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Nursing retention is a major challenge globally. Ongoing workforce instability across countries underscores the need to understand the factors influencing turnover and nursing retention. Trust is a crucial element in managing workplace relationships between nurse managers and nurses. Existing studies have shown the direct impact of trust on employees’ intention to leave their job but have not explored the effects of potential mediators such as organizational commitment. The aim of this study was to examine the impact of trust in the leader on nurses’ intention to leave their job through the mediation of organizational commitment. A cross-sectional study was conducted in Italy. A convenience sample of 1853 nurses completed a self-report survey. The study tested a hypothesis-based mediation model using structural equation modeling, which showed good fit indices. The results indicated that trust in the leader had a significant impact on nurses’ intention to leave, and this relationship was partially mediated by organizational commitment. Nurses who trust their leader are more likely to demonstrate higher levels of organizational commitment, resulting in a lower intention to leave their job. Furthermore, organizational commitment and trust emerge as critical factors in reducing nurses’ intention to leave their current positions. Therefore, managers can reduce nurses’ intention to leave by building trustful relationships that enhance organizational commitment.This study was not registered.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic disorders characterized by dysregulated immune response and persistent inflammation. Recent studies suggest that bile acid receptors, particularly GPBAR1, and the transcription factor RORγt play critical roles in modulating intestinal inflammation. This study evaluates the therapeutic potential of PBT002, a dual GPBAR1 agonist and RORγt inverse agonist, in IBD models. The effects of PBT002 were assessed through in vitro and in vivo experiments. Macrophages and T lymphocytes obtained from the buffy coat were exposed to PBT002 to evaluate its immunomodulatory activity. The beneficial effects in vivo were evaluated in mouse models of colitis induced by TNBS, DSS or DSS + IL-23 using also a Gpbar1 knock-out male mice. PBT002 exhibited an EC50 of 1.2 µM for GPBAR1 and an IC50 of 2.8 µM for RORγt. In in vitro, PBT002 modulated macrophage polarization towards an anti-inflammatory M2 phenotype and reduced Th17 cell markers while increasing Treg markers. In the TNBS-induced colitis model, PBT002 reduced weight loss, CDAI, and colon damage, while it modulated cytokine gene expression towards an anti-inflammatory profile. In GPBAR1-/-, the anti-inflammatory effects of PBT002 were attenuated, indicating partial GPBAR1 dependence. RNA sequencing revealed significant modulation of inflammatory pathways by PBT002. In DSS+IL-23 induced colitis, PBT002 mitigated disease exacerbation, reducing pro-inflammatory cytokine levels and immune cell infiltration. In conclusion, PBT002, a GPBAR1 agonist and RORγt inverse agonist, modulates both the innate and adaptive immune responses to reduce inflammation and disease severity in models of IBD.

Abstract Microbial diversity of caves is largely understudied and its possible applications are still unknown. Autochthonous fungi, in particular, may have the potential to biomineralize metals and may be used as promising agents for bioremediation of polluted sites; thus, unearthing the fungal diversity in hypogean ecosystems is nowadays of utmost importance. To start addressing this knowledge gap, the cultivable mycobiota of two neighbouring caves—one natural and one exploited for touristic purposes—were characterised and compared by studying fungi isolated from sediments collected at increasing distances from the entrance. Overall, 250 fungal isolates ascribable to 69 taxa (mainly Ascomycota) were found, a high percentage of which was reported in caves for the first time. The sediments of the touristic cave displayed a richer and more diversified community in comparison with the natural one, possibly due to visitors carrying propagules or organic material. Considering that these environments are still poorly explored, chances to detect new fungal lineages are not negligible.

BAR502, a bile acid analogue, is active as dual FXR/GPBAR1 agonist and represents a promising lead for the treatment of cholestasis and NASH. In this paper we report the synthesis and the biological evaluation of a library of hybrid compounds prepared by combining, through high-yield condensation reaction, some fibrates with BAR502.The activity of the new conjugates was evaluated towards FXR, GPBAR1 and PPARα receptors, employing transactivation or cofactor recruitment assays. Compound 1 resulted as the most promising of the series and was subjected to further pharmacological investigation, together with stability evaluation and cell permeation assessment. We have proved by LCMS analysis that compound 1 is hydrolyzed in mice releasing clofibric acid and BAR505, the oxidized metabolite of BAR502, endowed with retained dual FXR/GPBAR1 activity.

Introduction: Recently, a flow cytometric (FC) based test has been developed for detection of circulating fetal cells to replace the less accurate and reproducible Kleihauer-Betke test.FC test is easier to perform, it can distinguish the origin of fetal cells, but it is expensive and available in highly specialized laboratories. We evaluated the introduction of high-performance liquid chromatography (HPLC) approach as initial screening to identify patients who need an additional FC test to better discriminate the nature of haemoglobin-F (HbF) positive cells. Methods: Blood samples from 130 pregnant women suspected to have fetomaternal haemorrhage were analysed with HPLC and FC methods. The cut-off for HbF HPLC concentration was calculated. Statistical analyses for the evaluation of HPLC as a screening method were performed. The positivity cut-off of HbF to be used as decision-making value to continue the investigation was calculated. Results: An excellent agreement (R2 > 0.90) was observed between the percentage of HbF obtained by HPLC and the percentage of fetal cells detected by FC. Results obtained from each assay were compared to define the HPLC threshold below which it is not necessary to continue the investigations, confirming the maternal nature of the HbF positive cells detected. Our study demonstrated that a cut-off of 1.0 % HbF obtained by HPLC was associated with the lowest rate of false negative results in our patient cohort. Conclusions: This study provides a new FMH investigation approach that possibly leads to a reduction in times and costs of the analysis.

Questions about how closure is achieved in disputes involving new observational or experimental claims have highlighted the role of bodily knowledge possibly irreducible to written experimental protocols and instructions how to build and operate instruments. This essay asks similar questions about a scenario that is both related and significantly different: the replication of an invention, not of an observation or the instrument through which it produced. Furthermore, the machine considered here—Galileo’s compass or sector—was not a typical industrial invention (like a spinning jenny), but a mathematical invention (a calculator), that is, a machine that produces numbers, not yarn. This case study describes some of the similarities and differences between replicating experiments, traditional machines producing material outputs, and mathematical inventions yielding calculations or information. This comparison indicates that, as in other kinds of replication, the replication of mathematical inventions involves texts (the calculator’s instructions) but that in this case bodily knowledge cannot be properly described as either tacit or explicit. It rather takes the shape of memory—muscle memory—that may be recalled from reading the instructions.

This essay is about the unique role of proper nouns at the intersection of knowledge and property, both tangible and intangible. Nouns are central to any form of property and credit, from a person's name listed on a property deed or copyright registration, to the name of an artist to whom a work is attributed, or that of a scientist after whom a discovery or theory is named. And names can also be found on the other end of the property spectrum, not as the names of authors and owners but as objects of property, as in the case of brand names. Here I trace some of the functions of these names as they move across different scenarios of knowledge-making and property-making, focusing on some of the effects those trajectories are having in the contemporary technosciences as they bring together the function of the author and that of the brand.

Rooted in the traditional peer review model, the conceptualization of dialogue informing this collection may in fact constrain the ambitious rethinking of the process of editorial review we have been encouraged to pursue here. After suggesting ways to enhance the dialogical dimensions of the traditional peer review model, I will propose a substantially different conceptualization of dialogue, one framed by the more recent practice of post-publication review

Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease with no approved therapies. The ursodeoxycholic acid (UDCA) has been widely used, although there is no evidence that the use of UDCA delays the time to liver transplant or increases survival. Several candidate drugs are currently being developed. The largest group of these new agents is represented by FXR agonists, including obeticholic acid, cilofexor, and tropifexor. Other agents that target bile acid metabolism are ASTB/IBAP inhibitors and fibroblasts growth factor (FGF)19 analogues. Cholangiocytes, the epithelial bile duct cells, play a role in PSC development. Recent studies have revealed that these cells undergo a downregulation of GPBAR1 (TGR5), a bile acid receptor involved in bicarbonate secretion and immune regulation. Additional agents under evaluation are PPARs (elafibranor and seladelpar), anti-itching agents such as MAS-related G-protein–coupled receptors antagonists, and anti-fibrotic and immunosuppressive agents. Drugs targeting gut bacteria and bile acid pathways are also under investigation, given the strong link between PSC and gut microbiota.

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disorder characterized by progressive cholestatic that, if untreated, can progress to liver fibrosis, cirrhosis and liver decompensation requiring liver transplant. Although the pathogenesis of the disease is multifactorial, there is a consensus that individuals with a genetic predisposition develop the disease in the presence of specific environmental triggers. A dysbiosis of intestinal microbiota is increasingly considered among the potential pathogenic factors. Cholangiocytes, the epithelial cells lining the bile ducts, are the main target of a dysregulated immune response, and cholangiocytes senescence has been recognized as a driving mechanism, leading to impaired bile duct function, in disease progression. Bile acids are also recognized as playing an important role, both in disease development and therapy. Thus, while bile acid-based therapies, specifically ursodeoxycholic acid and obeticholic acid, have been the cornerstone of therapy in PBC, novel therapeutic approaches have been developed in recent years. In this review, we will examine published and ongoing clinical trials in PBC, including the recently approved peroxisome-proliferator-activated receptor (PPAR) agonist, elafibranor and seladelpar. These novel second-line therapies are expected to improve therapy in PBC and the development of personalized approaches.

Abstract Background Randomized controlled trials (RCTs) reported contrasting results about reverse left ventricular remodeling (LVR) after sodium-glucose co-transporter-2 inhibitors (SGLT2i) therapy in patients with heart failure (HF). Methods and results We performed a metanalysis of RCTs of SGLT2i administration in HF outpatients published until June 2022 searching four electronic databases. The protocol has been published in PROSPERO. Primary LVR outcome was change in absolute LV end-diastolic (LVEDV) and end-systolic volume (LVESV) from baseline to study endpoint. Secondary outcomes included changes in LVEDV and LVESV indexed to body surface area, LV Mass index (LVMi), LV ejection fraction (LVEF), and N-terminal pro-B-type natriuretic peptide (NTproBNP). Mean differences (MDs) with 95% CIs were pooled. A total of 9 RCTs (1385 patients) were analyzed. All of them reported data on LVEF. Six trials reported data on LVESV and LVEDV (n = 951); LVMi was available in 640. SGLT2i treatment significantly reduced LVEDV [MD= -10.59 ml (-17.27; -3.91), P = 0.0019], LVESV [MD= -8.80 ml (-16.91; -0.694), P = 0.0334], and LVMI [MD= -5.34 gr/m2 (-9.76; -0.922), P = 0.0178], while LVEF significantly increased [MD = + 1.98% (0.67; 0.306), P = 0.0031]. By subgroup analysis, the beneficial effects of SGLT2i on LVEF did not differ by imaging method used, time to follow-up re-evaluation, or HF phenotype. Reduction in LV volumes tended to be greater in HF with reduced EF (HFrEF) than in those with preserved EF (HFpEF), while the opposite was observed for LVMi. Conclusions Treatment with SGLT2i significantly reversed cardiac volumes, improving LV systolic function and LV mass, particularly in HFrEF patients.

Background Patients with nonalcoholic fatty liver disease are at increased risk to develop atherosclerotic cardiovascular diseases. FXR and GPBAR1 are 2 bile acid–activated receptors exploited in the treatment of nonalcoholic fatty liver disease: whether dual GPBAR1/FXR agonists synergize with statins in the treatment of the liver and cardiovascular components of nonalcoholic fatty liver disease is unknown. Methods and Results Investigations of human aortic samples obtained from patients who underwent surgery for aortic aneurysms and Gpbar1−/−, Fxr−/−, and dual Gpbar1−/‐Fxr−/− mice demonstrated that GPBAR1 and FXR are expressed in the aortic wall and regulate endothelial cell/macrophage interactions. The expression of GPBAR1 in the human endothelium correlated with the expression of inflammatory biomarkers. Mice lacking Fxr and Gpbar1−/−/Fxr−/− display hypotension and aortic inflammation, along with altered intestinal permeability that deteriorates with age, and severe dysbiosis, along with dysregulated bile acid synthesis. Vasomotor activities of aortic rings were altered by Gpbar1 and Fxr gene ablation. In apolipoprotein E−/− and wild‐type mice, BAR502, a dual GPBAR1/FXR agonist, alone or in combination with atorvastatin, reduced cholesterol and low‐density lipoprotein plasma levels, mitigated the development of liver steatosis and aortic plaque formation, and shifted the polarization of circulating leukocytes toward an anti‐inflammatory phenotype. BAR502/atorvastatin reversed intestinal dysbiosis and dysregulated bile acid synthesis, promoting a shift of bile acid pool composition toward FXR antagonists and GPBAR1 agonists. Conclusions FXR and GPBAR1 maintain intestinal, liver, and cardiovascular homeostasis, and their therapeutic targeting with a dual GPBAR1/FXR ligand and atorvastatin holds potential in the treatment of liver and cardiovascular components of nonalcoholic fatty liver disease.

Abstract Non-alcoholic steatosis (NAFLD) and steatohepatitis (NASH) are two highly prevalent human disorders for which therapy remains suboptimal. Bile acids are signaling molecules acting on two main receptors the Farnesoid-x-receptor (FXR) and G protein coupled receptor GPB AR1. Clinical trials have shown that FXR agonism might result in side effects along with lack of efficacy in restoring liver histopathology. For these reasons a multi-targets therapy combined FXR agonists with agent targeting additional molecular mechanisms might have improved efficacy over selective FXR agonists. In the present study we have compared the effects of BAR502, a dual FXR/GPBAR1 ligand) alone or in combination with ursodeoxycholic acid (UDCA) in a model of NAFLD/NASH induced by feeding mice with a Western diet for 10 weeks. The results demonstrated that while BAR502 and UDCA partially protected against liver damage caused by Western diet, the combination of the two, reversed the pro-atherogenic lipid profile and completely reversed the histopathology damage, attenuating liver steatosis, ballooning, inflammation and fibrosis. Additionally, while both agents increased insulin sensitivity and bile acid signaling, the combination of the two, modulated up top 85 genes in comparison of mice feed a Western diet, strongly reducing expression of inflammatory markers such as chemokines and cytokines. Additionally, the combination of the two agents redirected the bile acid metabolism toward bile acid species that are GPBAR1 agonist while reduced liver bile acid content and increased fecal excretion. Together, these data, highlight the potential role for a combinatorial therapy based on BAR502 and UDCA in treating of NAFLD.

Abstract To date, the highly adapted cave microbial communities are challenged by the expanding anthropization of these subterranean habitats. Although recent advances in characterizing show-caves microbiome composition and functionality, the anthropic effect on promoting the establishment, or reducing the presence of specific microbial guilds has never been studied in detail. This work aims to investigate the whole microbiome (Fungi, Algae, Bacteria and Archaea) of four Italian show-caves, displaying different environmental and geo-morphological conditions and one recently discovered natural cave to highlight potential human-induced microbial traits alterations. Results indicate how show-caves share common microbial traits in contrast to the natural one; the first are characterized by microorganisms related to outdoor environment and/or capable of exploiting extra inputs of organic matter eventually supplied by tourist flows (i.e. Chaetomium and Phoma for fungi and Pseudomonas for bacteria). Yet, variation in microalgae assemblage composition was reported in show-caves, probably related to the effect of the artificial lighting. This study provides insights into the potential microbiome cave contamination by human-related bacteria (e.g. Lactobacillus and Staphylococcus) and commensal/opportunistic human associated fungi (e.g. Candida) and dermatophytes. This work is critical to untangle caves microbiome towards management and conservation of these fragile ecosystems.

Alternative splicing (AS) appears to be altered in Huntington's disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD). The expanded Htt CAG repeats further reflect on a previously neglected, global impairment of back-splicing, leading to decreased circular RNAs production in neural progenitors. Integrative transcriptomic analyses unveil a network of transcriptionally altered micro-RNAs and RNA-binding proteins (Celf, hnRNPs, Ptbp, Srsf, Upf1, Ythd2) which might influence the AS machinery, primarily in neural cells. We suggest that this unbalanced expression of linear and circular RNAs might alter neural fitness, contributing to HD pathogenesis.

ObjectivesTo explore: (1) self-care behaviors in children and young people (range: 6 months–24 years) with complex chronic conditions, characterized by the diagnosis of a severe chronic condition, substantial family-identified needs, functional limitations associated with technology dependence, and intensive use of healthcare services; (2) the contribution to self-care of family members and other persons involved in the child's health and daily life context (e.g., health professionals and teachers), and (3) the principal factors that might have influenced the self-care process associated with developmental age.MethodsA qualitative descriptive study was conducted in an Italian academic tertiary pediatric hospital between September 2020 and May 2021. Overall, 25 focus groups and 7 online interviews were conducted via videoconferencing. Textual data were analyzed using Emotional Text Mining to identify three levels of communication: the factors, the main themes (clusters), and the sub-themes.ResultsA total of 104 participants were enrolled, including 27 patients with complex chronic conditions (12 males, mean age = 11.1 ± 4.40), 33 parents, 6 siblings, 33 health professionals, and 5 teachers. Participants described the process of self-care through four main factors: “self-care”, “external settings”, “family”, and “management”. Five clusters (themes) were identified: (1) Self-care management (device; consulting); (2) Shift of agency (influencing factors; parents; school); (3) Self-care support (normal life and personal development; multidisciplinary support); (4) Daily self-care maintenance/monitoring; (5) Treatment adherence. Self-care management was mostly relevant for parents of children aged between 6 months and 3 years.ConclusionThe self-care process varies according to the needs related to the specific developmental age and the evolution of the clinical condition over time. The contribution of the family, health professionals, and social networks is fundamental for adequate self-care. To help families manage the unstable condition of their children at home, it is necessary to strengthen support networks implement home care, and ensure continuity of care.

Introduction It is essential to choose a realistic anticipated intervention effect when calculating a sample size for a randomised clinical trial. Unfortunately, anticipated intervention effects are often inflated, when compared with the ‘true’ intervention effects. This is documented for mortality in critical care trials. A similar pattern might exist across different medical specialties. This study aims to estimate the range of observed intervention effects for all-cause mortality in trials included in Cochrane Reviews, within each Cochrane Review Group.Methods and analysis We will include randomised clinical trials assessing all-cause mortality as an outcome. Trials will be identified from Cochrane Reviews published in the Cochrane Database of Systematic Reviews. Cochrane Reviews will be clustered according to the registered Cochrane Review Group (eg, Anaesthesia, Emergency and Critical Care) and the statistical analyses will be conducted for each Cochrane Review Group and overall. The median relative risk and IQR for all-cause mortality and the proportion of trials with a relative all-cause mortality risk within seven different ranges will be reported (relative risk below 0.70, 0.70–0.79, 0.80–0.89, 0.90–1.09, 1.10–1.19, 1.20–1.30 and above 1.30). Subgroup analyses will explore the effects of original design, sample size, risk of bias, disease, intervention type, follow-up length, participating centres, funding type, information size and outcome hierarchy.Ethics and dissemination Since we will use summary data from trials already approved by relevant ethical committees, this study does not require ethical approval. Regardless of our findings, the results will be published in an international peer-reviewed journal.

Abstract We introduce a minimal stochastic lattice model for the column relative humidity (R) in the tropics, which incorporates convective moistening, horizontal transport and subsidence drying. The probability of convection occurring in a location increases with R, based on Tropical Rainfall Measuring Mission observations, providing a positive feedback that could lead to aggregation. We show that the simple model reproduces many aspects of full‐physics cloud resolving model experiments. Depending on model parameter settings and domain size and resolution choices, it can produce both random and aggregated equilibrium states. Clustering occurs more readily with larger domains and coarser resolutions, in agreement with full‐physics models. Using dimensional arguments and fits from empirical data, we derive a dimensionless parameter which we call the aggregation number, Nag, that predicts whether a specific model and experiment setup will result in an aggregated or random state. The parameter includes the moistening feedback strength, the horizontal moisture transport efficiency, the subsidence timescale, the domain size and spatial resolution. Using large ensembles of experiments, we show that the transition between random and aggregated states occurs at a critical value of Nag. We argue that Nag could help to understand the differences in aggregation states between full‐physics, cloud resolving models, which show little consensus about the robustness of self‐organized patterns, whose emergence appears to be sensitive to the model setup, physics and parameterizations.

Drawing inspiration from Denis de Rougemont’s 1936 text Penser avec les mains, Jean-Luc Godard’s most recent film brings together what the Swiss philosopher calls “penser engagé” with his own unique kind of “cinéma engagé.” The Image Book (Le Livre d’image, 2018) starts with three image-gestures that punctuate the film: the cropped close-up of the right hand of Leonardo da Vinci’s St. John The Baptist, French illustrator Joseph Pinchon’s drawing of Bécassine with her upwards pointing left hand, and the hands of the filmmaker joining together spools of film at a Steenbeck editing table. Like many other “late” Godard films, The Image Book is a multilayered assemblage of quotations, sounds, music, art and cinematic references. Yet, unlike some of its predecessors, this film questions the monolithic (Occidental) way of seeing the world, including Godard’s younger self. Combining citations from films, works of art and philosophical texts from the Maghreb and the Middle East, the film offers itself as an exercise in “thinking with one’s hands” that results in the unflinching critique of Orientalism in the twenty-first century as well as an imaginative attempt to reach out to, if not join alongside with, the other.

Abstract This study aimed to describe and compare, at a national level, the measures implemented in the pediatric onco-hematology units and the number of infections among patients and healthcare staff during the first and second wave of the COVID-19 pandemic in Italy. A multicenter, descriptive, online survey was conducted between15th March and 15th April 2020 (T1) and between 1 and 31st January 2021 (T2). All the Italian Pediatric Oncology and Hematology Association (AIEOP) centers were invited to participate in the study. Data of the pre-pandemic, first, and second phase were compared. Thirty-six of the 48 AIEOP centers completed the survey (75%). Several organizational, screening, and swab measures were implemented by AIEOP centers to prevent the SARS-CoV-2 infection among patients and visitors. During the pandemic, there was a significant reduction in the number of onco-hematology inpatient beds (p

Abstract Background Involvement in research activities is complex in pediatric nursing and allied health professionals (AHPs). It is important to understand which individual factors are associated with it to inform policy makers in promoting research. Methods A cross-sectional observational study was conducted to describe the level of participation in research activities over the last ten years of nurses and AHPs working in a tertiary pediatric hospital. A large sample of nurses and AHPs working in an Italian academic tertiary pediatric hospital completed an online self-report questionnaire between June and December 2018. Three multivariate logistic regression analyses were performed to predict participation in research projects, speaking at conferences, and writing scientific articles. Results Overall, data from 921 health professionals were analyzed (response rate = 66%), of which about 21% (n = 196) reported participating in a research project, while 33% (n = 297) had attended a scientific conference as a speaker, and 11% (n = 94) had written at least one scientific paper. Having a Master or a Regional Advanced Course, working as an AHP or a ward manager, as well as regularly reading scientific journals and participation in an internal hospital research group or attendance in a specific course about research in the hospital, significantly predicted participation in research projects, speaking at conferences and writing scientific papers. It is important to foster research interest and competencies among health professionals to improve participation in research projects, speaking at conferences, and writing scientific papers. Conclusions Overall, we found a good level of attendance at conferences as speakers (33%), a moderate level of participation in research (21%), and low levels for writing scientific papers (11%). Our study highlighted the need to support participation in research activities among nurses and AHPs. Policymakers should identify strategies to promote research among nurses and AHPs, such as protected rewarded time for research, specific education, strengthened collaboration with academics, and financial support. Moreover, hospital managers should promote the development of research culture among health professionals, to improve their research competencies and evidence-based practice.

Il tirocinio ha rappresentato a lungo l’elemento costante nella formazione iniziale degli insegnanti di scuola Primaria. Il Corso di Studi in …, a partire dall’Anno Accademico 2020-2021 ha sperimentato e validato un nuovo modello di tirocinio digitale integrato (TDDI), che ha arricchito ulteriormente la formazione dei futuri insegnanti. Nella fase successiva il Corso di Studi ha promosso poi un nuovo modello di accompagnamento indiretto dell’esperienza di stage curricolare, denominato tirocinio indiretto digitale integrato (TIDI) in cui una quota oraria è destinata allo sviluppo di competenze digitali correlate agli specifici standard professionali dei maestri.

When conducting randomised clinical trials, the choice of methodology and statistical analyses will influence the results. If the planned methodology is not of optimal quality and predefined in detail, there is a risk of biased trial results and interpretation. Even though clinical trial methodology is already at a very high standard, there are many trials that deliver biased results due to the implementation of inadequate methodology, poor data quality and erroneous or biased analyses. To increase the internal and external validity of randomised clinical trial results, several international institutions within clinical intervention research have formed The Centre for Statistical and Methodological Excellence (CESAME). Based on international consensus, the CESAME initiative will develop recommendations for the proper methodological planning, conduct and analysis of clinical intervention research. CESAME aims to increase the validity of randomised clinical trial results which will ultimately benefit patients worldwide across medical specialities. The work of CESAME will be performed within 3 closely interconnected pillars: (1) planning randomised clinical trials; (2) conducting randomised clinical trials; and (3) analysing randomised clinical trials.

IntroductionThe leukemia inhibitory factor (LIF), is a cytokine belonging to IL-6 family, whose overexpression correlate with poor prognosis in cancer patients, including pancreatic ductal adenocarcinoma (PDAC). LIF signaling is mediate by its binding to the heterodimeric LIF receptor (LIFR) complex formed by the LIFR receptor and Gp130, leading to JAK1/STAT3 activation. Bile acids are steroid that modulates the expression/activity of membrane and nuclear receptors, including the Farnesoid-X-Receptor (FXR) and G Protein Bile Acid Activated Receptor (GPBAR1).MethodsHerein we have investigated whether ligands to FXR and GPBAR1 modulate LIF/LIFR pathway in PDAC cells and whether these receptors are expressed in human neoplastic tissues. ResultsThe transcriptome analysis of a cohort of PDCA patients revealed that expression of LIF and LIFR is increased in the neoplastic tissue in comparison to paired non-neoplastic tissues. By in vitro assay we found that both primary and secondary bile acids exert a weak antagonistic effect on LIF/LIFR signaling. In contrast, BAR502 a non-bile acid steroidal dual FXR and GPBAR1 ligand, potently inhibits binding of LIF to LIFR with an IC50 of 3.8 µM.DiscussionBAR502 reverses the pattern LIF-induced in a FXR and GPBAR1 independent manner, suggesting a potential role for BAR502 in the treatment of LIFR overexpressing-PDAC.

Questo contributo riguarda la dispersione scolastica in Italia e in Europa. Partendo dall’analisi dei documenti prodotti a livello europeo, si intende ricostruire come si connota l’abbandono scolastico a livello nazionale e internazionale, indagandone le cause, le politiche dirette a contenerlo e l’efficacia delle misure messe in campo per contrastarlo. Successivamente, viene proposta una sintetica rassegna della letteratura dedicata, per meglio comprendere l’evoluzione del fenomeno così recente da non essere ancora del tutto definito e acquisire così una visione dello stato dell’arte.

The gastrointestinal tract (GIT) wet pool size (GITwps) refers to the total amount of wet contents in GIT, which in small ruminants can reach up to 19% of their body weight (BW). This study aimed to develop models to comprehensively predict GITwps in small ruminants using a meta-regression approach. A dataset was created based on 21 studies, comprising 750 individual records of sheep and goats. Various predictor variables, including BW, sex, breed, species, intake level, physiological states, stages and types of pregnancy, dry matter intake, and neutral detergent fiber intake (NDFI), were initially analyzed through simple linear regression. Subsequently, the variables were fitted using natural logarithm transformations, considering the random effect of the study and residual error, employing a supervised forward selection procedure. Overall, no significant relationship between GITwps and BW (p = 0.326) was observed for animals fed a milk-based diet. However, a strong negative linear relationship (p < 0.001) was found for animals on a solid diet, with the level of restriction influencing GITwps only at the intercept. Furthermore, the prediction of GITwps was independent of sex and influenced by species in cases where individuals were fed ad libitum. Pregnant females showed a noticeable reduction in GITwps, which was more pronounced in cases of multiple pregnancies, regardless of species (p < 0.01). The composition of the diet was found to be the primary factor affecting the modulation of GITwps, with NDFI able to override the species effect (p < 0.0001). Overall, this study sheds light on the factors influencing GITwps in small ruminants, providing valuable insights into their digestive processes and nutritional requirements.

The transformations taking place at global and local level widely affect people’s lives and accelerate the urgency to rethink in an organic way the practices and contexts for lifelong learning as a key to the achievement of the 17 Sustainable Development Goals (UN, 2015), through programmes that foster learning in schools, families, and communities. The contribution proposes a reflection on the urgency of rethinking public space as a place of relations and democratic participation, and therefore as a context of continuous quality learning in the perspective of overcoming inequalities in favour of the social and civic redefinition of children and young people as autonomous, empowered and socially active subjects, with important implications in educational practice linked to the territory and local communities. It is considered the Global Network of Learning Cities (UNESCO, 2017) to promote social inclusion, economic growth, public safety, and environmental protection.