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The aim of this paper is to evaluate the usefulness of educational software among teachers in Italy (N = 559). The evaluation of usefulness was conducted on the latest and most popular web-based software used by European teachers, namely: Quizizz, Mentimeter, Wakelet, Padlet, Canva, Emaze, Answergarden, Jamboard, Coggle, Createley, Wordwall, LearningApps, Prezi, Kahoot, Plickers, Trimino, Dobble, Genial.ly, ClassDojo, Explain Everything, KhanAcademy, and Easelly. Based on data collected in the first half of 2022 using an online survey, it was noted that: 1) The majority of teachers are not able to evaluate modern software because they do not use such teaching resources as those listed; 2) About 9.3% of teachers rate the listed software highly; 3) Most commonly teachers use and also rate highly: Canva, Wordwall, Padlet, LearningApps, Kahoot, Coggle, Jamboard, and Prezi; 4) Seniority and workplace does not always differentiate the evaluation of educational software.

This original paper, based on data from the Erasmus+Blurred Lives Project, presents a new multi-dimensional categorisation model to describe negative online experiences, including forms of cyberbullying, based on a study of internet usage among over N = 2,500 adolescents with lower socio-economic status (SES) backgrounds across five European countries. The paper first sets out the rationale for the development of a new coding system, before describing the current study and nature of the survey data collected. There follows a description of the development of the new system and the series of reliability checks undertaken by the research team (N= 11, from 5 countries) and of the refinements made to the categories and codes. The resulting coding system is presented with consideration of the strengths and limitations, and description of two early pilot studies which have successfully adopted the new system.

Abstract Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours.

There is ample evidence of bullying victimization-perpetration association. However, little is known about the role of socioemotional variables in reinforcing or mitigating it. There is a need to delve deeper into what victims feel and do that leads them to bully. This study aimed to analyze the moderating role of peer relationship management and anger regulation in the victimization-perpetration association, controlling gender and age. This cross-sectional study involved 874 Spanish middle school students (47.8% girls) aged 11 to 18 years (M = 13.92, SD = 1.45). The results revealed that the perpetration was positively related to victimization and negatively related to peer relationship management and anger regulation. In addition, peer relationship management can moderate the victimization-perpetration association, acting as a protective factor, when the ability of victims to regulate anger is sufficiently trained. These findings highlight the importance of designing effective prevention based on socio-emotional development to fully curb bullying.

Granite extraction waste represents an interesting alternative material for porcelain stoneware production, but information on its influence presents several gaps. For this reason, two different wastes were selected: a coarser iron-rich material from magnetic separation and a finer one from conveyance and abatement systems. Both were physically and chemically characterized. Batches were formulated by partial substitution of feldspar and technological behaviour of bodies was assessed by simulating the industrial manufacture at laboratory scale. Tiles were shaped by uniaxial pressure and fired by fast firing in electric roller kiln. The effect of waste addition was evaluated during the whole production process. Fired samples were characterized in terms of technological properties, mineralogical composition and microstructure evolution. The formulation optimization reduces firing temperature getting commercial technological constraints. A further increase of finer waste content affects compaction and mechanical strength. The presence of micaceous particles after the firing process may act as cracks initiation.

The aim of this research was to compare the level of digital competence of future pedagogical staff (students of pedagogical faculties) in Italy and Poland. The research was conducted using original measurement tools and knowledge tests. The triangulation of techniques and research tools made possible the determination of the level of knowledge of the positive and negative features of the development of the information society, as well as the proficiency and frequency of use of the most popular websites and software. The research was conducted in the first half of 2022 using stratified sampling in both countries (N = 1209, IT = 604, PL = 605). Based on the data collected, it was noted that: (1) Pre-service teachers most often use software such as word processors and presentation creation tools; (2) This group very rarely uses software to create web pages, create visual material, or edit video; (3) The least problematic software that students use are word processors and multimedia presentations; (4) Among the typical ICT mediated activities that cause problems are: searching for and installing freeware (PL), installing and configuring parental control software (PL, IT), creating websites (PL, IT), searching for freely licensed images, and identifying plagiarism (PL); (5) Polish students have more theoretical knowledge about e-risks and the possibilities of the digital world than their Italian counterparts; (6) In most domains, the Italian future teachers rate their competences higher; (7) 53.81% of the respondents in IT and 38.68% in PL received lower results in competence tests, and handling ICT in selected areas causes problems for these students; (8) Both in PL and IT the frequency of ICT use and its seamless integration are predictors for assessing the effectiveness of ICT use in education.

Castleman disease (CD) is a group of lymphoproliferative disorders that share common histopathological features yet have widely different aetiologies, clinical features and grades of severity as well as treatments and outcomes. Siltuximab is currently the only therapy approved by the FDA and EMA for idiopathic multicentric CD and is recommended as first-line therapy in treatment guidelines. Despite the extensive characterization of siltuximab treatment in clinical trials, available evidence from real-world practice is still scant. This collection of clinical experiences focuses on patients treated with siltuximab therapy, particularly regarding the idiopathic multicentric CD diagnostic work-up, and on treatment administration in patients with complex disease entering differential diagnosis with CD or concomitant diseases. Thus, these data help further characterize and improve the use of siltuximab in real practice in terms of effectiveness and safety of long-term administration as well as consequences of treatment interruption.

Triple negative breast cancer (TNBC) represents an aggressive disease associated with a high risk of recurrence after curative treatment and a poor prognosis in the metastatic setting. Chemotherapy was for years the only treatment available in the early and metastatic setting, due to the lack of actionable targets. Clinical practice has changed following the results obtained with the addition of immunotherapy to standard chemotherapy, the development of novel drugs [i.e. antibody-drug conjugates (ADCs)], and the use of targeted treatments for patients carrying germline pathogenic breast cancer susceptibility genes (BRCA) 1 or BRCA 2 variants. The treatment of early-stage disease has had a shift in clinical practice since July 2021, after the Food and Drug Administration (FDA) approval of pembrolizumab in association with chemotherapy as neoadjuvant treatment for TNBC and as a single agent in the subsequent adjuvant setting. This intensive treatment based on the combination of a poly-chemotherapy and an immune checkpoint inhibitor (ICI) led to the improvement of short- and long-term outcomes, but it has highlighted some new unmet clinical needs in the treatment of early-stage TNBC: the selection of the most effective adjuvant therapy and the integration of pembrolizumab with other therapeutic strategies [capecitabine, poly(ADP-ribose) polymerase (PARP) inhibitors] based on the achievement of pathologic complete response (pCR); the identification of predictive biomarkers to select patients who could most benefit from the addition of ICI, to minimize toxicities and to maximize outcomes; the possibility of de-escalating chemotherapy in favor of immune-combo or novel agents, such as ADCs; the role of immunotherapy in estrogen receptor (ER)-low patients. The advent of immunotherapy not only addresses current challenges in TNBC treatment but also holds the promise of a radical transformation in its therapeutic paradigm, enhancing significantly clinical outcomes and offering new perspectives for patients grappling with this aggressive form of breast cancer.

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Abstract A model was developed to forecast and compare changes in species presence assessed with either eDNA or traditional observations. We use it to explore how ecosystem conditions could affect the suitability of eDNA for Environmental Impact Assessment. First, a deterministic model simulated the dynamics of the impacted population (called “receptor” in EIA) and their shed DNA fragment concentrations. Second, random distributions of receptor organisms and eDNA fragment quantities at steady state were simulated within the impacted spatial domain (called “project area”). Then, simple random samplings were performed for both the receptor and eDNA. Third, post‐sampling processes (eDNA extraction, amplification, and analysis) were simulated to estimate the taxon detection probability. Fourth, we simulated an impact by modifying the growth, mortality, and mobility (null, passive, and active) parameters of the receptor taxon. eDNA detection probability curves were then estimated for a range of environmental sample volumes by fitting a Weibull cumulative distribution function. A F‐like statistic compared detection curves before and after impact. Statistically significant differences were detected with eDNA in impact scenarios where receptor taxon growth rate decreased and receptor mobility was null or passive. In scenarios where the project area accumulates DNA shed from multiple categories of the same taxon (e.g., from dead organisms if mortality increased or when individuals can cross project area boundaries), it is difficult to assess impact. Our study shows that results obtained from eDNA sampling will not always agree with an impact classically assessed on a receptor population. One reason is that sources of the total eDNA pool are not identified. The modeling highlights the need: to do preliminary testing of sample sizes, to develop new approaches that will identify sources from the pool of extracted DNA, and to improve descriptions of the ecogeochemical processes required to forecast shed DNA reactivity.

Abstract The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

The advent of immunotherapy and antibody–drug conjugates (ADCs) have revolutionized breast cancer treatment, offering new hope to patients. However, challenges, such as resistance and limited efficacy in certain cases, remain. Recently, the combination of these therapies has emerged as a promising approach to address these challenges. ADCs play a crucial role by delivering cytotoxic agents directly to breast cancer cells, minimizing damage to healthy tissue and enhancing the tumor-killing effect. Concurrently, immunotherapies harness the body’s immune system to recognize and eliminate cancer cells. This integration offers potential to overcome resistance mechanisms and significantly improve therapeutic outcomes. This review explores the rationale behind combining immunotherapies with ADCs, recent advances in this field, and the potential implications for breast cancer treatment.

In a global context, the identification of frameworks and assessment tools for achieving sustainable development requires the study of urban sustainability at different scales. While sustainability can be quantified more precisely on a larger scale, it is challenging to adapt these accounting techniques to smaller sites. Measuring becomes more challenging when researching urban sustainability from several viewpoints, especially when constructing an acceptable set of measurements while taking into account the several issues of the unique decision-making apparatus from theoretical and geographical perspectives. Which sorts of indicators should be prioritized above others? How many indicators should be used? Which criteria should be employed to choose the best indicators for the location of interest? This study addresses the aforementioned research problems by proposing a systematic, multidirectional approach to defining an adequate collection of indicators for sustainability accounting in urban situations. A top-down strategy, which provides a literature study to identify regularly used indicators in essential sustainability categories, is joined by a bottom-up approach, which creates indicators based on real-world circumstances. The combination of these two methodologies seeks to produce a set of relevant sustainability measurements. A neighborhood rehabilitation project for public housing in Le Lignon (Switzerland) serves as a pilot case for calibrating the proposed multidirectional technique. The final findings can support the public and private parties involved in sustainable urban planning procedures in assessing urban projects based on location-specific features.