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Abstract Background The growing diffusion of artificial intelligence, data science and digital health has highlighted the role of collection of data and biological samples, thus raising legal and ethical concerns regarding its use and dissemination. Further, the expansion of biobanking, from the basic collection of frozen specimens to the virtual biobanks of specimens and associated data that exist today, has given a revolutionary potential on healthcare systems, particularly in the field of neurological diseases, due to the inaccessibility of central nervous system and the need of non-invasive investigation approaches. Informed Consent (IC) is considered mandatory in all research studies and specimen collections, and must specifically take into account the ethical respect to the individuals to whom the used biological material and data belong. Methods We evaluated the attitudes of patients with neurological diseases (NP) and healthy volunteers (HV) towards the donation of biological samples to a biobank for future research studies on neurological diseases, and limitations on the use of data, related to the requirements set by the General Data Protection Regulation (GDPR). The study involved a total of 1454 subjects, including 502 HVs and 952 NPs, recruited at Santa Lucia Foundation IRCCS, Rome, from 2020 to 2024. Results We found that (i) almost all subjects agreed with the participation in biobanking (ii) and authorization to genetic studies (HV = 99.1%; NP = 98.3%); Regarding the return of results, (iii) we found a statistically significant difference between NP and HV, the latter preferring not to be informed of potential results (HV = 43%; NP = 11.3%; p

Abstract Climate change poses significant challenges to agricultural systems in the Mediterranean region, with Italy being significantly affected. This literature scoping review aims to examine existing research on the impact of climate change on yield and income on the three agri-food value chains in Italy: viticulture, fruit and vegetables, and dairy cattle. By analysing the available literature, this study seeks to outline the pros and cons, knowledge gaps, and potential areas for future research. A systematic search of scientific databases was conducted to identify relevant articles published between 2000 and 2022. The search terms included climate change, agriculture, Italy, yield, income, and related keywords. Articles were screened based on predetermined inclusion and exclusion criteria, resulting in a final selection of studies. Quantitative information was collected and organized into descriptive tables. The review encompassed 44 studies that investigated the impact of climate change on yield and income in various agricultural sectors across different regions of Italy. The findings indicate that climate change is already impacting crop productivity and income levels, with increased temperature, changes in precipitation patterns, and extreme weather events being identified as the primary drivers. Additionally, disparities were observed between different agricultural regions, crops, and farming systems, highlighting the need for location-specific and crop-specific assessments. The scoping review provides a prospective overview of the existing literature on climate change impacts on yield and income within the Italian agriculture system. It underscores the urgency for targeted adaptation strategies to minimize the negative consequences of climate change. Further research should focus on understanding the complex interactions between climate change, agricultural practices, socio-economic factors, and policy interventions to develop context-specific solutions for sustainable agriculture in Italy. Graphical abstract

Abstract Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p

Abstract Extravasation is a fundamental step in the metastatic journey, where cancer cells exit the bloodstream and breach the endothelial cell barrier to infiltrate target tissues. The tactics cancer cells employ are sophisticated, closely reflecting those used by the immune system for tissue surveillance. Remarkably, tumor cells have been observed to form distinct associations or clusters with immune cells where neutrophils stand out as particularly crucial partners. These interactions are not accidental; they are critical for cancer cells to exploit the immune functions of neutrophils and successfully extravasate. In another strategy, tumor cells mimic the behavior and characteristics of immune cells. They release a suite of inflammatory mediators, which under normal circumstances, guide the processes of endothelium reshaping and facilitate the entry and movement of immune cells within tissues. In this review, we offer a new perspective on the tactics employed by cancer cells to extravasate and infiltrate target tissues. We delve into the myriad mechanisms that tumor cells borrow, adapt, and refine from the immune playbook. Video Abstract

Abstract Background Secondary central nervous system lymphoma (SCNSL) is a known complication of immunocompromised patients with most cases involving the brain parenchyma. Reports of cauda equina syndrome (CES) caused by SCNSL are exceedingly scarce as involvement of this anatomical region is extremely uncommon. Case presentation We report a case of a 46-years-old, African, female patient with human immunodeficiency virus (HIV) who developed CES in the context of SCNSL. There were no blasts present in the peripheral blood smear. We provide a review of the literature, discussion of the clinical evolution of this patient and the radiological/histopathological findings. The patient ultimately responded well to induction chemotherapy and high dose methotrexate. Conclusion This case report demonstrates that CES, while a rare occurrence in this clinical context, should be considered in at-risk patients especially those presenting with abnormal neurological findings. Prompt recognition may prevent permanent neurological injury and obviate the need for more invasive therapeutic interventions.

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids’ serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients and healthy subjects with (GBA-HC) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn and Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-HC and HC were also considered. Clinical assessment included the Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with the triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-HC (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p < 0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p < 0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-dihydroprogesterone. Allopregnanolone was the only neurosteroid significantly lower (p < 0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

Group VI transition metal chalcogenides are the subject of increasing research interest for various electrochemical applications such as low-temperature water electrolysis, batteries, and supercapacitors due to their high activity, chemical stability, and the strong correlation between structure and electrochemical properties. Particularly appealing is their utilization as electrocatalysts for the synthesis of energy vectors and value-added chemicals such as C-based chemicals from the CO2 reduction reaction (CO2R) or ammonia from the nitrogen fixation reaction (NRR). This review discusses the role of structural and electronic properties of transition metal chalcogenides in enhancing selectivity and activity toward these two key reduction reactions. First, we discuss the morphological and electronic structure of these compounds, outlining design strategies to control and fine-tune them. Then, we discuss the role of the active sites and the strategies developed to enhance the activity of transition metal chalcogenide-based catalysts in the framework of CO2R and NRR against the parasitic hydrogen evolution reaction (HER); leveraging on the design rules applied for HER applications, we discuss their future perspective for the applications in CO2R and NRR. For these two reactions, we comprehensively review recent progress in unveiling reaction mechanisms at different sites and the most effective strategies for fabricating catalysts that, by exploiting the structural and electronic peculiarities of transition metal chalcogenides, can outperform many metallic compounds. Transition metal chalcogenides outperform state-of-the-art catalysts for CO2 to CO reduction in ionic liquids due to the favorable CO2 adsorption on the metal edge sites, whereas the basal sites, due to their conformation, represent an appealing design space for reduction of CO2 to complex carbon products. For the NRR instead, the resemblance of transition metal chalcogenides to the active centers of nitrogenase enzymes represents a powerful nature-mimicking approach for the design of catalysts with enhanced performance, although strategies to hinder the HER must be integrated in the catalytic architecture.

Abstract Background Allgrove disease is a rare genetic syndrome characterized by adrenal insufficiency, alacrimia, achalasia and complex neurological involvement. Allgrove disease is due to recessive mutations in the AAAS gene, which encodes for the nucleoporin Aladin, implicated in the nucleocytoplasmic transport. The adrenal insufficiency has been suggested to rely on adrenal gland-ACTH resistance. However, the link between the molecular pathology affecting the nucleoporin Aladin and the glucocorticoid deficiency is still unknown. Results By analyzing postmortem patient’s adrenal gland, we identified a downregulation of Aladin transcript and protein. We found a downregulation of Scavenger receptor class B-1 (SCARB1), a key component of the steroidogenic pathway, and SCARB1 regulatory miRNAs (mir125a, mir455) in patient’s tissues. With the hypothesis of an impairment in the nucleocytoplasmic transport of the SCARB1 transcription enhancer cyclic AMP-dependent protein kinase (PKA), we detected a reduction of nuclear Phospho-PKA and a cytoplasmic mislocalization in patient’s samples. Conclusions These results shed a light on the possible mechanisms linking ACTH resistance, SCARB1 impairment, and defective nucleocytoplasmic transport.

Abstract This review examines the role of defective carbon‐based electrodes in sodium‐ion and vanadium flow batteries. Methods for introducing defects into carbon structures are explored and their effectiveness in improving electrode performance is demonstrated. In sodium‐based systems, research focuses primarily on various precursor materials and heteroatom doping to optimise hard carbon electrodes. Defect engineering increases interlayer spacing, porosity, and changes the surface chemistry, which improves sodium intercalation and reversible capacities. Heteroatom functionalisation and surface modification affect solid electrolyte interface formation and coulombic efficiencies. For flow batteries, post‐fabrication electrode enhancement methods produce defects to improve electrode kinetics, although these methods often introduce oxygen functional groups as well, making isolation of defect effects difficult. Continued research efforts are key to developing carbon‐based electrodes that can meet the unique challenges of future battery systems.

An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far.To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers.These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.

Abstract Gaucher Disease (GD), the most common lysosomal disorder, arises from mutations in the GBA1 gene and is characterized by a wide spectrum of phenotypes, ranging from mild hematological and visceral involvement to severe neurological disease. Neuronopathic patients display dramatic neuronal loss and increased neuroinflammation, whose molecular basis are still unclear. Using a combination of Drosophila dGBA1b loss-of-function models and GD patient-derived iPSCs differentiated towards neuronal precursors and mature neurons we showed that different GD- tissues and neuronal cells display an impairment of growth mechanisms with an increased cell death and reduced proliferation. These phenotypes are coupled with the downregulation of several Hippo transcriptional targets, mainly involved in cells and tissue growth, and YAP exclusion from nuclei. Interestingly, Hippo knock-down in the GBA-KO flies rescues the proliferative defect, suggesting that targeting the Hippo pathway can be a promising therapeutic approach to neuronopathic GD.

Chronic lymphocytic leukemia (CLL) is a widespread type of leukemia that predominantly targets B lymphocytes, undermining the balance between cell proliferation and apoptosis. In healthy B cells, miR-15/16, a tandem of microRNAs, functions as a tumor suppressor, curbing the expression of the antiapoptotic B cell lymphoma 2 protein (Bcl-2). Conversely, in CLL patients, a recurring deletion on chromosome 13q14, home to the miR15-a and miR16-1 genes, results in Bcl-2 overexpression, thereby fostering the onset of the pathology. In the present research, a novel approach utilizing humanized ferritin-based nanoparticles was employed to successfully deliver miR15-a and miR-16-1 into MEG01 cells, a model characterized by the classic CLL deletion and overexpression of the human ferritin receptor (TfR1). The loaded miR15-a and miR16-1, housed within modified HumAfFt, were efficiently internalized via the MEG01 cells and properly directed into the cytoplasm. Impressively, the concurrent application of miR15-a and miR16-1 demonstrated a robust capacity to induce apoptosis through the reduction in Bcl-2 expression levels. This technology, employing RNA-loaded ferritin nanoparticles, hints at promising directions in the battle against CLL, bridging the substantial gap left by traditional transfection agents and indicating a pathway that may offer hope for more effective treatments.

The Water-ecosystems-food Nexus is a powerful framework developed for analyzing complex interlinkages among natural resource domains and overcoming "siloed" management practices. Multi-actor participatory approaches are increasingly recognized in Nexus research as the most effective way to identify trade-off solutions between divergent interests. Despite this acknowledged potential, the active engagement of stakeholders for the co-creation of knowledge is still limited to date, missing the opportunity for innovation processes and policy designs to be grounded in context-specific knowledge and experiences. This paper outlines the methodological framework developed to integrate stakeholder analysis and participatory tools for exploring Nexus challenges in a pilot area in Tarquinia, Italy, where a multi-stakeholder group was set up encompassing several categories at different levels, from policymakers and authorities to farmers and other end users. Systematic methodologies to target, analyze, and actively engage stakeholders were applied and multi-domain participatory tools were developed, i.e., stakeholder analysis and mapping, learning and action alliance, participatory system dynamic modelling, which broaden the agreement on potential locally-tailored solutions for sustainable farming practices and integrated management of natural resources. Mutual learning activities, tapping into actors' deep understanding of specific local dynamics, served to better frame the complexity of the Nexus and build a common understanding of local societal challenges as well as of potential innovations in farming practices, land, and water management. The methodological innovation of integrating stakeholder mapping and analysis with relevant spatial information from participatory activities, provides the fundamental baseline for spatially explicit scenario analysis in the area, ultimately increasing the relevance and transferability of the Nexus findings.