Exploring Pharmaceutical Powder Behavior in Commercial-Scale Bin Blending: A DEM Simulation Study.

Bin blending is one of the main steps in pharmaceutical production processes. Commercial-scale production of expensive products typically does not allow to perform a large number of experiments in order to optimize the process. Alternatively, Discrete Element Method (DEM) simulations can be used to evaluate the powder behavior (flow and blending pattern) during blending, identify the risks (e.g., segregation), and provide solutions to mitigate them. In this work, DEM simulations are used to investigate the blending of two granulated powders in commercial-scale cone and cylindrical (hoop) blenders. The DEM contact model parameters were calibrated based on the experimental compression and ring shear tests for both granulated powders to mimic the bulk powder behavior in the simulations. The model's output was compared to the experiments in one of the blending cases. The blending efficiency in the cone blenders was evaluated considering the fill levels, the presence of baffles, the rotating directions, the filling order, and the bin sizes. Furthermore, for the hoop blenders, the effects of blender's angle, rotation speed, and filling order were addressed. The main findings of the work were that, in cone blenders, the blending can be improved by introducing baffles and changing in the rotational direction frequently. In hoop blenders, blending can be improved by increasing the inclination angle from the horizontal plane and the rotational speed.

Floods modeling and analysis for Dubai using HEC-HMS model and remote sensing using GIS.

Floods accompanied by thunderstorms in developed cities are hazardous, causing damage to infrastructure. To secure infrastructure, it is important to employ an integrated approach, combining remote sensing, GIS and precipitation data. The model was developed based on the estimation of event-based runoff and investigated the relationship between runoff and impervious surfaces. The novel approach of combining Hydrologic Engineering Center's River Analysis System (HEC-GeoRAS) along with satellite imagery was utilized, where spatial data was combined with real-time values to run the model. As a first step, the Hydrologic Engineering Center-Hydrologic Modeling System (HEC-HMS) model was fed with information about precipitation, slope, soil type, as well as land use and land cover. The results reveal that the subbasins of Deira, Nief and Jumeirah have the largest impervious area and, thus, a higher probability of flood occurrence. The model was calibrated and validated using previous runoff events and by comparing observed and simulated streak flow and peak discharge against those reported in previous studies. It was found that the model is efficient and can be used in similar regions.

Survey on the resolution and accuracy of input data validity for SWAT-based hydrological models.

This review was conducted to highlight the most influential factors and specify the trends reducing uncertainty and increasing the accuracy of soil and water assessment tool (SWAT)-based hydrological models. Although the resolution of input data on the results of SWAT-based hydrological models has been extensively determined. There is still a gap in providing comprehensive review framework to be emerged for identifying the impact of the data resolution and accuracy. The factors taken into consideration in this study were the impact of digital elevation model (DEM) resolution, soil data resolution, land use and land cover (LULC) resolution, and the impact of weather data resolution. Identifying the best DEM resolution depends on the watershed response and hydrological processes. However, for sediment yield estimation, more attention should be paid to the accuracy of soil data. Furthermore, the impact of LULC resolution on the accuracy of streamflow is still not sufficiently understood, whereas fine resolution is required for an accurate simulation of the sediment yield. Sub-daily precipitation data is essential for an accurate estimation of streamflow. Despite the fact that climate forecast system reanalysis (CFSR) and tropical rainfall measuring mission (TRMM) are the most widely used climate products, climate hazards group infrared precipitation with station data (CHIRPS) produces an adequate estimation for streamflow when there is insufficient gauged data. However, other aspects have not been deeply taken into consideration, including the interactive and complementary impacts of these factors. Thus, more attention and focus should be given to these issues. This review and evaluation can be a significant guide for selecting the suitable input data to implement efficient SWAT-based watershed models.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 1. Calibration workflow.

In this work, a high-fidelity digital twin was developed to support the design and testing of control strategies for drug product manufacturing via direct compression. The high-fidelity digital twin platform was based on typical pharmaceutical equipment, materials, and direct compression continuous processes. The paper describes in detail the material characterization, the Discrete Element Method (DEM) model and the DEM model parameter calibration approach and provides a comparison of the system's response to the experimental results for stepwise changes in the API concentration at the mixer inlet. A calibration method for a cohesive DEM contact model parameter estimation was introduced. To assure a correct prediction for a wide range of processes, the calibration approach contained four characterization experiments using different stress states and different measurement principles, namely the bulk density test, compression with elastic recovery, the shear cell, and the rotating drum. To demonstrate the sensitivity of the DEM contact parameters to the process response, two powder characterization data sets with different powder flowability were applied. The results showed that the calibration method could differentiate between the different material batches of the same blend and that small-scale material characterization tests could be used to predict the residence time distribution in a continuous manufacturing process.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 2. Validation of calibration workflow.

This paper is the second in a series of two that describes the application of discrete element method (DEM) and reduced order modeling to predict the effect of disturbances in the concentration of drug substance at the inlet of a continuous powder mixer on the concentration of the drug substance at the outlet of the mixer. In the companion publication, small-scale material characterization tests, a careful DEM parameter calibration and DEM simulations of the manufacturing process were used to develop a reliable RTD models. In the current work, the same calibration workflow was employed to evaluate the predictive ability of the resulting reduced-order model for an extended design space. DEM simulations were extrapolated using a relay race method and the cumulative RTD was accurately parameterized using the n-CSTR model. By performing experiments and simulations, a calibrated DEM model predicted the response of a continuous powder mixer to step changes in the inlet concentration of an API. Thus, carefully calibrated DEM models was used to guide and reduce experimental work and to establish an adequate control strategy. In addition, a further reduction in the computational effort was obtained by using the relay race method to extrapolate results. The predicted RTD curves were then parameterized to develop reduced order models and used to simulate the process in a matter of seconds. Overall, a control strategy evaluation tool based on high-fidelity DEM simulations was developed using material-sparing small-scale characterization tests.

Coupled Computational Fluid Dynamics-Discrete Element Method Model for Investigation of Powder Effects in Nonconventional Laser Powder Bed Fusion Process.

The present study proposes a comprehensive 3D computational fluid dynamics-discrete element method (CFD-DEM) coupled simulation model to investigate the particle dynamics induced by SS316L metal vapor spouting during single-scan-track laser powder bed fusion (L-PBF) processing. The model provides the ability to examine the effects of nonconventional process variables such as the chamber pressure and gravitational force on the suppression of the spatter and denudation phenomena. The simulation results imply that adjusting the gravitational force provides an effective technique for suppressing both spatter formation and powder bed denudation. In addition, the chamber pressure has only a marginal effect on the denudation phenomenon. In particular, under a higher operating pressure, the metal vapor tends to spout in the upward direction, while under a lower pressure, the spouting is more radially distributed. As a result, the simulation results obtained in this study have suggested that the chamber pressure and gravitational force may both provide feasible approaches for suppressing the spattering and denudation phenomena, particularly in the L-PBF processing of light-weight materials.

Developmental eye movement test results of Hebrew-speaking children with cross-linguistic comparisons.

INTRODUCTION AND PURPOSE: The developmental eye movement (DEM) test is designed to assess saccadic eye movements and visual-verbal automaticity in children. This study aimed to assess whether there is a need for independent DEM Hebrew norms and to compare DEM results for Hebrew-speaking children with eight other language norms. METHODS: The DEM test was administered to 224 Hebrew-speaking children aged 6-13 years who met the inclusion criteria and read the numbers in Hebrew. Test C of the DEM was performed twice, once from right (R) to left (L) and once from L to R, in random order. Age group and language comparisons, including vertical and horizontal reading speeds, errors and horizontal/vertical (H/V) ratios in both directions were analysed. RESULTS: The participants were almost evenly distributed between the sexes (46.8% female). Statistically significant differences were found between age groups (6-9 and 10-13 years) for vertical and horizontal reading speeds and H/V ratios in both directions (p < 0.001). Older children, as compared to younger children, exhibited faster vertical and horizontal times, with fewer errors, as well as lower ratios (p < 0.001). No significant difference was noted between reading directions for horizontal time and H/V ratio within both age groups (6-9 year olds: p = 0.27 and p = 0.06; 10-13 year olds: p = 0.89 and p = 0.49, respectively). Comparison of DEM norms across languages showed significant differences, with post-hoc analysis revealing specific language-related variations. DEM results for Hebrew-speaking children had similar outcomes to both original English and French values. CONCLUSIONS: This study compared DEM results of Hebrew-speaking children and scores across nine languages. DEM test values for Hebrew-speaking children aligned with norms from other languages, particularly the French and original English norms, with consistent ratio scores. It is recommended for practitioners who test Hebrew-speaking children to continue using the original English norms and to enable the children to read using their preferred reading direction.

Optimization of and experimentation with a bifurcated swing tube strip fertilizer spreading device based on MBD-DEM coupling.

Introduction: To improve the utilization rate of fertilizers, realize the precise spreading of fertilizers in controllable strips, and ensure the uniformity of fertilizer spreading in both longitudinal and transversal directions, a bifurcated swing tube fertilizer spreading device driven by a spatial hammer pendulum crank mechanism was designed. Methods: First, the drive mechanism was designed based on the cylindrical pair of the mechanism. A mathematical model pendulum equation was used to design the swing tube, and the equation of motion of fertilizer particles was established by analyzing the motion and force of fertilizer particles in fertilizer spreading. The dynamic parameters of the fertilizer spreading device (nozzle height, forward velocity, and swing frequency) were identified as the test factors affecting the uniformity of fertilizer spreading. Second, the coupling model based on MBD-DEM was established, and the coupling simulation analysis of the fertilizer spreading process was carried out using EDEM-RecurDyn software. Taking the nozzle height, forward velocity, and swing frequency as test factors and the uniformity coefficient of longitudinal and transversal fertilizer spreading as evaluation indexes of the fertilizer discharging effect, we analyzed the influence of a single factor on the indexes. Moreover, the ternary quadratic generalized rotating combination response surface test established the regression equations of three factors and two evaluation indexes. Finally, the simulation and bench test were verified under the optimal combination of parameters and compared with the single swing tube bench test with the same parameter conditions. Results: The results of the single-factor test showed that the fertilizer discharge effect was better when the nozzle height was 350.0-450.0 mm, the forward velocity was 0.5-1.5 m/s, and the swing frequency was 1.40-2.00 Hz. The results of the response surface test proved that the nozzle height, forward velocity, and swing frequency all had a highly significant effect on the uniformity coefficient of fertilizer spreading in the longitudinal and transversal directions (P<0.01). Moreover, the optimization concluded that when the nozzle height is 450.0 mm, the forward velocity is 0.5-0.8 m/s, and when the swing frequency is within the range of 1.40-2.00 Hz, the uniformity coefficient of longitudinal fertilizer spreading is ≤25% and the uniformity coefficient of transversal fertilizer spreading is ≤45%. The results of bench validation showed that the errors of longitudinal and transversal fertilizer spreading uniformity coefficients in the bench test were 3.46% and 1.44%, respectively, and the simulation agreed with the bench test. The results of comparative tests showed that the uniformity coefficient of the longitudinal and transversal of the fertilizer spreading device was reduced by 50.33% and 14.95%, respectively, for the bifurcated swing tube compared with that of the single swing tube. It is proved that the bifurcated swing tube strip fertilizer spreading device can achieve the purpose of uniform fertilizer spreading and performs better than the single swing tube in fertilizer spreading. Conclusion: The results and methods of this study can provide a reference for the design of swing tube strip fertilizer spreading devices and related fertilizer spreading performance tests.

An unresolved SPH-DEM model for simulation of ductile and brittle surface erosion by abrasive water-jet (AWJ) impact.

The abrasive water-jet (AWJ) erosion process involves the complex interaction between fluid medium, abrasive particles and solid material, which brings great challenges to the establishment of numerical model. Because traditional grid-based methods are not suitable for the problems of local deformation and material removal, the meshfree method smoothed particle hydrodynamics (SPH), based on the unresolved coupling and the discrete element method (DEM), is adopted to establish the model for AWJ study. The fluid medium is treated as a weakly compressible viscous liquid, the solid material is treated as an elastic-plastic material, and the abrasives are treated as rigid bodies. The fluid and solid phases are discretized with SPH particles, and the abrasives are described with DEM particles. The Johnson-Cook (J-C) and Johnson-Holmquist-II (JH-2) constitutive models are used to describe the stress-strain behavior of ductile and brittle materials, respectively. The effectiveness of the numerical model is further verified by AWJ impact experiments. The plastic deformation and cumulative failure characteristics of ductile materials, and the crack formation and propagation characteristics of brittle materials are systematically analyzed. The results provide insight for the AWJ research and lay a foundation for investigation of other complex fluid-particle flow in a numerical way.

Robust self-propulsion in sand using simply controlled vibrating cubes.

Much of the Earth and many surfaces of extraterrestrial bodies are composed of non-cohesive particulate matter. Locomoting on such granular terrain is challenging for common robotic devices, either wheeled or legged. In this work, we discover a robust alternative locomotion mechanism on granular media-generating movement via self-vibration. To demonstrate the effectiveness of this locomotion mechanism, we develop a cube-shaped robot with an embedded vibratory motor and conduct systematic experiments on granular terrains of various particle properties and slopes. We investigate how locomotion changes as a function of vibration frequency/intensity on such granular terrains. Compared to hard surfaces, we find such a vibratory locomotion mechanism enables the robot to move faster, and more stably on granular surfaces, facilitated by the interaction between the body and surrounding grains. We develop a numerical simulation of a vibrating single cube on granular media, enabling us to justify our hypothesis that the cube achieves locomotion through the oscillations excited at a distance from the cube's center of mass. The simplicity in structural design and controls of this robotic system indicates that vibratory locomotion can be a valuable alternative way to produce robust locomotion on granular terrains. We further demonstrate that such cube-shaped robots can be used as modular units for vibratory robots with capabilities of maneuverable forward and turning motions, showing potential practical scenarios for robotic systems.

Characterization and validation of a prognostic model for the N6-methyladenosine-associated ferroptosis gene in colon adenocarcinoma.

Background: According to statistics, colon adenocarcinoma (COAD) ranks third in global incidence and second in mortality. The role of N6-methyladenosine (m6A) modification-dependent ferroptosis in tumor development and progression is gaining attention. Therefore, it is meaningful to explore the biological functions mediated by m6A ferroptosis related genes (m6A-Ferr-RGs) in the prognosis and treatment of COAD. This study aimed to explore the regulatory mechanisms and prognostic features of m6A-Ferr-RGs in COAD based on the COAD transcriptome dataset. Methods: The expression data of Ferr-RGs and the correlated analysis with prognosis related m6A regulators were conducted to obtain candidate m6A-Ferr-RGs. Then, the differentially expressed genes (DEGs) between COAD and normal samples were intersected with candidate m6A-Ferr-RGs to obtain differentially expressed m6A Ferr-RGs (DE-m6A-Ferr-RGs) in COAD. Cox regression analyses were performed to establish risk model and validated in the GSE17538 and GSE41258 datasets. The nomogram was constructed and verified by calibration curves. Moreover, tumor immune dysfunction and exclusion (TIDE) was used to assess immunotherapy response in two risk groups. Finally, the expression of m6A-Ferr-related prognostic genes was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: In total, 6 model genes (HSD17B11, VEGFA, CXCL2, ASNS, FABP4, and GPX2) were obtained to construct the risk model. The nomogram was established based on the independent prognostic factors for predicting survival of COAD. TIDE assessed that the high-risk group suffered from greater immune resistance. Ultimately, the experimental results confirmed that the expression trends of all model genes were consistent among data from public database. Conclusions: In this study, m6A-Ferr-related prognostic model for COAD was constructed using transcriptome data and clinical data of COAD in public database, which may have potential immunotherapy and chemotherapy guidance implications.

Vibration response of piles at different distances induced by shield tunneling in hard rock strata.

Excavation of subway tunnels in hard rock generates strong vibration waves that pose potential risks to the stability of surrounding structures. In this study, the discrete element method-finite difference method (DEM-FDM) coupling was adopted to build the model of tunnel structure-rock-pile, which was validated by field monitoring data. Then, the vibration response of piles under various pile-tunnel spacings was analyzed, revealing the occurrence of vibration peak rebound phenomena within certain distance ranges. The range of vibration effects was categorized. Furthermore, in shield tunneling construction, the energy induced by vibrations was mainly concentrated within the 50 Hz range. Low-frequency vibrations result in a wider effect range. The study also demonstrated that within a 1d (tunnel diameter) range of the pile-tunnel spacing, the vibration induced by shield tunneling construction had a more significant effect. As the pile-tunnel spacing increased, the piles transitioned from being subjected to bending forces to experiencing bending-shear forces. Finally, the vibration effects on the existing piles were evaluated under field working conditions. It also provided suggestions for construction based on the effects and laws of the pile dynamic response.

A Critical Analysis of the CFD-DEM Simulation of Pharmaceutical Aerosols Deposition in Upper Intra-Thoracic Airways: Considerations on Aerosol Transport and Deposition.

The reliability and accuracy of numerical models and computer simulations to study aerosol deposition in the human respiratory system is investigated for a patient-specific tracheobronchial tree geometry. A computational fluid dynamics (CFD) model coupled with discrete elements methods (DEM) is used to predict the transport and deposition of the aerosol. The results are compared to experimental and numerical data available in the literature to study and quantify the impact of the modeling parameters and numerical assumptions. Even if the total deposition compares very well with the reference data, it is clear from the present work how local deposition results can depend significantly upon spatial discretization and boundary conditions adopted to represent the respiratory act. The modeling of turbulent fluctuations in the airflow is also found to impact the local deposition and, to a minor extent, the flow characteristics at the inlet of the computational domain. Using the CFD-DEM model, it was also possible to calculate the airflow and particles splitting at bifurcations, which were found to depart from the assumption of being equally distributed among branches adopted by some of the simplified deposition models. The results thus suggest the need for further studies towards improving the quantitative prediction of aerosol transport and deposition in the human airways.

Modelling and optimization of an innovative facility for automated sorting of aluminium scraps.

The growing demand for aluminium worldwide makes aluminium recycling critical to realising a circular economy and increasing the sustainability of our world. One effective way to improve the impact of aluminium recycling is to develop cost-efficient automated sorting technologies for obtaining pre-defined high-quality aluminium scrap products, thus reducing undesirable downcycling and increasing environmental/economic benefits. In this work, an innovative facility, which includes singulation, sensor scanning, and ejection, is optimised for the automated sorting of aluminium scraps. The sorting facility is computationally studied by a virtual experiment model based on the discrete element method. The model considers particle-scale dynamics of complex-shaped scraps and mimics the automated operation of the facility. Based on virtual experiment modelling, the flow of scrap is optimized by computation, with the feasible operation of the sorting facility being proposed. Accordingly, the sorting facility has been built and model predictions are confirmed in actual operation.

Unresolved RBCs: An upscaling strategy for the CFD-DEM simulation of blood flow with deformable cells.

Numerical simulation of blood flow is a challenging topic due to the multiphase nature of this biological fluid. The choice of a specific method among the ones available in literature is often motivated by the physical scale of interest. Single-phase approximation allows for lower computational time, but does not consider this multiphase nature. Cell-level simulation, on the other hand, requires high computational resources and is limited to small scales. This work proposes a scale-up approach for cell-level simulation of blood flow, in the framework of unresolved CFD-DEM technique. This method offers the possibility to simulate hundreds of thousands of particles with limited computational effort, but requires specific models for fluid-particle interactions. Regarding blood flow, drag and lift force acting on the red blood cells (RBCs) are responsible for several macroscopic blood characteristics. Despite several correlations available for drag and lift force acting on rigid particles, specific force models for the simulation of deformable particles compatible with RBCs physics are missing. This study employs data obtained from cell-level simulations to derive equations then used in unresolved simulation of RBCs. The strategy followed during the modeling phase is presented, together with the model verification and validation. This approach returns satisfying results when used to simulate blood flow in large-scale channels. Up to half a million RBCs are considered, and computational effort is reported to allow a comparison with other existing methods. Future perspectives include further improvement of the model, such as a deeper understanding of particle-particle interactions.

The Computerized Developmental Eye Movement (DEM) Test: Normative Data for School-Aged Children.

The aim of the study was to determine the normative data of the computerized DEM test for school-age children in Latvia. The study analyzed data on the performance (test execution time, duration, number of fixations, and number of errors) of 291 children while completing the computerized DEM test. Eye movement fixations were recorded with a Tobii Pro Fusion video-oculograph (250 Hz). According to the results of the study, the performance of the computerized DEM test is 77 %. For the study, 1 SD (one standard deviation) was chosen as a criterion for determining test norms. In the study, the norms of the computerized DEM test in Latvia were developed in class groups-from 1st to 6th grade (aged 7 to 12 years), the results were summarized in a table as the minimum performance values of the computerized DEM test.

DEM parameters of slope cultivated purple soil in Southwest China and interaction mechanism between very narrow tine.

The establishment of discrete element method (DEM) model for simulating the behavior of viscous soil can significantly contribute to the development of agricultural machinery, particularly in hilly areas worldwide. There is limited research on the parameter calibration of the DEM for purple soil in the Southwest China and its interaction mechanism between very narrow tine. Piling up test, rotating drum test and design-expert 12.0 software were used to design Plackett-Burman test, steepest climb test and Box-Behnken test successively. Combined with soil intrinsic parameter measurement test, soil simulation parameter calibration and optimization were completed. Based on the optimized DEM simulation parameters, the average relative errors of static repose angle and dynamic repose angle were 1.934 and 2.289%, respectively. The accuracy of parameter calibration results of DEM simulation was proved. Three kinds of very narrow tines were designed and processed. The interaction model and mechanism between soil-touch parts and soil was established. The average relative errors between the DEM simulation results of the forward resistance and disturbance area of the three soil-touch parts and the soil bin test results were 7.22% and 11.24%, respectively, which further proved that the calibration results of DEM parameters of purple soil and the interaction model with the soil-touch parts in this study were reliable. The physical and interaction parameters of slope cultivated purple soil in Southwest China were determined based on static-dynamic repose angle, providing more accurate parameters for study of soil-touch parts.

Calibration and Validation of Simulation Parameters for Maize Straw Based on Discrete Element Method and Genetic Algorithm-Backpropagation.

There is a significant difference between the simulation effect and the actual effect in the design process of maize straw-breaking equipment due to the lack of accurate simulation model parameters in the breaking and processing of maize straw. This article used a combination of physical experiments, virtual simulation, and machine learning to calibrate the simulation parameters of maize straw. A bimodal-distribution discrete element model of maize straw was established based on the intrinsic and contact parameters measured via physical experiments. The significance analysis of the simulation parameters was conducted via the Plackett-Burman experiment. The Poisson ratio, shear modulus, and normal stiffness of the maize straw significantly impacted the peak compression force of the maize straw and steel plate. The steepest-climb test was carried out for the significance parameter, and the relative error between the peak compression force in the simulation test and the peak compression force in the physical test was used as the evaluation index. It was found that the optimal range intervals for the Poisson ratio, shear modulus, and normal stiffness of the maize straw were 0.32-0.36, 1.24 × 108-1.72 × 108 Pa, and 5.9 × 106-6.7 × 106 N/m3, respectively. Using the experimental data of the central composite design as the dataset, a GA-BP neural network prediction model for the peak compression force of maize straw was established, analyzed, and evaluated. The GA-BP prediction model's accuracy was verified via experiments. It was found that the ideal combination of parameters was a Poisson ratio of 0.357, a shear modulus of 1.511 × 108 Pa, and a normal stiffness of 6.285 × 106 N/m3 for the maize straw. The results provide a basis for analyzing the damage mechanism of maize straw during the grinding process.

Infection of Alfalfa Cotyledons by an Incompatible but Not a Compatible Species of Colletotrichum Induces Formation of Paramural Bodies and Secretion of EVs.

Hemibiotrophic fungi in the genus Colletotrichum employ a biotrophic phase to invade host epidermal cells followed by a necrotrophic phase to spread through neighboring mesophyll and epidermal cells. We used serial block face-scanning electron microscopy (SBF-SEM) to compare subcellular changes that occur in Medicago sativa (alfalfa) cotyledons during infection by Colletotrichum destructivum (compatible on M. sativa) and C. higginsianum (incompatible on M. sativa). Three-dimensional reconstruction of serial images revealed that alfalfa epidermal cells infected with C. destructivum undergo massive cytological changes during the first 60 h following inoculation to accommodate extensive intracellular hyphal growth. Conversely, inoculation with the incompatible species C. higginsianum resulted in no successful penetration events and frequent formation of papilla-like structures and cytoplasmic aggregates beneath attempted fungal penetration sites. Further analysis of the incompatible interaction using focused ion beam-scanning electron microscopy (FIB-SEM) revealed the formation of large multivesicular body-like structures that appeared spherical and were not visible in compatible interactions. These structures often fused with the host plasma membrane, giving rise to paramural bodies that appeared to be releasing extracellular vesicles (EVs). Isolation of EVs from the apoplastic space of alfalfa leaves at 60 h postinoculation showed significantly more vesicles secreted from alfalfa infected with incompatible fungus compared with compatible fungus, which in turn was more than produced by noninfected plants. Thus, the increased frequency of paramural bodies during incompatible interactions correlated with an increase in EV quantity in apoplastic wash fluids. Together, these results suggest that EVs and paramural bodies contribute to immunity during pathogen attack in alfalfa. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Prognostic Role of Lymphocyte-to-Monocyte Ratio (LMR) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations (DEM-TACE or cTACE) of the Liver: Exploring the Link between Tumor Microenvironment and Interventional Radiology.

Inflammation-based scores are biomarkers of the crosstalk between the tumor microenvironment and the immune response. Investigating the intricate relationship between the tumor stromal microenvironment, biomarkers, and the response to transcatheter arterial chemoembolization (TACE) is essential for early identification of TACE refractoriness or failure, providing insights into tumor biology and facilitating personalized therapeutic interventions. This study addresses a dearth of recent literature exploring the prognostic significance of the preoperative LMR in individuals from western countries diagnosed with stage B hepatocellular carcinoma (HCC) undergoing drug eluting microspheres TACE (DEM-TACE) or conventional TACE (cTACE). This international multi-center retrospective analysis included consecutive patients with stage B HCC who underwent TACE from January 2017 to June 2023. The study evaluated the ability of the preoperative LMR to predict complete response (CR), objective response (OR), sustained response duration (SRD) exceeding 6 months, successful downstaging at 6 months, progression-free survival (PFS) at 6 months, and overall survival (OS) at 6 months. The study population included 109 HCC patients and it was divided into low LMR (LMR < 2.24) and high LMR (LMR ≥ 2.24) groups, according to ROC curve analysis to select the optimal LMR cut-off value. High LMR was associated with lower Hepatitis C prevalence, higher absolute lymphocyte count, and a trend toward lower alpha-fetoprotein. The group with high LMRs exhibited superior CR rates (14.9% vs. 0%), overall OR (43.2% vs. 14.3%), and better PFS at 6 months (75.7% vs. 45.7%). The LMR, specifically categorized as <2.24 and ≥2.24, emerged as a robust predictor for treatment response and short-term outcomes in patients with stage B HCC undergoing DEM- or c-TACE.