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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.

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.

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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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.

Due to their remarkable intrinsic physical properties, carbon nanotubes (CNTs) can enhance mechanical properties and confer electrical and thermal conductivity to polymers currently being investigated for use in advanced applications based on thermal management. An epoxy resin filled with varying concentrations of CNTs (up to 3 wt%) was produced and experimentally characterized. The electrical percolation curve identified the following two critical filler concentrations: 0.5 wt%, which is near the electrical percolation threshold (EPT) and suitable for exploring mechanical and piezoresistive properties, and 3 wt% for investigating thermo-electric properties due to the Joule effect with applied voltages ranging from 70 V to 200 V. Near the electrical percolation threshold (EPT), the CNT concentration in epoxy composites forms a sparse, sensitive network ideal for deformation sensing due to significant changes in electrical resistance under strain. Above the EPT, a denser CNT network enhances electrical and thermal conductivity, making it suitable for Joule heating applications. Numerical models were developed using multiphysics simulation software. Once the models have been validated with experimental data, as a perfect agreement is found between numerical and experimental results, a simulation study is performed to investigate additional physical properties of the composites. Furthermore, a statistical approach based on the design of experiments (DoE) was employed to examine the influence of certain thermal parameters on the final performance of the materials. The purpose of this research is to promote the use of contemporary statistical and computational techniques alongside experimental methods to enhance understanding of materials science. New materials can be identified through these integrated approaches, or existing ones can be more thoroughly examined.

Background: With the rise in the mastectomy rate, the number of patients who choose to undergo postmastectomy reconstruction has been increasing, and implant-based procedures are the most performed methods for postmastectomy breast reconstruction. Among the possible complications, the most feared is the loss of reconstruction. It can be related to several reasons, but one of the most common is infection of the implant, which can lead to prolonged antibiotic treatment, undesired additional surgical procedures, increased incidence of capsular contracture, and unsatisfactory aesthetics results, with a huge psychological impact on patients. Aims: The primary intent of this study is to analyze the status of infection rates at our institution and evaluate the effectiveness of our prevention protocol since its introduction. Secondly, we compared data of the surgical site infections (SSIs) after implant-based breast reconstruction at Trieste Hospital, where the protocol has been employed since 2020, and in another center, where plastic surgeons of our team are involved, with different prevention procedures. Methods and Results: We enrolled 396 female patients, who underwent implant-based breast reconstruction, using definitive mammary implants or breast tissue expanders, with or without ADM (acellular dermal matrix), both for breast cancer and risk-reducing surgery in BRCA1/2 patients. Patients treated at the Hospital of Trieste, with the use of the prevention protocol, were considered the experimental group (group 1), while patients treated in Gorizia by the same breast team with standardized best-practice rules, but without the use of the prevention protocol, were considered the control group (group 2). Infected patients were 5 in the first group (1.7%) and 8 in the second one (7.9%), with a global infection rate of 3.2%. Conclusion: After the introduction of our prevention protocol, we faced a lower incidence of infection after breast surgery with implants or tissue expanders.

In recent years, self-healing polymers have emerged as a topic of considerable interest owing to their capability to partially restore material properties and thereby extend the product’s lifespan. The main purpose of this study is to investigate the nanoindentation response in terms of hardness, reduced modulus, contact depth, and coefficient of friction of a self-healing resin developed for use in aeronautical and aerospace contexts. To achieve this, the bifunctional epoxy precursor underwent tailored functionalization to improve its toughness, facilitating effective compatibilization with a rubber phase dispersed within the host epoxy resin. This approach aimed to highlight the significant impact of the quantity and distribution of rubber domains within the resin on enhancing its mechanical properties. The main results are that pure resin (EP sample) exhibits a higher hardness (about 36.7% more) and reduced modulus (about 7% more), consequently leading to a lower contact depth and coefficient of friction (11.4% less) compared to other formulations that, conversely, are well-suited for preserving damage from mechanical stresses due to their capabilities in absorbing mechanical energy. Furthermore, finite element method (FEM) simulations of the nanoindentation process were conducted. The numerical results were meticulously compared with experimental data, demonstrating good agreement. The simulation study confirms that the EP sample with higher hardness and reduced modulus shows less penetration depth under the same applied load with respect to the other analyzed samples. Values of 877 nm (close to the experimental result of 876.1 nm) and 1010 nm (close to the experimental result of 1008.8 nm) were calculated for EP and the toughened self-healing sample (EP-R-160-T), respectively. The numerical results of the hardness provide a value of 0.42 GPa and 0.32 GPa for EP and EP-R-160-T, respectively, which match the experimental data of 0.41 GPa and 0.30 GPa. This validation of the FEM model underscores its efficacy in predicting the mechanical behavior of nanocomposite materials under nanoindentation. The proposed investigation aims to contribute knowledge and optimization tips about self-healing resins.

Lung cancer presents significant therapeutic challenges, motivating the exploration of novel treatment strategies. Programmed cell death (PCD) mechanisms, encompassing apoptosis, autophagy, and programmed necrosis, are pivotal in lung cancer pathogenesis and the treatment response. Dysregulation of these pathways contributes to tumor progression and therapy resistance. Immunonutrition, employing specific nutrients to modulate immune function, and metabolic reprogramming, a hallmark of cancer cells, offer promising avenues for intervention. Nutritional interventions, such as omega-3 fatty acids, exert modulatory effects on PCD pathways in cancer cells, while targeting metabolic pathways implicated in apoptosis regulation represents a compelling therapeutic approach. Clinical evidence supports the role of immunonutritional interventions, including omega-3 fatty acids, in augmenting PCD and enhancing treatment outcomes in patients with lung cancer. Furthermore, synthetic analogs of natural compounds, such as resveratrol, demonstrate promising anticancer properties by modulating apoptotic signaling pathways. This review underscores the convergence of immunonutrition, metabolism, and PCD pathways in lung cancer biology, emphasizing the potential for therapeutic exploration in this complex disease. Further elucidation of the specific molecular mechanisms governing these interactions is imperative for translating these findings into clinical practice and improving lung cancer management.

The present work deals with the modeling of the response to neutrons of heteronuclear diatomic liquids, with special interest in the case of hydrogen deuteride (HD), as a possible candidate for the moderation process required in the production of cold neutrons. Preliminary evaluations of the model giving the neutron double differential cross section of a heteronuclear vibrating rotor were performed in the recent past by using, as a first approximation, the ideal gas law for the center-of-mass translational dynamics. Here, the state-of-the-art methodology (based on the use of quantum simulations of the velocity autocorrelation function) for predicting the neutron response of moderately quantum fluids (like molecular hydrogen and deuterium at low temperatures) is applied to the heteronuclear form of this molecular liquid. The unavailability of the double differential cross section experimental data on liquid HD still compels us to test the calculations only at an integral level, i.e., against the only available measurements of the total neutron cross section of HD. Despite the well-tested and parameter-free computational approach, which includes proper consideration of the quantum effects, the present findings on HD indicate the evident need for more accurate measurements of its total cross section in extended ranges of incident energy, as well as of an experimental determination of the double differential cross section of this mild quantum liquid. For further applicative purposes, a very useful by-product of this study is the determination of the self diffusion coefficient D of the HD in the liquid phase.

An outbreak species exhibits extreme, rapid population fluctuations that can be qualified as discrete events within a continuous dynamic. When outbreaks occur they may appear novel and disconcerting because the limiting factors of their dynamics are not readily identifiable. We present the first population hybrid dynamic model that combines continuous and discrete processes, designed to simulate marine species outbreaks. The deterministic framework was tested using the case of an unexploited benthic invertebrate species: the small, serpulid polychaete Ditrupa arietina. This species is distributed throughout the northeast Atlantic Ocean and Mediterranean Sea; it has a life cycle characterised by a pelagic dispersive larval stage, while juveniles and adults are sedentary. Sporadic reports of extremely high, variable densities (from 10,000 ind.m−2) have attracted attention from marine ecologists for a century. However, except for one decade-long field study from the Bay of Banyuls (France, Gulf of Lions, Mediterranean Sea), observations are sparse. Minimal formulations quantified the processes governing the population dynamics. Local population continuous dynamics were simulated from a size-structured model with a null immigration–emigration flux balance. The mathematical properties, based on the derived hybrid model, demonstrated the possibilities of reaching an equilibrium for the population using a single number of recruits per reproducer. Two extrapolations were made: (1) local population dynamics were simulated over 180 years using North Atlantic Oscillation indices to force recruitment variability and (2) steady-state population densities over the Gulf of Lions were calculated from a connectivity matrix in a metapopulation. The dynamics reach a macroscopic stability in both extrapolations, despite the absence of density regulating mechanisms. This ensures the persistence of D. arietina, even when strong, irregular oscillations characteristic of an outbreak species are observed. The hybrid model suggests that a macroscopic equilibrium for a population with variable recruitment conditions can only be characterised for time periods which contain several outbreak occurrences distributed over a regional scale.

In adolescence individuals enlarge their social relationships and peer groups acquire a strong importance for their identity. Moreover, adolescents can experiment negative relationships with peers, i.e., bullying/cyberbullying. The present study aims to investigate the relationship between the feeling of belonging to a specific group, social identification, the distance that adolescents maintain interacting with others, interpersonal distance, and bullying/cyberbullying behaviors. Adolescents (age range 10-15 years) completed online measures of group identification (social identification with classmates, friends and family), interpersonal distance, and bullying and cyberbullying (perpetration and victimization). Results showed that adolescents with low social identification with classmates and friends chose larger interpersonal distance. Additionally, low scores in social identification with classmates were associated with higher victimization in cyberbullying. In contrast, adolescents with low scores in social identification with family were more involved as bullies in bullying and as victims in cyberbullying. Male adolescents were more likely to be victimized in bullying than females. This study underlines how social identification with peers and family works as a buffer in interfacing strangers, adjusting the distance maintained with them, and as a protective factor against aggressive relationships in adolescence. This study provides new opportunities for psychologists in understanding the psychological dynamics that shape social interactions among adolescents.

Plasma membrane (PM) H+-ATPases of the P-type family are highly conserved in yeast, other fungi, and plants. Their main role is to establish an H+ gradient driving active transport of small ions and metabolites across the PM and providing the main component of the PM potential. Furthermore, in both yeast and plant cells, conditions have been described under which active H+-ATPases promote activation of TORC1, the rapamycin-sensitive kinase complex controlling cell growth. Fungal and plant PM H+-ATPases are self-inhibited by their respective cytosolic carboxyterminal tails unless this domain is phosphorylated at specific residues. In the yeast H+-ATPase Pma1, neutralization of this autoinhibitory domain depends mostly on phosphorylation of the adjacent Ser911 and Thr912 residues, but the kinase(s) and phosphatase(s) controlling this tandem phosphorylation remain unknown. In this study, we show that S911-T912 phosphorylation in Pma1 is mediated by the largely redundant Ptk1 and Ptk2 kinase paralogs. Dephosphorylation of S911-T912, as occurs under glucose starvation, is dependent on the Glc7 PP1 phosphatase. Furthermore, proper S911-T912 phosphorylation in Pma1 is required for optimal TORC1 activation upon H+ influx coupled amino-acid uptake. We finally show that TORC1 controls S911-T912 phosphorylation in a manner suggesting that activated TORC1 promotes feedback inhibition of Pma1. Our results shed important new light on phosphoregulation of the yeast Pma1 H+-ATPase and on its interconnections with TORC1.

In their 2023 book, “The Blue Compendium: From Knowledge to Action for a Sustainable Ocean Economy”, Lubchenko and Haugan invoked alternate stable (AS) states marginally as an undesired consequence of sources of disturbance on populations, communities and ecosystems. They did not provide detailed arguments, but considered the existence of AS states as a given. Conversely, May, in his 1977 Nature article, pointed out that, when applied to systems that are complex, “the [AS states] theory remains largely metaphorical”. This is the starting point of this critical review, which aims to re-examine the general theory behind AS states in ecological systems and its applications to marine ecology and conservation. The focus is first on theory, taking as examples communities that sustain competition and studying the relative importance of the fluxes of individuals between simple low-dimension, interconnected systems. We find that a minimal formulation of fluxes is sufficient to obtain a set of non-null multiple stable (MS) states and to trigger shifts between AS states when fluxes become large enough. This provides new insights into the theory of rescue and mass effects by distinguishing them through a threshold at which the system dynamics shift from one stable equilibrium to another. Then, we consider how the theoretical framework of AS states has been applied in marine environments. It appears that many applications have confounded shifts between AS states and changes in the structure of systems, particularly when the complexity of the systems increases. The main difficulty for any application remains that the concepts of MS and AS states can only be established and validated for low-dimension systems and simplified experiments. This is because the mathematical properties of models that describe large-dimension, complex systems deviate from the observed characteristics of their real-world counterparts. There are many intriguing scientific challenges around the plausible shifts between AS states, but a deeper understanding and characterization of their occurrence in nature would require a significant investment in modeling to formulate predictive ecosystem models.