Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c...Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.展开更多
The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functio...The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
This study proposes a novel approach to optimizing individual work schedules for book digitization using mixed-integer programming (MIP). By leveraging the power of MIP solvers, we aimed to minimize the overall digiti...This study proposes a novel approach to optimizing individual work schedules for book digitization using mixed-integer programming (MIP). By leveraging the power of MIP solvers, we aimed to minimize the overall digitization time while considering various constraints and process dependencies. The book digitization process involves three key steps: cutting, scanning, and binding. Each step has specific requirements and limitations such as the number of pages that can be processed simultaneously and potential bottlenecks. To address these complexities, we formulate the problem as a one-machine job shop scheduling problem with additional constraints to capture the unique characteristics of book digitization. We conducted a series of experiments to evaluate the performance of our proposed approach. By comparing the optimized schedules with the baseline approach, we demonstrated significant reductions in the overall processing time. In addition, we analyzed the impact of different weighting schemes on the optimization results, highlighting the importance of identifying and prioritizing critical processes. Our findings suggest that MIP-based optimization can be a valuable tool for improving the efficiency of individual work schedules, even in seemingly simple tasks, such as book digitization. By carefully considering specific constraints and objectives, we can save time and leverage resources by carefully considering specific constraints and objectives.展开更多
In order to solve the code debugging difficulties faced by students and relieve the pressure of manual personalized tutoring,this paper proposes a method for locating faults in student code,called SCFL(student code fa...In order to solve the code debugging difficulties faced by students and relieve the pressure of manual personalized tutoring,this paper proposes a method for locating faults in student code,called SCFL(student code fault location).This method utilizes a historical correct code repository composed of correct codes submitted by previous students in the same assignments.It standardizes the erroneous code and historical correct code variables simultaneously and calculates the abstract syntax change tree.Then,by establishing the mapping between the abstract syntax change tree and the student assignment code,the fault location results of the student assignment are calculated.The evaluation experiments show that the SCFL method has a result of 9.25 in the cumulative inspection statement count and 15.9%in the fault localization cost indicator.Both indicators are better than the three currently commonly used spectrum-based baseline methods.展开更多
Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disruptin...Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.展开更多
Objective: To assess the effectiveness of the created program in enhancing the knowledge of emergency room (ER) nurses in the emergency management of cardiovascular diseases (CVD). Methods: This study used a quasi-exp...Objective: To assess the effectiveness of the created program in enhancing the knowledge of emergency room (ER) nurses in the emergency management of cardiovascular diseases (CVD). Methods: This study used a quasi-experimental design with a one-group pretest-posttest research design to identify the knowledge and skills of emergency department (ED) nurses in managing CVD. There were 16 participants in this study. The mean, standard deviation (SD), and t-test were used to analyze the data. Results: Before the participants undergo the program, they have a mean (SD) score of 17.63 (5.19). After the completion of the didactic part of the program, they garnered a mean (SD) score of 19.94 (5.22). Moreover, after completion of the practicum part of the program, the mean (SD) score was 21.94 (5.04). Comparing the scores before the program and after finishing the didactic part of the program, the t-test scored (t (15) = -3.87, P = 0.001). Further, comparing the scores before the program and after finishing the didactic and practicum parts of the program, the t-test scored (t (15) = -5.57, P = 0.001). Conclusions: Based on the study’s results, the researchers conclude that the respondents had acceptable knowledge regarding the emergency management of CVD before the program. However, the Cardiac Enhancement Program for Emergency Cardiac Care boosted their knowledge. Also, the program is effective in enhancing the participants’ knowledge of the emergency management of CVD.展开更多
Background Follicular atresia significantly impairs female fertility and hastens reproductive senescence.Apoptosis of granulosa cells is the primary cause of follicular atresia.Pyroptosis and necroptosis,as additional...Background Follicular atresia significantly impairs female fertility and hastens reproductive senescence.Apoptosis of granulosa cells is the primary cause of follicular atresia.Pyroptosis and necroptosis,as additional forms of pro-grammed cell death,have been reported in mammalian cells.However,the understanding of pyroptosis and necrop-tosis pathways in granulosa cells during follicular atresia remains unclear.This study explored the effects of pro-grammed cell death in granulosa cells on follicular atresia and the underlying mechanisms.Results The results revealed that granulosa cells undergo programmed cell death including apoptosis,pyroptosis,and necroptosis during follicular atresia.For the first time,we identified the formation of a PANoptosome com-plex in porcine granulosa cells.This complex was initially identified as being composed of ZBP1,RIPK3,and RIPK1,and is recruited through the RHIM domain.Additionally,we demonstrated that caspase-6 is activated and cleaved,interacting with RIPK3 as a component of the PANoptosome.Heat stress may exacerbate the activation of the PANop-tosome,leading to programmed cell death in granulosa cells.Conclusions Our data identified the formation of a PANoptosome complex that promoted programmed cell death in granulosa cells during the process of follicular atresia.These findings provide new insights into the molecular mechanisms underlying follicular atresia.展开更多
In response to the current issues in the construction of software engineering(SE)degree granting program,such as insufficient resource integration,low level of internationalization,and inadequate quality control,we pr...In response to the current issues in the construction of software engineering(SE)degree granting program,such as insufficient resource integration,low level of internationalization,and inadequate quality control,we propose the Software Engineering Degree Granting Program Construction Practice Project at Harbin Institute of Technology(HIT).This project aims to explore new models for software talent cultivation,establish a superior SE degree granting program,and ultimately cultivate outstanding internationalized composite SE professionals to support the high-quality development of the national software industry.To this end,we design a distinctive overall construction idea and plan for the SE degree granting program,which are characterized by“3I3S:three highlights for specialized cultivation and strictness in three aspects to ensure quality control”.After years of practice and validation of the project at the School of Software at HIT,this project has proven effective in optimizing talent cultivation models,enhancing students’practical abilities,promoting international exchange and cooperation,advancing industry-education integration,and meeting industrial needs.展开更多
Evolutionary algorithms have been extensively utilized in practical applications.However,manually designed population updating formulas are inherently prone to the subjective influence of the designer.Genetic programm...Evolutionary algorithms have been extensively utilized in practical applications.However,manually designed population updating formulas are inherently prone to the subjective influence of the designer.Genetic programming(GP),characterized by its tree-based solution structure,is a widely adopted technique for optimizing the structure of mathematical models tailored to real-world problems.This paper introduces a GP-based framework(GPEAs)for the autonomous generation of update formulas,aiming to reduce human intervention.Partial modifications to tree-based GP have been instigated,encompassing adjustments to its initialization process and fundamental update operations such as crossover and mutation within the algorithm.By designing suitable function sets and terminal sets tailored to the selected evolutionary algorithm,and ultimately derive an improved update formula.The Cat Swarm Optimization Algorithm(CSO)is chosen as a case study,and the GP-EAs is employed to regenerate the speed update formulas of the CSO.To validate the feasibility of the GP-EAs,the comprehensive performance of the enhanced algorithm(GP-CSO)was evaluated on the CEC2017 benchmark suite.Furthermore,GP-CSO is applied to deduce suitable embedding factors,thereby improving the robustness of the digital watermarking process.The experimental results indicate that the update formulas generated through training with GP-EAs possess excellent performance scalability and practical application proficiency.展开更多
The purpose of this study is to investigate the effectiveness of the“expiration manager”mini program in managing the validity of ward items.The program was used to manage frequently and infrequently used consumables...The purpose of this study is to investigate the effectiveness of the“expiration manager”mini program in managing the validity of ward items.The program was used to manage frequently and infrequently used consumables by setting up an automatic reminder function.The item failure rate and the time required for nurses to conduct counts over 6 months before and after implementation were compared,as well as evaluated system availability using the System Usability scale(SUS).Results showed that after implementing the mini program,both the item failure rate and non-recognition rate significantly decreased(P<0.05),while the inspection pass rate significantly increased(P<0.05),and the monthly inventory time was reduced(P<0.05).The SUS evaluation yielded a total score of 74.38±11.73,with learnability at 80.21±20.27 and availability at 72.92±11.18,all indicating good user acceptance.In conclusion,the“expiration manager”mini program can effectively improve the efficiency of item expiration management,reduce the risk of expiration,and save inspection time,thereby demonstrating high user acceptance and promising potential for wider adoption.展开更多
Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its im...Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.展开更多
Tailoring thermal history during additive manufacturing(AM)offers a feasible approach to customise the microstructure and properties of materials without changing alloy compositions or post-heat treatment,which is gen...Tailoring thermal history during additive manufacturing(AM)offers a feasible approach to customise the microstructure and properties of materials without changing alloy compositions or post-heat treatment,which is generally overlooked as it is hard to achieve in commercial materials.Herein,a customised Fe-Ni-Ti-Al maraging steel with rapid precipitation kinetics offers the opportunity to leverage thermal history during AM for achieving large-range tunable strength-ductility combinations.The Fe-Ni-Ti-Al steel was processed by laser-directed energy deposition(LDED)with different deposition strategies to tailor the thermal history.As the phase transformation and in-situ formation of multi-scale secondary phases of the Fe-Ni-Ti-Al steel are sensitive to the thermal histories,the deposited steel achieved a large range of tuneable mechanical properties.Specifically,the interlayer paused deposited sample exhibits superior tensile strength(∼1.54 GPa)and moderate elongation(∼8.1%),which is attributed to the formation of unique hierarchical structures and the in-situ precipitation of high-densityη-Ni_(3)(Ti,Al)during LDED.In contrast,the substrate heating deposited sample has an excellent elongation of 19.3%together with a high tensile strength of 1.24 GPa.The achievable mechanical property range via tailoring thermal history in the LDED-built Fe-Ni-Ti-Al steel is significantly larger than most commercial materials.The findings highlight the material customisation along with AM’s unique thermal history to achieve versatile mechanical performances of deposited materials,which could inspire more property or function manipulations of materials by AM process control or innovation.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
Assessing the stability of pillars in underground mines(especially in deep underground mines)is a critical concern during both the design and the operational phases of a project.This study mainly focuses on developing...Assessing the stability of pillars in underground mines(especially in deep underground mines)is a critical concern during both the design and the operational phases of a project.This study mainly focuses on developing two practical models to predict pillar stability status.For this purpose,two robust models were developed using a database including 236 case histories from seven underground hard rock mines,based on gene expression programming(GEP)and decision tree-support vector machine(DT-SVM)hybrid algorithms.The performance of the developed models was evaluated based on four common statistical criteria(sensitivity,specificity,Matthews correlation coefficient,and accuracy),receiver operating characteristic(ROC)curve,and testing data sets.The results showed that the GEP and DT-SVM models performed exceptionally well in assessing pillar stability,showing a high level of accuracy.The DT-SVM model,in particular,outperformed the GEP model(accuracy of 0.914,sensitivity of 0.842,specificity of 0.929,Matthews correlation coefficient of 0.767,and area under the ROC of 0.897 for the test data set).Furthermore,upon comparing the developed models with the previous ones,it was revealed that both models can effectively determine the condition of pillar stability with low uncertainty and acceptable accuracy.This suggests that these models could serve as dependable tools for project managers,aiding in the evaluation of pillar stability during the design and operational phases of mining projects,despite the inherent challenges in this domain.展开更多
Objectives:This study aimed to explore the effects of the“FuekFone(F.F.)home-based program”on the upper limb and cognitive function of ischemic stroke patients after discharge.Methods:A single group pre-and post-tes...Objectives:This study aimed to explore the effects of the“FuekFone(F.F.)home-based program”on the upper limb and cognitive function of ischemic stroke patients after discharge.Methods:A single group pre-and post-test design was conducted.A total of 40 patients with recovery after ischemic stroke were recruited from two university hospitals in Thailand.The study was conducted between June 2022 and January 2023.Participants underwent a six-week“F.F.home-based program,”which combined an upper limb and cognitive function rehabilitation device with Android games,including stationary barrel,adventure walk,adventure stroll,sliding barrel,sauce squeeze,and cut objects.Each game has different difficulty levels.Patients can perform corresponding exercises through the games according to their conditions under the guidance of medical staff.The patients played for 24 min per time,4 min each game,three days a week.The second week,let the patients play games for 30 min per time,5 min each game,3 days a week.Then,in the 3e6 weeks,let the patients play games for 1 h per time,10 min each game,5 days a week.At the pre-and post-intervention,the Thai version of the National Institutes of Health Stroke Scale(NIHSS),the Motor Assessment Scale,and the Montreal Cognitive Assessment(MoCA score)were administered to patients at discharge and at 2,4,and 6 weeksafter discharge,and the results were compared.Results:All participants completed this program.Participants had statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 2,4,and 6 weeks after discharge(P<0.001).In the comparison of upper limb function and cognitive function at each of the study times,we found statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 4,and 6 weeks after discharge when compared to after discharge and 2 weeks after discharge,respectively(P<0.05).Conclusions:Continuing care of patients post-stroke after discharge from hospital,such as F.F.homebased program should be applied at home to enhance upper limb and cognitive function.展开更多
BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated a...BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.展开更多
Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conv...Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems.In this study,a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model(ROM)and probabilistic programming.The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems.Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering.A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution.The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty.Then,a slope case was employed to demonstrate the performance of the developed framework.The results prove that the proposed framework provides a scientific,feasible,and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.展开更多
基金supported by Canada First Research Excellence Fund,Medicine by Design(to CMM)。
文摘Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.
基金supported by National Institute on Aging(NIH-NIA)R21 AG074152(to KMA)National Institute of Allergy and Infectious Diseases(NIAID)grant DP2 AI171150(to KMA)Department of Defense(DoD)grant AZ210089(to KMA)。
文摘The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
文摘This study proposes a novel approach to optimizing individual work schedules for book digitization using mixed-integer programming (MIP). By leveraging the power of MIP solvers, we aimed to minimize the overall digitization time while considering various constraints and process dependencies. The book digitization process involves three key steps: cutting, scanning, and binding. Each step has specific requirements and limitations such as the number of pages that can be processed simultaneously and potential bottlenecks. To address these complexities, we formulate the problem as a one-machine job shop scheduling problem with additional constraints to capture the unique characteristics of book digitization. We conducted a series of experiments to evaluate the performance of our proposed approach. By comparing the optimized schedules with the baseline approach, we demonstrated significant reductions in the overall processing time. In addition, we analyzed the impact of different weighting schemes on the optimization results, highlighting the importance of identifying and prioritizing critical processes. Our findings suggest that MIP-based optimization can be a valuable tool for improving the efficiency of individual work schedules, even in seemingly simple tasks, such as book digitization. By carefully considering specific constraints and objectives, we can save time and leverage resources by carefully considering specific constraints and objectives.
基金supported by the National Natural Science Foundation of China(Grant No.62177003)the Fundamental Research Funds for the Central Universities of Ministry of Education of China(Grant No.JKF-20240213)。
文摘In order to solve the code debugging difficulties faced by students and relieve the pressure of manual personalized tutoring,this paper proposes a method for locating faults in student code,called SCFL(student code fault location).This method utilizes a historical correct code repository composed of correct codes submitted by previous students in the same assignments.It standardizes the erroneous code and historical correct code variables simultaneously and calculates the abstract syntax change tree.Then,by establishing the mapping between the abstract syntax change tree and the student assignment code,the fault location results of the student assignment are calculated.The evaluation experiments show that the SCFL method has a result of 9.25 in the cumulative inspection statement count and 15.9%in the fault localization cost indicator.Both indicators are better than the three currently commonly used spectrum-based baseline methods.
基金financially supported by Ministerio de Ciencia e Innovación projects SAF2017-82736-C2-1-R to MTMFin Universidad Autónoma de Madrid and by Fundación Universidad Francisco de Vitoria to JS+2 种基金a predoctoral scholarship from Fundación Universidad Francisco de Vitoriafinancial support from a 6-month contract from Universidad Autónoma de Madrida 3-month contract from the School of Medicine of Universidad Francisco de Vitoria。
文摘Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
文摘Objective: To assess the effectiveness of the created program in enhancing the knowledge of emergency room (ER) nurses in the emergency management of cardiovascular diseases (CVD). Methods: This study used a quasi-experimental design with a one-group pretest-posttest research design to identify the knowledge and skills of emergency department (ED) nurses in managing CVD. There were 16 participants in this study. The mean, standard deviation (SD), and t-test were used to analyze the data. Results: Before the participants undergo the program, they have a mean (SD) score of 17.63 (5.19). After the completion of the didactic part of the program, they garnered a mean (SD) score of 19.94 (5.22). Moreover, after completion of the practicum part of the program, the mean (SD) score was 21.94 (5.04). Comparing the scores before the program and after finishing the didactic part of the program, the t-test scored (t (15) = -3.87, P = 0.001). Further, comparing the scores before the program and after finishing the didactic and practicum parts of the program, the t-test scored (t (15) = -5.57, P = 0.001). Conclusions: Based on the study’s results, the researchers conclude that the respondents had acceptable knowledge regarding the emergency management of CVD before the program. However, the Cardiac Enhancement Program for Emergency Cardiac Care boosted their knowledge. Also, the program is effective in enhancing the participants’ knowledge of the emergency management of CVD.
基金National Key Research and Development Program of China(2022YFD1300405)National Natural Science Foundation of China(32202671)Open project of State Key Laboratory of Animal Biotech Breeding(Grant No.2024SKLAB6-5).
文摘Background Follicular atresia significantly impairs female fertility and hastens reproductive senescence.Apoptosis of granulosa cells is the primary cause of follicular atresia.Pyroptosis and necroptosis,as additional forms of pro-grammed cell death,have been reported in mammalian cells.However,the understanding of pyroptosis and necrop-tosis pathways in granulosa cells during follicular atresia remains unclear.This study explored the effects of pro-grammed cell death in granulosa cells on follicular atresia and the underlying mechanisms.Results The results revealed that granulosa cells undergo programmed cell death including apoptosis,pyroptosis,and necroptosis during follicular atresia.For the first time,we identified the formation of a PANoptosome com-plex in porcine granulosa cells.This complex was initially identified as being composed of ZBP1,RIPK3,and RIPK1,and is recruited through the RHIM domain.Additionally,we demonstrated that caspase-6 is activated and cleaved,interacting with RIPK3 as a component of the PANoptosome.Heat stress may exacerbate the activation of the PANop-tosome,leading to programmed cell death in granulosa cells.Conclusions Our data identified the formation of a PANoptosome complex that promoted programmed cell death in granulosa cells during the process of follicular atresia.These findings provide new insights into the molecular mechanisms underlying follicular atresia.
基金supported in part by the Education Reform Key Projects of Heilongjiang Province under Grant Nos.SJGZ20220011,SJGZ20220012,and SJGZY2024008。
文摘In response to the current issues in the construction of software engineering(SE)degree granting program,such as insufficient resource integration,low level of internationalization,and inadequate quality control,we propose the Software Engineering Degree Granting Program Construction Practice Project at Harbin Institute of Technology(HIT).This project aims to explore new models for software talent cultivation,establish a superior SE degree granting program,and ultimately cultivate outstanding internationalized composite SE professionals to support the high-quality development of the national software industry.To this end,we design a distinctive overall construction idea and plan for the SE degree granting program,which are characterized by“3I3S:three highlights for specialized cultivation and strictness in three aspects to ensure quality control”.After years of practice and validation of the project at the School of Software at HIT,this project has proven effective in optimizing talent cultivation models,enhancing students’practical abilities,promoting international exchange and cooperation,advancing industry-education integration,and meeting industrial needs.
文摘Evolutionary algorithms have been extensively utilized in practical applications.However,manually designed population updating formulas are inherently prone to the subjective influence of the designer.Genetic programming(GP),characterized by its tree-based solution structure,is a widely adopted technique for optimizing the structure of mathematical models tailored to real-world problems.This paper introduces a GP-based framework(GPEAs)for the autonomous generation of update formulas,aiming to reduce human intervention.Partial modifications to tree-based GP have been instigated,encompassing adjustments to its initialization process and fundamental update operations such as crossover and mutation within the algorithm.By designing suitable function sets and terminal sets tailored to the selected evolutionary algorithm,and ultimately derive an improved update formula.The Cat Swarm Optimization Algorithm(CSO)is chosen as a case study,and the GP-EAs is employed to regenerate the speed update formulas of the CSO.To validate the feasibility of the GP-EAs,the comprehensive performance of the enhanced algorithm(GP-CSO)was evaluated on the CEC2017 benchmark suite.Furthermore,GP-CSO is applied to deduce suitable embedding factors,thereby improving the robustness of the digital watermarking process.The experimental results indicate that the update formulas generated through training with GP-EAs possess excellent performance scalability and practical application proficiency.
基金The First Affiliated Hospital of Shaoyang University,China(Project No.:23FY1015)。
文摘The purpose of this study is to investigate the effectiveness of the“expiration manager”mini program in managing the validity of ward items.The program was used to manage frequently and infrequently used consumables by setting up an automatic reminder function.The item failure rate and the time required for nurses to conduct counts over 6 months before and after implementation were compared,as well as evaluated system availability using the System Usability scale(SUS).Results showed that after implementing the mini program,both the item failure rate and non-recognition rate significantly decreased(P<0.05),while the inspection pass rate significantly increased(P<0.05),and the monthly inventory time was reduced(P<0.05).The SUS evaluation yielded a total score of 74.38±11.73,with learnability at 80.21±20.27 and availability at 72.92±11.18,all indicating good user acceptance.In conclusion,the“expiration manager”mini program can effectively improve the efficiency of item expiration management,reduce the risk of expiration,and save inspection time,thereby demonstrating high user acceptance and promising potential for wider adoption.
基金partially supported by the National Natural Science Foundation of China(42177164,52474121)the Outstanding Youth Project of Hunan Provincial Department of Education(23B0008).
文摘Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.
基金financially supported by the Career Development Fund(Grant No.C210112051)under the Agency for Science,Technology and Research(A*STAR)of Singapore2022 MTC Young Individual Research Grants(Grant No:M22K3c0097)under Singapore Research,Innovation and Enterprise(RIE)2025 Plan,led by C Tan。
文摘Tailoring thermal history during additive manufacturing(AM)offers a feasible approach to customise the microstructure and properties of materials without changing alloy compositions or post-heat treatment,which is generally overlooked as it is hard to achieve in commercial materials.Herein,a customised Fe-Ni-Ti-Al maraging steel with rapid precipitation kinetics offers the opportunity to leverage thermal history during AM for achieving large-range tunable strength-ductility combinations.The Fe-Ni-Ti-Al steel was processed by laser-directed energy deposition(LDED)with different deposition strategies to tailor the thermal history.As the phase transformation and in-situ formation of multi-scale secondary phases of the Fe-Ni-Ti-Al steel are sensitive to the thermal histories,the deposited steel achieved a large range of tuneable mechanical properties.Specifically,the interlayer paused deposited sample exhibits superior tensile strength(∼1.54 GPa)and moderate elongation(∼8.1%),which is attributed to the formation of unique hierarchical structures and the in-situ precipitation of high-densityη-Ni_(3)(Ti,Al)during LDED.In contrast,the substrate heating deposited sample has an excellent elongation of 19.3%together with a high tensile strength of 1.24 GPa.The achievable mechanical property range via tailoring thermal history in the LDED-built Fe-Ni-Ti-Al steel is significantly larger than most commercial materials.The findings highlight the material customisation along with AM’s unique thermal history to achieve versatile mechanical performances of deposited materials,which could inspire more property or function manipulations of materials by AM process control or innovation.
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
文摘Assessing the stability of pillars in underground mines(especially in deep underground mines)is a critical concern during both the design and the operational phases of a project.This study mainly focuses on developing two practical models to predict pillar stability status.For this purpose,two robust models were developed using a database including 236 case histories from seven underground hard rock mines,based on gene expression programming(GEP)and decision tree-support vector machine(DT-SVM)hybrid algorithms.The performance of the developed models was evaluated based on four common statistical criteria(sensitivity,specificity,Matthews correlation coefficient,and accuracy),receiver operating characteristic(ROC)curve,and testing data sets.The results showed that the GEP and DT-SVM models performed exceptionally well in assessing pillar stability,showing a high level of accuracy.The DT-SVM model,in particular,outperformed the GEP model(accuracy of 0.914,sensitivity of 0.842,specificity of 0.929,Matthews correlation coefficient of 0.767,and area under the ROC of 0.897 for the test data set).Furthermore,upon comparing the developed models with the previous ones,it was revealed that both models can effectively determine the condition of pillar stability with low uncertainty and acceptable accuracy.This suggests that these models could serve as dependable tools for project managers,aiding in the evaluation of pillar stability during the design and operational phases of mining projects,despite the inherent challenges in this domain.
文摘Objectives:This study aimed to explore the effects of the“FuekFone(F.F.)home-based program”on the upper limb and cognitive function of ischemic stroke patients after discharge.Methods:A single group pre-and post-test design was conducted.A total of 40 patients with recovery after ischemic stroke were recruited from two university hospitals in Thailand.The study was conducted between June 2022 and January 2023.Participants underwent a six-week“F.F.home-based program,”which combined an upper limb and cognitive function rehabilitation device with Android games,including stationary barrel,adventure walk,adventure stroll,sliding barrel,sauce squeeze,and cut objects.Each game has different difficulty levels.Patients can perform corresponding exercises through the games according to their conditions under the guidance of medical staff.The patients played for 24 min per time,4 min each game,three days a week.The second week,let the patients play games for 30 min per time,5 min each game,3 days a week.Then,in the 3e6 weeks,let the patients play games for 1 h per time,10 min each game,5 days a week.At the pre-and post-intervention,the Thai version of the National Institutes of Health Stroke Scale(NIHSS),the Motor Assessment Scale,and the Montreal Cognitive Assessment(MoCA score)were administered to patients at discharge and at 2,4,and 6 weeksafter discharge,and the results were compared.Results:All participants completed this program.Participants had statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 2,4,and 6 weeks after discharge(P<0.001).In the comparison of upper limb function and cognitive function at each of the study times,we found statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 4,and 6 weeks after discharge when compared to after discharge and 2 weeks after discharge,respectively(P<0.05).Conclusions:Continuing care of patients post-stroke after discharge from hospital,such as F.F.homebased program should be applied at home to enhance upper limb and cognitive function.
文摘BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.
基金The authors gratefully acknowledge the support from the National Natural Science Foundation of China(Grant No.42377174)the Natural Science Foundation of Shandong Province,China(Grant No.ZR2022ME198)the Open Research Fund of State Key Laboratory of Geomechanics and Geotechnical Engineering,Institute of Rock and Soil Mechanics,Chinese Academy of Sciences(Grant No.Z020006).
文摘Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems.In this study,a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model(ROM)and probabilistic programming.The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems.Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering.A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution.The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty.Then,a slope case was employed to demonstrate the performance of the developed framework.The results prove that the proposed framework provides a scientific,feasible,and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.
