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Matteo Bellia, Mariangela Greco, Monia Lunghi, Riccardo Moia, Gianluca Gaidano, Andrea Patriarca Department of Translational Medicine, Division of Hematology, Universita’ del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, 28100, ItalyCorrespondence: Matteo Bellia, Department of Translational Medicine, Division of Hematology, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Via Solaroli 17, Novara, 28100, Italy, Tel +39-346-5988355, Email matteo.bellia@uniupo.itBackground: Jaundice and hyperbilirubinemia are common clinical problems characterized by the presence of bile pigments in the blood and their deposition in body tissues. This clinical condition can be associated with a broad spectrum of potential benign and malignant causes, including hepatic inflammation, biliary obstruction, impaired bilirubin conjugation and bilirubin overproduction Therefore, the hyperbilirubinemia diagnostic work-up sometimes can be highly challenging and its therapeutic management can require a multidisciplinary approach.Case Report: We report on a unique case of life-threatening jaundice and hepatic failure in a 20-year-old female who presented to the emergency room with complaints of fever, constant left abdominal pain and generalized profuse fatigue. A complete and detailed medical history, multiple tests for various infection, radiologic investigations and histological tests were performed in order to clarify the etiology of that rapidly progressive clinical condition. Based on the results, the patient jaundice was caused by an Epstein-Barr virus (EBV) infection and secondary cold agglutinin syndrome. Given the rare and complex diagnosis, multiple clinical specialists were asked to carry out the best patient management.Conclusion: This rare case highlights how challenging the differential diagnosis and treatment of hyperbilirubinemia can be, presenting a unique case of life-threatening multifactorial hepatic failure treated successfully with rituximab.Keywords: jaundice, Epstein-Barr virus infection, secondary cold agglutinin syndrome, rituximab

Abstract We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

Background: Practices to include youth with intellectual and/or developmental disabilities (IDD) are necessary to design and implement research that specifically meets the behavioral health needs of this population. This article describes a protocol for engaging youth with IDD as collaborators in a comparative effectiveness clinical trial using a community-engaged research (CEnR) approach. Methods: Our engagement protocol, guided by the Community Engaged Research (CEnR) Framework, emphasized harm avoidance, accessibility, demonstrated value, capacity bridging and co-learning, shared power and equity in decision-making, accountability and respect, and transparent communication. We involved seven youth with IDD in a Youth Advisory Committee (YAC) and four youth with IDD in a Summer Scholars program, ensuring consistent and structured engagement throughout the study. Results: Youth with IDD maintained high levels of engagement in both the YAC and Summer Scholars Program with 100 % retention across two years. Youth used multiple modalities to provide feedback on aspects of the research project, resulting in study modifications, the co-development of products, and tangible improvements in the accessibility and relevance of the study for youth with IDD. Conclusion: Researchers and clinicians seeking to engage the historically underserved population of disabled youth in clinical trial research can leverage our findings to enhance the accessibility and inclusivity of their studies.

ABSTRACT Introduction MGRS are new rare clinical entities, whose recognition and optimal management is evolving. Methods To implement real‐life data, we retrospectively analysed a multicentre cohort of 60 patients with renal biopsy‐proven MGRS receiving mainly novel treatments (between 2006 and 2021) in eight Italian centres. Based on renal biopsy, patients were divided into two subgroups: AL amyloidosis (70%, n = 42) and other‐MGRS (30%, n = 18). Results Baseline characteristics follow typical manifestations of MGRS disorders in terms of small clonal burden, laboratory and clinical features. More patients with AL amyloidosis had monotypic lambda light‐chain disease, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min and nephrotic proteinuria than other‐MGRS group. The most widely used drug was bortezomib, and about one‐third of patients underwent ASCT. Overall response rate was 86% with no differences in the two subgroups. However, high‐quality hematologic responses ≥very good partial response (VGPR) were greater in AL amyloidosis than in other‐MGRS group (67% vs 28%, p = 0.015). The depth of haematological response influenced renal response, obtained in 32 (59%) of evaluable patients, similarly in the subgroups. Indeed, 75% patients with ≥ VGPR (p = 0.049) and none with stable disease (p ≤ 0.001) obtained a renal response. No association between renal response and histotypes (p = 0.9) or type of first‐line therapy (p = 0.3) was found. At a median follow‐up of 54.4 months (IQR 24.8–102.8), median progression‐free survival (PFS) was 100.1 months (95% CI 34.9–NR), and median overall survival not reached (95% CI 129.8–NR). No significant difference emerged between the two groups in terms of survival outcomes. Achieving ≥ VGPR was confirmed as the main independent predictor of prolonged PFS in the general population (HR = 0.29, p = 0.023) and AL amyloidosis group (HR 0.23; p = 0.023). Preserved renal function at diagnosis was predictive of improved PFS in the AL amyloidosis group (eGFR ≥ 60 mL/min: HR = 0.003; p = 0.018; eGFR 30–60 mL/min: HR = 0.04, p = 0.046). Conclusion Further research is warranted to develop standardised response criteria and treatment strategies to improve MGRS management.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer with an aggressive metastatic phenotype and very poor clinical prognosis. Interestingly, a lower occurrence of PDAC has been described in individuals with severe and long-standing asthma. Here we explored the potential link between PDAC and the glucocorticoid (GC) budesonide, a first-line therapy to treat asthma. Methods We tested the effect of budesonide and the classical GCs on the morphology, proliferation, migration and invasiveness of patient-derived PDAC cells and pancreatic cancer cell lines, using 2D and 3D cultures in vitro. Furthermore, a xenograft model was used to investigate the effect of budesonide on PDAC tumor growth in vivo. Finally, we combined genome-wide transcriptome analysis with genetic and pharmacological approaches to explore the mechanisms underlying budesonide activities in the different environmental conditions. Results We found that in 2D culture settings, high micromolar concentrations of budesonide reduced the mesenchymal invasive/migrating features of PDAC cells, without affecting proliferation or survival. This activity was specific and independent of the Glucocorticoid Receptor (GR). Conversely, in a more physiological 3D environment, low nanomolar concentrations of budesonide strongly reduced PDAC cell proliferation in a GR-dependent manner. Accordingly, we found that budesonide reduced PDAC tumor growth in vivo. Mechanistically, we demonstrated that the 3D environment drives the cells towards a general metabolic reprogramming involving protein, lipid, and energy metabolism (e.g., increased glycolysis dependency). This metabolic change sensitizes PDAC cells to the anti-proliferative effect of budesonide, which instead induces opposite changes (e.g., increased mitochondrial oxidative phosphorylation). Finally, we provide evidence that budesonide inhibits PDAC growth, at least in part, through the tumor suppressor CDKN1C/p57Kip2. Conclusions Collectively, our study reveals that the microenvironment influences the susceptibility of PDAC cells to GCs and provides unprecedented evidence for the anti-proliferative activity of budesonide on PDAC cells in 3D conditions, in vitro and in vivo. Our findings may explain, at least in part, the reason for the lower occurrence of pancreatic cancer in asthmatic patients and suggest a potential suitability of budesonide for clinical trials as a therapeutic approach to fight pancreatic cancer.

Abstract The biology underlying proton minibeam radiation therapy (pMBRT) is not fully understood. Here we aim to elucidate the biological effects of pMBRT using Fourier Transform Infrared Microspectroscopy (FTIRM). In vitro (CTX-TNA2 astrocytes and F98 glioma rat cell lines) and in vivo (healthy and F98-bearing Fischer rats) irradiations were conducted, with conventional proton radiotherapy and pMBRT. FTIRM measurements were performed at ALBA Synchrotron, and multivariate data analysis methods were employed to assess spectral differences between irradiation configurations and doses. For astrocytes, the spectral regions related to proteins and nucleic acids were highly affected by conventional irradiations and the high-dose regions of pMBRT, suggesting important modifications on these biomolecules. For glioma, pMBRT had a great effect on the nucleic acids and carbohydrates. In animals, conventional radiotherapy had a remarkable impact on the proteins and nucleic acids of healthy rats; analysis of tumour regions in glioma-bearing rats suggested major nucleic acid modifications due to pMBRT.

The widespread use of hydrogen as an energy carrier for road transport and industrial applications was indicated as a promising solution for reducing pollutant emissions. The high flammability of this substance and its tendency to permeate and embrittle most structural materials make hydrogen handling and storage inherently challenging. Hence, inspection and maintenance activities are essential to guarantee the components' integrity and fitness for service. However, guidelines for inspecting and maintaining hydrogen refueling stations are still under development. The manufacturer is responsible for indicating the optimal inspection procedures for each facility. The lack of a unified regulatory framework and the limited operational experience with these technologies make human errors a potential cause of undesired events. In this context, the study evaluates the probability of human error during the high-pressure storage system inspection procedures in hydrogen refueling stations. The Petro-HRA methodology has been used to quantify the likelihood of unsafe or inappropriate actions. In addition, a Bayesian Network approach is proposed to investigate the conditional dependencies among human errors and performance shaping factors. The critical analysis of the results allowed the authors to provide recommendations regarding safety procedures that operators can adopt to reduce the likelihood of accidents in the hydrogen industry.

Abstract The global decline in insect biomass has far‐reaching implications for terrestrial and freshwater food webs, impacting species reliant on insects as a crucial component of their diet. This issue extends to species traditionally considered agricultural pests, such as the common cockchafer Melolontha melolontha. In the race to combat cockchafers through collection, insecticide use, and other control methods, the repercussions of their numerical fluctuations on predators, including species of high conservation importance like bats, have been largely overlooked. Drawing on 31‐years of monitoring data for a greater horseshoe bat Rhinolophus ferrumequinum population in the Aosta Valley (Western Italian Alps), we investigated whether annual fluctuations in bat counts are influenced by cockchafer availability and weather conditions. Despite an overall positive trend in bat abundance, we observed pronounced annual fluctuations, mostly driven by cockchafer availability rather than variations in temperature and precipitation. Furthermore, we found a significant association between cockchafer availability and the median date of birth and birth rate of bats. Births occurred approximately 5 days earlier in cockchafer flight years, with earlier births also linked to warmer spring temperatures and higher numbers of warm days in April. Moreover, the ratio pups/older bats was 0.56 in cockchafer flight years, compared to 0.47 in other years. Our results underscore the importance of considering predator–prey dynamics when examining the long‐term population trends of species of conservation concern. We recommend implementing restrictions on the use of chemicals and other potentially harmful practices that may diminish prey abundance or quality, including that of species considered as agricultural pests. In designing conservation strategies, a delicate balance should be struck between the current interests of farmers and the overarching goal of preserving biodiversity against potential future threats.

Este artigo apresenta um balanço da literatura sobre o setor de segurança privada no Brasil, composta por artigos, dissertações e teses das ciências sociais publicadas até o ano de 2020. Nossos objetivos são identificar as vinculações disciplinares e institucionais, os temas estudados e os procedimentos metodológicos dessa literatura. Por pesquisadores(as) de quais das ciências sociais e de quais instituições os estudos sobre esse setor foram desenvolvidos? Quais são os temas abordados nesses estudos e suas delimitações de escopo? Quais suas características metodológicas? Para responder a essas perguntas, realizamos buscas com 11 strings em seis repositórios on-line. 68 estudos foram coletados e analisados por meio de estatística descritiva a partir de variáveis em três dimensões: formal, substantiva e metodológica. Os resultados apontam para um crescimento dos estudos a partir dos anos 2000, uma diversidade temática e a predominância de análises qualitativas.

Introdução: No contexto da formação de nutricionistas, é preciso refletir sobre as relações étnico-raciais e suas interseções com a Segurança Alimentar e Nutricional (SAN) e a Educação Alimentar e Nutricional. Objetivo: Este artigo original visa refletir sobre a formação de nutricionistas no que concerne à problemática das desigualdades raciais, à luz da experiência da disciplina de Educação Alimentar e Nutricional 2 de um curso de Nutrição de instituição pública de ensino superior no Norte Fluminense. Método: A investigação qualitativa envolveu observação participante, análise documental e sistematização de experiência. Resultados: A reflexão em classe sobre a realidade vivenciada, à luz de referenciais teóricos que tratam das relações étnico-raciais e de SAN, possibilitou problematizar como o racismo institucional compromete a realização do Direito Humano à Alimentação Adequada da população negra. As experiências proporcionaram a reflexão crítica sobre o processo de desumanização gerado pelo racismo, que fomenta a negação de direitos fundamentais à população negra, incluindo o direito à alimentação. O tema das desigualdades étnico-raciais se tornou mais presente nos trabalhos finais da disciplina, em trabalhos de conclusão de curso, artigos e resumos apresentados em congressos científicos e acadêmicos. Conclusão: Apesar das estruturas de poder que operam no campo do conhecimento acadêmico e silenciam epistemologias e cosmovisões outras, a disciplina analisada conseguiu adotar propostas criativas sobre as relações étnico-raciais. A Educação Popular fomentou a capacidade de reflexão crítica dos educandos sobre as desigualdades raciais que permeiam a SAN.

Background Nursing is pivotal to healthcare delivery but is often associated with high levels of organizational stress. In this cross-sectional study, we aimed to investigate the associations between exposure to organizational stressors, measured using the Health and Safety Executive Management Standards Indicator Tool, and psychosomatic complaints among nurses in a medium-sized city hospital in northeastern Italy. Methods A total of 215 nurses participated in the study, completing self-report questionnaires assessing organizational stressors and the prevalence of psychosomatic complaints experienced over the preceding six months. Results Significant associations were observed between various organizational stressors and psychosomatic complaints among nurses. Specifically, the Relationships factor emerged as a significant predictor of palpitations, irritability, anxiety, physical and mental tiredness, and headache. Additionally, Demands and Managers' support were identified as significant predictors of specific psychosomatic complaints. Conclusion This study highlights the critical role of addressing organizational stressors, particularly those related to interpersonal relationships, in promoting nurse well-being and optimizing patient care delivery. Despite its strengths, including the use of a well-established measurement tool and a comprehensive assessment of psychosomatic complaints, limitations such as the cross-sectional design and self-report measures warrant consideration. By prioritizing supportive work environments and implementing targeted interventions, healthcare organizations can cultivate a culture of well-being among nurses, ultimately enhancing the quality and safety of healthcare delivery.

Hyperspectral imagery and advanced classification techniques can significantly enhance remote sensing’s role in forest monitoring. Thanks to recent missions, such as the Italian Space Agency’s PRISMA (PRecursore IperSpettrale della Missione Applicativa—Hyperspectral PRecursor of the Application Mission), hyperspectral data in narrow bands spanning visible/near infrared to shortwave infrared are now available. In this study, hyperspectral data from PRISMA were used with the aim of testing the applicability of PRISMA with different band sizes to classify tree species in highly biodiverse forest environments. The Serre Regional Park in southern Italy was used as a case study. The classification focused on forest category classes based on the predominant tree species in sample plots. Ground truth data were collected using a global positioning system together with a smartphone application to test its contribution to facilitating field data collection. The final result, measured on a test dataset, showed an F1 greater than 0.75 for four classes: fir (0.81), pine (0.77), beech (0.90), and holm oak (0.82). Beech forests showed the highest accuracy (0.92), while chestnut forests (0.68) and a mixed class of hygrophilous species (0.69) showed lower accuracy. These results demonstrate the potential of hyperspectral spaceborne data for identifying trends in spectral signatures for forest tree classification.

Toxoplasmosis is a neglected disease that represents a significant public health problem. The antigenic profile of T. gondii is complex, and the immune response can lead to either susceptibility or resistance. Some antigens, such as surface antigen glycoprotein (SAG), are expressed on the surface of tachyzoite stages and interact with the host immune cells. In this study, we investigated the potential of the recombinant SAG2A protein of T. gondii to control parasitism and modulate the immune response in the peritoneal exudate cells (PECs) of both susceptible (C57BL/6) and resistant (BALB/c) mice using an in vitro infection model, gene expression, proteomic analysis, and bioinformatic tools. Our results showed that rSAG2A-treated PECs presented a lower parasitism in C57BL/6 mice but not in the PECs from BALB/c mice, and induced a pro-inflammatory cytokine profile in C57BL/6 mice (iNOS, TNF-α, and IL-6). rSAG2A modulated different exclusive proteins in each mouse lineage, with PECs from the C57BL/6 mice being more sensitive to modulation by rSAG2A. Additionally, biological processes crucial to parasite survival and immune response were modulated by rSAG2A in the C57BL/6 PECs, including fatty acid beta-oxidation, reactive oxygen species metabolism, interferon production, and cytokine-mediated signaling pathways. Together, our study indicates that rSAG2A controls T. gondii parasitism in susceptible C57BL/6 PECs through the modulation of pro-inflammatory cytokines and enhanced expression of proteins involved in the cytotoxic response.