Search Results (288)

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder responsible for nearly a quarter of sports-related sudden cardiac deaths. ACM cases caused by mutations in desmosome proteins lead to right ventricular enlargement, the loss of cardiomyocytes, and fibrofatty tissue replacement, disrupting electrical and mechanical stability. It is currently unknown how paracrine factors secreted by infiltrating fatty tissues affect ACM cardiomyocyte electrophysiology. Methods: A normal and a PKP2 mutant (c.971_972InsT) ACM hiPSC line were cultivated and differentiated into cardiomyocytes (CMs). Adipocytes were differentiated from human adipose stem cells, and adipocyte conditioned medium (AdCM) was collected. Optical mapping and phenotypic analyses were conducted on human iPSC-cardiomyocytes (hiPSC-CMs) cultured in cardiac maintenance medium (CMM) and either with AdCM or specific cytokines. Results: Significant differences were observed in voltage parameters such as the action potential duration (APD₈₀, APD₃₀), conduction velocity (CV), and CV heterogeneity. When cultured in AdCM relative to CMM, the APD₈₀ increased and the CV decreased significantly in both groups; however, the magnitudes of changes often differed significantly between 1 and 7 days of cultivation. Cytokine exposure (IL-6, IL-8, MCP-1, CFD) affected the APD and CV in both the normal and PKP2 mutant hiPSC-CMs, with opposite effects. NF-kB signaling was also found to differ between the normal and PKP2 mutant hiPSC-CMs in response to AdCM and IL-6. Conclusions: Our study shows that hiPSC-CMs from normal and mPKP2 ACM lines exhibit distinct molecular and functional responses to paracrine factors, with differences in RNA expression and electrophysiology. These different responses to paracrine factors may contribute to arrhythmogenic propensity. Full article

Three-dimensional virtual modeling is one of the tools being rapidly implemented in the construction industry, leading to the need for strategies based on intelligent 3D models of cities and/or digital twins, which allow simulation by interacting with their real physical counterparts, anticipating the outcomes of decision making. In practice, problems arise when creating and managing these twins, as different data, models, technology, and tools must be used, and they cannot all be combined as desired due to certain incompatibilities. On the other hand, today’s traditional building management demands a more optimized process to prevent errors and enable timely reactions to failures and defects. Managing and using a large amount of complex and disparate data are required, which is why the use of CMMS-type software is common (Computerized Maintenance Management System). However, such software is rarely designed for management in a 3D format, often due to the absence of three-dimensional models of the assets. This research aims to contribute to the technological development of the digitalization of the built environment, providing a simple methodology for generating and managing 3D models of cities. To achieve this, the tools and information useful for generating an integrated GIS 3D and BIM model, and for Computer-Aided Maintenance Management in a three-dimensional format (CMMS-3D), are identified. The final model obtained is used to optimize the three-dimensional management of a classroom building on the “Campus de Las Llamas” at the University of Cantabria in Spain. The results demonstrate that it is possible to integrate digital models with simple linking mechanisms between the existing tools, thus achieving an optimal three-dimensional management model. Full article

Background: This study introduces a novel dexamethasone (DEX) mixed micellar system (DEX-MM) using Soluplus^® and Pluronic F-127 (PF127) to enhance ocular drug delivery. The enhancement of ocular application properties was achieved by creating a chitosan-coated DEX-MM (DEX-CMM), which promotes better adherence to the ocular surface, thereby improving drug absorption. Methods: Using the solvent evaporation method, a formulation was developed with a Soluplus^®-to-drug ratio of 1:10, enhanced with 0.25% PF127. After dispersing in water, 1% chitosan (CS) was added. The stability and integrity of DEX within the micelles were verified using attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). Additionally, in vitro and ex vivo drug release studies were conducted. Results: DEX-CMM (F6) demonstrated a particle size of 151.9 ± 1 nm and a polydispersity index (PDI) of 0.168 ± 0.003, suggesting uniformity and high electrostatic stability with a zeta potential of +35.96 ± 2.13 mV. The non-Fickian drug release mechanism indicated prolonged drug retention. Comparative analyses showed DEX-CMM outperforming a standard DEX suspension in drug release and ocular tissue permeation, with flux measurements significantly higher than the DEX suspension. Conclusion: The study confirmed the efficacy of DEX-CMM in enhancing drug delivery to ocular tissues, evidenced by improved permeability. Safety evaluations using the HET-CAM test demonstrated that DEX-CMM was non-irritant, supporting its potential for effective ocular drug delivery. Full article

In this paper, a heating device is implemented by considering two large factors in a 100 cmm RTO design. First, when the combustion chamber is used for a long time with a high temperature of 750–1100 °C depending on the high concentration VOC gas capacity, there is a problem that the combustion chamber explodes or the function of the rotary is stopped due to the fatigue and load of the device. To prevent this, the 100 cmm RTO design with a changed rotary position is improved. Second, an RTO design with a high-heating element is implemented to combust VOC gas discharged from the duct at a stable temperature. Through this, low-emission combustion emissions and energy consumption are reduced. By implementing a high heat generation device, the heat storage combustion oxidation function is improved through the preservation of renewable heat. Over 177 h of demonstration time, we improved the function of 100 cm by discharging 99% of VOC’s removal efficiency, 95.78% of waste heat recovery rate, 21.95% of fuel consumption, and 3.9 ppm of nitrogen oxide concentration. Full article

Dimensional and profile measurements of deep-hole parts are key processes both in manufacturing and product lifecycle management. Due to the particularity of the space conditions of deep-hole parts, the existing measurement instruments and methods exhibit some limitations. Based on the multi-axis, highly precise servo drive system, a novel measuring device is developed. The laser displacement sensors are fed by the flux-switching permanent magnet linear motor, and the part is rotated by the servo motor. On this basis, the assessment methods of roundness, straightness, and cylindricity are proposed by employing the least square method (LSM). Additionally, considering the axial center deviation between the sensors and the part, the rotating center coordinate is optimized by the gradient descent algorithm (GDM). Then, the measurement system is constructed and the experiment study is conducted. The results indicate favorable evaluation error of the LSM fitting and GDM iteration. Compared with the coordinate measuring machine (CMM), the measured results show good consistency. In the error analysis, the angle positioning error of measured point is less than 0.01°, and the axial positioning error is less than 0.05 mm. The proposed system and assessment method are regarded as a feasible and promising solution for deep-hole part measurements. Full article

Canine malignant melanoma (CMM) is highly aggressive and mostly located in the oral cavity. CMM is the predominant type of canine oral malignancy and shows striking homologies with human mucosal melanoma. In comparative oncology, canine oral melanomas (COMs), as spontaneous tumor models, have the potential to acquire a unique value as a translational model of rare human melanoma subtypes. This review aims to provide a comprehensive summary of targeted therapies for canine malignant melanoma and to enrich the field of comparative oncology. Following the PRISMA guidelines, a comprehensive literature search was conducted across databases for studies from 1976 to April 2024. Studies were selected based on their relevance to targeted treatments. A total of 30 studies met the inclusion criteria. Based on the treatment approaches, the studies were further categorized into immunotherapies, small molecule signaling inhibitors, indirect kinase inhibitors, and other alternative strategies. Some treatments have been shown to result in stable disease or partial response, accounting for 29% (monoclonal antibody) and 76.5% (micro-RNA therapies) in clinical trials. Moreover, in vitro experiments of small molecule inhibitors, including cell signaling inhibitors and indirect kinase inhibitors, have shown the potential to be an effective treatment option for the development of therapeutic strategies in canine malignant melanoma. The observed response in in vitro experiments of CMM (particularly the oral and certain cutaneous subtypes) to drugs used in the treatment of human melanoma underlines the resemblance to human melanoma, therefore supporting the notion that CMM may be a valuable model for understanding rare human melanoma subtypes and exploring potential therapeutic avenues in preclinical trials. Finally, this literature review serves as a valuable resource for the development of therapeutic strategies for CMM and highlights the potential for translating these findings to human cancer treatment. Full article

Additive Manufacturing (AM) is a pivotal technology for transforming complex geometries with minimal tooling requirements. Among the several AM techniques, Wire Arc Additive Manufacturing (WAAM) is notable for its ability to produce large metal components, which makes it particularly appealing in the aerospace sector. However, precise control of the bead geometry, specifically bead width and height, is essential for maintaining the structural integrity of WAAM-manufactured parts. This paper introduces a methodology using a Deep Neural Network (DNN) model for forecasting the bead geometry in the WAAM process, focusing on gas metal arc welding cold metal transfer (GMAW-CMT) WAAM. This study addresses the challenges of bead geometry prediction by developing a robust predictive framework. Key process parameters, such as the wire travel speed, wire feed rate, and bead dimensions of the previous layer, were monitored using a Coordinate Measuring Machine (CMM) to ensure precision. The collected data were used to train and validate various regression models, including linear regression, ridge regression, regression, polynomial regression (Quadratic and Cubic), Random Forest, and a custom-designed DNN. Among these, the Random Forest and DNN models were particularly effective, with the DNN showing significant accuracy owing to its ability to learn complex nonlinear relationships inherent in the WAAM process. The DNN model architecture consists of multiple hidden layers with varying neuron counts, trained using backpropagation, and optimized using the Adam optimizer. The model achieved mean absolute percentage error (MAPE) values of 0.014% for the width and 0.012% for the height, and root mean squared error (RMSE) values of 0.122 for the width and 0.153 for the height. These results highlight the superior capability of the DNN model in predicting bead geometry compared to other regression models, including the Random Forest and traditional regression techniques. These findings emphasize the potential of deep learning techniques to enhance the accuracy and efficiency of WAAM processes. Full article

Coordinate measuring machines (CMMs) are utilized to acquire coordinate data from manufactured surfaces for inspection reasons. These data are employed to gauge the geometric form errors associated with the surface. An optimization procedure of fitting a substitute surface to the measured points is applied to assess the form error. Since the traditional least-squares approach is susceptible to overestimation, it leads to unreasonable rejections. This paper implements a modified differential evolution (DE) algorithm to estimate the minimum zone femoral head sphericity. In this algorithm, opposition-based learning is considered for population initialization, and an adaptive scheme is enacted for scaling factor and crossover probability. The coefficients of the correlation factor and the uncertainty propagation are also measured so that the result’s uncertainty can be determined. Undoubtedly, the credibility and plausibility of inspection outcomes are strengthened by evaluating measurement uncertainty. Several data sets are used to corroborate the outcome of the DE algorithm. CMM validation shows that the modified DE algorithm can measure sphericity with high precision and consistency. This algorithm allows for an adequate initial solution and adaptability to address a wide range of industrial problems. It ensures a proper balance between exploitation and exploration capabilities. Thus, the suggested methodology, based on the computational results, is feasible for the online deployment of the sphericity evaluation. The adopted DE strategy is simple to use, has few controlling variables, and is computationally less expensive. It guarantees a robust solution and can be used to compute different form errors. Full article

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC₅₀ = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior. Full article

Understanding shock wave behavior in supersonic flow environments is critical for optimizing the aerodynamic performance of turbomachinery components. This study introduces a novel transonic linear cascade design, focusing on advanced blade manufacturing and experimental validation. Blades were 3D-printed using Inconel 625, enabling tight control over the geometry and surface quality, which were verified through extensive dimensional accuracy assessments and surface finish quality checks using coordinate measuring machines (CMMs). Numerical simulations were performed using Ansys CFX with an implicit pressure-based solver and high-order numerical schemes to accurately model the shock wave phenomena. To validate the simulations, experimental tests were conducted using Schlieren visualization, ensuring high fidelity in capturing the shock wave dynamics. A custom-designed test rig was commissioned to replicate the specific requirements of the cascade, enabling stable and repeatable testing conditions. Experiments were conducted at three different inlet pressures (0.7-bar, 0.8-bar, and 0.9-bar gauges) at a constant temperature of 21 °C. Results indicated that the shock wave intensity and position are highly sensitive to the inlet pressure, with higher pressures producing more intense and extensive shock waves. While the numerical simulations aligned broadly with the experimental observations, discrepancies at finer flow scales suggest the need for the further refinement of the computational models to capture detailed flow phenomena accurately. Full article

Szechwan lovage rhizome (SLR, the rhizome of Ligusticum chuanxiong Hort., Chuanxiong in Chinese transliteration) is one Chinese materia medica (CMM) commonly used to activate blood circulation and remove blood stasis. SLR is applicable to most blood stasis syndromes. It has significant clinical efficacy in relation to human diseases of the cardiocerebrovascular system, nervous system, respiratory system, digestive system, urinary system, etc. Apart from China, SLR is also used in Singapore, Malaysia, the European Union, and the United States of America. However, the current chemical markers in pharmacopeia or monography for the quality assessment of SLR are not well characterized or specifically characterized, nor do they fully reflect the medicinal efficacy of SLR, resulting in the quality of SLR not being effectively controlled. CMM can only have medicinal efficacy when they are applied in vivo to an organism. The intensity of their pharmaceutical activities can more directly represent the quality of CMM. Therefore, the chemical constituents and pharmacological actions of SLR are reviewed in this paper. In order to demonstrate the medicinal efficacy of SLR in promoting blood circulation and removing blood stasis, bioassay methods are put forward to evaluate the pharmaceutical activities of SLR to improve hemorheology, hemodynamics, and vascular microcirculation, as well as its anti-platelet aggregation and anticoagulation properties. Through comprehensive analyses of these pharmaceutical properties, the quality and therapeutic value of SLR are ascertained. Full article

Background: Body composition (BC) techniques, including bioelectrical impedance analysis (BIVA), nutritional ultrasound^® (NU), and computed tomography (CT), can detect nutritional diagnoses such as sarcopenia (Sc). Sc in idiopathic pulmonary fibrosis (IPF) is associated with greater severity and lower survival. Our aim was to explore the correlation of BIVA, NU and functional parameters with BC at T12 level CT scans in patients with IPF but also its relationship with degree of Sc, malnutrition and mortality. Methods: This bicentric cross-sectional study included 60 IPF patients (85.2% male, 70.9 ± 7.8 years). Morphofunctional assessment (MFA) techniques included BIVA, NU, CT at T12 level (T12-CT), handgrip strength, and timed up and go. CT data were obtained using FocusedON^®. Statistical analysis was conducted using JAMOVI version 2.3.22 to determine the cutoff points for Sc in T12-CT and to analyze correlations with other MFA techniques. Results: the cutoff for muscle area in T12-CT was ≤77.44 cm² (area under the curve (AUC) = 0.734, sensitivity = 41.7%, specificity = 100%). The skeletal muscle index (SMI_T12CT) cutoff was ≤24.5 cm²/m² (AUC = 0.689, sensitivity = 66.7%, specificity = 66.7%). Low SMI_T12CT exhibited significantly reduced median survival and higher risk of mortality compared to those with normal muscle mass (SMI cut off ≥ 28.8 cm/m²). SMI_T12CT was highly correlated with body cell mass from BIVA (r = 0.681) and rectus femoris cross-sectional area (RF-CSA) from NU (r = 0.599). Cronbach’s α for muscle parameters across different MFA techniques and CT was 0.735, confirming their validity for evaluating muscle composition. Conclusions: T12-CT scan is a reliable technique for measuring low muscle mass in patients with IPF, specifically when the L3 vertebrae are not captured. An SMI value of <28.8 is a good predictor of low lean mass and 12-month mortality in IPF patients. Full article

Additive Manufacturing (AM) is advancing technologically towards the production of components for high-demand mechanical applications with stringent dimensional accuracy, leveraging metallic and ceramic raw materials. The AM process for ceramic components, known as Ultraviolet Laser Stereolithography (SLA), enables the fabrication of unique parts or small batches without substantial investments in molds and dies, and avoids the problems associated with traditional manufacturing, which involves multiple stages and final machining for precision. This study addresses the need to produce reference elements or targets for metrological applications, including verification, adjustment, or calibration of 3D scanners and mid- to high-range optical sensors. Precision spheres are a primary geometry in this context due to their straightforward mathematical definition, facilitating rapid and accurate error detection in equipment. Our objective is to exploit this novel SLA process along with the advantageous optical properties of technical ceramics (such as being white, matte, lightweight, and corrosion-resistant) to materialize these reference objects. Specifically, this work involves the fabrication of alumina hemispheres using SLA. The manufacturing process incorporates four design variables (wall thickness, support shape, fill type, and orientation) and one manufacturing variable (the arrangement of spheres on the printing tray). To evaluate the impact of the design variables, dimensional and geometric parameters (GD&T), including diameters, form errors, and their distribution on the surface of the sphere, have been characterized. These measurements are conducted with high accuracy using a Coordinate Measuring Machine (CMM). The study also examines the influence of these variables in the dimensional and geometric accuracy of the spheres. Correlations between various parameters were identified, specifically highlighting critical factors affecting process precision, such as the position of the piece on the print tray and the wall thickness value. The smallest diameter errors were recorded at the outermost positions of the tray (rear and front), while the smallest shape errors were found at the central position, in both cases with errors in the range of tens of micrometers. In any case, the smallest deformations were observed with the highest wall thickness (2 mm). Full article

Background: The global population is aging rapidly, leading to an increase in the prevalence of cardiometabolic multimorbidity (CMM). This study aims to investigate the association between dietary patterns and CMM among Chinese rural older adults. Methods: The sample was selected using a multi-stage cluster random sampling method and a total of 3331 rural older adults were ultimately included. Multivariate logistic regression analysis was used to examine the association between the latent dietary patterns and CMM. Results: The prevalence of CMM among rural older adults was 44.64%. This study identified four potential categories: “Low Consumption of All Foods Dietary Pattern (C1)”, “High Dairy, Egg, and Red Meat Consumption, Low Vegetable and High-Salt Consumption Dietary Pattern (C2)”, “High Egg, Vegetable, and Grain Consumption, Low Dairy and White Meat Consumption Dietary Pattern (C3)” and “High Meat and Fish Consumption, Low Dairy and High-Salt Consumption Dietary Pattern (C4)”. Individuals with a C3 dietary pattern (OR, 0.80; 95% CI, 0.66–0.98; p = 0.028) and a C4 dietary pattern (OR, 0.70; 95% CI, 0.51–0.97; p = 0.034) significantly reduced the prevalence of CMM compared with the C1 dietary pattern. Conclusions: Rural older adults have diverse dietary patterns, and healthy dietary patterns may reduce the risk of CMM. Full article

Due to the increasing requirements for the improvement of the accuracy of large coordinate-measuring machines (CMMs), the laser-tracing multi-station measurement technology, as one of the advanced precision measurement technologies, is worth studying in depth in terms of its practical application for the compensation of errors in large CMMs. Since it is difficult to maintain a constant temperature of about 20 °C in the actual workshop under the influence of solar radiation and convective heat transfer, there is a gradient in the spatial temperature distribution, and the overall temperature changes with the influence of external factors with synchronous hysteresis, it is difficult for the actual calibration environment to meet the standard environmental requirements. Therefore, the influence of temperature and other environmental factors on the accuracy of laser ranging and large-scale CMM calibration should not be ignored. In this paper, on the basis of analyzing the temperature distribution and change rule of large CMM measurement space under different working conditions, the radial basis function (RBF) neural network algorithm was used to build a non-uniform-temperature field model, and based on this model and the measurement principle of the laser-tracking instrument, the method of laser tracking and interferometric ranging accuracy enhancement was put forward under a non-uniform-temperature field. Finally, based on the multi-station technique of laser tracing, an accurate solution for the volumetric error of large CMMs under the condition of non −20 °C ambient temperature was realized. Simulation results proved that compared with the traditional temperature-compensation method, the proposed method improved the measurement accuracy of the volumetric error of a large-scale CMM using laser-tracing multi-station technology in a non-uniform-temperature field by 33.5%. This study provides a new approach for improving the accuracy of laser-tracer multi-station measurement systems. Full article