α-Fetoprotein assay on dried blood spot for hepatoblastoma screening in children with overgrowth-cancer predisposition syndromes

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Religious freedom before, during and after Covid-19 between Europe and the Member States

Interventi tenuti il 26 novembre 2021 in occasione del Seminario di studio sul tema “Religious freedom before, during and after covid-19 between Europe and the Member States” organizzato dall’Eulerit Academic Forum dell’Università degli Studi di Trieste col supporto del Modulo Jean Monnet su “The European impact on the regulation Law&Religion in Italy and Beyond

Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34(+) hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34(+) cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34(+) cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34(+) absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34(+) cells/μl, 4.9; range, 1.3–17.5), whereas the CD34(+) cell apoptotic rate was significantly decreased in comparison with the controls (median, 8.6%; range, 0–27.7% vs. median, 17.6%; range, 2.8–49.6%), suggesting an increased CD34(+) cell survival. The functional evaluation of circulating hematopoietic progenitors showed specific patterns in NS and NS/MPD. These tests are a reliable integrative tool that, together with clinical data and other hematological parameters, could help detect NS patients with a high risk for a myeloproliferative evolution

Transcriptional Hallmarks of Noonan Syndrome and Noonan-Like Syndrome with Loose Anagen Hair

Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth. NS is genetically heterogeneous, being caused by germline mutations affecting various genes implicated in the RAS signaling network. This network transduces extracellular signals into intracellular biochemical and transcriptional responses controlling cell proliferation, differentiation, metabolism, and senescence. To explore the transcriptional consequences of NS-causing mutations, we performed global mRNA expression profiling on peripheral blood mononuclear cells obtained from 23 NS patients carrying heterozygous mutations in PTPN11 or SOS1. Gene expression profiling was also resolved in five subjects with Noonan-like syndrome with loose anagen hair (NS/LAH), a condition clinically related to NS and caused by an invariant mutation in SHOC2. Robust transcriptional signatures were found to specifically discriminate each of the three mutation groups from 21 age- and sex-matched controls. Despite the only partial overlap in terms of gene composition, the three signatures showed a notable concordance in terms of biological processes and regulatory circuits affected. These data establish expression profiling of peripheral blood mononuclear cells as a powerful tool to appreciate differential perturbations driven by germline mutations of transducers involved in RAS signaling and to dissect molecular mechanisms underlying NS and other RASopathies. Hum Mutat 33:703–709, 2012. © 2012 Wiley Periodicals, Inc

Empirical experiments on intrinsic motivations and action acquisition: results, evaluation, and redefinition

This document presents Deliverable D3.2 of the EU-funded Integrated Project "IM-CLeVeR - Intrinsically Motivated Cumulative Learning Versatile Robots", contract n. FP7-ICT-IP-231722.The aims of the deliverable, as given in the original IM-CLEVER proposal were to identify new key empirical phenomena and processes, allowing the design of a second set of experiments. This report covers: (1) novelty detection and discovery of when/what/how of agency in experiments with humans ("joystick experiment") and Parkinson patients. (2) how object properties that stimulate intrinsically motivated interaction and facilitate the acquisition of adaptive knowledge and skills in monkeys and children ("board experiment")