BACKGROUND: Intraluminal irreversible electroporation (IRE) can be used for recanalizing occluded metal stents. However, optimal IRE parameters for consistent effects across different stent designs remain unclear. The aim of this study was to simulate the process of stent recanalization in silico by employing finite element analysis. METHODS: A virtual model of an occluded biliary stent with an experimental 3-electrode IRE catheter was developed. Electric field distribution, temperature changes, and potential ablation volumes were simulated across various parameters: IRE voltage (300 - 1300 V), stent wire width (0.1 - 0.5 mm) and stent mesh size (0.7 - 5.58 mm). Simulations incorporated five representative stent types commonly used in clinical practice. 685 unique simulations were conducted, analyzing 1162 unique values. RESULTS: Higher voltages generally led to larger ablation zones and increased temperatures. Thinner stent wires and larger mesh sizes also increased the extent of ablation zone. While in-stent ablation was largely independent of stent design, out-of-stent ablation was significantly impacted by mesh size and tissue thickness between the stent and irreversible electroporation electrodes. Voltages above 1000 V produced significant thermal effects, with substantial volumes of tissue heated above 50 °C. Specific stent designs exhibited variations in maximum temperature (72.1 - 83.1 °C) and ablation volume (8.7 - 14.7 mm3). CONCLUSION: Tailored IRE protocols for different stent designs are required due to differences in in- and out-stent ablation volumes. High voltages (>1000 V) induce both thermal and nonthermal ablation mechanisms.
- Keywords
- Irreversible electroporation, ablation, computer simulation, metal stents, temperature distribution,
- MeSH
- Electroporation * methods MeSH
- Humans MeSH
- Stents * MeSH
- Models, Theoretical * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Ultrahigh-performance supercritical fluid chromatography-mass spectrometry (UHPSFC/MS) method is optimized for the high-throughput quantitation of lipids in human serum and plasma with an emphasis on robustness and accurate quantitation. Bridged ethylene hybrid (BEH) silica column (100 × 3 mm; 1.7 μm) is used for the separation of 17 nonpolar and polar lipid classes in 4.4 min using the positive ion electrospray ionization mode. The lipid class separation approach in UHPSFC/MS results in the coelution of all lipid species within one lipid class in one chromatographic peak, including two exogenous internal standards (IS) per lipid class, which provides the optimal conditions for robust quantitation. The method was validated according to European Medicines Agency and Food and Drug Administration recommendations. UHPSFC/MS combined with LipidQuant software allows a semiautomated process to determine lipid concentrations with a total run time of only 8 min including column equilibration, which enables the analysis of 160 samples per day.
- Keywords
- High-throughput lipidomics, Mass spectrometry, Plasma, Quantitation, Serum, Ultrahigh-performance supercritical fluid chromatography, Validation,
- MeSH
- Mass Spectrometry methods MeSH
- Humans MeSH
- Lipidomics * methods MeSH
- Lipids * analysis blood MeSH
- Chromatography, Supercritical Fluid * methods MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Lipids * MeSH
BACKGROUND: Surgery-related adverse events are among the most common adverse events in-hospital. However, no comprehensive, multidisciplinary perioperative guidelines exist at the European level. The aim of this study is to describe the process and results in achieving European multidisciplinary consensus on perioperative patient safety recommendations. METHODS: This multimethod study included: (1) a systematic review of guidelines; (2) selection and synthesis of recommendations; and (3) a two-round modified Delphi technique including a 2-day face-to-face consensus conference. We recruited a panel of two expert groups balanced in terms of gender, geographical origin, and professional background, with meaningful participation from patient representatives. Consensus was defined as at least 70% of the panel rating a recommendation 7-9 on a 9-point Likert scale for importance to patient safety and feasibility of implementation. RESULTS: The systematic review included 267 guidelines, from which 4666 patient safety recommendations were identified and extracted. After four synthesis rounds, 99 recommendations were presented for the Delphi survey, detailing their strength of recommendation, level of evidence, and methodological quality of the cited guidelines. An expert group, composed of 66 multidisciplinary experts from 19 European countries, participated with a response rate of 80.3%. After the two Delphi rounds and the consensus conference, the panel agreed on a final set of 101 recommended perioperative patient safety practices. CONCLUSIONS: A set of 101 comprehensive, evidence-based, patient-centred perioperative patient safety practices was developed through a European consensus process to improve the quality of care in healthcare facilities across Europe and beyond.
- Keywords
- evidence-based practice, medical errors patient safety, perioperative care, practice guidelines, quality, risk management, safety,
- MeSH
- Patient Safety * standards MeSH
- Delphi Technique MeSH
- Consensus MeSH
- Humans MeSH
- Evidence-Based Medicine * methods MeSH
- Patient-Centered Care * standards MeSH
- Perioperative Care * standards methods MeSH
- Practice Guidelines as Topic * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
- Geographicals
- Europe MeSH
Urbanization with a rapid expansion of the road network disrupts ecological processes, fragmenting the landscape, and reducing biodiversity. The frequent machine and human activities involved in road construction led to significant pressure on ecosystems. However, research on the impact of roading building processes in different stages remains lacking information. We performed a bird census for a new highway construction, the SE-40 ring road in Seville, with three-stages: a) active works, b) suspended works stage surrounding, and c) control stage in a natural condition. We analyzed similarities in community composition and bioindicators using the Indicator Value (IndVal) analysis between different stages. Additionally, we calculated several avian biodiversity metrics, including bird species richness, abundance, biodiversity, and diet-specialist species richness (DSR) and abundance (TAB). Road construction significantly impacted species composition (NMDS, ANOSIM p < 0.001, R2 = 0.1692); both active (P. adjusted = 0.006) and suspended work (P. adjusted = 0.009) stages display differences compared to the control group. The number of species and bioindicator increases, but diet-specialist species decreased, from active works (bioindicator = 3; mean TAB = 6; mean DSR = 19) to control group (4; 4.89; 12.61) to suspended works (5; 5.67; 14.89), reflecting a higher homogeneity during the active works with lowest biodiversity (mean Shannon = 2.69 and Simpson = 0.92). Our findings highlight the overlooked value of suspended works as provisional habitats for bird assemblages, suggesting that areas with intensive human activity need specific biodiversity monitoring and implications for conservation efforts. Rigorous specific biodiversity monitoring is essential to mitigate long-term impacts and inform adaptive road planning strategies.
- Keywords
- Anthropic pressure, Avian assemblages, Bird conservation, Road network, Spain,
- Publication type
- Journal Article MeSH
The use of artificial intelligence (AI) is increasingly integral to the drug-discovery process, and among AI-driven methodologies, deep generative models stand out as one of the most promising approaches for hit identification and optimization. Here, we report a retrospective benchmarking analysis of a series of tubulin inhibitors, 3-aroyl-1,4-diarylpyrroles (ARDAP), using the deep-generative algorithm Molecule Optimization by Reinforcement Learning and Docking (MORLD) in combination with five docking software (QuickVina 2, AutoDock-GPU, PLANTS, GOLD, and Glide). Our results indicate that the performance of the MORLD/docking workflow is highly dependent on the availability of initial structural information; only the incorporation of a core constraint in Glide yields satisfactory predictions. To address this limitation, we developed a docking-free variant of MORLD that exploits receptor-derived shape similarity and pharmacophore alignment. Kernel-density estimation, convergence analysis, and SMARTS-based success-rate metrics confirmed that this Shape-Pharmacophore implementation autonomously generates chemically valid, SAR-consistent analogues of the reference compounds. Collectively, this work demonstrates a practical, structure-only driven paradigm for reinforcement-learning-based compound optimization, thereby extending the reach of AI-enabled drug design beyond traditional docking workflows.
- MeSH
- Algorithms MeSH
- Benchmarking MeSH
- Pharmacophore MeSH
- Tubulin Modulators * chemistry pharmacology metabolism MeSH
- Drug Discovery MeSH
- Pyrroles * chemistry pharmacology metabolism MeSH
- Retrospective Studies MeSH
- Molecular Docking Simulation * MeSH
- Tubulin metabolism chemistry MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Tubulin Modulators * MeSH
- Pyrroles * MeSH
- Tubulin MeSH
This study investigates the passive viscoelastic properties of cardiac muscle by introducing a theoretical model that explains the observed power-law kinetics of murine cardiac trabeculae passive stress decay. The model accounts for two parallel processes contributing to passive mechanics: an elastic component and a viscoelastic component designed to simulate stress/strain-mediated unfolding of serial domains in the titin molecule. Under stress, serial globular domains within the elastic region of the titin molecule reversibly unfold. This unfolding phenomenon contributes to both hysteresis (a lag in stress between loading and unloading) and preconditioning effects in simulated mechanics. Experimental evidence indicates that stress relaxation in cardiac muscle follows a power law and that the muscle's non-linear stress-strain relationship and hysteresis behaviour are calcium-dependent. To analyse these phenomena, we simulate the apparent viscous element as a mesoscopic-scale ensemble of chains, each composed of serial globular domains that unfold in a stress-dependent manner. The observed increase in passive tension with increased Ca2+ concentration is attributed to Ca2+-mediated: (1) PEVK attachment to actin; (2) stiffening of the proximal element; and (3) stabilization of folded conformations of serial domains in the titin chain. Although the model was developed to represent the behaviour of titin, it equivalently represents any contributing process involving a linked series of domains that undergo stress-mediated unfolding. By providing a unified basis for the observed viscoelastic and preconditioning effects, calcium dependency, and power-law stress relaxation phenomena, this study offers a novel theoretical basis for understanding and simulating the role of titin in striated muscle mechanics. KEY POINTS: Passive stress relaxation of cardiac muscle follows a power-law decay, a phenomenon that is explained using a theoretical model of dynamic unfolding of globular domains along polymer chain. The theoretical model simulates the behaviour of titin, a giant sarcomere protein linking myosin thick filaments to the Z disk and providing passive restoring force during muscle stretch. The theoretical model is able to account the observed effects of Ca2+ on the effective viscoelastic passive mechanics of cardiac muscle. This model provides a theoretical basis for understanding passive viscocelastic properties and titin's role in striated muscle mechanics.
- Keywords
- calcium, cardiomyocyte, model, power law, titin, viscoelasticity,
- Publication type
- Journal Article MeSH
BACKGROUND: Most countries now have physical activity (PA) policies but translating them into action at national and subnational levels remains poor. To better understand the disconnect, the "Interaction between National and Local Government Levels in Development and Implementation of Physical Activity Policies Tool" (INTEGRATE-PA-Pol) was developed by the Global Observatory for Physical Activity (GoPA!). METHODS: The Czech Republic was chosen as a European pilot site based on existing research capacity and relationships. The INTEGRATE-PA-Pol tool was translated and adapted for use in the country. This questionnaire-based tool has 8 components assessing government levels, political system, and sectors across the 5 stages of the PA policy process. Key informants were from the health, sport, and recreation sectors at the national, regional (Olomouc Region), and municipal (Olomouc City) levels of government. Data was collected via online surveys. RESULTS: PA policy documents and budgets were identified at all levels, but implementation of policy and programs was noted to be limited. In 10 of the 12 interaction categories, the roles of other government levels in PA policy were rated as low. A wide range of populations, settings, and sectors were identified as important for PA promotion across the 3 levels of government, with notable variability. CONCLUSIONS: This pilot study suggests that PA policy in the Czech Republic is well developed, despite gaps in sector engagement, and inconsistent prioritization of populations and settings. Even with budget allocated, PA policy implementation remains challenging, probably in part due to poor articulation between national and subnational governments.
- Keywords
- INTEGRATE-PA-Pol, evaluation, interaction, policymaking,
- Publication type
- Journal Article MeSH
With the advancement of digitalization and blended learning, the integration of internationalization and technology has become increasingly significant in the context of English-medium Instruction (EMI). Both in-person and live online EMI courses delivered by foreign teachers (EMI-FT) have emerged as key components of Chinese universities' internationalization strategies. EMI refers to the use of English to teach academic subjects in non-English-speaking countries, exposing students to the challenges of intercultural learning and communication. Prior research indicates that such environments often provoke emotional disturbances, especially in virtual settings where interpersonal engagement is limited. As an essential component of intercultural competence, intercultural sensitivity (IS) is believed to play a crucial role in enhancing students' ability to adapt and succeed in EMI-FT environments. Specifically, IS may influence deep learning (DL), which promotes a deeper understanding and the application of knowledge. However, existing studies have rarely examined how IS affects students' learning experiences and outcomes in both in-person and online EMI-FT contexts. Guided by Biggs' 3P (Presage-Process-Product) model, our study constructs a mediation framework to investigate the relationships among IS, DL, and learning outcomes (LO) across both delivery modes. Data were collected using self-reported instruments from 1192 students across five universities in southern China. The results revealed that: (1) students perceived live online EMI-FT as less effective than in-person EMI-FT in promoting DL and LO; (2) IS was positively associated with both DL and LO; (3) DL mediated the relationship between IS and LO, with a more substantial mediation effect in the online setting; and (4) multi-group analysis revealed significant differences in the IS-DL-LO pathways between in-person and online samples. These findings offer actionable insights for universities seeking to tailor EMI-FT strategies to enhance student engagement and learning across diverse instructional formats.
- Keywords
- Deep learning, English medium instruction, Foreign teachers, In-person learning, Intercultural sensitivity, Learning outcomes, Online learning,
- Publication type
- Journal Article MeSH
Root aerenchyma is essential for survival under waterlogged conditions for plants. It has been necessary to explore a model system of schizogenous aerenchyma in Brassicaceae. Here, we report the formation of schizogenous aerenchyma in primary roots of seedlings of Cardamine amara showing a rather simple cartwheel pattern. The formation of the aerenchyma was suggested to involve three developmental processes: (1) formation of a three-layered cortex, (2) circumferential division of the outer layer of the cortex, and (3) circumferential detachment of cells in the middle layer of the cortex. The root aerenchyma of the C. amara seedling discovered here is the simplest one ever reported, and is a suitable candidate for the model of schizogenous aerenchyma development in plants.
- Keywords
- Plant anatomy, Plant biology, Plant development, Plant physiology,
- Publication type
- Journal Article MeSH
This work deals with the peculiarities of the growth of carbon nanotubes (CNTs) by radiofrequency (RF) magnetron sputtering and with the effect of deposition parameters on the RF sputtering. In the deposition process, a type of plasma gas, power of the RF generator, deposition time of catalysts, and a type of catalyst metals were modified to reveal the impact of these changes on the CNT's growth. The obtained nanostructures were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) as well as energy-dispersive X-ray (EDX) and Raman spectroscopies. The best results were obtained when the deposition conditions were as follows: argon-assisted plasma, generator power 120 W, catalyst sputtering duration 20 s, and nickel serving as a catalyst. A flexible propylene glycol vapor (PGV) and hydrogen peroxide vapor (HPV) sensors based on RF-sputtered CNTs combined with the Fe2O3:ZnO material were fabricated, and its DC and AC gas-sensing properties were studied. Impedance spectroscopy was used to evaluate an equivalent electrical circuit of the sensor. Temperature modulation led to the effective use of the same nanostructured film for PGV and HPV detection at 150 and 50 °C, respectively. At 50 °C temperature, the sensor response ranged from 3 to 27 values in the HPV concentrations of 0.5-25 ppm, respectively, demonstrating short response/recovery times, high response repeatability, and temporal stability.
- Publication type
- Journal Article MeSH