University of Udine
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Ensemble of KalmanNets with innovation-based attention for robust target tracking
No full textModel-based tracking algorithms often suffer from significant performance degradation when tracking maneuvering targets, primarily due to inherent uncertainties in target dynamics. To address this limitation, we propose a novel ensemble-based approach that integrates multiple neural-aided Kalman filters, referred to as KalmanNet, within a multiple-model framework, inspired by traditional interacting multiple-model (IMM) filtering techniques. Each KalmanNet instance is specialized in tracking targets governed by a distinct motion model. The ensemble fuses their state estimates using a Recurrent Neural Network (RNN), which learns to adaptively weigh and combine the predictions based on the underlying target dynamics. This fusion mechanism enables the system to model complex motion patterns more effectively and achieves lower estimation bias and variance compared to relying on a single KalmanNet when tracking maneuvering targets, as demonstrated through extensive simulation experiments. Furthermore, we introduce an explainable, innovation-based attention mechanism to enhance the interpretability of our results, inspired by traditional model-based tracking algorithms, that aids the identification of target motion dynamics. Our findings indicate that this attention mechanism improves robustness to sensor noise, out-of-distribution data, and missing measurements. Overall, this innovative approach has the potential to advance state-of-the-art target tracking applications
Cerebrospinal fluid metabolomic signatures in paediatric MOGAD and POMS
No full textIntroduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and paediatric-onset multiple sclerosis (POMS) are acquired demyelinating syndromes (ADSs) that are increasingly recognised in paediatric care. They share clinical and magnetic resonance imaging (MRI) features, but they differ in prognosis and management, as POMS is a chronic inflammatory neurodegenerative disorder, whereas MOGAD is not. Early POMS diagnosis is essential to limit disability accumulation. Thus, early identification of these syndromes is key to their adequate management and family counselling and improving the outcome. Cerebrospinal fluid (CSF) biochemistry and cell count, oligoclonal band, IgG index, and serum MOG antibodies, together with brain and spine MRI, are the most valuable diagnostic biomarkers for differential diagnosis. However, it is not always possible to rely on these specific biomarkers to correctly identify these syndromes, especially at disease onset. In this perspective, metabolomic and lipidomic analyses have recently gained ground as a novel diagnostic approach. Methods: In the present study, high-sensitivity shotgun mass spectrometry was used to characterise the CSF metabolome and lipidome of children with MOGAD and POMS disorders compared with the CSF of children with non-demyelinating diseases used as controls. Results: The identification of 128 CSF hydrophilic metabolites and 210 lipids revealed characteristic changes in the relative metabolic concentrations in MOGAD compared with POMS, mainly related to the energy metabolism pathways. The lipidomic profile revealed the accumulation of the plasmalogens phosphatidylethanolamine (PE) and cholesterol esters as specific features of the lipid metabolic derangement. In this exploratory cohort, POMS showed higher very-long-chain PE and triglyceride (TG) signal intensities after false discovery rate (FDR) correction and effect size evaluation; however, these trends require confirmation in larger, independent cohorts. Conclusion: By exploring the CSF metabolomic profile, we demonstrated the usefulness of broad-range omic analysis as a fast and reliable method of biomarker discovery in children with demyelinating neurological disorders at the onset of the disease, which may be a valuable diagnostic complement to the existing biomarkers
Risk Profile and Outcomes of Patients Requiring Coronary Revascularization as Concomitant Procedure to Repair of Type A Aortic Dissection
No full textBackground The present study aimed to report the early and late clinical outcomes of patients who underwent surgical repair for acute type A aortic dissection requiring concomitant coronary artery bypass grafting (CABG), and to explore potential risk factors associated with the need for this additional procedure. Methods Data were retrieved from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). Bootstrapped least absolute shrinkage and selection operator logistic regression and multilevel multivariate logistic regression were performed for variable selection to identify predictors of hospital death, and logistic regression was used for the prediction of CABG. Results A total of 292 (8.04%) of 3633 patients required additional CABG. The in-hospital mortality rate was 33% for patients undergoing CABG vs 16% of non-CABG recipients ( P < .001; odds ratio [OR], 2.52; 95% CI, 1.93-3.35). Dissection of the aortic root involving the right coronary cusp ( P < .001; OR, 7.83; 95% CI, 5.55-11.0), a tear in the aortic root ( P = .002; OR, 2.08; 95% CI, 1.29-3.32), mitral valve insufficiency ( P = .034; OR, 1.33; 95% CI, 1.01-1.71), and a genetic syndrome ( P < .001; OR, 3.23; 95% CI, 1.66-5.99) independently predicted the need for CABG. Conclusions The need for additional CABG is not a rare occurrence during repair of type A aortic dissection and is associated with an increased mortality risk. Intimal tear localization and right coronary sinus dissection should be carefully examined in the preoperative image evaluation to stratify the risk of revascularization and plan the most appropriate approach
Exploring PIPAC for managing platinum resistant and refractory ovarian cancer with peritoneal spread: A collaborative multi-institutional study
No full textBackground: Platinum-resistant or refractory epithelial ovarian cancer (EOC) remains a significant clinical challenge, often leading to rapid progression and poor prognosis. Palliative treatments aimed at improving quality of life are warranted. Objective: To assess the feasibility and potential benefits of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in patients with platinum-resistant or refractory EOC. Methods: Prospective multicenter observational study (2016–2023). Primary endpoint: feasibility, defined as completion of ≥3 planned PIPAC cycles within 120 days without ≥ grade 3 treatment related adverse events (CTCAE v5.0). Secondary endpoints: safety; disease control (RECIST 1.1); changes in Peritoneal Cancer Index and Fagotti score; ascites control; CA-125 response; conversion to cytoreductive surgery (±HIPEC); and overall survival (OS). Results: Forty patients were enrolled. Ninety-seven percent of procedures were completed. Feasibility was 65.0 % (26/40; 95 % CI 49.51–77.87); no grade ≥3 events occurred. Key secondary outcomes included a clinical benefit rate of 35 % in the intention-to-treat (ITT) population and 53.8 % in the per-protocol (PP) population, median time to ascites resolution of one cycle, and median overall survival of 14 months (17 months in PP). Higher white blood cell count and ascites volume were significantly associated with progression (p = 0.035 and p = 0.025). Three platinum-refractory patients became eligible for surgery, two underwent optimal cytoreduction. Median OS was 14 months (17 months in PP). A non-significant trend toward longer OS was observed in platinum-refractory versus platinum-resistant disease (18 vs 9 months; p = 0.093). Conclusions: PIPAC is a feasible, well-tolerated option in platinum-resistant and refractory EOC with potential to stabilize disease, relieve ascites and enable surgery in selected cases
Detection of antibiotic resistance gene mecA in foodborne Staphylococcus aureus with electrochemical biosensor
No full textThe increasing spread of antibiotic resistance and the transmission of antibiotic resistance genes require the urgent development of rapid and cost-effective detection methods. The food chain plays a significant role in the dissemination of resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, MRSA were isolated from milk and meat. A DNA MECA probe specific to the mecA gene was designed, evaluated in silico for specificity and experimentally through dot blot hybridization using DNA from S. aureus isolates confirmed by PCR. The probe was then integrated into an electrochemical biosensor based on Screen Printed gold Electrodes. In the absence of the target gene, the current signal stayed above baseline, whereas the presence of mecA gene resulted in a concentration-dependent decrease in signal, indicating effective hybridization within the range of 10 fg/μL - 1 ng/μL. Scanning electron microscopy analysis confirmed the presence of biological material exclusively on functionalized working electrode exposed to mecA-positive DNA. The system was further tested on S. aureus DNA extracted from 13 raw milk and meat matrices, demonstrating the biosensor's applicability for rapid (20-min), easy-to-perform, and low-cost detection of mecA gene. This work provides a promising basis for the development of on-site screening tools to monitor AR in the food production chain
E. Fabbro, Gli atleti e il cantore. Su alcuni codici poetici pindarici, in Olympia. Il mito dello sport. Significati, valori, problemi tra guerra e pace dagli eroi di Omero al nostro tempo, edd. A Camerotto, E. Chies, V. Melis, Vittorio Veneto
No full textIn vitro interactions of sulbactam/durlobactam in combination with meropenem, ceftazidime/avibactam, piperacillin/tazobactam, cefiderocol and fosfomycin against carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates
No full textWe evaluated in vitro activity of sulbactam/durlobactam in combination with different antimicrobials against Carbapenem-Resistant Acinetobacter baumannii (CRAB) clinical isolates with different susceptibility profiles, including sulbactam/durlobactam-resistant strains. The genomes of 13 CRAB clinical isolates were characterized by whole-genome sequencing and synergy testing was performed with MIC Test Strips. Sulbactam/durlobactam, when combined with piperacillin/tazobactam or ceftazidime/avibactam, showed synergistic activity against 53.8% (7/13) of CRAB isolates and restored meropenem MIC values below the clinical breakpoint in 46.2% (6/13) of them. Our results demonstrate that sulbactam-durlobactam in combination with β-lactams exhibited high in vitro synergistic activity against CRAB strains
Upcycling of spent coffee grounds solid-state fermentation by Aspergillus strains: in vitro assessment of prebiotic activity and gut health benefits
No full textThis study aimed to explore the upcycling of spent coffee ground (SCG) by solid-state fermentation (SSF) using fungal strains of Aspergillus oryzae and Aspergillus awamori . The results indicated that SCG was a suitable substrate for the growth of both fungal strains, showing a 3-log unit increase in spores. SSF significantly improved the recovery of soluble dry matter from SCG, with increases of almost 2-fold for A. oryzae and 4-fold for A. awamori . Notably, SSF resulted in a 64 % reduction in the browning index, indicating the potential of A. awamori to degrade coffee melanoidins. Both fungal strains were effective in releasing free sugars from SCG: A. awamori -fermentation yielded the highest concentrations of mannose and galactose. A. oryzae -fermentation increased the oligosaccharide content to a final level of 14.15 mg/100 g. In vitro batch fermentation showed that fermented SCG supported the short-chain fatty acid production capability especially in distal colon. The genus composition in medium supplied with fungal fermented SCG included Enterobacteriaceae, Klebsiella, Clostridium, Bacteroides, and Akkermansia. These findings suggest that solid state fermentation of SCG could produce a prebiotic ingredient having beneficial effects on gut health
Risk factors and reasons for switching from front-line therapy in the Italian chronic myeloid leukaemia network: A cohort study
No full textIdentifying chronic myeloid leukaemia (CML) patients at risk of therapeutic switch remains debated. We analysed the cumulative risk of treatment change in the CML Italian network prospective cohort based on first-line tyrosine kinase inhibitors and patient characteristics. Sub-hazard ratios (sHRs) were estimated using Fine and Gray multivariable models. Among 1662 patients, initial treatment consisted of imatinib for 840 (50.5%), nilotinib for 490 (29.5%) and dasatinib for 332 (20.0%). Subsequently, 492 patients (29.6%) required second-line therapy, with 232 (47.1%) switching due to resistance and 176 (35.8%) due to intolerance. At 2 years, the risk of resistance was 18.3% for imatinib, 8.4% for dasatinib (sHR = 0.32; 95% confidence interval 0.21–0.49) and 6.8% for nilotinib (0.29; 0.19–0.42). The risk of switching increased in intermediate (1.95; 1.40–2.72) and high Eutos long term survival (ELTS) risk (3.19; 2.10–4.83) but was reduced with older age (0.97 per year; p < 0.0001). Intolerance at 2 years was 8.5% for imatinib, 12.4% for dasatinib (2.55; 1.73–3.75) and 5.2% for nilotinib (1.04; 0.65–1.65). Switching to a third-line therapy at 3 years was 8% for imatinib, 5% for dasatinib and 4% for nilotinib. The results showed that the time to first treatment switch for resistance is shorter for younger patients, for imatinib and for intermediate/high ELTS risks. The risk of switching for intolerance is higher for patients initially treated with dasatinib
An Exploratory Study on the Impact of MIPEF-Assisted Extraction on Recovery of Proteins, Pigments, and Polyphenols from Sub-Standard Pea Waste
No full textThe growing demand for sustainable protein sources has intensified the need for efficient valorisation of legume by-products. This study investigated the application of moderate intensity pulsed electric fields (MIPEF; 5 kV/cm, 4 μs, 500 pulses) as a green technology for assisting the co-extraction of proteins, pigments, and polyphenols from industrial substandard peas (Pisum sativum L.). Aqueous pea dispersions (20 g/100 g) were subjected to alkalinization (pH 9–12), and MIPEF applied either before or after the pH adjustment. The highest protein recovery was achieved when MIPEF was applied after alkalinization at pH 9.0, due to the increased conductivity and energy input enhancing electroporation-driven protein release. Although higher pH levels increased energy delivery, they did not significantly improve protein extraction. Conversely, MIPEF application decreased total polyphenol and pigment concentrations in the extract, likely due to aggregation phenomena. Overall, these preliminary results indicate that combining mild alkalinization with MIPEF might represent a promising and energy-efficient approach for protein recovery from legume side-streams. Further optimization is required to improve protein recovery while preserving the stability of co-extracted bioactive compounds