Neurological features of 14q24-q32 interstitial deletion: report of a new case

Background: Interstitial deletions of the long arm of chromosome 14 involving the 14q24-q32 region have been reported in less than 20 patients. Previous studies mainly attempted to delineate recognizable facial dysmorphisms; conversely, descriptions on neurological features are limited to the presence of cognitive and motor delay, but no better characterization exists. Case presentation: In this paper we report on a patient with a de novo interstitial deletion of 5.5 Mb at 14q24.3-q31.1. The deletion encompasses 84 genes, including fourteen Mendelian genes. He presented with dysmorphic face, developmental delay, paroxysmal non-epileptic events and, subsequently, epilepsy. Conclusions: The clinical and molecular evaluation of this patient and the review of the literature expand the phenotype of 14q23-q32 deletion syndrome to include paroxysmal non-epileptic events and infantile-onset focal seizures. © 2015 Nicita et al

Pathological complete response induced by first-line chemotherapy with single agent docetaxel in a patient with advanced non small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Defining the optimal treatment for patients with inoperable non small cell lung cancer (NSCLC), presenting with metastatic mediastinal lymph nodes, is challenging. Nevertheless, preoperative chemotherapy or radiotherapy might offer a chance for these patients for radical surgical resection and, possibly, complete recovery.</p> <p>Case Presentation</p> <p>A 62-year old man with IIIA-N2 inoperable NSCLC was treated with first-line single agent docetaxel. A platinum-based treatment, though considered more active, was ruled out because of renal impairment. The patient tolerated the treatment very well and, although his initial response was not impressive, after 14 cycles he obtained a complete clinical response, which was confirmed pathologically after he underwent surgical lobectomy.</p> <p>Conclusion</p> <p>In non-operable NSCLC patients not eligible for a platinum-based treatment, single-agent docetaxel can provide complete pathologic responses. Failure to obtain a response after the first few cycles should not automatically discourage to continue treatment.</p

DNA methylation episignature testing improves molecular diagnosis of Mendelian chromatinopathies

Purpose: Chromatinopathies include more than 50 disorders caused by disease-causing variants of various components of chromatin structure and function. Many of these disorders exhibit unique genome-wide DNA methylation profiles, known as episignatures. In this study, the methylation profile of a large cohort of individuals with chromatinopathies was analyzed for episignature detection. Methods: DNA methylation data was generated on extracted blood samples from 129 affected individuals with the Illumina Infinium EPIC arrays and analyzed using an established bioinformatic pipeline. Results: The DNA methylation profiles matched and confirmed the sequence findings in both the discovery and validation cohorts. Twenty-five affected individuals carrying a variant of uncertain significance, did not show a methylation profile matching any of the known episignatures. Three additional variant of uncertain significance cases with an identified KDM6A variant were re-classified as likely pathogenic (n = 2) or re-assigned as Wolf-Hirschhorn syndrome (n = 1). Thirty of the 33 Next Generation Sequencing negative cases did not match a defined episignature while three matched Kabuki syndrome, Rubinstein-Taybi syndrome and BAFopathy respectively. Conclusion: With the expanding clinical utility of the EpiSign assay, DNA methylation analysis should be considered part of the testing cascade for individuals presenting with clinical features of Mendelian chromatinopathy disorders

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway(1,2). Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Visita all'Osservatorio della Biodiversità marina e terrestre della Regione Sicilia - ORBS

Con il taglio inaugurale del nastro il 16 dicembre 2015, prende vita la struttura museale permanente dell'Osservatorio della Biodiversità marina e terrestre della Regione Sicilia che porta lo stesso nome del Progetto di Ricerca "ORBS – Sistema di comunicazione, informazione e diffusione dell'Osservatorio Regionale della Sicilia", intitolata il 21 dicembre 2018 al Dott. Sandro Fiorelli. Ad oggi, la struttura, è operativa presso la Sede Secondaria dell'Istituto per lo studio degli impatti Antropici e Sostenibilità in ambiente marino del Consiglio Nazionale delle Ricerche (IAS – CNR) di Capo Granitola. Il progetto ORBS, finanziato da Regione Siciliana - Assessorato alla Cooperazione, Commercio, Artigianato e Pesca - Dipartimento Pesca, con periodo di attività 2013 - 2015, si è concluso proprio con la realizzazione della struttura museale; l'Osservatorio è stato istituito dall'Assessorato del Territorio e dell'Ambiente della Regione Siciliana nell'ambito di un accordo quadro con ARPA, ISPRA e CNR. Grazie al progetto ORBS, docenti e allievi dell'Accademia di Belle Arti di Palermo e il personale CNR – IAS (ex IAMC) S. S. di Capo Granitola, hanno collaborato sinergicamente permettendo di realizzare delle azioni didattiche e creative di valore scientifico espresse con straordinaria forza e bellezza. Ricercatori e professori si sono confrontati al fine di combinare le proprie competenze riuscendo nel progetto ambizioso di coinvolgere e fondere i diversi ambiti scientifici sensibilizzando gli artisti ai temi della Biodiversità. Le opere prodotte, corredate da schede scientifiche, hanno oltre al valore artistico un aggiunto valore didattico. L'apertura della sezione espositiva dedicata alla diffusione e alla comunicazione della biodiversità rappresenta da un lato l'importante tappa conclusiva del progetto, dall'altro l'inizio di un percorso mirato alla diffusione della biodiversità verso il mondo giovanile, le scuole e per tutto il territorio. Questa strepitosa collaborazione "CNR – Accademia di Belle Arti di Palermo" conferma l'importanza e l'opportunità di unire arte e scienza per esaltare la percezione della ricerca scientifica da parte della comunità. La divulgazione della scienza è un'attività complessa e sicuramente necessita di competenze e attitudini multidisciplinari oltreché di motivazione ed entusiasmo. La comunicazione delle tematiche scientifiche, di per sé ardua nella traduzione al grande pubblico, grazie alla forza esplicativa dell'arte, diviene opportunità di riflessione, osservazione, confronto per le comunità di visitatori. Il coordinamento delle visite delle scuole di ogni ordine e grado, Enti Pubblici, Comunità Scientifica, Cariche Istituzionali, Delegazioni di Politici Italiani e Stranieri, Associazioni Culturali, Associazioni No-Profit di Volontariato, Associazioni di Promozione Sociale, Organizzazioni di Volontariato, Onlus, pubblico in generale, presso ORBS, è affidato al qualificato personale (tecnici, tecnologi e ricercatori) dell'IAS – CNR S. S. di Capo Granitola, che gestisce in prima persona i visitatori nel percorso didattico e promuove il valore della divulgazione scientifica perseguendo la terza missione degli Enti di Ricerca, attraverso l'applicazione diretta, la valorizzazione e l'impiego della conoscenza