Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas

SummaryMalignant gliomas are the most aggressive forms of brain tumors, associated with high rates of morbidity and mortality. Recurrence and tumorigenesis are attributed to a subpopulation of tumor-initiating glioma stem cells (GSCs) that are intrinsically resistant to therapy. Initiation and progression of gliomas have been linked to alterations in microRNA expression. Here, we report the identification of microRNA-138 (miR-138) as a molecular signature of GSCs and demonstrate a vital role for miR-138 in promoting growth and survival of bona fide tumor-initiating cells with self-renewal potential. Sequence-specific functional inhibition of miR-138 prevents tumorsphere formation in vitro and impedes tumorigenesis in vivo. We delineate the components of the miR-138 regulatory network by loss-of-function analysis to identify specific regulators of apoptosis. Finally, the higher expression of miR-138 in GSCs compared to non-neoplastic tissue and association with tumor recurrence and survival highlights the clinical significance of miR-138 as a prognostic biomarker and a therapeutic target for treatment of malignant gliomas

The Effectiveness and Cost-Effectiveness of Screening for HIV in Migrants in the EU/EEA: A Systematic Review

Migrants, defined as individuals who move from their country of origin to another, account for 40% of newly-diagnosed cases of human immunodeficiency virus (HIV) in the European Union/European Economic Area (EU/EEA). Populations at high risk for HIV include migrants, from countries or living in neighbourhoods where HIV is prevalent, and those participating in high risk behaviour. These migrants are at risk of low CD4 counts at diagnosis, increased morbidity, mortality, and onward transmission. The aim of this systematic review is to evaluate the effectiveness and cost-effectiveness of HIV testing strategies in migrant populations and to estimate their effect on testing uptake, mortality, and resource requirements. Following a systematic overview, we included four systematic reviews on the effectiveness of strategies in non-migrant populations and inferred their effect on migrant populations, as well as eight individual studies on cost-effectiveness/resource requirements. We assessed the certainty of our results using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The systematic reviews reported that HIV tests are highly accurate (rapid test >90% sensitivity, Western blot and ELISA >99% sensitivity). A meta-analysis showed that rapid testing approaches improve the access and uptake of testing (risk ratio = 2.95, 95% CI: 1.69 to 5.16), and were associated with a lower incidence of HIV in the middle-aged women subgroup among marginalised populations at a high risk of HIV exposure and HIV related stigma. Economic evidence on rapid counselling and testing identified strategic advantages with rapid tests. In conclusion, community-based rapid testing programmes may have the potential to improve uptake of HIV testing among migrant populations across a range of EU/EEA settings

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Étude de l\u27effet de la convergence des parois axiales sur la rétention des couronnes scellées

The aim of this in vitro study is to investigate the variation in the retention of ceramo-metallic crowns on identical dental preparations, differing only by the convergence of their axial walls. Materials and methods: Sixty molars were prepared; the convergence of the axial walls was of 20 degrees (maximum convergence), 30 degrees (acceptable convergence) or 60 degrees (critical convergence putting at risk the durability of treatment). Infrastructures were sealed using two types of ciment- a resin and a glass ionomer ciments- for the same axial convergence. Results: for small angulations (\u3c30 degrees), the use of glass ionomer ciment provided a higher retention than that provided by the resin ciment. For conical dental preparations (≥30 degrees), bonding with resin ciment offered a better retention and a greater resistance to displacement forces

Modulation of adult neurogenesis by catecholaminergic neurotransmission in the rodent brain

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF