Pharmacokinetic-Pharmacodynamic modeling of the analgesic effect of bupredermTM, in mice

Purpose: BupredermTM-Buprenorphine transdermal delivery system (BTDS) was developed for the treatment of post-operative and chronic pains. This study examined the relationship between the plasma concentration of buprenorphine and its analgesic effect (tail flick test) in order to assess the usefulness of pharmacokinetic-pharmacodynamic (PK-PD) modeling in describing this relationship. Methods: After patch application, plasma concentrations of bu- prenorphine in mice were measured for 72 hours with a validated LC/MS/MS system, and the analgesic effects were assessed by tail flick test for the period of 24 hours. A modified two- compartment open model was used to explain the PK properties of BTDS, and the PD model was characterized by slow receptor binding. Results: The peak buprenorphine level in plasma was achieved at 1-24 h and the effective therapeutic drug concentration was maintained for 72 hours. BupredermTM induced prolongation of tail-flick latency in a dose and time dependent manner. Maximum analgesic effect was attained at 3-6 h and was maintained for 24 h after patch application. Counter-clockwise hysteresis between the plasma concentration and the analgesic efficacy of BTDS was observed after BupredermTM application, indicating there was a delay between plasma concentrations and the effect observed. From the developed PK-PD model, Kd values (0.69-0.82 nM) that were derived from the pharmacodynamic parameters (Kon and Koff) are similar to the reported values (Kd = 0.76 ± 0.14 nM). Good agreement between the predicted and observed values was noted for the rate of change in analgesic effect data (R2 = 0.822, 0.852 and 0.774 for 0.24, 0.8 and 2.4 mg/patch, respectively). Conclusions: The established PK- PD model successfully described the relationship between plasma concentration of buprenorphine and its analgesic efficacy measured by the tail flick test. Our model might be useful in estimation and prediction of onset, magnitude and time course of concentration and pharmacological effects of BTDS and will be useful to simulate PK-PD profiles with clinical regimens.

Displacement field reconstruction in landslide physical modeling by using a terrain laser scanner e Part 2:Application and large strain/displacement and water effect analysis

Deformation analysis is fundamental in geotechnical modeling.Nevertheless,there is still a lack of an effective method to obtain the deformation field under various experimental conditions.In this study,we introduce a processebased physical modeling of a pileereinforced reservoir landslide and present an improved deformation analysis involving large strains and water effects.We collect multieperiod point clouds using a terrain laser scanner and reconstruct its deformation field through a point cloud processing workflow.The results show that this method can accurately describe the landslide surface deformation at any time and area by both scalar and vector fields.The deformation fields in different profiles of the physical model and different stages of the evolutionary process provide adequate and detailed landslide information.We analyze the large strain upstream of the pile caused by the pile installation and the consequent violent deformation during the evolutionary process.Furthermore,our method effectively overcomes the challenges of identifying targets commonly encountered in geotechnical modeling where water effects are considered and targets are polluted,which facilitates the deformation analysis at the wading area in a reservoir landslide.Eventually,combining subsurface deformation as well as numerical modeling,we comprehensively analyze the kinematics and failure mechanisms of this complicated object involving landslides and pile foundations as well as water effects.This method is of great significance for any geotechnical modeling concerning large-strain analysis and water effects.

Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique

BACKGROUND Postoperative delirium,particularly prevalent in elderly patients after abdominal cancer surgery,presents significant challenges in clinical management.AIM To develop a synthetic minority oversampling technique(SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients.METHODS In this retrospective cohort study,we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022.The incidence of postoperative delirium was recorded for 7 d post-surgery.Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not.A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium.The SMOTE technique was applied to enhance the model by oversampling the delirium cases.The model’s predictive accuracy was then validated.RESULTS In our study involving 611 elderly patients with abdominal malignant tumors,multivariate logistic regression analysis identified significant risk factors for postoperative delirium.These included the Charlson comorbidity index,American Society of Anesthesiologists classification,history of cerebrovascular disease,surgical duration,perioperative blood transfusion,and postoperative pain score.The incidence rate of postoperative delirium in our study was 22.91%.The original predictive model(P1)exhibited an area under the receiver operating characteristic curve of 0.862.In comparison,the SMOTE-based logistic early warning model(P2),which utilized the SMOTE oversampling algorithm,showed a slightly lower but comparable area under the curve of 0.856,suggesting no significant difference in performance between the two predictive approaches.CONCLUSION This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods,effectively addressing data imbalance.

Volume-averaged modeling of multiphase solidification with equiaxed crystal sedimentation in a steel ingot

Macrosegregation is a critical factor that limits the mechanical properties of materials.The impact of equiaxed crystal sedimentation on macrosegregation has been extensively studied,as it plays a significant role in determining the distribution of alloying elements and impurities within a material.To improve macrosegregation in steel connecting shafts,a multiphase solidification model that couples melt flow,heat transfer,microstructure evolution,and solute transport was established based on the volume-averaged Eulerian-Eulerian approach.In this model,the effects of liquid phase,equiaxed crystals,columnar dendrites,and columnar-to-equiaxed transition(CET)during solidification and evolution of microstructure can be considered simultaneously.The sedimentation of equiaxed crystals contributes to negative macrosegregation,where regions between columnar dendrites and equiaxed crystals undergo significant A-type positive macrosegregation due to the CET.Additionally,noticeable positive macrosegregation occurs in the area of final solidification in the ingot.The improvement in macrosegregation is beneficial for enhancing the mechanical properties of connecting shafts.To mitigate the thermal convection of molten steel resulting from excessive superheating,reducing the superheating during casting without employing external fields or altering the design of the ingot mold is indeed an effective approach to control macrosegregation.

Background removal from global auroral images:Data-driven dayglow modeling

Global images of auroras obtained by cameras on spacecraft are a key tool for studying the near-Earth environment.However,the cameras are sensitive not only to auroral emissions produced by precipitating particles,but also to dayglow emissions produced by photoelectrons induced by sunlight.Nightglow emissions and scattered sunlight can contribute to the background signal.To fully utilize such images in space science,background contamination must be removed to isolate the auroral signal.Here we outline a data-driven approach to modeling the background intensity in multiple images by formulating linear inverse problems based on B-splines and spherical harmonics.The approach is robust,flexible,and iteratively deselects outliers,such as auroral emissions.The final model is smooth across the terminator and accounts for slow temporal variations and large-scale asymmetries in the dayglow.We demonstrate the model by using the three far ultraviolet cameras on the Imager for Magnetopause-to-Aurora Global Exploration(IMAGE)mission.The method can be applied to historical missions and is relevant for upcoming missions,such as the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission.

Surrogate modeling for unsaturated infiltration via the physics and equality-constrained artificial neural networks

Machine learning(ML)provides a new surrogate method for investigating groundwater flow dynamics in unsaturated soils.Traditional pure data-driven methods(e.g.deep neural network,DNN)can provide rapid predictions,but they do require sufficient on-site data for accurate training,and lack interpretability to the physical processes within the data.In this paper,we provide a physics and equalityconstrained artificial neural network(PECANN),to derive unsaturated infiltration solutions with a small amount of initial and boundary data.PECANN takes the physics-informed neural network(PINN)as a foundation,encodes the unsaturated infiltration physical laws(i.e.Richards equation,RE)into the loss function,and uses the augmented Lagrangian method to constrain the learning process of the solutions of RE by adding stronger penalty for the initial and boundary conditions.Four unsaturated infiltration cases are designed to test the training performance of PECANN,i.e.one-dimensional(1D)steady-state unsaturated infiltration,1D transient-state infiltration,two-dimensional(2D)transient-state infiltration,and 1D coupled unsaturated infiltration and deformation.The predicted results of PECANN are compared with the finite difference solutions or analytical solutions.The results indicate that PECANN can accurately capture the variations of pressure head during the unsaturated infiltration,and present higher precision and robustness than DNN and PINN.It is also revealed that PECANN can achieve the same accuracy as the finite difference method with fewer initial and boundary training data.Additionally,we investigate the effect of the hyperparameters of PECANN on solving RE problem.PECANN provides an effective tool for simulating unsaturated infiltration.

A methodology for damage evaluation of underground tunnels subjected to static loading using numerical modeling

We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensities.To account for these variations,we utilized a Monte Carlo Simulation(MCS)technique coupled with the finite difference code FLAC^(3D),to conduct two thousand seven hundred numerical simulations of a horseshoe tunnel located within a rock mass with different geological strength index system(GSIs)and subjected to different states of static loading.To quantify the severity of damage within the rock mass,we selected one stress-based(brittle shear ratio(BSR))and one strain-based failure criterion(plastic damage index(PDI)).Based on these criteria,we then developed fragility curves.Additionally,we used mathematical approximation techniques to produce vulnerability functions that relate the probabilities of various damage states to loading intensities for different quality classes of blocky rock mass.The results indicated that the fragility curves we obtained could accurately depict the evolution of the inner and outer shell damage around the tunnel.Therefore,we have provided engineers with a tool that can predict levels of damages associated with different failure mechanisms based on variations in rock mass quality and in situ stress state.Our method is a numerically developed,multi-variate approach that can aid engineers in making informed decisions about the robustness of underground tunnels.

Artificial intelligence-driven radiomics study in cancer:the role of feature engineering and modeling

Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians.Moreover,some potentially useful quantitative information in medical images,especially that which is not visible to the naked eye,is often ignored during clinical practice.In contrast,radiomics performs high-throughput feature extraction from medical images,which enables quantitative analysis of medical images and prediction of various clinical endpoints.Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis,demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine.However,radiomics remains in a developmental phase as numerous technical challenges have yet to be solved,especially in feature engineering and statistical modeling.In this review,we introduce the current utility of radiomics by summarizing research on its application in the diagnosis,prognosis,and prediction of treatment responses in patients with cancer.We focus on machine learning approaches,for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling.Furthermore,we introduce the stability,reproducibility,and interpretability of features,and the generalizability and interpretability of models.Finally,we offer possible solutions to current challenges in radiomics research.

Modeling time-dependent mechanical behavior of hard rock considering excavation-induced damage and complex 3D stress states

To investigate the long-term stability of deep rocks,a three-dimensional(3D)time-dependent model that accounts for excavation-induced damage and complex stress state is developed.This model comprises three main components:a 3D viscoplastic isotropic constitutive relation that considers excavation damage and complex stress state,a quantitative relationship between critical irreversible deformation and complex stress state,and evolution characteristics of strength parameters.The proposed model is implemented in a self-developed numerical code,i.e.CASRock.The reliability of the model is validated through experiments.It is indicated that the time-dependent fracturing potential index(xTFPI)at a given time during the attenuation creep stage shows a negative correlation with the extent of excavationinduced damage.The time-dependent fracturing process of rock demonstrates a distinct interval effect of the intermediate principal stress,thereby highlighting the 3D stress-dependent characteristic of the model.Finally,the influence of excavation-induced damage and intermediate principal stress on the time-dependent fracturing characteristics of the surrounding rocks around the tunnel is discussed.

Progressive fragmentation of granular assemblies within rockslides: Insights from discrete-continuous numerical modeling

Rock fragmentation plays a critical role in rock avalanches,yet conventional approaches such as classical granular flow models or the bonded particle model have limitations in accurately characterizing the progressive disintegration and kinematics of multi-deformable rock blocks during rockslides.The present study proposes a discrete-continuous numerical model,based on a cohesive zone model,to explicitly incorporate the progressive fragmentation and intricate interparticle interactions inherent in rockslides.Breakable rock granular assemblies are released along an inclined plane and flow onto a horizontal plane.The numerical scenarios are established to incorporate variations in slope angle,initial height,friction coefficient,and particle number.The evolutions of fragmentation,kinematic,runout and depositional characteristics are quantitatively analyzed and compared with experimental and field data.A positive linear relationship between the equivalent friction coefficient and the apparent friction coefficient is identified.In general,the granular mass predominantly exhibits characteristics of a dense granular flow,with the Savage number exhibiting a decreasing trend as the volume of mass increases.The process of particle breakage gradually occurs in a bottom-up manner,leading to a significant increase in the angular velocities of the rock blocks with increasing depth.The simulation results reproduce the field observations of inverse grading and source stratigraphy preservation in the deposit.We propose a disintegration index that incorporates factors such as drop height,rock mass volume,and rock strength.Our findings demonstrate a consistent linear relationship between this index and the fragmentation degree in all tested scenarios.

Discontinuity development patterns and the challenges for 3D discrete fracture network modeling on complicated exposed rock surfaces

Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls.This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope,and the qualitative and quantitative study of the complex phenomena impact on threedimensional(3D)discrete fracture network(DFN)modeling.As the studies of the outcrop fracture pattern have been so far focused on local variations,thus,we put forward a statistical analysis of global variations.The entire outcrop is partitioned into several subzones,and the subzone-scale variability of fracture geometric properties is analyzed(including the orientation,the density,and the trace length).The results reveal significant variations in fracture characteristics(such as the concentrative degree,the average orientation,the density,and the trace length)among different subzones.Moreover,the density of fracture sets,which is approximately parallel to the slope surface,exhibits a notably higher value compared to other fracture sets across all subzones.To improve the accuracy of the DFN modeling,the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed.Subsequently,the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions.The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3e4 times.The study results present precise geological structural information,improve modeling accuracy,and provide practical solutions for addressing complex outcrop issues.

The relationship between compartment models and their stochastic counterparts:A comparative study with examples of the COVID-19 epidemic modeling

Deterministic compartment models(CMs)and stochastic models,including stochastic CMs and agent-based models,are widely utilized in epidemic modeling.However,the relationship between CMs and their corresponding stochastic models is not well understood.The present study aimed to address this gap by conducting a comparative study using the susceptible,exposed,infectious,and recovered(SEIR)model and its extended CMs from the coronavirus disease 2019 modeling literature.We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations.Based on this equivalence,we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment.The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics.However,it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs.Additionally,we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents.This model offered a balance between computational efficiency and accuracy.The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling.Furthermore,the results had implications for the development of hybrid models that integrated the strengths of both frameworks.Overall,the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.

Hybrid modeling for carbon monoxide gas-phase catalytic coupling to synthesize dimethyl oxalate process

Ethylene glycol(EG)plays a pivotal role as a primary raw material in the polyester industry,and the syngas-to-EG route has become a significant technical route in production.The carbon monoxide(CO)gas-phase catalytic coupling to synthesize dimethyl oxalate(DMO)is a crucial process in the syngas-to-EG route,whereby the composition of the reactor outlet exerts influence on the ultimate quality of the EG product and the energy consumption during the subsequent separation process.However,measuring product quality in real time or establishing accurate dynamic mechanism models is challenging.To effectively model the DMO synthesis process,this study proposes a hybrid modeling strategy that integrates process mechanisms and data-driven approaches.The CO gas-phase catalytic coupling mechanism model is developed based on intrinsic kinetics and material balance,while a long short-term memory(LSTM)neural network is employed to predict the macroscopic reaction rate by leveraging temporal relationships derived from archived measurements.The proposed model is trained semi-supervised to accommodate limited-label data scenarios,leveraging historical data.By integrating these predictions with the mechanism model,the hybrid modeling approach provides reliable and interpretable forecasts of mass fractions.Empirical investigations unequivocally validate the superiority of the proposed hybrid modeling approach over conventional data-driven models(DDMs)and other hybrid modeling techniques.

Exploring Capillary Fringe Flow:Quasilinear Modeling with Kirchhoff Transforms and Gardner Model

Recent studies have underscored the significance of the capillary fringe in hydrological and biochemical processes.Moreover,its role in shallow waters is expected to be considerable.Traditionally,the study of groundwater flow has centered on unsaturated-saturated zones,often overlooking the impact of the capillary fringe.In this study,we introduce a steady-state two-dimensional model that integrates the capillary fringe into a 2-D numerical solution.Our novel approach employs the potential form of the Richards equation,facilitating the determination of boundaries,pressures,and velocities across different ground surface zones.We utilized a two-dimensional Freefem++finite element model to compute the stationary solution.The validation of the model was conducted using experimental data.We employed the OFAT(One_Factor-At-Time)method to identify the most sensitive soil parameters and understand how changes in these parameters may affect the behavior and water dynamics of the capillary fringe.The results emphasize the role of hydraulic conductivity as a key parameter influencing capillary fringe shape and dynamics.Velocity values within the capillary fringe suggest the prevalence of horizontal flow.By variation of the water table level and the incoming flow q0,we have shown the correlation between water table elevation and the upper limit of the capillary fringe.

Total ionizing dose effect modeling method for CMOS digital-integrated circuit

Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID effects in complementary metaloxide semiconductor(CMOS)digital ICs based on the input/output buffer information specification(IBIS)was proposed.The digital IC was first divided into three parts based on its internal structure:the input buffer,output buffer,and functional area.Each of these three parts was separately modeled.Using the IBIS model,the transistor V-I characteristic curves of the buffers were processed,and the physical parameters were extracted and modeled using VHDL-AMS.In the functional area,logic functions were modeled in VHDL according to the data sheet.A golden digital IC model was developed by combining the input buffer,output buffer,and functional area models.Furthermore,the golden ratio was reconstructed based on TID experimental data,enabling the assessment of TID effects on the threshold voltage,carrier mobility,and time series of the digital IC.TID experiments were conducted using a CMOS non-inverting multiplexer,NC7SZ157,and the results were compared with the simulation results,which showed that the relative errors were less than 2%at each dose point.This confirms the practicality and accuracy of the proposed modeling method.The TID effect model for digital ICs developed using this modeling technique includes both the logical function of the IC and changes in electrical properties and functional degradation impacted by TID,which has potential applications in the design of radiation-hardening tolerance in digital ICs.

Modularized and Parametric Modeling Technology for Finite Element Simulations of Underground Engineering under Complicated Geological Conditions

The surrounding geological conditions and supporting structures of underground engineering are often updated during construction,and these updates require repeated numerical modeling.To improve the numerical modeling efficiency of underground engineering,a modularized and parametric modeling cloud server is developed by using Python codes.The basic framework of the cloud server is as follows:input the modeling parameters into the web platform,implement Rhino software and FLAC3D software to model and run simulations in the cloud server,and return the simulation results to the web platform.The modeling program can automatically generate instructions that can run the modeling process in Rhino based on the input modeling parameters.The main modules of the modeling program include modeling the 3D geological structures,the underground engineering structures,and the supporting structures as well as meshing the geometric models.In particular,various cross-sections of underground caverns are crafted as parametricmodules in themodeling program.Themodularized and parametric modeling program is used for a finite element simulation of the underground powerhouse of the Shuangjiangkou Hydropower Station.This complicatedmodel is rapidly generated for the simulation,and the simulation results are reasonable.Thus,this modularized and parametric modeling program is applicable for three-dimensional finite element simulations and analyses.

Modeling Analysis of Factors Influencing Wind-Borne Seed Dispersal: A Case Study on Dandelion

A weed is a plant that thrives in areas of human disturbance, such as gardens, fields, pastures, waysides, and waste places where it is not intentionally cultivated. Dispersal affects community dynamics and vegetation response to global change. The process of seed disposal is influenced by wind, which plays a crucial role in determining the distance and probability of seed dispersal. Existing models of seed dispersal consider wind direction but fail to incorporate wind intensity. In this paper, a novel seed disposal model was proposed in this paper, incorporating wind intensity based on relevant references. According to various climatic conditions, including temperate, arid, and tropical regions, three specific regions were selected to establish a wind dispersal model that accurately reflects the density function distribution of dispersal distance. Additionally, dandelions growth is influenced by a multitude of factors, encompassing temperature, humidity, climate, and various environmental variables that necessitate meticulous consideration. Based on Factor Analysis model, which completely considers temperature, precipitation, solar radiation, wind, and land carrying capacity, a conclusion is presented, indicating that the growth of seeds is primarily influenced by plant attributes and climate conditions, with the former exerting a relatively stronger impact. Subsequently, the remaining two plants were chosen based on seed weight, yielding consistent conclusion.

Effects of Andrade and Burgers rheologies on glacial isostatic adjustment modeling in Antarctica

Variations in ice mass deform the Earth and modify its gravity field,a process known as Glacial Isostatic Adjustment(GIA).GIA in Antarctica remains poorly constrained due to the cumulative effect of past and present ice-mass changes,the unknown history of the past ice-mass change,and the uncertainties on the mechanical properties of the Earth.This paper investigates the effect of using Andrade and Burgers viscoelastic rheologies,rather than the commonly used Maxwell rheology,to model GIA-induced deformation in Antarctica.The Love number and Green's function formalism are used to compute the radial surface displacements and the gravity changes induced by the past and present ice-mass changes.We consider an Earth model whose elastic properties and radial structure are averaged from the Preliminary Reference Earth Model and two viscosity profiles to account for the recently published results on the present ice-mass changes.Using the three rheological laws affects the temporal response of the Earth differently,leading to smaller discrepancies than those induced by the two viscosity structures.The differences are the largest between Maxwell and Burgers rheologies during the 100-1000 years following the beginning of the surface-mass change.Results show that using the Andrade and Burgers rheologies allows the Earth to respond on decennial to centennial time scales,up to 10 m more than Maxwell.Considering only the recent ice-mass changes,the deformation rates derived from Burgers and Andrade rheologies are several times larger than those estimated by Maxwell rheology.

Integrated Hydrological Modeling of the Godavari River Basin in Maharashtra Using the SWAT Model: Streamflow Simulation and Analysis

Hydrological modeling plays a crucial role in efficiently managing water resources and understanding the hydrologic behavior of watersheds. This study aims to simulate daily streamflow in the Godavari River Basin in Maharashtra using the Soil and Water Assessment Tool (SWAT). SWAT is a process-based hydrological model used to predict water balance components, sediment levels, and nutrient contamination. In this research, we used integrated remote sensing and GIS data, including Digital Elevation Models (DEM), land use and land cover (LULC) maps, soil maps, and observed precipitation and temperature data, as input for developing the SWAT model to assess surface runoff in this large river basin. The Godavari River Basin under study was divided into 25 sub-basins, comprising 151 hydrological response units categorized by unique land cover, soil, and slope characteristics using the SWAT model. The model was calibrated and validated against observed runoff data for two time periods: 2003-2006 and 2007-2010 respectively. Model performance was assessed using the Nash-Sutcliffe efficiency (NSE) and the coefficient of determination (R2). The results show the effectiveness of the SWAT2012 model, with R2 value of 0.84 during calibration and 0.86 during validation. NSE values also ranged from 0.84 during calibration to 0.85 during validation. These findings enhance our understanding of surface runoff dynamics in the Godavari River Basin under study and highlight the suit-ability of the SWAT model for this region.

Modeling human gastric cancers in immunocompetent mice

Gastric cancer(GC)is a major cause of cancer-related mortality worldwide.GC is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular features.This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics.In the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and dynamics.Preclinical mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic strategies.Herein,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.