1,722,184 research outputs found
Network analysis to dissect glioblastoma immunosuppression complexity: identification of C-type lectins as potential therapeutic candidates and biomarkers
No full textIntroduction: Glioblastoma (GBM) is one of the most threatening tumors in adults. The failure of treatments, GBM aggressiveness and the poorness of patients’ quality of life underline the unmet need to identify novel therapeutic targets. The strong immunosuppression, hypoxia and altered vasculature make account for GBM resistance. Lectins are immunoregulatory receptors, that in tumors promote immunosuppression. Lectins expression on distinct cell type (i.e.myeloid, lymphoid and cancer cells) and the distribution of their respective ligands generate a complex and intricate network of interactions that support immunosuppressive mechanisms. So far, little is known about lectins contribution to immunosuppression and progression in GBM.
Aims: to investigate the lectin profile relevant in glioblastoma immunosuppression exploiting network-based approaches and to investigate their possible role as immune biomarkers and target
Results: Using three public databases (TCGA and CGGA for GBM; GTEx for healthy brain tissue), we selected a panel of 67 lectins from the Siglec, galectin, and C-type lectin families. Setting rigorous filtering parameters based on lectins expression levels, a final set of 39 lectins was employed to construct co-expression and differential co-expression networks. The analysis revealed significant correlations between lectin profiles across TCGA and CGGA. C-type lectins, that have never been investigated in GBM, were the most represented (ASGR2, CLEC12A, CLEC10A, CLEC4A, CLEC7A, CLEC2B, CD209) followed by Siglec7, Siglec9 and galectin-9, that have been already described in GBM progression and immunosuppression. The results obtained by computational analysis were validated on patients-matched tumor samples and liquid biopsies. CLEC10A was expressed in GBM-infiltrating immune cells and particularly its high expression on infiltrating macrophages correlated with poor survival. Distinct CLEC10A+ myeloid cells subsets correlate with different T cell infiltrate. Indeed, CLEC10A+ macrophages were positively associated with activated CD4+ T cells, that are likely to be regulatory T cells, while CLEC10A+ LOX1+ PMN-MDSCs negatively correlate with effector and antitumor CD8+ T cells. These results underline that distinct CLEC10A+ myeloid cells may be involved in different immunomodulatory mechanisms in GBM.
CLEC10A ligands Tn and STn were expressed in GBM tissues. Tn is exclusively expressed on cancer cells in GBM in correspondence of macrophages, while STn was expressed also in low-grade gliomas in vascular area. These results highlight a possible role of CLEC10A-Tn axis in GBM TME and immunosuppression, as already described in other cancer histytopes. However, GBM immunosuppression is complex and likely several actors may contribute, thus the intricate network of interactions is not associated to a single lectin and a single cell type. The novel C-type lectins cluster (ASGR2, CLEC12A, CLEC4A, CLEC7A) identified by network analysis was investigated in GBM patients. ASGR2 and CLEC12A emerged as strongest hub of both GBM differential co-
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expression networks and low levels of both lectins were associated with improved prognosis. Combining ASGR2 and CLEC12A expression with lectins of other families already known (siglec7, siglec9, and galectin9), we identified a lectin profile that better discriminated survival of GBM patients. So far, no evidence of these C-type lectins is available in cancer. We found that all C-type lectins are expressed on GBM-infiltrating immune cells. ASGR2 levels were significantly higher on MDMs compared to resident microglia (MG) and it was undetectable on circulating immune cells, suggesting a specific role in the GBM TME. CLEC7A expression was higher in macrophagic subpopulations compared to MDSCs. CLEC4A and CLEC12A were highly expressed on all circulating immune cell subsets, particularly those of monocytic origin. Their expression was significantly higher on circulating cells than in infiltrating cells. Similar lectin expression patterns were observed in patients with other cancers (NSCLC, head and neck cancer, HER2+ breast cancer), indicating that CLEC4A and CLEC12A may be relevant across different tumor types.
Conclusions:
We described for the first time C-type lectins cluster (ASGR2, CLEC4A, CLEC7A, CLEC12A, CLEC10A) that have never been described in GBM by exploiting network-based approaches. CLEC10A-Tn axis emerged as possible mechanism that supports GBM immunosuppression, underlining an interplay between macrophages and cancer cells. Moreover, ASGR2 expression appeared to be restricted to GBM TME and in association to macrophages and could represent a lectin that is induced under pathological context and may be involved in immunosuppressive mechanisms. The C-type lectins profile appears to be associated to distinct immunosuppressive myeloid cell subsets that are found not only in GBM TME but also peripheral blood, underlining their possible role as circulating immune biomarkers. Further analysis is required to investigate the metabolic and transcriptomic profile of lectins-expressing myeloid cells. Moreover, identifying the lectins ligands and understanding the impact of their engagement on the myeloid cells may be relevant to identify novel possible target to be exploited in GBM treatment. Investigating changes in lectin expression post-surgery or treatment, along with their relationship to immune features and clinical outcomes, could provide valuable insights into their roles in tumor progression and response to therapies
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
Prototyping of Automated Guided Vehicle for Teaching Practical Mechatronics
No full textThis paper presents an innovative approach to teaching mechatronics at the bachelor’s level, using the design and construction of an Automated Guided Vehicle (AGV) as a comprehensive example of a mechatronic system. The course, titled Laboratory of Electronic Systems, is part of a newly established professionalizing bachelor’s degree program at the University of Pisa, focused on techniques for mechanics and production. This program was developed to meet industry demands for technically skilled personnel with an engineering-related background but without the need for a full traditional engineering education. The course is designed to provide students with hands-on experience, integrating fundamental concepts from mechanical, electronic, and control engineering, along with software development. The curriculum emphasizes practical applications rather than theoretical depth, aligning with the program’s goal of preparing students for operational roles in industrial settings. We present the course structure, educational objectives, and the interdisciplinary nature of mechatronics as addressed in this teaching approach. A dedicated section outlines the critical steps involved in the AGV prototype development, highlighting practical challenges and learning opportunities. The effectiveness of the course is assessed through the evaluation of student projects, specifically via a technical report and a final discussion on the design of a mechatronic system. The results demonstrate the value of a project-based learning approach in equipping students with the practical skills and knowledge required for careers in mechatronics and industrial automation
Multisensing IIoT Platform Enabled by Custom BAP RFID TAG
No full textIn this work, we introduce the design of a Battery-Assisted Passive (BAP) Radio Frequency IDentification (RFID) tag incorporating sensing capabilities. The tag operates at the Ultra High Frequency (UHF) band to allow remote detection and data exchange. Designed for environmental monitoring in both industrial indoor facilities and outdoor environments, the tag is characterized by a general purpose microcontroller facilitating the data transmission between the RFID interface and the sensors. Particularly, the RFID chip integrated in the proposed system is configured as bridge for SPI communications, whereas the RFID reader acts as master node. Up on reader requests, the microcontroller triggers the required sensor to perform a measurement which result is stored in the RFID chip memory, easily accessible by the reader throughout standard RFID protocol operations. The tag encapsulates temperature, relative humidity, pressure, and 3D acceleration sensors. After the tag antenna design, fabrication, and system integration, the whole proposed system is verified experimentally in operating conditions to show its reliability
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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