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According to the socio-constructivist theories of learning, collaborative learning allows negotiation of shared meanings and co-construction of new knowledge among peers. This approach fits particularly well with healthcare professional education needs, as these professionals often face challenging issues that require the ability to fully understand the complexity of the patients' health conditions through working with others. However, while collaborative learning approaches are widely used in face-to-face nurse education contexts, their online equivalent still seem to be understudied, in spite of their great potential for the field. This systematic literature review investigates: (1) to what extent are online collaborative learning activities being adopted and investigated in formal nurse education, (2) What kind of online collaborative learning activities/techniques are proposed and what team structures are employed, (3) what technologies are used to run these learning activities, and (4) what methods are used to evaluate the impact of these activities. Studies were included if they presented online collaborative learning activities proposed by Universities or VET (Vocational Education and Training) providers. Articles published in 2015 or later were collected in November 2022 from Scopus, Web of Science and Medline. A total of 1059 records were retrieved, selected and analysed by four coders, resulting in a final dataset of 75 papers that were coded for type of collaborative approach, study characteristics, research methodology used, strength of evidence, and relevance to the research questions. Most of them described the use of activities like Discussions, Case Studies and Peer Reviews, sometimes in association with Role Play. In terms of technologies, Learning Managements Systems, forums and social media were already common pre-pandemic, but during the lockdown synchronous communication tools -- often used to support simulations -- took over. Data collection was carried out quantitatively, qualitatively or using mixed methods, but in many cases data reporting is weak or absent at all. The majority of the retrieved papers illustrate activities where collaboration was not structured in any way and there was no joint assignment or common objective/artefact that learners needed to reach/produce. In case of blended interventions, often collaboration is limited to the face-to-face sessions, while the digital setting is used for individual work. In terms of social structure, most of the time small groups or plenaries are used. In summary, the review reveals that studies on online collaborative learning for nurses are limited, especially in Europe, and the design of online collaborative activities often clashes with the principles put forward by the Computer Supported Collaborative Learning (CSCL) research community. Based on the results of the review we put forth some key recommendations, such as ensuring that online collaboration involves the creation of a shared artefact and striving to make virtual simulations actually collaborative, rather than limited to envisage student interactions in the debriefing phase. The paper also proposes a number of research areas seldom investigated and that would deserve further attention in the future.

The Ketogenic Diet (KD) improves memory and longevity in aged C57BL/6 mice. We tested 7 months KD vs. control diet (CD) in the mouse Alzheimer's Disease (AD) model APP/PS1. KD significantly rescued Long-Term-Potentiation (LTP) to wild-type levels, not by changing Amyloid-β (Aβ) levels. KD's 'main actor' is thought to be Beta-Hydroxy-butyrate (BHB) whose levels rose significantly in KD vs. CD mice, and BHB itself significantly rescued LTP in APP/PS1 hippocampi. KD's 6 most significant pathways induced in brains by RNAseq all related to Synaptic Plasticity. KD induced significant increases in synaptic plasticity enzymes p-ERK and p-CREB in both sexes, and of brain-derived neurotrophic factor (BDNF) in APP/PS1 females. We suggest KD rescues LTP through BHB's enhancement of synaptic plasticity. LTP falls in Mild-Cognitive Impairment (MCI) of human AD. KD and BHB, because they are an approved diet and supplement respectively, may be most therapeutically and translationally relevant to the MCI phase of Alzheimer's Disease.

Abstract Background Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD). Objectives To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels. Methods 70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC. Results Our sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p

Abstract During embryonic and neonatal development, mitochondria have essential effects on metabolic and energetic regulation, shaping cell fate decisions and leading to significant short- and long-term effects on embryonic and offspring health. Therefore, perturbation on mitochondrial function can have a pathological effect on pregnancy. Several shreds of evidence collected in preclinical models revealed that severe mitochondrial dysfunction is incompatible with life or leads to critical developmental defects, highlighting the importance of correct mitochondrial function during embryo-fetal development. The mechanism impairing the correct development is unknown and may include a dysfunctional metabolic switch in differentiating cells due to decreased ATP production or altered apoptotic signalling. Given the central role of mitochondria in embryonic and fetal development, the mitochondrial dysfunction typical of Mitochondrial Diseases (MDs) should, in principle, be detectable during pregnancy. However, little is known about the clinical manifestations of MDs in embryonic and fetal development. In this manuscript, we review preclinical and clinical evidence suggesting that MDs may affect fetal development and highlight the fetal and maternal outcomes that may provide a wake-up call for targeted genetic diagnosis.

Abstract Background Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants. Case presentation We describe two male infants with prenatal diagnosis of dilated cardiomyopathy with impaired ventricular contractility. One of the patients showed hydrops and polyhydramnios. Postnatally, a DCM with severely reduced systolic function was confirmed and required medical treatment. In patient 1, Whole Exome Sequencing (WES) revealed a homozygous NEXN variant: c.1156dup (p.Met386fs) while in patient 2 a custom Next Generation Sequencing (NGS) panel revealed the homozygous NEXN variant c.1579_1584delp. (Glu527_Glu528del). These NEXN variants have not been previously described. Unlike the unfavorable prognosis described for biallelic NEXN variants, we observed in both our patients a favorable clinical course over time. Conclusion This report might help to broaden the present knowledge regarding NEXN biallelic variants and their clinical expression. It might be worthy to consider the inclusion of the NEXN gene sequencing in the investigation of pediatric patients with DCM.

Cinzia Bragato,1 Andrea Persico,1 Guillem Ferreres,2 Tzanko Tzanov,2 Paride Mantecca1 1POLARIS Research Center, Department of Earth and Environmental Sciences, University of Milano-Bicocca, Milan, 20126, Italy; 2Group of Molecular and Industrial Biotechnology, Universitat Politècnica de Catalunya, Terrassa, 08222, SpainCorrespondence: Cinzia Bragato, Piazza della Scienza 1, Milan, 20126, Italy, Tel +39 0264482928,, Email cinzia.bragato@unimib.itPurpose: Lignin is the most abundant source of aromatic biopolymers and has gained interest in industrial and biomedical applications due to the reported biocompatibility and defense provided against bacterial and fungal pathogens, besides antioxidant and UV-blocking properties. Especially in the form of nanoparticles (NPs), lignin may display also antioxidant and anti-inflammatory activities.Methods: To evaluate these characteristics, sonochemically nano-formulated pristine lignin (LigNPs) and enzymatically-phenolated one (PheLigNPs) were used to expose zebrafish embryos, without chorion, at different concentrations. Furthermore, two different zebrafish inflammation models were generated, by injecting Pseudomonas aeruginosa lipopolysaccharide (LPS) and by provoking a wound injury in the embryo caudal fin. The inflammatory process was investigated in both models by qPCR, analyzing the level of genes as il8, il6, il1β, tnfα, nfkbiaa, nfk2, and ccl34a.4, and by the evaluation of neutrophils recruitment, taking advantage of the Sudan Black staining, in the presence or not of LigNPs and PheLigNPs. Finally, the Wnt/β-catenin pathway, related to tissue regeneration, was investigated at the molecular level in embryos wounded and exposed to NPs.Results: The data obtained demonstrated that the lignin-based NPs showed the capacity to induce a positive response during an inflammatory event, increasing the recruitment of cytokines to accelerate their chemotactic function. Moreover, the LigNPs and PheLigNPs have a role in the resolution of wounds, favoring the regeneration process.Conclusion: In this paper, we used zebrafish embryos within 5 days post fertilization (hpf). Despite being an early-stage exemplary, the zebrafish embryos have proven their potential as predicting models. Further long-term experiments in adults will be needed to explore completely the biomedical capabilities of lignin NPs. The results underlined the safety of both NPs tested paved the way for further evaluations to exploit the anti-inflammatory and pro-healing properties of the lignin nanoparticles examined. Keywords: bio-based nanoparticles, zebrafish embryo, inflammation, LPS, wound

Since the European Green Deal was launched (European Commission, 2019), social media and especially Twitter (now X) has become the one main socio-political virtual space where the European Commission is promoting the European Union’s twinned (Just, Green, and Digital) Transitions. This multidisciplinary exploratory research crosscuts Spatial Planning & Territorial Governance (Nadine et al., 2018; Berisha, et al, 2021), and Social Media Studies and Digital Methods (Rogers, 2018; 2019), investigating the existence of the term “Just Green Transitions” on Twitter, highlighting the potential benefits that social media analysis could add to the disciplines of Governance and Policymaking. Utilizing Social Network Analysis, both Mention Analysis and Co-hashtag- Analysis were applied to capture and analyse three million original tweets over the first twenty months since the Just Transition Mechanism entered into force (European Parliament, 2021). The results highlighted the fragmentation of the terminologies and Twitter user communities, discussing the expected transitions of Europe which are expected to be Just and Green (European Commission, 2021).

Abstract Background Unhealthy lifestyles represent a key element fueling Non-alcoholic fatty liver disease (NAFLD) onset and worsening. We aimed to evaluate the effects of forced acute lifestyle changes on NAFLD evolution. Methods 187 NAFLD patients were followed two years pre- and two years during the lockdown social restrictions in three Italian medical centers. For each patient, biochemical, clinical, non-invasive liver fibrosis, nutritional, and body composition data were collected. Results An increase in fats and carbohydrate intake associated with impaired weekly physical activity during the lockdown was demonstrated as well as an increase in body mass index and waist-hip-ratio (p

Abstract Background Severe overcrowding of emergency departments (EDs) affects the quality of healthcare. One factor of overcrowding is precariousness, but it has rarely been considered a key factor in designing interventions to improve ED care. Health mediation (HM) aims to facilitate access to rights, prevention, and care for the most vulnerable persons and to raise awareness among healthcare providers about obstacles in accessing healthcare. The primary aim was to determine whether HM intervention for frequent users of EDs (FUED) living in precarious conditions could reduce the readmission rate at 90 days. Methods Between February 2019 and May 2022, we enrolled and interviewed 726 FUED in four EDs of southeastern France in this randomised controlled trial. The HM intervention started in the ED and lasted 90 days. In addition to the primary endpoint (first readmission at 90 days), secondary endpoints (readmission at 30 and 180 days, number of hospitalisations at 30, 90, 180 days, admissions for the same reasons as the first admission) were also studied. The outcomes were measured in the ED information systems. Statistical methods included an intention-to-treat analysis and a per-protocol analysis. Comparisons were adjusted for gender, age, ED, and health mediator. Results 46% of patients reported attending the ED because they felt their life was in danger, and 42% had been referred to the ED by the emergency medical dispatch centre or their GP; 40% of patients were considered to be in a serious condition by ED physicians. The proportion of patients who were readmitted at 90 days was high but did not differ between the control and the HM intervention groups (31.7% vs. 36.3%, p = 0.23). There was no significant difference in any of the secondary outcome measures between the control and HM intervention groups. Per-protocol analysis also showed no significant difference for the primary and secondary endpoints. Conclusions This randomised controlled trial did not show that our health mediation intervention was effective in reducing the use of emergency services by FUED living in precarious conditions. Some limitations are discussed: the duration of the intervention (90 days), the long-term effects (> 6 months), the involvement of the ED staff. Trial registration Registered on clinicaltrials.gov as NCT03660215 on 4th September 2018.

Cardioneuroablation (CNA) is a novel interventional procedure for the treatment of recurrent vasovagal syncope (VVS) and advanced atrioventricular block secondary to hyperactivation of vagal tone in young patients. By damaging the cardiac parasympathetic ganglia, CNA seems to be able to mitigate and/or abolish the excessive vagal activity and improve patients’ outcome. This review is intended to give a detailed and comprehensive overview of the current evidences regarding (1) the clinical applications of CNA (2) the identification of ablation targets and procedural endpoints (3) the medium-long term effect of the procedure and its future perspectives. However, clinical data are still limited, and expert consensus or recommendations in the guidelines regarding this technique are still lacking.

Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.

Injury to the Luschka ducts (LDs), also named “subvesicular” ducts, is an under-reported cause of biliary leak following laparoscopic cholecystectomy (LC). A systematic literature search according to PRISMA guidelines was conducted in PubMed, EMBASE and Cochrane Library including all publications that described a bile leak from an LD. A total of 136 articles were retrieved from the searched databases. After the removal of duplicates and non-eligible papers, 48 studies reporting 231 leaks were included: 20 (41.6%) case reports, 2 (4.3%) comparative studies, 7 (14.9%) meeting abstracts and 19 (40.4%) retrospective cohort articles. The rate of LD leak ranges from 0.05% to 1.9%, but injury to a duct of Luschka was the second most common cause of biliary leakage in all the cohort studies (5.5% to 41%). In 21 (43.7%) cases, the leak was successfully treated with a sphincterotomy through Endoscopic Retrograde Cholangiopancreatography (ERCP) plus or minus stenting, and in 12 (25%), re-laparoscopy was necessary.

Abstract In the digital age, poor public communication catalyzes the spread of disinformation within public opinion. Anyone can produce political content that can reach a global audience, and social media has become a vital tool for political leaders to convey messages to the electorate. The 2022 Italian election campaign has seen the term “nuclear” debated with two different declinations: on the one hand, regarding nuclear energy for civilian use, and on the other hand, regarding the fear of an escalation of the conflict in Ukraine and the use of atomic weapons. This research aims to analyze the social media debate by exploring multiplatform dynamics to qualitatively identify and analyze the connections between social media platforms that we have termed Bridges, a concept drawn from Transmedia Theory to describe the narrative relationship between platforms. The methodological approach will follow an explanatory sequential design that will rely on digital methods to identify connections between platforms (bridges) and then apply an exploratory qualitative approach to enrich the data and capture the nuances of the debate. As expected, we found polarized positions and fragmentation on both issues of civilian nuclear energy and the atomic conflict narrative. Primary evidence shows bridges spreading affective, defective, and infective content across platforms in a multifaceted social media ecosystem. Affective refers to rhetoric that appeals to people’s feelings. Defective means the discussion that brings attention to hyper-partisan news channels, fake news, and misinformation. Infective means bridges with below-the-radar platforms, niche channels, or pseudo-information channels. They use bridges with mainstream platforms to gain the potential to go viral. The paper highlights the importance of cross-platform and interdisciplinary approaches to addressing disinformation in a media ecosystem where social media plays an increasing role in a country’s democratic dynamics.

Abstract The Ketogenic Diet (KD) improves memory and longevity in aged C57BL/6 mice. We tested 7 months KD vs. control diet (CD) in the mouse Alzheimer’s Disease (AD) model APP/PS1. KD significantly rescued Long-Term-Potentiation (LTP) to wild-type levels, not by changing Amyloid-β (Aβ) levels. KD’s ‘main actor’ is thought to be Beta-Hydroxy-butyrate (BHB) whose levels rose significantly in KD vs. CD mice, and BHB itself significantly rescued LTP in APP/PS1 hippocampi. KD’s 6 most significant pathways induced in brains by RNAseq all related to Synaptic Plasticity. KD induced significant increases in synaptic plasticity enzymes p-ERK and p-CREB in both sexes, and of brain-derived neurotrophic factor (BDNF) in APP/PS1 females. We suggest KD rescues LTP through BHB’s enhancement of synaptic plasticity. LTP falls in Mild-Cognitive Impairment (MCI) of human AD. KD and BHB, because they are an approved diet and supplement respectively, may be most therapeutically and translationally relevant to the MCI phase of Alzheimer’s Disease.

In today’s digital landscape, critical services are increasingly dependent on network connectivity, thus cybersecurity has become paramount. Indeed, the constant escalation of cyberattacks, including zero-day exploits, poses a significant threat. While Network Intrusion Detection Systems (NIDSs) leveraging machine-learning and deep-learning models have proven effective in recent studies, they encounter limitations such as the need for abundant samples of malicious traffic and full retraining upon encountering new attacks. These limitations hinder their adaptability in real-world scenarios. To address these challenges, we design a novel NIDS capable of promptly adapting to classify new attacks and provide timely predictions. Our proposal for attack-traffic classification adopts Few-Shot Class-Incremental Learning (FSCIL) and is based on the Rethinking Few-Shot (RFS) approach, which we experimentally prove to overcome other FSCIL state-of-the-art alternatives based on either meta-learning or transfer learning. We evaluate the proposed NIDS across a wide array of cyberattacks whose traffic is collected in recent publicly available datasets to demonstrate its robustness across diverse network-attack scenarios, including malicious activities in an Internet-of-Things context and cyberattacks targeting servers. We validate various design choices as well, involving the number of traffic samples per attack available, the impact of the features used to represent the traffic objects, and the time to deliver the classification verdict. Experimental results witness that our proposed NIDS effectively retains previously acquired knowledge (with over 94% F1-score) while adapting to new attacks with only few samples available (with over 98% F1-score). Thus, it outperforms non-FSCIL state of the art in terms of classification effectiveness and adaptation time. Moreover, our NIDS exhibits high performance even with traffic collected within short time frames, achieving 95% F1-score while reducing the time-to-insight. Finally, we identify possible limitations likely arising in specific application contexts and envision promising research avenues to mitigate them.

Abstract Background Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia. Methods A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms. Results Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival. Conclusions The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.

Significant in lifestyle have reshaped the Internet landscape, resulting in notable shifts in both the magnitude of Internet traffic and the diversity of apps utilized. The increased adoption of communication-and-collaboration apps, also fueled by lockdowns in the COVID pandemic years, has heavily impacted the management of network infrastructures and their traffic. A notable characteristic of these apps is their multi-activity nature, e.g., they can be used for chat and (interactive) audio/video in the same usage session: predicting and managing the traffic they generate is an important but especially challenging task. In this study, we focus on real data from four popular apps belonging to the aforementioned category: Skype, Teams, Webex, and Zoom. First, we collect traffic data from these apps, reliably label it with both the app and the specific user activity and analyze it from the perspective of traffic prediction. Second, we design data-driven models to predict this traffic at the finest granularity (i.e., at packet level) employing four advanced multitask deep learning architectures and investigating three different training strategies. The trade-off between performance and complexity is explored as well. We publish the dataset and release our code as open source to foster the replicability of our analysis. Third, we leverage the packet-level prediction approach to perform aggregate prediction at different timescales. Fourth, our study pioneers the trustworthiness analysis of these predictors via the application of eXplainable Artificial Intelligence to $(a)$ interpret their forecasting results and $(b)$ evaluate their reliability, highlighting the relative importance of different parts of observed traffic and thus offering insights for future analyses and applications. The insights gained from the analysis provided with this work have implications for various network management tasks, including monitoring, planning, resource allocation, and enforcing security policies.

In grapevine, metabolic activity of absorptive roots changes rapidly as roots age but it is unclear whether nearby microbial assemblages shift as well. Here, we investigated whether first-order root age affects bacterial and fungal variation adjacent to the root surface, and whether root age should be integrated into future studies on root functional traits and associated microbes. We hypothesized that microbial diversity and composition would differ between young (≤11 days old) and old (11.5 to 40 days old) first-order roots due to expected differences in metabolism over the root lifespan (i.e., higher metabolism in young roots). Overall, we found that microbial composition was distinct between young and old absorptive roots, with stronger evidence at the phylum and amplicon sequence variant (ASV) taxonomic levels for fungi (P = 0.003 and P = 0.038, respectively) than bacteria (P = 0.082 and P = 0.129, respectively). Furthermore, we identified differentially abundant fungal and bacterial ASVs in young and old roots that related to expected differences in root function, including instances of microbes previously described as copiotrophs more abundant adjacent to young roots and microbes described as oligotrophs and saprotrophs more abundant adjacent to old roots. In contrast to the distinct shifts in microbial composition, there was little evidence of shifts in α diversity (i.e., observed ASVs and Shannon diversity) between young and old roots. Our study suggests that future work on the impacts of root functional traits on localized microbial composition may improve results interpretation and reduce some variation by accounting for root age at sampling.

Abstract The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast cancer. After an initial delay in the tumor onset, SIRT6-OE induces a more aggressive phenotype of Delta16HER2 tumors promoting the formation of higher number of tumor foci and metastases than controls. This phenotype of SIRT6-OE tumors is associated with cancer stem cell (CSC)-like features and tumor dormancy, and low senescence and oxidative DNA damage. Accordingly, a sub-set of HER2-positive breast cancer patients with concurrent SIRT6-OE has a significant poorer relapse-free survival (RFS) probability than patients with low expression of SIRT6. ChIP-seq, RNA-seq and RT-PCR experiments indicate that SIRT6-OE represses the expression of the T-box transcription factor 3 (Tbx3) by deacetylation of H3K9ac. Accordingly, loss-of-function mutations of TBX3 or low TBX3 expression levels are predictive of poor prognosis in HER2-positive breast cancer patients. Our work indicates that high levels of SIRT6 are indicative of poor prognosis and high risk of metastasis in HER2-positive breast cancer and suggests further investigation of TBX3 as a downstream target of SIRT6 and co-marker of poor-prognosis. Our results point to a breast cancer subtype-specific effect of SIRT6 and warrant future studies dissecting the mechanisms of SIRT6 regulation in different breast cancer subtypes.

This study reports the outcomes of a survey investigating the beliefs and self-reported behaviours of a sample of 238 in-service school teachers in Italy and Spain concerning their self-regulated professional learning about the design of learning interventions, an activity generally referred to as Learning Design (LD). The study adopts the lens of the 4C Framework for Self-Regulated Professional Learning, which distinguishes between Consume, Create, Connect and Contribute behaviours. The results indicate that all four Cs are deemed important by respondents, but there are statistically significant differences between perceived importance and behaviours, especially for the two Cs that can be termed 'altruistic' (Connect and Contribute). As for the 'individualistic' behaviours (Consume and Create), the gap between perceived importance and practice is narrower, especially for Create. The main conclusion is that, at least in the teaching populations of the two countries involved, the participatory culture of LD is far from being a reality, despite being strongly advocated in the literature. To this end, the authors believe that to achieve truly collaborative professionalism, responsive actions should be directed especially towards removing motivational and emotional barriers hindering 'altruistic' behaviours.

University ranking systems are being implemented with the aim of assessing and comparing higher education institutions at a global level. Despite their being increasingly used, rankings are often strongly criticized for their social and economic implications, as well as for limitations in their technical implementation. One of these limitations is that they do not consider the specific characteristics of online education. This study used a participatory approach to define a set of criteria and indicators suitable to reflect the specific nature of distance education. This endeavour will help evaluate and rank online higher education institutions more appropriately than in current practice, where indicators are devised for traditional universities. To this end, several stakeholders and informants were involved in a Delphi study in an attempt to reach the broader higher education institutions (HEI) community. According to the study participants, apart from students' achievements and general quantitative measures of HEI performance, which are quite common in traditional ranking systems, teaching and student learning experience turned out to be the most important criteria. Student support, teacher support, technological infrastructure, research and organization were deemed middle ground criteria, while sustainability and reputation were regarded as the least important criteria.

IntroductionThe effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed.MethodsWe conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment.ResultsFour children (12.5%) were “strong responders”, 8 children (25.0%) were “moderate responders”, and 20 children (62.5%) were “poor responders”. A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level.DiscussionMost predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children.

BackgroundIn the Mediterranean basin, three Leishmania species have been identified: L. infantum, L. major and L. tropica, causing zoonotic visceral leishmaniasis (VL), zoonotic cutaneous leishmaniasis (CL) and anthroponotic CL, respectively. Despite animal models and genomic/transcriptomic studies provided important insights, the pathogenic determinants modulating the development of VL and CL are still poorly understood. This work aimed to identify host transcriptional signatures shared by cells infected with L. infantum, L. major, and L. tropica, as well as specific transcriptional signatures elicited by parasites causing VL (i.e., L. infantum) and parasites involved in CL (i.e., L. major, L. tropica).Methodology/principal findingsU937 cells differentiated into macrophage-like cells were infected with L. infantum, L. major and L. tropica for 24h and 48h, and total RNA was extracted. RNA sequencing, performed on an Illumina NovaSeq 6000 platform, was used to evaluate the transcriptional signatures of infected cells with respect to non-infected cells at both time points. The EdgeR package was used to identify differentially expressed genes (fold change > 2 and FDR-adjusted p-values < 0.05). Then, functional enrichment analysis was employed to identify the enriched ontology terms in which these genes are involved. At 24h post-infection, a common signature of 463 dysregulated genes shared among all infection conditions was recognized, while at 48h post-infection the common signature was reduced to 120 genes. Aside from a common transcriptional response, we evidenced different upregulated functional pathways characterizing L. infantum-infected cells, such as VEGFA-VEGFR2 and NFE2L2-related pathways, indicating vascular remodeling and reduction of oxidative stress as potentially important factors for visceralization.ConclusionsThe identification of pathways elicited by parasites causing VL or CL could lead to new therapeutic strategies for leishmaniasis, combining the canonical anti-leishmania compounds with host-directed therapy.

Although the subject of disinformation has been studied in the pre-digital era and in recent years in relation to changes in global geopolitics, the war in Ukraine opens up a new phase in which it is possible to identify the persistence of processes that were already in place, and at the same time to trace a new order of information disorder. The new element is the emergence of a media ecosystem in which, alongside mainstream social networks such as Facebook, Instagram, and Twitter, the role of under-the-radar platforms such as Telegram, Gab, and 4Chan Rumble emerges. Using a computational approach based on digital methods, the research identified, from a collection of data from Facebook and Twitter, recurring bridges to environments such as Telegram and Rumble. However, the content analysis revealed the prevalence of hyper-partisan content over disinformation content, with a significant presence of videos and news channels featuring Russian sources, video interviews with relevant figures in Ukrainian politics, and a marginal volume of conspiracy or disinformation content. In the latter case, the role of political influencers who divert connected audiences to marginal platforms and more problematic sources proves to be strategic.