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Bortezomib-melphalan-prednisone versus lenalidomide-dexamethasone in elderly patients with multiple myeloma: the Real MM phase IV trial
No full textOptic Axes rotation and Bertin surfaces deformations in Lead Tungstate (PWO) and other Tetragonal crystals by stress and misalignment of crystallographic cells: a theoretical study
No full textFor tetragonal Lead Tungstate (PWO) and other Tetragonal crystals we study the modifications of the Bertin surfaces induced by either the distortion of crystallographic cells, induced by applied plane stress, or the cell misalignment with respect to the specimen faces. In both cases the distorsions of the Bertin surfaces result in a reshaping of the interference pattern observed by conoscopy. We provide, for different observation directions of the crystals, the analytical relations which allow for the evaluation of the optic plane, optical indicatrix rotation with or without stress and, by the means of these relations, the interference images reshaping allows to detect, provided some conditions hold, the crystallographic axes rotation. The scope of this work is a theoretical study aiming the evaluation of the Optic axes and crystallographic cell orientation by means of conoscopic observation
Real-world experience with the pentaspline pulsed field ablation system: one-year outcomes of the FARADISE registry
Get PDFAims Clinical studies with protocol-mandated workflow and monitoring have analysed performance of pulsed field ablation (PFA) for treating atrial fibrillation (AF). The FARADISE registry captures global use of the pentaspline PFA catheter in real-world clinical practice with a follow-up of 3 years Methods FARADISE is a prospective, non-randomized, multi-national registry (NCT05501873) that enrolled subjects clinically indi- and results cated for ablation using the pentaspline PFA catheter per medical judgement and hospital standard-of-care. Procedural characteristics, safety, and clinical effectiveness up to 12-months were collected. In total, 1158 AF patients received PFA across 48 centres in 21 countries (64 ± 11 years, 33% female, 90% de novo, 65% paroxysmal AF). Pulmonary vein isolation (PVI)only procedures were performed in 80.8% of paroxysmal vs. 57.5% for non-paroxysmal patients (P < 0.01). Median procedure, left atrial dwell, and fluoroscopy times were 51[40–70], 31[24–41], and 12[8–17] min, respectively. The rate of early onset serious adverse events was 1.5% and did not differ by ablation strategy or AF indication. At 1-year, clinical effectiveness was 80.8% for paroxysmal AF and 67.7% for non-paroxysmal AF, with no difference within indication by lesion set (paroxysmal: 81.2% PVI-only vs. 79.0% PVI+, P = 0.65; non-paroxysmal: 67.5% PVI-only vs. 67.7% PVI+, P = 0.79). Acute results reinforce a short procedural learning curve with no difference in 1-year effectiveness by operator experience. Conclusion The FARADISE registry provides a snapshot of real-world clinical use of the pentaspline PFA catheter. Acute results demonstrate favourable procedural and safety outcomes regardless of AF indication. One-year outcomes are encouraging, with no differences seen within indication based on ablation strateg
Molecular targeting of the deubiquitinase USP14 to circumvent cisplatin resistance in ovarian carcinoma and identification of novel inhibitors
No full textAim: This study aims to investigate the biological role of the proteasome-associated deubiquitinase ubiquitinspecific protease 14 (USP14) in ovarian carcinoma drug resistance and to identify novel USP14 inhibitors (USP14i) for further preclinical development. Methods: USP14 expression was evaluated in clinical samples from 134 ovarian carcinoma patients and in a broad panel of human ovarian carcinoma cell lines. Functional studies, including gain-and loss-of-function assays, migration and invasion, and apoptosis induction assays, were conducted using cisplatin-sensitive IGROV-1 cells and their cisplatin-resistant derivative IGROV-1/Pt1. A library of 1,056 small molecules was screened using an optimized hydrolysis assay. Docking and molecular dynamics simulations were employed to predict binding modes of candidate inhibitors within the USP14 domain. Results: In clinical specimens, USP14 mRNA expression was associated with tumor grade. Exogenous overexpression of USP14 enhanced the survival of cisplatin-resistant IGROV-1/Pt1 cells, but not parental IGROV-1 cells, upon cisplatin exposure. USP14 knockdown by small interfering RNAs in resistant cells reduced aggressive features and restored cisplatin sensitivity, whereas no sensitization was observed in IGROV-1 cells. Medium-throughput screening identified five candidate molecules, among which ARN12502 showed the strongest inhibitory activity against USP14. ARN12502 exhibited an IC50 of 18.4 mu M, and molecular dynamics simulations confirmed stable binding in two distinct modes. In proteasome sensor-expressing cells, ARN12502 displayed proteasomeinhibitory activity. Conclusion: USP14 contributes to the aggressiveness of ovarian carcinoma, particularly to the cisplatin-resistant phenotype, and represents a relevant promising druggable target. ARN12502 serves as a starting point for chemical optimization toward the development of more potent USP14i
Evaluating Ex Vivo Fluorescence Confocal Microscopy for Intraoperative Diagnosis in Pediatric Surgery: A Feasibility Study
No full textBackground: Ex vivo fluorescence confocal microscopy (FCM) is an emerging technology that enables real-time, high-resolution digital imaging of freshly excised tissues without requiring standard histological preparation. This study aims to evaluate the diagnostic performance of FCM compared to conventional histology in a pediatric population with suspected oncological pathology. Materials and methods: A total of 18 tissue samples from pediatric patients with suspected oncological lesions were analyzed using FCM. The results were compared to the definitive diagnoses obtained via conventional histology, serving as the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the diagnostic accuracy. Cohen's kappa coefficient (K), 95% confidence interval (95%CI) and p-value were computed to evaluate the interobserver agreement and the concordance between FCM and histology. Results: FCM correctly identified 10 positive cases (true positives) and 7 negative cases (true negatives), with 1 false positive and no false negatives. Interobserver agreement was perfect, with a Cohen's kappa coefficient of 1.00 (95% CI: 0.81-1.00, p < 0.001). Sensitivity was 100% (95% CI: 72.2%-100%), specificity 87.5% (95% CI: 52.9%-97.8%), PPV 90.9% (95% CI: 62.3%-98.4%), and NPV 100% (95% CI: 64.6%-100%). The Cohen's kappa coefficient was 0.89, indicating excellent agreement between FCM and histology (95% CI: 0.67-1.10, p < 0.001). FCM provided rapid diagnostic results, significantly reducing turnaround time compared to conventional methods. Conclusions: FCM demonstrates exceptional diagnostic accuracy, with excellent sensitivity and specificity in evaluating pediatric specimens. Its ability to deliver reliable intraoperative results highlights its potential as a valuable adjunct to conventional histopathology in pediatric surgery. Larger studies are warranted to confirm these findings and establish its role in clinical practice
Dipendenti pubblici e incarichi non autorizzati
No full textL’ordinanza affronta il tema degli incarichi non autorizzati svolti da pubblici dipendenti, dando continuità a ormai consolidati orientamenti giurisprudenziali in materia di riparto di giurisdizione, natura dell’apparato rimediale e durata della prescrizione.The decision, addressing the issue of unauthorized assignments related to public employee, gives continuity to well-established jurisprudential guidelines on the division of jurisdiction, legal nature and limitation of remedies provided by law
Is accelerated biological aging the hidden link between physical frailty, social deficits, cognitive impairment and risk of incident diseases?
No full textA recommender-based web platform to boost tourism in marginal territories
No full textRecommender engines are software applications employed in online tourism information searches to suggest useful content and guide user choices. They represent a significant area of research within the tourism sector, crucially influencing traveler decisions through personalized recommendations. This paper focuses specifically on the Branding4Resilience (B4R) project, whose objective is to promote inner areas, by co-designing virtuous transformations with their inhabitants through novel branding strategies and digital enabling infrastructures. All experiments and assessments described in this study were conducted within the italian area of Sassoferrato, corresponding to the criteria defined by the B4R initiative. The paper introduces a dedicated web platform aimed at enhancing tourism by directing attention towards inland destinations and networking opportunities. The platform enables local providers of tourism-related services, such as guides, event organizers, and restaurateurs, to connect effectively with tourists seeking distinctive experiences. By facilitating interactions, the platform promotes collaboration, innovation, and the co-creation of personalized experiences, transforming tourists into active participants and contributors. To evaluate user experience, perceived usefulness, and innovation of the platform, we analyzed user responses to a structured questionnaire, which combined frequently addressed questions from existing literature with newly developed items specific to our platform. Constructs included tourist platform usage, perceived utility, content quality, design and usability, and innovative elements. The implemented algorithm demonstrated an average sensitivity of 79.74%, highlighting its efficacy in providing relevant suggestions to the platform’s “consumers” users
Comprendere | Innovare | Pianificare. Lungo il cammino della nuova Legge Regionale per Il Governo del Territorio
No full textL’esercizio improprio del diritto di critica e i presupposti giustificativi del licenziamento
No full textL’esercizio del diritto di critica ha sempre dato vita, oltre che a numerose discussioni teorico-giuridiche, a complesse controversie giudiziarie. Una questione assai rilevante, spesso oggetto di attenzione da parte dei giudici, e` lo spazio entro il quale (e il limite fino al quale) puo` spingersi il diritto di critica del dipendente nei confronti del datore di lavoro, alla luce innanzitutto delle norme (anche) costituzionali che lo tutelano, ed in virtu` dei limiti imposti dalle esigenze, anch’esse costituzionalmente garantite (artt. 2 e 41 Cost.), di tutela della persona umana e dell’iniziativa economica privata