1,720,971 research outputs found
Migliorare la comunicazione e la relazione a scuola. Proposte per una tecnica della cura educativa
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An integrative in-silico analysis discloses a novel molecular subset of colorectal cancer possibly eligible for immune checkpoint immunotherapy
Full text linkBackground: Historically, the molecular classification of colorectal cancer (CRC) was based on the global genomic status, which identified microsatellite instability in mismatch repair (MMR) deficient CRC, and chromosomal instability in MMR proficient CRC. With the introduction of immune checkpoint inhibitors, the microsatellite and chromosomal instability classification regained momentum as the microsatellite instability condition predicted sensitivity to immune checkpoint inhibitors, possibly due to both high tumor mutation burden (TMB) and high levels of infiltrating lymphocytes. Conversely, proficient MMR CRC are mostly resistant to immunotherapy. To better understand the relationship between the microsatellite and chromosomal instability classification, and eventually discover additional CRC subgroups relevant for therapeutic decisions, we developed a computational pipeline that include molecular integrative analysis of genomic, epigenomic and transcriptomic data. Results: The first step of the pipeline was based on unsupervised hierarchical clustering analysis of copy number variations (CNVs) versus hypermutation status that identified a first CRC cluster with few CNVs enriched in Hypermutated and microsatellite instability samples, a second CRC cluster with a high number of CNVs mostly including non-HM and microsatellite stable samples, and a third cluster (7.8% of the entire dataset) with low CNVs and low TMB, which shared clinical-pathological features with Hypermutated CRCs and thus defined Hypermutated-like CRCs. The mutational features, DNA methylation profile and base substitution fingerprints of these tumors revealed that Hypermutated-like patients are molecularly distinct from Hypermutated and non-Hypermutated tumors and are likely to develop and progress through different genetic events. Transcriptomic analysis highlighted further differences amongst the three groups and revealed an inflamed tumor microenvironment and modulation Immune Checkpoint Genes in Hypermutated-like CRCs. Conclusion: Therefore, our work highlights Hypermutated-like tumors as a distinct and previously unidentified CRC subgroup possibly responsive to immune checkpoint inhibitors. If further validated, these findings can lead to expanding the fraction of patients eligible to immunotherapy
An Overview of the computational models dealing with the regulatory ceRNA mechanism and ceRNA deregulation in cancer
No full textPools of RNA molecules can act as competing endogenous RNAs (ceRNAs) and indirectly alter their expression levels by competitively binding shared microRNAs. This ceRNA cross talk yields an additional posttranscriptional regulatory layer, which plays key roles in both physiological and pathological processes. MicroRNAs can act as decoys by binding multiple RNAs, as well as RNAs can act as ceRNAs by competing for binding multiple microRNAs, leading to many cross talk interactions that could favor significant large-scale effects in spite of the weakness of single interactions. Identifying and studying these extended ceRNA interaction networks could provide a global view of the fine-tuning gene regulation in a wide range of biological processes and tumor progressions. In this chapter, we review current progress of predicting ceRNA cross talk, by summarizing the most up-to-date databases, which collect computationally predicted and/or experimentally validated miRNA–target and ceRNA–ceRNA interactions, as well as the widespread computational methods for discovering and modeling possible evidences of ceRNA–ceRNA interaction networks. These methods can be grouped in two categories: statistics-based methods exploit multivariate analysis to build ceRNA networks, by considering the miRNA expression levels when evaluating miRNA sponging relationships; mathematical methods build deterministic or stochastic models to analyze and predict the behavior of ceRNA cross talk
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
Mappe e processo evolutivo inclusivo: strategie pedagogico-didattiche in Formazione e ricerca per una didattica inclusiva
No full textL’esigenza di favorire competenze pedagogico-didattiche per il raggiungimento del successo formativo di tutti e di ciascuno costituisce il focus delle politiche educative nazionali e internazionali che, in tal senso, stanno rispondendo, attraverso specifici interventi legislativi e di indirizzo, all’istanza di aggiornamento del profilo di competenze dei docenti al fine di fronteggiare l’eterogeneità e la complessità degli attuali contesti educativi. Per il conseguimento di tale finalità, la collaborazione tra Scuola e Università rappresenta una valida strategia di azione per andare incontro ai bisogni formativi espressi dai docenti.
In questo scenario di riflessioni, il testo, che si configura come il prodotto dell’esperienza progettuale “Didattica laboratoriale, valutazione e nuove tecnologie a supporto della disabilità”, realizzata dall’Ufficio Scolastico Regionale per la Campania del MIUR e dal Dipartimento di Scienze Umane, Filosofiche e della Formazione (DiSUFF) dell’Università degli Studi di Salerno, raccoglie contributi scientifici sul tema dell’inclusione da quattro prospettive disciplinari diverse, suggerendo alcuni approcci laboratoriali e itinerari di ricerca finalizzati a rendere attuativi i principi fondanti di una didattica inclusiva.
Il volume si rivolge principalmente ai docenti frequentanti i corsi di specializzazione sulle attività di sostegno e master e/o corsi di perfezionamento inerenti la disabilità ei bisogni educativi speciali, nonché agli studenti dei corsi di Didattica e Pedagogia speciale delle lauree triennali di Scienze dell’Educazione e delle lauree magistrali di ambito pedagogico
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
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