1,725,131 research outputs found

    CRISPR screens in 3D tumourspheres identified miR-4787-3p as a transcriptional start site miRNA essential for breast tumour-initiating cell growth

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    Our study employs pooled CRISPR screens, integrating 2D and 3D culture models, to identify miRNAs critical in Breast Cancer (BC) tumoursphere formation. These screens combine with RNA-seq experiments allowing identification of miRNA signatures and targets essential for tumoursphere growth. miR-4787-3p exhibits significant up-regulation in BC, particularly in basal-like BCs, suggesting its association with aggressive disease. Surprisingly, despite its location within the 5’UTR of a protein coding gene, which defines DROSHA-independent transcription start site (TSS)-miRNAs, we find it dependant on both DROSHA and DICER1 for maturation. Inhibition of miR-4787-3p hinders tumoursphere formation, highlighting its potential as a therapeutic target in BC. Our study proposes elevated miR-4787-3p expression as a potential prognostic biomarker for adverse outcomes in BC. We find that protein-coding genes positively selected in the CRISPR screens are enriched of miR-4787-3p targets. Of these targets, we select ARHGAP17, FOXO3A, and PDCD4 as known tumour suppressors in cancer and experimentally validate the interaction of miR-4787-3p with their 3’UTRs. Our work illuminates the molecular mechanisms underpinning miR-4787-3p’s oncogenic role in BC. These findings advocate for clinical investigations targeting miR-4787-3p and underscore its prognostic significance, offering promising avenues for tailored therapeutic interventions and prognostic assessments in BC.</p

    Pharmacy (ISSN 2226-4787) — A Journal of Pharmacy Education and Practice

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    Pharmacy (ISSN 2226-4787) — A journal of pharmacy education and practice is an international scientific open access journal on pharmacy education and practice, and is published by MDPI online quarterly. The practice of pharmacy is changing at an unprecedented rate as the profession moves from a focus upon preparation and supply of medicines to a clinical patient-facing role. While an understanding of the science related to medicines remains core to pharmacy education, the changes in practice are driving changes to the traditional methods of pharmacy education. This is reflected at an international level by major changes in the educational standards set by statutory regulators and by policy statements from bodies such as the World Health Organisation. These changes reflect an increasing trend to look at educational policy at a supra-national level, typified by the “Pharmine Project” led by the Association of European Faculties of Pharmacy

    Linked collectors and determiners for: The Ando-Patagonian Stigmella magnispinella group (Lepidoptera, Nepticulidae) with description of new species from Ecuador, Peru and Argentina.

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    Natural history specimen data linked to collectors and determiners held within, "The Ando-Patagonian Stigmella magnispinella group (Lepidoptera, Nepticulidae) with description of new species from Ecuador, Peru and Argentina". Claims or attributions were made on Bionomia by volunteer Scribes, &lt;a href="http://bionomia.net/dataset/c207b55d-3ec0-4787-8c81-74e315d14eb5"&gt;https://bionomia.net/dataset/c207b55d-3ec0-4787-8c81-74e315d14eb5&lt;/a&gt; using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, &lt;a href="https://gbif.org/dataset/c207b55d-3ec0-4787-8c81-74e315d14eb5"&gt;https://gbif.org/dataset/c207b55d-3ec0-4787-8c81-74e315d14eb5&lt;/a&gt;. Formatted as a Frictionless Data package

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

    Specialist Clinicians' Management of Dependence on Non-Prescription Medicines and Barriers to Treatment Provision : An Exploratory Mixed Methods Study Using Behavioural Theory

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    This research was funded by THE SOCIETY FOR THE STUDY OF ADDICTION in the form a PhD studentship awarded to Niamh Fingleton. Supplementary Materials: The following are available online at http://www.mdpi.com/2226-4787/7/1/25/s1, Table S1: Summary of belief statements and illustrative quotes assigned to the theoretical domainsPeer reviewe

    Variations on the Author

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    “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

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    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
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