Genetic signature of differentiated thyroid carcinoma susceptibility: a machine learning approach

To identify a peculiar genetic combination predisposing to differentiated thyroid carcinoma (DTC), we selected a set of single-nucleotide polymorphisms (SNPs) associated with DTC risk, considering polygenic risk score (PRS), Bayesian statistics, and a machine learning (ML) classifier to describe cases and controls in 3 different datasets. Dataset 1 (649 DTC, 431 controls) has been previously genotyped in a genome-wide association study (GWAS) on Italian DTC. Dataset 2 (234 DTC, 101 controls) and dataset 3 (404 DTC, 392 controls) were genotyped. Associations of 171 SNPs reported to predispose to DTC in candidate studies were extracted from the GWAS of dataset 1, followed by replication of SNPs associated with DTC risk (P<0.05) in dataset 2. The reliability of the identified SNPs was confirmed by PRS and Bayesian statistics after merging the three datasets. SNPs were used to describe the case/control state of individuals by ML classifier. Starting from 171 SNPs associated with DTC, 15 were positive in both the datasets 1 and 2. Using these markers, PRS revealed that individuals in the fifth quintile had a 7-fold increased risk of DTC than those in the first. Bayesian inference confirmed that the selected 15 SNPs differentiate cases from controls. Results were corroborated by ML, finding a maximum AUC of about 0.7. A restricted selection of only 15 DTC-associated SNPs is able to describe the inner genetic structure of Italian individuals and ML allows a fair prediction of case or control status based solely on the individual genetic background

Extraosseus Ewing sarcoma: An uncommon periclavicular location

A rapidly enlarging right sternoclavicular mass in a young male was labeled as a nonspecific mass. MRI played a crucial role in characterizing the lesion, helping to define the possible mesenchymal origin and the relative involvement of the surrounding structures. We also discuss the differential diagnosis of an extraosseus Ewing sarcoma (ES), with its imaging findings

A Molecular Dynamics study of a miRNA:mRNA interaction

none5noIn this paper we present a methodology to evaluate the binding free energy of a miRNA:mRNA complex through molecular dynamics (MD)-thermodynamic integration (TI) simulations. We applied our method to the Caenorhabditis elegans let-7 miRNA:lin-41 mRNA complex-a validated miRNA:mRNA interaction-in order to estimate the energetic stability of the structure. To make the miRNA:mRNA simulation possible and realistic, the methodology introduces specific solutions to overcome some of the general challenges of nucleic acid simulations and binding free energy computations that have been discussed widely in many previous research reports. The main features of the proposed methodology are: (1) positioning of the restraints imposed on the simulations in order to guarantee complex stability; (2) optimal sampling of the phase space to achieve satisfactory accuracy in the binding energy value; (3) determination of a suitable trade-off between computational costs and accuracy of binding free energy computation by the assessment of the scalability characteristics of the parallel simulations required for the TI. The experiments carried out demonstrate that MD simulations are a viable strategy for the study of miRNA binding characteristics, opening the way to the development of new computational target prediction methods based on three-dimensional structure information.nonePACIELLO, GIULIA; ACQUAVIVA, ANDREA; FICARRA, ELISA; DERIU, MARCO AGOSTINO; MACII, EnricoPACIELLO, GIULIA; ACQUAVIVA, ANDREA; FICARRA, ELISA; DERIU, MARCO AGOSTINO; MACII, Enric

Predatory journals enter biomedical databases through public funding

Predatory publishing is an international, cross disciplinary threat to the integrity of the scientific system • A worrying number of articles published in predatory journals are indexed in biomedical databases such as PubMed, the free access biomedical database maintained by the National Library of Medicine • Public funding, under open access policies, seems to be the mechanism by which articles are displayed in PubMed. • Providing guidance to publicly funded authors on how to publish their work in legitimate open-access venues will likely stop the wasteful use of public money to cover the fees of predatory journals

Extraosseus Ewing sarcoma: An uncommon periclavicular location

A rapidly enlarging right sternoclavicular mass in a young male was labeled as a nonspecific mass. MRI played a crucial role in characterizing the lesion, helping to define the possible mesenchymal origin and the relative involvement of the surrounding structures. We also discuss the differential diagnosis of an extraosseus Ewing sarcoma (ES), with its imaging findings

Narrative del disturbo da gioco d’azzardo e del disturbo da uso di sostanze. Una analisi multidimensionale per la caratterizzazione di possibili marcatori narrativi e linguistici delle dipendenze

Diversi studi hanno dimostrato che l’analisi della dimensione narrativa può rappresentare un valido strumento per far luce su alcuni aspetti psicologici critici; in questo senso, può essere utile per capire meglio il disturbo da dipendenza. Il presente articolo riporta tra l’altro alcuni tra i dati principali di una ricerca da noi condotta e pubblicata nella rivista Journal of Gambling Issues nel 2021. In tale ricerca abbiamo indagato gli aspetti psicologico-narrativi coinvolti nelle dipendenze, specificamente nel DUS e nel DGA, attraverso un’analisi quali-quantitativa multidimensionale di un’intervista semi-strutturata, che ha invitato due gruppi di soggetti dipendenti in trattamento (DGA e DUS) a raccontare le varie fasi della dipendenza. Le analisi narrative multidimensionali da noi condotte sembrano aver portato alla luce alcuni punti critici su cui focalizzare l’attenzione per la costruzione di un adeguato trattamento dei soggetti con dipendenza. Nello specifico, i risultati suggerirebbero la necessità di lavorare su aspetti dissociati del Sé al fine di: 1) favorire il processo di integrazione di motivazioni e azioni, aumentando la consapevolezza e il senso di autoefficacia, soprattutto con i giocatori d’azzardo; 2) migliorare la coerenza globale nella narrazione del desiderio al fine di diminuire la disregolazione emotiva tipica di questa fase; 3) migliorare la capacità di proiezione del Sé nel tempo. Quest’ultimo punto potrebbe essere particolarmente rilevante in una prospettiva di intervento riabilitativo, soprattutto per quanto riguarda gli strumenti di trattamento legati alla dimensione narrativa. Il rapporto circolare tra regolazione dell’impulsività, autocontrollo, integrità dell’Io, funzioni cognitive e dimensione narrativa trova nel fattore temporale uno dei principali perni comuni

A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids

<div><p>A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary <i>in vitro</i> biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection, increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future.</p></div

Flow field within the bioreactor.

<p>Flow field visualization of the mutual interaction between the medium (primary phase) and the cells/constructs (dispersed phase) within the culture chamber for ultralow (A and A1) and low-to-moderate (B and B1) shear stress conditions. Flow field is depicted using both linear integral convolution lines (A and B), and a classical streamline representation (A1 and B1). Yellow arrows indicate the flow inlet and outlet. Blue arrows indicate the primary buoyant vortices. Red arrows indicate the secondary vortices.</p