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Glutathione (GSH), a tripeptide essential for maintaining redox balance in the human body, plays a critical role in protecting cells from oxidative stress. A deficiency in GSH is linked to increased oxidative damage and the progression of various disorders, including cancer and neurological diseases. Herein, gold nanoparticles (Au NPs) coated with GSH and further functionalized with galactose moieties are developed to selectively target glucose transporters (GLUT), which is overexpressed on the surface of the blood‐brain barrier (BBB) and could be exploited for the selective recognition and internalization of the Au@GSH‐Gal NPs, that could then exert an antioxidant effect. As a proof of concept, brain cancer cells are treated with Au@GSH‐Gal NPs, evidencing their increased internalization and a significant reduction of H2O2‐induced oxidative stress.

Recent studies highlighted the potential role of Red cell distribution width (RDW) as a prognostic biomarker in oncology. RDW has been associated with systemic inflammation, a key factor in cancer progression. While clinical trials and cohort studies suggest a correlation between RDW alterations and poor prognosis, its specific role in patients undergoing Immune Checkpoint Inhibitor (ICI) therapy remains unclear. This study aims to explore the potential relationship between RDW alterations and treatment outcomes in patients treated with PD-1 inhibitors using pharmacovigilance data from Eudra Vigilance (EV). We retrieved Individual Case Safety Reports from EV database, reporting pembrolizumab or nivolumab as suspected drug (January 2015 to March 2025). The Reporting Odds Ratio (ROR) with its 95% of Confidence Interval (95% CI) was computed to assess if drugs of interest have a lower/higher probability of reporting adverse events (AEs) belonging to the System Organ Class “Investigation”. Of 12,289 ICSRs, 6981 (56.8%) involved pembrolizumab and 5308 (43.2%) nivolumab. Most ICSRs referred to male patients aged 18–64. Pembrolizumab showed higher reporting probability of “Platelet count decreased” (ROR 2.41, 95% CI 2.14–2.72), “Neutrophil count decreased” (ROR 1.55, 95% CI 1.34–1.80), “White blood cell count decreased” (ROR 1.50, 95% CI 1.26–1.78), “Blood creatinine increased” (ROR 1.19, 95% CI 1.01–1.42), “C-reactive protein increased” (ROR 1.28, 95% CI 1.07–1.53) compared to nivolumab. This study provides new insights into the potential prognostic value of RDW in patients treated with ICIs. These results warrant further investigations to determine its utility in monitoring ICI therapy.

Purpose Meniscal extrusion alters joint biomechanics and accelerates cartilage degeneration, contributing to the progression of knee osteoarthritis (OA). Meniscal centralization techniques aim to reposition the meniscus, addressing extrusion and restoring load distribution. This systematic review aims to evaluate meniscal centralization's clinical and radiological outcomes, hypothesizing its efficacy in treating symptomatic meniscal extrusion with minimal complications. Methods This review followed Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines and was registered with PROSPERO (CRD42023484353). Literature searches were conducted in PubMed, Science Direct and Scopus. Studies reporting clinical and/or radiological outcomes of meniscal centralization with ≥24 months of follow‐up were included. Data on demographics, surgical techniques, patient‐reported outcome measures (PROMs), imaging findings and complications were extracted. Methodological quality was assessed using the ROBINS‐I tool, and heterogeneity was evaluated via the I² statistic. Results Four studies (113 patients, mean follow‐up: 24–35 months) met inclusion criteria. Arthroscopic meniscal centralization with suture anchors significantly improved PROMs, including International Knee Documentation Committee (IKDC), Lysholm and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores, demonstrating symptom relief and functional recovery. Lysholm scores improved from 46.0 to 96.5, KOOS pain from 47.4 to 88.9, and IKDC from 51.8 to 75.8 (p < 0.05 for all). Imaging showed reduced meniscal extrusion and improved joint space width. Complications were minimal, though one study reported a 26.9% failure rate due to incomplete healing and OA progression. Rehabilitation protocols allowed return to full activity within 4–6 months. Conclusions Meniscal centralization effectively reduces extrusion, improves clinical outcomes, and restores knee function with minimal complications. However, further long‐term and comparative studies are needed to validate these findings and refine surgical indications. Level of Evidence Level IV.

Background HDV depends on HBsAg for its infectivity. HBsAg can derive from cccDNA and also from the integration of the so-called linear HBV-DNA in the genome of infected hepatocytes. Here, we elucidate the contribution of HBsAg production from linear HBV-DNA integration in sustaining HDV activity and its pathogenetic potential. Material and Methods 70 liver biopsies from eAg-negative individuals (74% NUC-treated) were included: 35 with CHB and 35 with CHD. Droplet-digital PCR was used to quantify intrahepatic levels of cccDNA, pgRNA, HDV-RNA and HBs transcripts from cccDNA and from integrated HBV-DNA (Grudda, 2022). Next-generation sequencing by Illumina was applied to assess the integration of linear HBV-DNA in hepatocytes’ genome (in 22 CHB and 32 CHD). Results Individuals with CHD and CHB had comparable age and NUC-treatment duration. CHD was characterized by lower cccDNA and pgRNA than CHB (median [IQR]: 1 [0.02–12] vs 24 [8–93] copies (cps)/1000 cells and 8 [1–147] vs 518 [57–3,894] cps/1000cells, P<0.0001 for both). In CHD, no correlation was observed between cccDNA and intrahepatic HDV-RNA, supporting that HDV replicative activity is not strictly related to the extent of HBV reservoir.At least 1 event of linear HBV-DNA integration was observed in 100% and 78.1% (25/32) of individuals with CHB and CHD (total number of unique HBV-integration events: 847 in CHB and 427 in CHD). Furthermore, in both CHB and CHD, a comparable production of HBs transcripts was observed, with >99% of them from integrated HBV-DNA (median [IQR] cps/1000cells: 12,776 [4,570–55,977] in CHB and 6,041 [323–29,446] in CHD). Among the 427 HBV-integration events observed in CHD, 180 involved coding regions of the hepatocytes’ genome, corresponding to a median (IQR) number of 5 (2–10) unique events per patient. Notably, the number of HBV-integration events in coding regions showed a positive correlation with the amount of integration-derived HBsAg transcripts and with serum HBsAg (Rho=0.54 and 0.64, P<0.01 for both). Even more, HBV-integration events were significantly more frequent in individuals with CHD characterized by higher serum HBsAg levels (median [IQR] number of unique HBV-integration events: 10 [7–16] in people with vs 2 [1–7] in people without serum HBsAg >4 logIU/ml; P=0.01). In 19/25 individuals with CHD characterized by >1 HBV-integration event, HBV-DNA integrants localised in human genes regulating cell proliferation. Among the 60 genes identified, 40 genes are already known to be specifically involved in hepatocarcinogenesis. Conclusions HDV persistence is independent from the intrahepatic HBV reservoir and is sustained by HBsAg production from integrated HBV-DNA. Higher HBsAg levels (>4logIU/ml) can reflect an enrichment of HBV-DNA integration events in coding regions of hepatocytes’ genome.Localization of HBV integrants suggests that these events may potentially induce hepatocytes proliferation, paving the way for carcinogenesis.

Background Limited information is available on the extent of HDV genetic diversification in ribozyme (critical for HDV replication) and HDAg domains (crucial for viral morphogenesis and containing cytotoxic T lymphocytes epitopes [CTLE]) and their correlation with virological and biochemical parameters. Methods 103 individuals with chronic HDV infection were included. Full-length HDV genome sequences were obtained by Illumina (median [IQR] reads/seq: 62045[30460–91899]). Sub-genotypes 1 were defined by phylogenetic analysis. Amino acid (aa) residues were defined conserved if not mutated in 99% of sequences. HDAg domains and CTLE (N=18) were defined according to Pascarella 2010 and Kohsar 2021. Results Individuals were mostly males with a median age of 54 (44–60) years, mainly from Eastern Europe (EE,51%) and Italy (IT,44.8%). Serum HDV-RNA and ALT were 5.6 (4.9–6.2)logIU/ml and 94 (65–152)U/L. Sub-genotypes 1c and 1e were the most prevalent (47.1% and 45.2%): 1c predominated in individuals from EE(77.6% vs 22.4%,P<0.001) while 1e in IT(77.5% vs 22.5%,P<0.001).HDV ribozyme was characterised by a high degree of genetic conservation. An opposite scenario was observed for HDAg in which the number of conserved aa in HDAg dropped to 36.7% (79/214), with 18.2% in coiled coil sequence (CCS), 27.3% RNA binding domain (RDB)2, 30.8% in RBD1, 33.3% in nuclear localization sequence (NLS), 40% in virus assembly signal (VAS) and 63.3% in RBD3. The degree of genetic conservation of CTLEs ranges from 11.1% in CTLEs 46–54 and 43–51 to 60.0% in 140–149. Notably, CTLE 170–179 from individuals with HDV-RNA >5logIU/ml (70% of conserved aa with vs 20% without HDV-RNA <5 logIU/ml, P=0.025) showed lower genetic conservation, suggesting that an enrichment of mutations in this CTLE can enhance viral replication. Finally, despite a comparable degree of genetic conservation between sub-genotypes 1e and 1c, they were characterized by divergent genetic pathways. In particular, sub-genotype 1c was significantly associated with the selection of 7 specific mutations (I16T/V, N22S, D47E, R112K, T180A, A202S, prevalence ranging from 26.5% to 44.9% vs 0% in 1e, P<0.001). Conversely, sub-genotype 1e was significantly associated with the selection of 6 specific mutations (D29E, D46E, K113R, R131K, M171L, I188V prevalence ranging from 23.9% to 43.5% vs 0% in 1c, P<0.009). Notably, in sub-genotype 1c, the co-presence of I16V/T+D47E+A202S correlated with ALT>3ULN (100% vs 27.5%, P=0.001) Conclusion Sub-genotypes 1 are characterized by a conspicuous degree of genetic diversification in HDAg that has contributed to the selection of divergent genetic signatures. The enrichment of mutations in specific CTL epitopes could potentially hamper HDV recognition by immune response and in turn enhancing viral replication.Overall, the role of the high degree of genetic variability in affecting the proper HDV detection by the currently available diagnostic assays deserves further investigation.

Background HIV infection is often associated with hepatitis D virus (HDV) in HBsAg-positive individuals due to shared transmission routes, such as injection drug use (IDU) and unprotected sex. However, most available data come from historical cohorts of people with HIV (PWH), and recent trends in HDV prevalence and epidemiological characteristics among HBsAg-positive PWH compared to HIV-negative individuals remain unclear. Materials and Methods We conducted two cross-sectional analyses assessing HDV prevalence and epidemiological characteristics among HBsAg-positive PWH tested for anti-HDV in the ICONA cohort in 2009–2012 (n=257) and 2019–2023 (n=289). These data were compared with two cohorts of HIV-negative HBsAg-positive individuals: MASTER (n=1938, enrolled in 2009–2012) and PITER (n=3813, enrolled in 2019–2023). Descriptive statistics were used to compare continuous and categorical variables. Results In 2009–2012, anti-HDV prevalence was 19% in ICONA vs. 8.3% in MASTER (p<0.01). Among PWH, 20.0% reported IDU. Compared to HIV-negative individuals, HBsAg/anti-HDV-positive PWH had a similar median age (48 vs. 47 years), but a higher proportion of males (89.8% vs. 64.6%) and Italians (89.8% vs. 63.4%). HBeAg prevalence was higher in PWH (23.5% vs. 14.4%), as was HCVAb positivity (67.3% vs. 19.7%) and NUC therapy use (85.7% vs. 26.7%). The proportion of patients with FIB-4 > 3.25 was similar (35.4% vs. 34.2%, p=0.928) [table 1].In 2019–2023, anti-HDV prevalence was 12.5% in ICONA and 11.8% in PITER (p=0.729). The proportion of IDU among PWH decreased to 11.8%. Demographic and clinical differences between HIV-positive and HIV-negative individuals remained similar. The proportion of patients with FIB-4 > 3.25 was lower in PWH (20.0% vs. 42.0%, p<0.01) [table 2]. View this table: • View inline • View popup • Download powerpoint Abstract P78 Table 1 Demographic and clinical characteristics of HDVAb pos individuals in period 2009–2012 View this table: • View inline • View popup • Download powerpoint Abstract P78 Table 2 Demographic and clinical characteristics of HDVAb pos individuals in period 2019–2023 Conclusion Over time, anti-HDV prevalence among HBsAg-positive PWH has declined, now aligning with HIV-negative individuals. The reduction in IDU among PWH may have contributed to the decreasing prevalence of HDV.Although the cross-sectional design prevents establishing causality between HIV co-infection and liver disease severity, factors such as competing mortality and cirrhosis progression in PWH observed in 2009–2012, may have influenced the differences in liver disease severity over time.

This study examines the effect of green human resource management practices on organizational sustainable development, while analyzing the mediating role of the circular economy and the moderating effect of green organizational culture within this mediated relationship based on resource‐based view. Data were gathered from a sample of 326 banking sector employees using convenience sampling, and the presented hypotheses were evaluated using partial least squares structural equation modeling (PLS‐SEM). The findings indicate that green human resource management methods have a considerable and positive impact on both organizational sustainable development and the circular economy. Moreover, the circular economy was identified as a mediator in the interaction between green human resource management practices and organizational sustainable development, underscoring its essential function as a facilitator of sustainable transformation. This mediated association was further reinforced by green organizational culture, underscoring the significance of environmentally conscious attitudes in augmenting the efficacy of green human resource management practices. This study provides a novel viewpoint on the interplay between intangible organizational resources and cultural dynamics in promoting sustainability by incorporating the circular economy and green organizational culture, thereby enhancing the resource‐based view framework. The findings enhance the theoretical framework of resource‐based view literature and provide practical guidance for managers seeking to integrate sustainability into human resource practices.

The search for novel therapeutic agents has led to increasing interest in natural products, driven by the recognition that they may offer safer and more sustainable alternatives to synthetic drugs. This study aims to fill the gap in knowledge regarding the biological activity and safety of the water extract of chestnut (Castanea mollissima) (chestnut), a plant species with a long history of use in traditional medicine, by conducting a comprehensive evaluation of its antioxidant, antidiabetic, and neuroprotective properties. This study presents a comprehensive analysis of the water extract of chestnut for the first time using various bioanalytical antioxidant methods. The extract's inhibitory effects on key enzymes like acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α‐glycosidase were evaluated due to their relevance in metabolic and neurodegenerative disorders such as diabetes and Alzheimer's disease. Developmental toxicity and cytotoxicity were assessed using zebrafish (Danio rerio) embryos to evaluate the extract's biological safety. The major phenolic compounds present in the extract were identified by liquid chromatography‐electrospray ionization tandem mass spectrometry (LC‐ESI‐MS/MS), revealing catechin, gallic acid, taxifolin, and epicatechin as the predominant constituents. Antioxidant capacity was determined through radical scavenging assays using 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH•) and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS•+), alongside ferric (Fe³⁺), cupric (Cu²⁺), and Fe³⁺‐TPTZ (ferric‐tripyridyltriazine) reducing power assays. The findings highlight the significant antioxidant, antidiabetic, and neuroprotective potential of the chestnut water extract, supporting its prospective use in pharmaceutical and nutraceutical applications.

Introduction This study explores the complexities and distinctive traits of end-of-life (EOL) care and assisted suicide in cancer patients across Europe, and the challenges they entail. It analyzes various countries in the Southern, Central, and Northern regions. Legal, ethical, and cultural dimensions of euthanasia are examined. Differences in practices across Europe are highlighted. Materials and methods The aim of this study is to provide an overview of EOL care policies in Europe by delving into the legislative/policy-making approaches of three selected nations, and implications thereof. Results Disparities between regions are identified, to figure out margins for improvement. This includes advocating for a balanced approach that both upholds legal frameworks and respects patient autonomy. By doing so, the ultimate objective is to foster a culture of ethical and empathetic EOL care for cancer patients throughout Europe, ensuring that their needs and preferences are prioritized till the end. Advocacy for a balanced approach is recommended. Conclusion Ultimately, the findings herein presented point to the need for a collaborative effort among policymakers, healthcare providers, and communities to build a more holistic approach to end-of-life care that harmonizes legal regulations with the ethical imperative of respecting individual choice in an environment marked by sensitivity and compassion.

Cancer early detection is one of the most challenging purposes of preventive medicine. Liquid biopsy represents a revolutionary approach, fostering access to early screening and increasing patients’ compliance, two crucial issues in reaching the largest possible audience in prevention campaigns. To facilitate this approach, the deployment of innovative methods for easy manipulation of biological fluids and the availability of devices for the rapid and low-cost detection of biomarkers is essential. The aim of this study was the optimization of multifunctional Lab-On-Chips with the final aim of realizing a platform for oral carcinoma cells trapping from a complex biological fluid as saliva and for specific subcellular components like extracellular vesicles (EVs) from the neuroblastoma cell model. A set of different microfluidic building blocks was realized through poly-methyl methacrylate (PMMA) micromilling, microfabricated and functionalized to optimize surface chemistry for capturing tumor cells or EVs in multiple channels, assess working concentration for biological fluids and combine sample preparation with detection modules all in the same chip. After optimization, a proof-of-concept device was realized mimicking liquid biopsy analysis from saliva, a biological fluid readily available and with a high compliance from patients, useful for the early diagnosis of cancer.

Terminal deoxynucleotidyl transferase (TdT) is overexpressed in some cancer types, where it drives the mutagenic repair of double strand breaks through non canonical non-homologous end joining pathway. The TdT enzyme belongs to the X family of polymerases, together with the DNA polymerase λ (pol λ) and β (pol β). However, TdT exclusively displays template-independent nucleotide polymerisation. Pursuing our studies in developing TdT inhibitors, herein we deepened the structure-activity relationships of new structural analogues of our previously identified hit compounds. The diketo hexenoic acid derivatives here analysed showed high selectivity towards TdT and inhibition potencies spanning from the low micromolar range to the nanomolar. Docking studies highlighted the chemical features involved in the TdT binding, well contributing to the rationalisation of the structural requirements needed for the enzymatic inhibition.

Statement of the Problem The application of digital impressions for complete‐arch implant supported fixed dental prostheses (FDP) remains controversial, and data from a systematic review with meta‐analysis comparing intraoral scanning (IOS) and stereophotogrammetry (SPG) remain limited. Purpose To evaluate and compare the accuracy of currently available digital technologies, specifically IOS and SPG, in capturing complete‐arch implant impressions. Materials and Methods An electronic and manual search was conducted on May 4, 2024, across PubMed, Embase, and Cochrane CENTRAL databases following PRISMA guidelines. The search targeted studies (excluding case reports) that assessed the in vivo, in vitro, or ex vivo accuracy of IOS and SPG for complete‐arch implant impressions. Two investigators screened eligible studies using the QUADAS‐2 tool. Accuracy was the primary outcome, including linear, angular, surface deviations, and inter‐implant distance. Three meta‐analyses were performed on angular deviations, trueness, and surface deviations, trueness, and precision using a random‐effect model. Results Thirteen studies (3 in vivo and 10 in vitro) met inclusion criteria, displaying methodological heterogeneity (8 analyzing surface, 3 linear, 8 angular, and 3 interimplant distance deviations). The studies evaluated seven IOS (Aoralscan 3, Carestream 3600, iTero Element 2, iTero Element 5D, Primescan, Trios 3, and Trios 4) and two SPG devices (PIC and ICam4D). The number of implants ranged from 4 to 8. SPG reported higher accuracy than IOS in 10 of 13 studies. One in vitro study found IOS to have higher trueness but lower precision, another in vitro study found higher accuracy with IOS, and one in vivo study showed comparable trueness. Meta‐analyses of in vitro studies revealed significant differences favoring SPG in surface deviation trueness and precision, and angular deviation trueness ( p < 0.05), with reported effects of 3.426, 4.893, and 1.199. SPG showed surface trueness and precision, and angular trueness mean ranges 5.18–48.74 and 0.10–5.46 μm, and 0.24°–0.80°, while IOS ranges 14.8–67.72 and 3.90–37.07 μm, and 0.28°–1.74°. Conclusions Within study limitations, SPG showed to be a more reliable technology than IOS for complete‐arch digital implant impression, exhibiting significantly greater trueness and precision. IOS reported an angular deviation exceeding the 1° threshold required for a passive fit. Further clinical trials are required for conclusive evidence. Until then, a rigid prototype try‐in is still recommended. Trial Registration: CRD42024490844

Peptide's applications frequently present problems of solubility, stability, activity, or membrane permeability. To overcome these issues, cyclodextrins (CDs) can be used to form inclusion complexes with peptide hydrophobic parts; alkyl‐chains or aromatic‐rings inclusion strongly influences the interacting peptide properties. The study of model tripeptides has revealed that, among the three aromatic amino acids, tyrosine is the best suited to be included within CDs. The interaction with β‐CD of five model peptides (Tyr1‐5), each constituted by one tyrosine and four alanines, is reported: the tyrosine occupies one of the five position within each peptide chain. Among natural CDs, β‐CD has been chosen as it is the most economic, used, and only moderately toxic; its cavity size is the best suited to accommodate the tyrosine ring. Stoichiometry and affinity of each complex are evaluated and in silico and experimental data to describe the molecular determinants of each interaction are combined. The data further defines the role of the aromatic ring position in dictating the stability of formed complexes and demonstrates Tyr3, with its central Tyr, as the most stable complex. Noteworthy, the interaction with β‐CD induces Tyr3 to assume a U‐shaped conformation representing a nice example of conformation stabilization upon formation of inclusion complexes.

Scope Valproic acid (VPA) postnatal exposure in mice results in behavioral impairment, aberrant sensitivity to sensory stimuli, and self‐harming behavior, hallmarks of autism. According to previous reports, Coriolus versicolor (CV) has a protective effect on the brain. The goal of the current investigation was to assess how CV affected the neurobehavioral and metabolic changes caused by VPA in mice. Methods and Results Mice pups were injected with VPA at 14 days of age and orally administered CV at a dose of 200 mg/kg daily from 14 to 40 days of age. Mice pups were placed through behavioral tests during the trial to evaluate motor skill growth, nociceptive response, locomotion, anxiety, and cognition. Following behavioral testing, mice were killed, and the brain was removed and subjected to biochemical analyses (glutathione, malondialdehyde, and nitric oxide) and histopathological analysis. Additionally, to further investigate the role of the TLR‐4/Myd88/NF‐κB signaling pathway, we examined the modulation of this pathway and the alteration in gamma‐amino butyric acid (GABA) production using Western blot analysis. Conclusion According to our research, CV daily administration greatly reduced behavioral alteration, reversed the disorganization of the cerebellum and hippocampus, and significantly improved the VPA‐induced neuroinflammation via the TLR‐4/Myd88/NF‐κB signaling cascade.

Aim In recent years an increase in deaths and serious injuries caused by driving under the influence of psychoactive drugs was recorded on Europe’s roads. Alcohol is the most commonly used psychoactive substance worldwide, whereas, among illicit substances, cannabis is the most used, being also the most common substance found in injured drivers in Europe, showing a higher use prevalence in young people. In this context, the aim of our retrospective study was to analyze drivers who accessed the emergency room of hospitals in Latina area between 2020 and 2022 following a road accident, for which the police requested toxicological tests to check possible driving under the influence of alcohol and/or illicit substances. Subject and methods We enrolled 1956 subjects, 1534 males and 422 females; blood and urine samples were analyzed using screening enzyme immunoassay. Results We reported 564 positive patients. Drivers most frequently tested positive for alcohol 43.6%, cannabinoids 27.7% and cocaine 23.6%. Polydrug users represented 31% of the positive cases and 8.9% of the study population. Age group analysis showed that the highest number of positives was found among 21–30 year olds (33%). Furthermore, among the younger generation (< 21 years old) the use of cannabinoids was prevalent. Conclusion This retrospective study represented a snapshot of which substances were mainly abused by the driver population examined and highlighted how the problem concerns mainly the younger generation, opening up questions about interventions to be implemented in order to limit the phenomenon, acting on the socio-cultural aspects that fuel it.

Background/Objectives: In hospital settings, the wide variability of acute and complex chronic conditions—among both adult and pediatric patients—requires advanced approaches to detect early signs of clinical deterioration and the risk of transfer to the intensive care unit (ICU). Nursing diagnoses (NDs), standardized representations of patient responses to actual or potential health problems, reflect nursing complexity. However, most studies have focused on the total number of NDs rather than the individual role each diagnosis may play in relation to outcomes such as ICU transfer. This study aimed to identify and rank the specific NDs most strongly associated with ICU transfers in hospitalized adult and pediatric patients. Methods: A retrospective, monocentric observational study was conducted using electronic health records from an Italian tertiary hospital. The dataset included 42,735 patients (40,649 adults and 2086 pediatric), and sociodemographic, clinical, and nursing data were collected. A random forest model was applied to assess the predictive relevance (i.e., variable importance) of individual NDs in relation to ICU transfers. Results: Among adult patients, the NDs most strongly associated with ICU transfer were Physical mobility impairment, Injury risk, Skin integrity impairment risk, Acute pain, and Fall risk. In the pediatric population, Acute pain, Injury risk, Sleep pattern disturbance, Skin integrity impairment risk, and Airway clearance impairment emerged as the NDs most frequently linked to ICU transfer. The models showed good performance and generalizability, with stable out-of-bag and validation errors across iterations. Conclusions: A prioritized ranking of NDs appears to be associated with ICU transfers, suggesting their potential utility as early warning indicators of clinical deterioration. Patients presenting with high-risk diagnostic profiles should be prioritized for enhanced clinical surveillance and proactive intervention, as they may represent vulnerable populations.

Background/Objectives Spastic paraplegia type 4 (SPG4; also known as SPAST-HSP), the most prevalent variant among pure Hereditary Spastic Paraplegias (HSPs), is clinically characterized by progressive spasticity and weakness in the lower limbs. The present neuroimaging study specifically investigated possible changes in the corticospinal (CST) and thalamo-cortical tracts (TCT) structural integrity and broader cortical, subcortical and spinal pathways, topographically related to upper and lower limbs in SPG4. Methods Forty patients with SPG4 and 40 age- and sex-matched healthy controls underwent 3 T MRI scanning. MRI analyses included: (1) global and primary motor areas cortical thickness; (2) cortical, basal ganglia, thalamic and cerebellar volumetry; (3) diffusion-based probabilistic tractography of CST and TCT serving the arms and legs; and (4) spinal cord area. Results SPG4 patients showed significant reductions in thalamic volumes as well as spinal cord area when compared with controls. The volume reduction in thalamic regions correlated with disease severity and spasticity-related impairments. Structural changes in CST and TCT tracts in SPG4 patients were prominent in bundles topographically related to the lower limbs compared with the upper limbs. Conclusions Our findings point to significant thalamic atrophy as well as white matter tract degeneration topographically related to the lower limbs in SPG4 patients. The findings overall suggest new potential markers for disease progression and functional decline in SPG4 patients.

Potentially inappropriate prescriptions are associated with an increased risk of drug-drug interactions, adverse events, and unfavorable clinical outcomes, especially in older adults. Although different tools to improve appropriate prescribing have been developed to support healthcare professionals, their application and the barriers to their use remain insufficiently explored. This study aimed to assess Italian healthcare professionals’ knowledge of these tools and identify obstacles to their adoption. The study used a purposefully designed questionnaire to assess knowledge, adoption, and barriers related to appropriateness tools. The tools included were identified through a literature review and subsequently refined via expert consensus. Open-ended responses were analyzed using a conventional content analysis approach, and the analyses focused on differences across professional groups. The survey collected 657 responses from pharmacists (35%), nurses (26%), general practitioners (22%), geriatricians/internists (9%), and other physicians (8%). The Beers and STOPP/START criteria were used by 38% and 34% of participants, respectively, with geriatricians and other physicians being the primary users. Additionally, 34% of participants reported using specific software integrated into their institutional computer systems. Among 294 respondents identifying barriers to appropriate prescribing, the most common were lack of time (14%), lack of knowledge (10%), and accessibility/costs of digital tools (8%). Key facilitators included specific training (38%), integrated software/apps (29%), and more time with patients (11%). The adoption of tools supporting appropriate prescribing remains limited among healthcare professionals in Italy, with significant differences among professionals. Policymakers and healthcare institutions should focus on education, interprofessional collaboration, and user-friendly digital solutions to improve prescribing process and patient safety.

Background. Postoperative pancreatic fistula (POPF) remains one of the most relevant complications following pancreaticoduodenectomy (PD), significantly impacting short-term outcomes and delaying adjuvant therapies. Current predictive models offer limited accuracy, often failing to incorporate early postoperative data. This retrospective study aimed to develop and validate machine learning (ML) models to predict the absence and severity of POPF using clinical, surgical, and early postoperative variables. Methods. Data from 216 patients undergoing PD were analyzed. A total of twenty-four machine learning (ML) algorithms were systematically evaluated using the Matthews Correlation Coefficient (MCC) and AUC-ROC metrics. Among these, the GradientBoostingClassifier consistently outperformed all other models, demonstrating the best predictive performance, particularly in identifying patients at low risk of postoperative pancreatic fistula (POPF) during the early postoperative period. To enhance transparency and interpretability, a SHAP (SHapley Additive exPlanations) analysis was applied, highlighting the key role of early postoperative biomarkers in the model predictions. Results. The performance of the GradientBoostingClassifier was also directly compared to that of a traditional logistic regression model, confirming the superior predictive performance over conventional approaches. This study demonstrates that ML can effectively stratify POPF risk, potentially supporting early drain removal and optimizing postoperative management. Conclusions. While the model showed promising performance in a single-center cohort, external validation across different surgical settings will be essential to confirm its generalizability and clinical utility. The integration of ML into clinical workflows may represent a step forward in delivering personalized and dynamic care after pancreatic surgery.