1,721,026 research outputs found
In Vivo Selection for Gene-Corrected HSPCs Advances Gene Therapy for a Rare Stem Cell Disease
No full textTwo recent papers (one by Román-Rodríguez et al., 2019 in this issue of Cell Stem Cell) highlight how the power of biological selection on hematopoietic stem cell fitness can facilitate gene therapies for Fanconi Anemia. A clinical trial using lentiviral gene replacement and a proof-of-concept targeted genome editing study show robust engraftment and expansion of gene-corrected cells at levels reaching therapeutic relevance
Characterization of glutamate excitotoxicity and its role in high-grade gliomas biology
No full textRationale This project aims to unveil the interactions of glutamate (Glut) excitotoxicity and tryptophan (TRP) metabolism derangements via the kynurenine (KP) and serotonin pathways (SP) in the interplay contributing to glioblastoma IDH-wt (GBM) invasion, immune escape, angiogenesis, and therapies response. Methods Planned enrollment of 140 patients (retrospective analyses of neuroimaging, clinical data, and biological samples from OSR-CRB Biobank + prospective enrollment and follow-up). Baseline blood levels of Glut, TRP, KP and SP mediators will be controlled against healthy controls and monitored following surgery and adjuvant therapies. Perfusion MRI data, GBM cell expression of Glut receptors and KP/SP enzymes, the extent of angiogenesis, and immune-infiltrate features will be addressed. Preliminary results (retrospective, n=62) The baseline serum levels of 5-HT, KYN, 5-HTP, and 5-HT/TRP were reduced (-76%, -87%, -76%, -75%, p<0.001) in GBM compared to controls. The median OS was shorter when Glut > 56.3mg/ml (p=0.002), 5-HT < 78ng/mL (p=0.01), KYN < 18ng/mL (p=0.004). Interestingly, circulating myeloid-derived suppressor cells (MDSC) and T-regs were inversely correlated with KYN (r=-0.51, p=0.01; r=-0.46, p=0.03), while dendritic (DC) and B cells positively correlated with 5-HT (r=0.47, p=0.02; r=0.60, p=0.003). Systemic platelet activation (MPV > 10.3·10-15L) was associated with worse OS (p=0.04). Prospective enrollment, follow-up, neuroimaging, and histological analyses are ongoing. Future directions We plan to develop a predictive model of tumoral invasiveness, immune escape, and angiogenesis based on the direction and extent of Glut-KP/SP metabolism derangement, neuroimaging, and histological features. The aim is to improve patient selection for interventions targeting these pathways, enhancing the likelihood of treatment response and survival benefit
A double-switch vector system positively regulates transgene expression by endogenous microRNA expression (miR-ON vector)
No full textEngineered tumor-infiltrating macrophages as gene delivery vehicles for interferon-α activates immunity and inhibits breast cancer progression
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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
A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice
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