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    26957 research outputs found

    Abstract Fri076: Endothelial Mitochondria-rich Extracellular Vesicles Protect In Vitro Cardiomyocytes from Doxorubicin Toxicity by Restoring ATP Production, Reducing Oxidative Stress, and Modulating Free Calcium

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    Doxorubicin (Doxo) is a first-line chemotherapeutic agent that leads to heart failure due to irreversible mitochondrial dysfunction. Endothelial-derived extracellular vesicles (e-EVs) may protect cardiomyocytes from injury, though the role of large mitochondria-rich e-EVs (e-mtEVs) in cardiotoxicity remains unknown. We hypothesized that e-mtEVs uptake by cardiomyocytes may counteract Doxo-induced toxicity. e-mtEVs were isolated via serial centrifugation from human aortic endothelial cell culture media, with JC-1 staining confirming ∼90% contained active mitochondria. H9c2 cardiomyocytes were exposed to 0.3 μM Doxo for 12h and treated with e-mtEVs (~1 EV/cell). At 24h, Seahorse analysis showed a 52% reduction in glycolytic ATP production in Doxo cells (Control Mdn 0.02 [IQR 0.02-0.03] vs Doxo Mdn 0.009 [IQR .003-.010], p=0.046), which normalized after e-mtEVs treatment. Extracellular acidification rate (ECAR) decreased by 46% with Doxo (Control Mdn 0.005 [IQR 0.004-0.006] vs Doxo Mdn 0.003 [IQR 0.002-0.003], p=0.025), but remained at control levels in Doxo+e-mtEVs cells. Cell viability, reduced by 67% in Doxo cells (p≤0.001), improved by 30% with e-mtEVs (p=0.029). Spectrofluorimetric analysis showed increased oxidative stress in Doxo-treated cells, with superoxide (O2–, +82%, Control Mdn 0.180 [IQR 0.139-0.181] vs Doxo Mdn 0.990 [IQR 0.915-1.044], p≤0.0001) and hydrogen peroxide (H2O2, +76%, Control Mdn 0.225 [IQR 0.138-0.362] vs Doxo Mdn 0.933 [IQR 0.815-1.190], p≤0.0001), whereas e-mtEVs significantly reduced O2– (-57%, e-mtEVs Mdn 0.421 [IQR 0.290-0.566], p=0.077) and H2O2 (-40%, e-mtEVs Mdn 0.561 [IQR 0.337-0.708], p=0.021) after Doxo. Intracellular Ca++ levels, measured with Fluo-4 AM and Fura-2 AM, increased after Doxo (+80% bound Ca++, Control Mdn 0.193 [IQR 0.158-0.572] vs Doxo Mdn 0.978 [IQR 0.929-1.110], p=0.026; +61% free Ca++, Control Mdn 0.324 [IQR 0.087-0.494] vs Doxo Mdn 0.825 [IQR 0.697-1.478], p=0.002), but were reduced by 60% with e-mtEVs (Mdn 0.334 [IQR 0.263-0.339], p=0.009) compared to Doxo cells. In conclusion, the uptake of e-mtEVs protects cardiomyocytes from Doxo toxicity, restoring glycolytic ATP production, reducing oxidative stress, and modulating calcium dynamics. These findings suggest that transplanting e-mtEVs could offer a groundbreaking therapeutic approach to combat chemotherapy-induced cardiotoxicity

    Space-time mesh adaptation for the VMS-Smagorinsky modeling of high Reynolds number flows

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    Traditional methods, such as Reynolds-Averaged Navier-Stokes (RANS) equations and Large Eddy Simulations (LES), provide consolidated tools for the numerical approximation of high Reynolds number flows in a wide range of applications - from green energy to industrial design. In general, RANS modeling is practical when the main interest is the time-averaged flow behavior. LES equations offer detailed insights into flow dynamics and a more accurate solution, but the high computational demand necessitates innovative strategies to reduce costs while maintaining precision. In this study, we enhance the Variational MultiScale (VMS)-Smagorinsky LES model by relying on an adaptive discretization strategy in both space and time, driven by a recovery-based a posteriori error analysis. We assess the effectiveness of the approach in capturing flow characteristics across a wide range of Reynolds numbers through benchmark tests

    Towards a European Research Freedom Act: A Proposal for an EU-Wide Secondary Publication Right

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    As of 2025, six EU Member States – Germany, France, Austria, Belgium, the Netherlands and Bulgaria – have introduced forms of Secondary Publication Rights (SPRs) as an effective tool for rebalancing the bargaining powers of authors and publishers, enhancing Open Access (OA) to scientific publications, and fostering national Open Science (OS) policies. Building on the results of a study conducted for the European Commission and published in 2024, this article supports the introduction of an EU-wide SPR as one of the key priority actions needed to fully align EU copyright law with the policy goals of the European Research Area (ERA). Given the fragmented nature of national approaches and the inherently transnational nature of much of scientific communication and publishing, a harmonised SPR with carefully tailored and balanced features is a precondition for creating a level-playing field for all scientific authors operating within the ERA. This article explores the potential of SPRs and where they intersect with OS, analysing their origins and underlying rationales. It then makes a comparative analysis of national SPR implementations and their main features. On this basis, it makes specific proposals for an EU-wide SPR, emphasising design, scope, and potential impact on stakeholders. It concludes by reflecting on the broader significance of integrating an SPR into the EU’s OS agenda

    Time synchronization and performance analysis of the openSAFETY protocol via UDP over ethernet

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    The growing demand for Ethernet-based Industrial Internet of Things (IIoT) is changing the shape of modern industrial systems and emphasizing the need for high-speed, reliable, scalable, and safe communication among industrial devices. Ethernet-based networks provide the basis for seamless device integration, real-time data exchange, and increased operational efficiency, making them the key to Industry 5.0 applications. As industrial automation becomes increasingly complex, the importance of functional safety grows exponentially. The openSAFETY protocol is a fieldbus-independent, scalable, and robust protocol for implementing functional safety. Our contribution is twofold. First, we analyze time synchronization in the openSAFETY to fully understand the interrelated timing parameters and give some practical guidelines to tune the safety application. We have proposed the parameter tuning approach, which is better in terms of performance and ensures continuous, safe operations. Second, we analyze the protocol’s performance via UDP over Ethernet under normal and degraded network conditions. We found the protocol resilient to network impairments under certain levels during the experiments. Under normal working conditions, the cycle time was successfully achieved in the microsecond range, even at full payload capacity

    Enhancing Learning Systems in Using Patient Experience Data: An Exploratory Mixed-Method Study in Two Italian Regions

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    In the quest for healthcare systems enhancement, the improvement of patient experience plays a central role. The challenge lies in converting patient-reported experience data into actionable knowledge for quality improvement. This study aims to investigate the use of patient-reported data as knowledge base for actions and to identify and map actions derived from the use of patient-experience data within two Italian regional healthcare systems. Patient Experience Data are systematically collected in both systems, providing real-time updates accessible by professionals and managers through web-based reporting systems and including a collaborative network among practitioners. A sequential exploratory mixed-method study was carried out in several qualitative and quantitative phases. In the first phase, a qualitative method was conducted to discuss the actionability of patient-reported data and to design a tool for collecting the improvement actions based on these data. In the second phase, a quali-quantitative survey was performed to explore the professionals' use of patient-reported information and the types of actions implemented. Finally, a workshop was held to discuss, interpret and validate the results. The initial workshop identified key dimensions for improvement initiatives. After design and distribution of survey, a total of 189 responses was collected, respectively 96 from Region A and 93 from Region B. Both regions ensured widespread use of patient-reported data (89%). The establishment of a collaborative network seemed to reduce the learning curve in using patient-reported data and fostered a culture of using patient feedback effectively. The results reveal a difference between the two regions, with a more extensive patient-reported data use in Region A, attributed to its systematic joining the PREMs Observatory, prior experiences with patient-feedback collection and use, and patient-experience indicators integrated into the performance evaluation system. Regarding practices of data use, four themes emerged, namely, internal actions addressed to hospital staff (35.9%), external actions addressed to users (18.6%), comfort and hospitality aspects (34.7%) and review of processes and procedures (10.8%). The study highlights the importance of effectively using patient-reported data to achieve organisational goals, by combining different managerial strategies. It demonstrates how professionals use such data for improvement actions and underscores the significance of various forms of knowledge dissemination and sharing. It advocates for fostering a culture of continuous learning and improvement within and across healthcare organisations

    Effectiveness and Safety of Ticagrelor Monotherapy After Short-Duration Dual Antiplatelet Therapy in PCI Patients: A Systematic Review and Meta-Analysis

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    Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor, is the standard treatment for patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). However, the optimal duration of DAPT remains debated due to the need to balance ischemic event reduction with bleeding risks. This study evaluates the efficacy and safety of ticagrelor monotherapy after short-duration DAPT (1 to 3 months) compared to extended DAPT, focusing on major bleeding and cardiovascular outcomes. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Randomized controlled trials (RCTs) comparing ticagrelor monotherapy after short-duration DAPT to extended DAPT were identified from PubMed, Embase, and the Cochrane Library. Data on major bleeding, major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction, stroke, stent thrombosis, and mortality were analyzed, and risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. Five RCTs involving 32,393 patients were included. Ticagrelor monotherapy significantly reduced MACCE (RR: 0.88; 95% CI: 0.77 to 0.99; p = 0.04) and major bleeding (RR: 0.53; 95% CI: 0.37 to 0.77; p = 0.0008) compared to extended DAPT. It also significantly reduced all-cause mortality (RR: 0.82; 95% CI: 0.67 to 0.99; p = 0.04) and cardiovascular death (RR: 0.68; 95% CI: 0.49 to 0.94; p = 0.02). The incidence of myocardial infarction, stent thrombosis, and stroke were similar between the groups. Net adverse clinical events (NACE) were 27% lower with ticagrelor monotherapy (RR: 0.73; 95% CI: 0.63 to 0.85; p <0.0001). In conclusion, ticagrelor monotherapy after short-duration DAPT reduces major bleeding complications without compromising cardiovascular protection. This approach offers a promising strategy to optimize outcomes for PCI patients, particularly those at high bleeding risk. Further studies are needed to refine the optimal DAPT duration in various patient populations, especially those with higher ischemic risk

    Raided by the storm: How three decades of thunderstorms shaped U.S. incomes and wages

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    Climate change and weather events are increasingly affecting the macroeconomic performance of countries and regions. However, their effects on income inequality are less understood. We estimate the dynamic impact of thunderstorms on income and wages and reveal a robust asymmetric effect. We leverage a comprehensive dataset covering more than 200,000 events affecting contiguous U.S. counties across three decades. Storms have caused the highest number of billion-dollar disaster events since the eighties, but they have the lowest average event cost. They are short-lived, locally confined, relatively frequent, difficult-to-predict, and hazardous albeit not fully destructive events. While such features are convenient for the identification of impacts, previous studies mostly focused on more extreme events. We document a robust negative association between storm activity, income and wages growth. While income tends to recover in the long run, wages exhibit a significantly more stubborn decline, suggesting persistent and adverse impacts on (functional) income inequality. A one standard deviation increase in wind exposure generates a loss of 0.15% (0.21%) in wages after three (nine) years; incomes fall by a larger extent initially (0.19% after three years) while fully recovering in the longer run. In addition to their notable asymmetry, such estimates are non-negligible—especially given the downward rigidity of U.S. wages. Our analyses also highlight a lack of effective adaptation and stronger negative impacts in economically disadvantaged regions. Finally, we find evidence for a sizable shock-absorbing role of federal assistance

    Object and Distance Processing System (ODPS)

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    RGB-D cameras were utilized by Object and Distance Processing System (ODPS) software, which gathered spatial information about the mobile robot. The system is based on a process running on a personal computer that sends UDP (User Datagram Protocol) packets within the Local Area Network (LAN) through a wireless router, where a robot and a haptic-actuated glove are also connected. This system also employed a deep neural network model named YOLOv11x to detect objects and calculate their distance from the robot

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