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SETBP1 mutations are found in various clonal myeloid disorders. However, it is unclear whether they can initiate leukemia, because SETBP1 mutations typically appear as later events during oncogenesis. To answer this question, we generated a mouse model expressing mutated SETBP1 in hematopoietic tissue: this model showed profound alterations in the differentiation program of hematopoietic progenitors and developed a myeloid neoplasm with megakaryocytic dysplasia, splenomegaly, and bone marrow fibrosis, prompting us to investigate SETBP1 mutations in a cohort of 36 triple-negative primary myelofibrosis (TN-PMF) cases. We identified 2 distinct subgroups, one carrying SETBP1 mutations and the other completely devoid of somatic variants. Clinically, a striking difference in disease aggressiveness was noted, with patients with SETBP1 mutation showing a much worse clinical course. In contrast to myelodysplastic/myeloproliferative neoplasms, in which SETBP1 mutations are mostly found as a late clonal event, single-cell clonal hierarchy reconstruction in 3 patients with TN-PMF from our cohort revealed SETBP1 to be a very early event, suggesting that the phenotype of the different SETBP1+ disorders may be shaped by the opposite hierarchy of the same clonal SETBP1 variants.

Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, < 10%) in only 14 (25%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.

Il capitolo affronta il rapporto tra bambini, ragazzi, adolescenti e media digitali con l’obiettivo di illustrarne le specificità legate alle particolari caratteristiche di età e posizione sociale; nello stesso tempo, intende evidenziare la rete dei discorsi e delle pratiche sociali adulte che condizionano tanto l’esperienza online realizzata quotidianamente dai più giovani quanto l’approccio delle scienze umane e sociali a questo oggetto di studio. Dopo una sintetica introduzione al tema, si riflette sull’istituzione dell’infanzia come pubblico dei media e sulle diverse strategie con cui essi lo hanno tradizionalmente interpellato, fino alla novità rappresentata dalla loro digitalizzazione e dall’avvento di internet. In seguito si mostra come nei confronti dei nuovi media digitali si siano riprodotti gli stessi atteggiamenti che hanno caratterizzato, in passato, l’agire degli adulti rispetto al rapporto tra infanzia e media, sempre in bilico tra paure, istanze educative e aspettative di emancipazione. Vengono dunque proposti i principali approcci che hanno orientato lo studio di tale rapporto: il bilanciamento tra rischi e opportunità e le diverse prospettive focalizzate sulle competenze digitali, sul benessere digitale e sui diritti dell’infanzia negli ambienti digitali. Infine, si getta uno sguardo sui principali ambiti di socializzazione all’interno dei quali bambini, ragazzi e adolescenti fanno esperienza dei media – la famiglia, la scuola e il gruppo dei pari – per evidenziare alcuni temi di ricerca emergenti e le contraddizioni che spesso li accompagnano.

In a first-of-its-kind study, we assessed the capabilities of large language models (LLMs) in making complex decisions in haematopoietic stem cell transplantation. The evaluation was conducted not only for Generative Pre-trained Transformer 4 (GPT-4) but also conducted on other artificial intelligence models: PaLm 2 and Llama-2. Using detailed haematological histories that include both clinical, molecular and donor data, we conducted a triple-blind survey to compare LLMs to haematology residents. We found that residents significantly outperformed LLMs (p = 0.02), particularly in transplant eligibility assessment (p = 0.01). Our triple-blind methodology aimed to mitigate potential biases in evaluating LLMs and revealed both their promise and limitations in deciphering complex haematological clinical scenarios.

The article aims to assess the long post-Covid-19 phase from the point of view of the relationship between seniors and ICTs, with an Italian focus. During the first phase of the pandemic (in some ways the most acute and dramatic, because of its newness and the uncertainties to be able to face it) an increase in the overall production and consumption of digital contents and tools was at large empirically observed. At that stage, interesting hypotheses were formulated based on the assumption that the pandemic should spread the ICTs even among the most resistant categories, including the seniors. Three years after the pandemic outbreak, it is time to empirically test how reasonable this hypothesis was, how well it is borne out by the facts, and what general interpretations regarding the effect of major events and crises on the diffusion of technologies among seniors can be made. Our thesis is that, in Italy, the effect on current seniors in terms of diffusion is limited if not null. Instead, the data show that the pandemic has strengthened the divide between seniors and younger generations, and consequently supports the interpretation of technologies as markers for second-level digital divide.

La premessa introduce il senso della raccolta dei contributi, nell'ambito delle iniziative del corso di Laurea magistrale in Media Education.

The chapter offers a brief history of Children's Television (CT) in Italy as a significant part of the Italian television system and its political and cultural economy. The research perspective takes into account four constitutive factors: the technological dimension, relative to the technical modalities of production and distribution of TV contents; the political dimension, which results in the regulatory framework; the economic dimension, which involves the industrial and financial nature of broadcasting to children and young people; and finally the cultural dimension, which refers to contents and textualities of programming, social meanings, shared values, cultural heritage, and professionals involved in the design of CT. From a historiographical point of view, the chapter presents a scan in four main phases: 1. The public service monopoly (1954-1975), characterized by the educational mission assumed by the public service concessionaire RAI as part of its national cultural policy; 2. Deregulation and commercial competition (1976-1990), characterized by competition between RAI and the commercial model introduced in Italy by Silvio Berlusconi's Fininvest. The struggle for audience shifts the content provisions towards pure entertainment and opens up to new television markets, especially the Japanese one. 3. Globalization, digitalization and thematic multichannel (1990-2012), marked by technological revolutions (satellite and DTT). Italian CT is characterized by: the multiplication of players, especially multinational, strong of the large US libraries; the coexistence of (premium) pay and free TV channels; a new season of legal and economic regulation, led in part by the European Union in order to protect children; migration of children's programming from generalist to thematic TV; 4. Chlidren's multiplatform TV (2012-onward), characterized by digital convergence and multiplatform supply. CT extends to new video on demand services (e.g. Disney+ or Netflix) and socia

Human beings become and remain social, across time and space, in and by communication. Communication accomplishes the socialization and acculturation of individuals in the mostly ordinary, if occasionally extraordinary, processes of their everyday interactions. This chapter introduces the idea of affordances from ecological psychology to specify the scaling of human communication and social networks in current communication systems. It draws on the ethnographic fieldwork data from each region to explore the contexts in which, and the criteria by which, people elect to engage in communication with others, and to make themselves available for communication in the first place. The chapter identify some general patterns of how people in the three world regions of the study become social, in and through a range of media modalities. Furthermore the chapter explore the context in which, and the criteria by which, people elect (not) to engage in communication with others, and to make themselves available to various social networks, small and large. A third section of the chapter explores, the extended range of ways in which it has become possible to be social through "social media". Departing from the notion of scalable sociality (Miller et al. 2016), the authors examine the different kinds and degrees of being social that social media afford, and which turn out to vary not just with world region but also with different spheres of human and social activity. In the final section the authors briefly consider the question of how communicative practices relate to people's affiliation with social and cultural organization - which constitute consolidated, institutionalized indicators of specific ways of being social.

We present a large-scale analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) substitutions, considering 1,585,456 high-quality raw sequencing samples, aimed at investigating the existence and quantifying the effect of mutational processes causing mutations in SARS-CoV-2 genomes when interacting with the human host. As a result, we confirmed the presence of three well-differentiated mutational processes likely ruled by reactive oxygen species (ROS), apolipoprotein B editing complex (APOBEC), and adenosine deaminase acting on RNA (ADAR). We then evaluated the activity of these mutational processes in different continental groups, showing that some samples from Africa present a significantly higher number of substitutions, most likely due to higher APOBEC activity. We finally analyzed the activity of mutational processes across different SARS-CoV-2 variants, and we found a significantly lower number of mutations attributable to APOBEC activity in samples assigned to the Omicron variant.

Based on the cross-national survey part of the so called Peoples’ Internet (PIN) Project, the article analyzes social media uses in three different world regions: Europe, US, and China. Within the tradition of the studies on the social uses of the media, the article describes different kinds of social media uses, focusing on different factors that contribute to shape them in a more or less private or public way. Social media practices do not differentiate in a simply dichotomous way, as “private” or “public”; rather, they are gradually articulated in a “scalable sociality” that integrates, in different ways, elements of privateness and publicness. In the definition of such a scale, structural and cultural differences among different world regions and single countries play a role, alongside with variables as socio-demographic features, available capitals, and civic attitudes.