324677 research outputs found
Sort by
Alle origini di San Salvatore in Alife. Una fondazione di Arechi nel Mezzogiorno longobardo?
No full textMean-Field Modeling of Green Technology Adoption: A Competition for Incentives
No full textThis paper investigates the role of fiscal incentives in promoting the transition to a green economy using a dynamic mean-field game framework. By modeling firms as representative agents undergoing an environmentally sustainable transition, we analyze two distinct types of incentive structure: fixed incentives and incentives based on the average behavior of firms. The findings underscore the importance of balancing incentive structures to avoid economic inefficiencies and ensure a smooth ecological transition
Cryoanalgesia for Pain Management After Pectus Excavatum Repair (COPPER) in Adolescents: A Randomized Controlled Trial
No full textBackground: Patients undergoing Pectus Excavatum repair with the minimally invasive approach frequently report severe postoperative pain. The goal of the study is to determine the superiority of cryoanalgesia compared to standard of care for return to normal quality of life. Methods: A randomized, active controlled, parallel groups trial (category IIb medical device) was designed for patients undergoing pectus excavatum repair. Participants were screened from the elective surgical lists at Istituto Gaslini, Genova, Italy, and they all were part of the academic practice setting. Once enrolled, patients were randomly assigned to one of the two study arms: cryoanalgesia vs. standard of care (epidural-based analgesia). The primary outcome was the Pediatric Quality of Life (PedsQL) and the subcomponents (psychosocial and physical health) 14 days after surgery. Results: Protocol was approved by the Ethics Committee (278/2021—DB id 11 421) and conducted between February 2022 and October 2023. Eighty-eight patients were enrolled in the study: forty-five to cryoanalgesia and forty-three in the epidural arm. The PedsQL median (IQR) at the 14th day was 59.8 (48.4, 71.2) vs. 67.9 (58.7, 73.9) (95% CI: 0.46–13; difference 6.5; p = 0.07) with ITT analysis, and 59.8 (48.37, 71.20) vs. 69.02 (58.70, 73.91) (95% CI: 0.82, 14; difference 7.4; p = 0.028) with PP analysis, in the cryoanalgesia and in the standard of care group, respectively. Irrespective of treatment, a significant decrease in both the PedsQL total score and its subcomponents was found. This effect persisted when stratified by treatment: physical health showed a decrease in both arms, while psychosocial health demonstrated a more marked decrease in the standard of care arm (q-value = 0.028), but not in the cryoanalgesia arm (q-value = 0.056). Conclusions: Cryoanalgesia did not improve return to baseline quality of life 2 weeks after surgery. However, it showed to be beneficial in the psychosocial component of the PedsQL scale. Trial Registration: NCT05201820
Two-loop running effects in Higgs physics in Standard Model Effective Field Theory
Get PDFWe consider the renormalization group equations within the Standard Model Effective Field Theory and compute two-loop contributions proportional to the top quark Yukawa coupling for the operator generating an effective Higgs-gluon coupling, focusing on the Yukawa-like operator. These two-loop running effects are relevant for processes where the effective Higgs-gluon coupling contributes at a lower loop order compared to the Standard Model contribution and where a dynamical scale choice is adopted. Such a situation arises, for instance, in the Higgs transverse momentum distribution and Higgs pair production. We investigate the phenomenological impact of our computations on these two processes and find that the two-loop contributions are significant and can lead to deviations of up to 20% in the scenarios we consider
Clarifying the Specificity of Transcranial Pulse Stimulation in Neuromodulatory‐Based Therapeutic Applications
Get PDFPoint mutations of the mitochondrial chaperone TRAP1 affect its functions and pro-neoplastic activity
Get PDFThe mitochondrial chaperone TRAP1 is a key regulator of cellular homeostasis and its activity has important implications in neurodegeneration, ischemia and cancer. Recent evidence has indicated that TRAP1 mutations are involved in several disorders, even though the structural basis for the impact of point mutations on TRAP1 functions has never been studied. By exploiting a modular structure-based framework and molecular dynamics simulations, we investigated the effect of five TRAP1 mutations on its structure and stability. Each mutation differentially impacts long-range interactions, intra and inter-protomer dynamics and ATPase activity. Changes in these parameters influence TRAP1 functions, as revealed by their effects on the activity of the TRAP1 interactor succinate dehydrogenase (SDH). In keeping with this, TRAP1 point mutations affect the growth and migration of aggressive sarcoma cells, and alter sensitivity to a selective TRAP1 inhibitor. Our work provides new insights on the st..
Efficacy and safety of posaconazole and liposomal amphotericin B use for prophylaxis of invasive fungal infections in a paediatric and young adult haemato-oncological population
No full textBackground: The prevention of invasive fungal infections (IFIs) is crucial for paediatric haemato-oncological patients. This study evaluates the clinical efficacy and side-effects of posaconazole and liposomal amphotericin B (L-AmB) as primary prophylaxis. Materials and methods: This cohort study included patients aged 3 months to 21 years who received posaconazole or L-AmB (5 mg/kg twice weekly) as prophylaxis from January 2017 to March 2022 at the Hemato-oncological Pediatric Unit, University Hospital of Padua, Italy. Outcomes included adverse events and IFI diagnoses after the start of prophylaxis. Separate analyses were performed for patients with ALL and non-ALL diagnoses, and high-risk and low-risk groups. Cumulative incidence was calculated using the Kaplan-Meier estimator, with significant differences assessed using the log-rank test. Hazard ratios (HR) were estimated using Cox regression. Results: Fifty-one patients received posaconazole, and 37 received L-AmB. Adverse events occurred in 26% of L-AmB patients and 5.6% of posaconazole patients. IFI breakthrough events were similar in both groups (four events each). In ALL patients, 41% experienced adverse events with L-AmB, compared to 5% with posaconazole. After 1 year, the probability of adverse events was lower in the posaconazole group (54% versus 65%, P < 0.001). Overall, posaconazole was associated with a 91% lower risk of adverse events (HR: 0.07, P < 0.001). Among high-risk patients, IFI breakthrough rates were similar between groups (P = 0.964). Conclusions: Posaconazole was associated with fewer adverse events than L-AmB, and both drugs showed similar efficacy in preventing IFI breakthroughs, making posaconazole a viable alternative for primary prophylaxis
IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer
No full textBackground: Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision. Methods: This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg. Results: Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60–0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53–0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61–0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85–0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87–0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76–0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78–0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively). Conclusion: Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice
Morphing Distributed and Transfer Learning Paradigms for Visual Understanding
No full textThis thesis addresses key limitations of machine learning (ML) models for visual understanding, particularly their difficulty in adapting to dynamic, real-world conditions without requiring extensive retraining. We focus on three emerging paradigms, Domain Adaptation, Continual Learning, and Federated Learning, to tackle this challenge. Domain Adaptation enables models to adapt to new data distributions, Continual Learning allows systems to learn from a continuous stream of information without forgetting prior knowledge, and Federated Learning offers a privacy-preserving approach to model training by learning from decentralized data sources without the need for raw data centralization.
By revisiting and combining these paradigms, this thesis seeks to propose novel insights into visual understanding, addressing practical challenges related to model adaptability, efficiency, and privacy. The insights gained from this research contribute to the development of ML systems that are more flexible, generalize better across domains, and respect user privacy, all while reducing computational and environmental costs
Novel Lipid-Based Formulation to Enhance Coenzyme Q10 Bioavailability: Preclinical Assessment and Phase 1 Pharmacokinetic Trial
Get PDFNutraceuticals represent a strategy for maintaining health and constitute a brilliant market in Italy and across Europe. However, the absence of strict regulations regarding formulation requirements highlights a critical issue: their poor bioavailability. An example is coenzyme Q10 (CoQ10), a quinone known for its potential as a mitochondrial protective agent but characterized by low intestinal absorption. CoQ10 is a hydrophobic molecule with high molecular weight and poor water solubility, factors that significantly limit its intestinal bioaccessibility and, consequently, its oral bioavailability. Objectives: In this context, the present study describes a novel formulation designed to enhance CoQ10 bioaccessibility through in situ emulsification upon contact with gastroenteric fluids. This technology, termed Lipid-Based Auto-Emulsifying Drug Delivery System (LiBADDS), is unique because it combines a medium-chain triglyceride (MCT), a long-chain fatty acid, conjugated linoleic acid (CLA) with a high HLB solubilizer, Polysorbate 80 (PS80), and a sodium octenyl succinate starch derivative (SOS), which can create a nanometric emulsion simply by aqueous dispersion and upon contact with gastrointestinal fluids. This phenomenon promotes the prompt dispersion of CoQ10 and its rapid translocation into the serosal compartment of the intestinal epithelium. Methods: Its efficacy was evaluated in vitro through the Caco-2 cellular model and in vivo through a crossover study on healthy volunteers, measuring pharmacokinetic parameters such as AUC, Cmax, Tmax, ΔAUC, and ΔCmax. Results: Overall, LiBADDS demonstrated a significant improvement in both the bioaccessibility and bioavailability of CoQ10 compared to the unformulated substance. Conclusions: LiBADDS showed to be a promising tool to improve CoQ10 bioavailability by enhancing its bio-accessibility