glomeruli to identify conditions such as glomerulosclerosis and glomerulonephritis. GNCnn offers a user-friendly interface that enables nephropathologists to detect glomeruli with high accuracy (Dice coefficient of 0.807) and categorize them as either sclerotic or non-sclerotic, achieving a balanced accuracy of 98.46%. Furthermore, it facilitates the classification of non-sclerotic glomeruli into 12 commonly diagnosed types of glomerulonephritis, with a top-3 balanced accuracy of 84.41%. GNCnn provides real-time updates of results, which are available at both the glomerulus and slide levels. This allows users to complete a typical analysis task without leaving the main application, QuPath. This tool is the first to integrate the entire workflow for the assessment of glomerulonephritis directly into the nephropathologists' workspace, accelerating and supporting their diagnosis
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