1,724,057 research outputs found
Recommended from our members
Abstract 4638: Integrated proteogenomic characterization of longitudinal glioblastoma
No full textAbstract Glioblastoma multiforme (GBM) is the most aggressive form of primary brain tumor, with no curative treatment options and median patient survival time of almost one year. Despite multi-modal therapy including surgery, irradiation and chemotherapy, all patients experience tumor progression and recurrence. Our group proposed and validated the first single cell guided functional classification of primary GBM in four tumor-intrinsic cell states which informed clinical outcome and delivered therapeutic options. However, recurrent GBM remains therapeutically unresolved due in part to the diffusely invasive nature and in part to marked cellular heterogeneity of the tumor.The evolutionary trajectory of glioblastoma after therapy is a multifaceted biological process that extends beyond discrete genetic alterations alone. Here, we profiled by multi-omics platforms the largest dataset of matched primary and recurrent GBM including 123 longitudinal glioblastoma pairs, temporally separated by standard-of-care treatment. Genomics, proteomics, and phosphoproteomics all independently captured the loss of proliferative-progenitor characteristics and a significant upregulation of specialized neuronal and synaptic signaling programs in recurrent GBM. Proteomic and phosphoproteomic analyses revealed that the molecular transition from proliferative to neuronal state at recurrence is marked by coherent post-translational activation of the WNT/PCP signaling pathway and the BRAF protein kinase. Multi-omic analysis of Patient-Derived Xenograft (PDX) models mimicked the patterns of evolutionary trajectory, consisting of marked activation of neuronal signaling programs in recurrent patients. Inhibition of the BRAF kinase with small molecule inhibitors impaired both neuronal transition and migration capability of recurrent glioblastoma cells, which are the phenotypic hallmarks of glioblastoma progression after therapy. Accordingly, combinatorial treatment of temozolomide with BRAF inhibitor, vemurafenib, significantly prolonged the survival of mouse PDX models. This work provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance and highlights new therapeutic opportunities to effectively counter them in the clinic. Citation Format: Simona Migliozzi, Kyung-Hee Kim, Harim Koo, Jun-Hee Hong, Seung Min Park, Hyung Joon Kwon, Luciano Garofano, Young Taek Oh, Fulvio D'Angelo, Chan Il Kim, Anna-Luisa Di Stefano, Franck Bielle, Jinlong Yin, Marc Sanson, Do-Hyun Nam, Jason K. Sa, Anna Lasorella, Jong Bae Park, Antonio Iavarone. Integrated proteogenomic characterization of longitudinal glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4638
Block Card 4638 Angola Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: 4638 Angola Road (Toledo, Ohio) | Dwelling | Adams Township Area (Toledo, Ohio) | Colonial Styl
Block Card 4638 Hannaford Drive
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Cape Cod Style | 4638 Hannaford Drive (Toledo, Ohio) | Dwelling | Monroe Acres | Franklin Park Area (Toledo, Ohio) | Trilby Area (Toledo, Ohio)
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
