Through the use of a survey and statistical methods, this study explores the effects and interventions of handheld Tai Chi water resistance fitness balls on the elderly with Parkinson’s disease. Firstly, a questionna...Through the use of a survey and statistical methods, this study explores the effects and interventions of handheld Tai Chi water resistance fitness balls on the elderly with Parkinson’s disease. Firstly, a questionnaire on exercise compliance for patients with Parkinson’s disease was developed, and its reliability and validity were tested. Then, a survey was conducted to investigate the current status of exercise compliance among Parkinson’s disease patients, including general information, scoring status, and single and multiple factor analyses of influencing factors [1]. The results of the study show that through qualitative research, the dimensions and item pools of the questionnaire were initially constructed, and the reliability analysis of the questionnaire was conducted through Delphi expert consultation, with favorable results in terms of its reliability and validity [2]. Regarding the current status of exercise compliance among Parkinson’s disease patients, the study found that the level of exercise compliance needs improvement, and there are significant differences in exercise compliance levels among patients under different circumstances. Finally, the research results were discussed and conclusions were drawn. The innovation of this study lies in the development of a questionnaire on exercise compliance for patients with Parkinson’s disease and the preliminary qualitative research and Delphi expert consultation conducted on it, providing new ideas and methods for the study of exercise compliance. However, the study also has limitations as it did not examine the effects of other interventions on Parkinson’s disease, so further research should be conducted [3].展开更多
Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinea...Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinear and combinatorial nature of the HEN problem,it is not easy to find solutions of high quality for large-scale problems.The reinforcement learning(RL)method,which learns strategies through ongoing exploration and exploitation,reveals advantages in such area.However,due to the complexity of the HEN design problem,the RL method for HEN should be dedicated and designed.A hybrid strategy combining RL with mathematical programming is proposed to take better advantage of both methods.An insightful state representation of the HEN structure as well as a customized reward function is introduced.A Q-learning algorithm is applied to update the HEN structure using theε-greedy strategy.Better results are obtained from three literature cases of different scales.展开更多
BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase...BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)CRC.Due to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than monotherapy.AIM To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical practice.METHODS A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally included.RESULTS A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)groups.The key clinical characteristics were well balanced among the groups.The median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,respectively.The median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 months.The FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with RP.No significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than R.FP has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical efficacy.Therefore,FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.展开更多
BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for ...BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.展开更多
BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the t...BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.展开更多
BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,i...BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.展开更多
Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to pro...Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to provide a reference for future epidemic prevention and control.Methods:The data of reported varicella cases in Banan District from 2014 to 2023 were collected and analyzed using the China Disease Prevention and Control Information System.Descriptive epidemiological methods were employed to assess the changes in the reported incidence of varicella before(2014-2018)and after(2019-2023)the implementation of the two-dose VarV immunization program.Results:The average annual reported incidence rate of varicella in Banan District from 2014 to 2023 was 81.53 per 100,000.From 2014 to 2018,the reported incidence rate showed an upward trend year by year(trend x2=223.96,P<0.05).However,the reported incidence rate decreased from 2019 to 2023(trend x?=189.51,P<0.05).Before and after the adjustment of the immunization program,the reported incidence rate for the 5-9 years old group was 774.62 per 100,000 and 476.98 per 100,000,respectively,with a statistically significant difference(x2=161.26,P<0.05).The onset of varicella showed a bimodal distribution,with peak incidence periods in May-June and October-December.From 2014 to 2023,a total of 155,181 doses of VarV were administered in Banan District.The estimated annual vaccination rate for the first varicella vaccine(VarV1)from 2019 to 2023 was 86.28%,and for the second dose(VarV2)was 59.18%.The primary vaccination targets were the 5-9-year-old group,accounting for 64.21%.Conclusion:After implementing the two-dose VarV immunization program in Banan District,the vaccination rate increased yearly,and the reported incidence of varicella showed a downward trend.The incidence rate of varicella in children aged 5-9 years reduced significantly,but the overall downward trend for the entire population was not as pronounced.Therefore,it is necessary to increase the vaccination rate of VarV2.展开更多
This study focused on the development and evaluation of the implementation of a preceptorship program adapted to ICU practice in the Ab.-T.region to provide preceptors with tools to support novice nurses.This action r...This study focused on the development and evaluation of the implementation of a preceptorship program adapted to ICU practice in the Ab.-T.region to provide preceptors with tools to support novice nurses.This action research was made possible with the involvement of the centers,preceptors,and novice nurses throughout the development and implementation of the program.This approach enabled participants to take ownership of the training content and fully utilize various tools.The program was implemented throughout the CISSS,where this study was subsequently carried out.Several novices mentioned that the program reinforced their sense of security and made them feel more equipped to handle complex care situations.The preceptors said they were better equipped to offer clinical support and novices were better prepared to work in the ICU.It is important to evaluate the development of the novice nurses’skills following their participation in this program and the long-term impact of this preceptorship.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
In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarc...In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.展开更多
Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early mar...Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.展开更多
Females actively seek extra-pair paternity(EPP)to acquire a fitness advantage for their offspring.The“contextdependence hypothesis”posits that female extra-pair mate choice has plasticity in response to environmenta...Females actively seek extra-pair paternity(EPP)to acquire a fitness advantage for their offspring.The“contextdependence hypothesis”posits that female extra-pair mate choice has plasticity in response to environmental conditions,and therefore magnitude of female genetic benefits from EPP depends on the environmental variation.Furthermore,chronic heavy metal pollution can cause adverse effects on fitness-related traits of wild birds.However,few studies were available on the interactions between heavy metal pollution and EPP.We selected an area that was contaminated by heavy metals for more than 60 years(Baiyin,BY),a relatively unpolluted area(Liujiaxia,LJX),and Tree Sparrows(Passer montanus)as study species to explore the response of female extrapair mate choice and genetic benefits from EPP to heavy metal pollution in socially monogamous birds.The relatedness between social mates and extra-pair mates was investigated.Additionally,we compared the body size and heterozygosity of extra-pair offspring(EPO),within-pair offspring(WPO),social males and extra-pair males from the two Tree Sparrow populations.We found that at BY,female Tree Sparrows tended to choose extra-pair males with larger body size and lower genetic similarity,thereby producing higher heterozygosity and larger body size of EPO compared with those of WPO.However,no similar phenomenon was observed in the Tree Sparrow population from LJX.In addition,there was a significant interaction between population and paternity in the analyses of the fitness-related traits,suggesting that environmental variation could affect female genetic benefits from EPP.This study confirmed the existence of presumed interactions between environmental pollution and EPP within the natural population of socially monogamous Tree Sparrows.Our findings shed lights on the possible effects of long-term environmental stress on mating system in wild birds.展开更多
The energy spectrum of energetic electrons is a key factor representing the dynamic variations of Earth’s Van Allen radiation belts.Increased measurements have indicated that the commonly used Maxwellian and Kappa di...The energy spectrum of energetic electrons is a key factor representing the dynamic variations of Earth’s Van Allen radiation belts.Increased measurements have indicated that the commonly used Maxwellian and Kappa distributions are inadequate for capturing the realistic spectral distributions of radiation belt electrons.Here we adopt the Kappa-type(KT)distribution as the fitting function and perform a statistical analysis to investigate the radiation belt electron flux spectra observed by the Van Allen Probes.By calculating the optimal values of the key KT distribution parameters(i.e.,κandθ2)from the observed spectral shapes,we fit the radiation belt electron fluxes at different L-shells under different geomagnetic conditions.In this manner,we obtain typical values of the KT distribution parameters,which are statistically feasible for modeling the radiation belt electron flux profiles during either geomagnetically quiet or active periods.A comparison of the KT distribution model results with those using the Maxwellian or Kappa distribution reveals the advantage of the KT distribution for studying the overall properties of the radiation belt electron spectral distribution,which has important implications for deepening the current understanding of the radiation belt electron dynamics under evolving geomagnetic conditions.展开更多
Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer ...Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.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
Microsoft Excel is essential for the End-User Approach (EUA), offering versatility in data organization, analysis, and visualization, as well as widespread accessibility. It fosters collaboration and informed decision...Microsoft Excel is essential for the End-User Approach (EUA), offering versatility in data organization, analysis, and visualization, as well as widespread accessibility. It fosters collaboration and informed decision-making across diverse domains. Conversely, Python is indispensable for professional programming due to its versatility, readability, extensive libraries, and robust community support. It enables efficient development, advanced data analysis, data mining, and automation, catering to diverse industries and applications. However, one primary issue when using Microsoft Excel with Python libraries is compatibility and interoperability. While Excel is a widely used tool for data storage and analysis, it may not seamlessly integrate with Python libraries, leading to challenges in reading and writing data, especially in complex or large datasets. Additionally, manipulating Excel files with Python may not always preserve formatting or formulas accurately, potentially affecting data integrity. Moreover, dependency on Excel’s graphical user interface (GUI) for automation can limit scalability and reproducibility compared to Python’s scripting capabilities. This paper covers the integration solution of empowering non-programmers to leverage Python’s capabilities within the familiar Excel environment. This enables users to perform advanced data analysis and automation tasks without requiring extensive programming knowledge. Based on Soliciting feedback from non-programmers who have tested the integration solution, the case study shows how the solution evaluates the ease of implementation, performance, and compatibility of Python with Excel versions.展开更多
Due to the overwhelming characteristics of the Internet of Things(IoT)and its adoption in approximately every aspect of our lives,the concept of individual devices’privacy has gained prominent attention from both cus...Due to the overwhelming characteristics of the Internet of Things(IoT)and its adoption in approximately every aspect of our lives,the concept of individual devices’privacy has gained prominent attention from both customers,i.e.,people,and industries as wearable devices collect sensitive information about patients(both admitted and outdoor)in smart healthcare infrastructures.In addition to privacy,outliers or noise are among the crucial issues,which are directly correlated with IoT infrastructures,as most member devices are resource-limited and could generate or transmit false data that is required to be refined before processing,i.e.,transmitting.Therefore,the development of privacy-preserving information fusion techniques is highly encouraged,especially those designed for smart IoT-enabled domains.In this paper,we are going to present an effective hybrid approach that can refine raw data values captured by the respectivemember device before transmission while preserving its privacy through the utilization of the differential privacy technique in IoT infrastructures.Sliding window,i.e.,δi based dynamic programming methodology,is implemented at the device level to ensure precise and accurate detection of outliers or noisy data,and refine it prior to activation of the respective transmission activity.Additionally,an appropriate privacy budget has been selected,which is enough to ensure the privacy of every individualmodule,i.e.,a wearable device such as a smartwatch attached to the patient’s body.In contrast,the end module,i.e.,the server in this case,can extract important information with approximately the maximum level of accuracy.Moreover,refined data has been processed by adding an appropriate nose through the Laplace mechanism to make it useless or meaningless for the adversary modules in the IoT.The proposed hybrid approach is trusted from both the device’s privacy and the integrity of the transmitted information perspectives.Simulation and analytical results have proved that the proposed privacy-preserving information fusion technique for wearable devices is an ideal solution for resource-constrained infrastructures such as IoT and the Internet ofMedical Things,where both device privacy and information integrity are important.Finally,the proposed hybrid approach is proven against well-known intruder attacks,especially those related to the privacy of the respective device in IoT infrastructures.展开更多
Wheat stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is one of the most destructive fungal diseases of wheat,and seriously threatens safe production of the crop worldwide.In China,new races historically ...Wheat stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is one of the most destructive fungal diseases of wheat,and seriously threatens safe production of the crop worldwide.In China,new races historically appeared and rapidly developed to be predominant races and have resulted in ineffectiveness and replacement of wheat resistance cultivars as well as massive reduction in yield.In the present study,the relative parasitic fitness of the two newlyemerged Yr5-virulent races(TSA-6 and TSA-9)were compared with those of four currently predominant Chinese races(CYR31,CYR32,CYR33,and CYR34)based on evaluation on 10 Chinese wheat cultivars.As a result,there were significant differences in the relative parasitic fitness parameters among overall tested races based on multiple comparison(LSD)analysis(P<0.05).The principal component analysis(PCA)of overall parasitic fitness parameters indicated that the sporulation ability,infection and spore survivability,expansion capacity,and potential pathogenicity were the most important parasitic fitness attributes of the tested races.Based on the establishment of extracted three principal components and a comprehensive factor score mathematical models,evaluations of the parasitic fitness attributes of tested races showed that the level of relative parasitic fitness of the tested six races was:CYR32(1.15)>TSA-9(0.95)>TSA-6(0.92)>CYR34(0.29)>CYR31(–1.54)>CYR33(–1.77).The results indicated that two Yr5-virulent races TSA-9 and TSA-6 possessed relative parasitic fitness higher than races CYR34,CYR31,and CYR33,but lower than race CYR32,and have potential risks in developing to be predominant races.Therefore,continual monitoring of both Yr5-virulent races,and their variants is needed.The use of wheat cultivars(lines)with Yr5 resistance gene singly in wheat breeding is essential for being avoided,and is suggested to combine with other effective stripe rust resistance genes.展开更多
BACKGROUND Flight cadets need to have good physical fitness to cope with the challenges of flying missions.The continuous development of science and technology has led to the constant upgrading of fighter jets and the...BACKGROUND Flight cadets need to have good physical fitness to cope with the challenges of flying missions.The continuous development of science and technology has led to the constant upgrading of fighter jets and the improvement of their performance,which has resulted in new and higher requirements for the physical fitness of flight personnel.The traditional physical training mode,method,and assessment have been used for many years and do not meet current fitness needs.AIM To investigate the impact of a 12-wk comprehensive anti-G fitness training program on the aerobic capacity of aviation cadets and to evaluate its effectiveness.METHODS Fifty-five cadets were randomly assigned to control and experimental groups using a randomized,single-blind design.The control group maintained their existing training regimen,while the experimental group participated in a 12-wk comprehensive training intervention.The training program comprised strength training twice per week,high-intensity interval training three times per week,and supplemental nutritional and psychological support.Maximal oxygen uptake(VO2max),lower limb strength,and hemoglobin levels were measured at baseline,at 6 wk and 12 wk post-intervention.RESULTS Repeated measures analysis of variance revealed significant differences of both VO2max and relative VO2 in both groups across time points(P<0.05).However,no significant time-group interaction was observed(P>0.05).Paired t-tests comparing baseline and 12-wk results showed that VO2max and relative VO2 were significantly higher in the experimental group than the control group(P<0.05).This suggests that the training program effectively enhanced the aerobic capacity of the experimental group.Key indicators of aerobic capacity,bilateral lower limb strength and hemoglobin levels,were also significantly different over time and between groups(P<0.05).No significant differences were noted in heart-rate metrics(P>0.05).CONCLUSION A 12-wk comprehensive anti-G fitness training program significantly improved the aerobic capacity of aviation cadets,thereby enhancing their overall capacity and laying a physiological foundation for enduring high-G flights.展开更多
Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advance...Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.展开更多
文摘Through the use of a survey and statistical methods, this study explores the effects and interventions of handheld Tai Chi water resistance fitness balls on the elderly with Parkinson’s disease. Firstly, a questionnaire on exercise compliance for patients with Parkinson’s disease was developed, and its reliability and validity were tested. Then, a survey was conducted to investigate the current status of exercise compliance among Parkinson’s disease patients, including general information, scoring status, and single and multiple factor analyses of influencing factors [1]. The results of the study show that through qualitative research, the dimensions and item pools of the questionnaire were initially constructed, and the reliability analysis of the questionnaire was conducted through Delphi expert consultation, with favorable results in terms of its reliability and validity [2]. Regarding the current status of exercise compliance among Parkinson’s disease patients, the study found that the level of exercise compliance needs improvement, and there are significant differences in exercise compliance levels among patients under different circumstances. Finally, the research results were discussed and conclusions were drawn. The innovation of this study lies in the development of a questionnaire on exercise compliance for patients with Parkinson’s disease and the preliminary qualitative research and Delphi expert consultation conducted on it, providing new ideas and methods for the study of exercise compliance. However, the study also has limitations as it did not examine the effects of other interventions on Parkinson’s disease, so further research should be conducted [3].
基金The financial support provided by the Project of National Natural Science Foundation of China(U22A20415,21978256,22308314)“Pioneer”and“Leading Goose”Research&Development Program of Zhejiang(2022C01SA442617)。
文摘Heat integration is important for energy-saving in the process industry.It is linked to the persistently challenging task of optimal design of heat exchanger networks(HEN).Due to the inherent highly nonconvex nonlinear and combinatorial nature of the HEN problem,it is not easy to find solutions of high quality for large-scale problems.The reinforcement learning(RL)method,which learns strategies through ongoing exploration and exploitation,reveals advantages in such area.However,due to the complexity of the HEN design problem,the RL method for HEN should be dedicated and designed.A hybrid strategy combining RL with mathematical programming is proposed to take better advantage of both methods.An insightful state representation of the HEN structure as well as a customized reward function is introduced.A Q-learning algorithm is applied to update the HEN structure using theε-greedy strategy.Better results are obtained from three literature cases of different scales.
文摘BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)CRC.Due to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than monotherapy.AIM To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical practice.METHODS A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally included.RESULTS A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)groups.The key clinical characteristics were well balanced among the groups.The median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,respectively.The median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 months.The FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with RP.No significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than R.FP has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical efficacy.Therefore,FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.
文摘BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.
文摘BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.
文摘BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.
文摘Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to provide a reference for future epidemic prevention and control.Methods:The data of reported varicella cases in Banan District from 2014 to 2023 were collected and analyzed using the China Disease Prevention and Control Information System.Descriptive epidemiological methods were employed to assess the changes in the reported incidence of varicella before(2014-2018)and after(2019-2023)the implementation of the two-dose VarV immunization program.Results:The average annual reported incidence rate of varicella in Banan District from 2014 to 2023 was 81.53 per 100,000.From 2014 to 2018,the reported incidence rate showed an upward trend year by year(trend x2=223.96,P<0.05).However,the reported incidence rate decreased from 2019 to 2023(trend x?=189.51,P<0.05).Before and after the adjustment of the immunization program,the reported incidence rate for the 5-9 years old group was 774.62 per 100,000 and 476.98 per 100,000,respectively,with a statistically significant difference(x2=161.26,P<0.05).The onset of varicella showed a bimodal distribution,with peak incidence periods in May-June and October-December.From 2014 to 2023,a total of 155,181 doses of VarV were administered in Banan District.The estimated annual vaccination rate for the first varicella vaccine(VarV1)from 2019 to 2023 was 86.28%,and for the second dose(VarV2)was 59.18%.The primary vaccination targets were the 5-9-year-old group,accounting for 64.21%.Conclusion:After implementing the two-dose VarV immunization program in Banan District,the vaccination rate increased yearly,and the reported incidence of varicella showed a downward trend.The incidence rate of varicella in children aged 5-9 years reduced significantly,but the overall downward trend for the entire population was not as pronounced.Therefore,it is necessary to increase the vaccination rate of VarV2.
文摘This study focused on the development and evaluation of the implementation of a preceptorship program adapted to ICU practice in the Ab.-T.region to provide preceptors with tools to support novice nurses.This action research was made possible with the involvement of the centers,preceptors,and novice nurses throughout the development and implementation of the program.This approach enabled participants to take ownership of the training content and fully utilize various tools.The program was implemented throughout the CISSS,where this study was subsequently carried out.Several novices mentioned that the program reinforced their sense of security and made them feel more equipped to handle complex care situations.The preceptors said they were better equipped to offer clinical support and novices were better prepared to work in the ICU.It is important to evaluate the development of the novice nurses’skills following their participation in this program and the long-term impact of this preceptorship.
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.
文摘In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.
基金funded by the Central Hessen Research Campus,Flexi Fund,Project No.20121_1_1.
文摘Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.
基金supported by the National Natural Science Foundation of China(No.32370508)the Foundation for Excellent Doctoral Student of Science and Technology Program of Gansu Province(No.23JRRA1125)。
文摘Females actively seek extra-pair paternity(EPP)to acquire a fitness advantage for their offspring.The“contextdependence hypothesis”posits that female extra-pair mate choice has plasticity in response to environmental conditions,and therefore magnitude of female genetic benefits from EPP depends on the environmental variation.Furthermore,chronic heavy metal pollution can cause adverse effects on fitness-related traits of wild birds.However,few studies were available on the interactions between heavy metal pollution and EPP.We selected an area that was contaminated by heavy metals for more than 60 years(Baiyin,BY),a relatively unpolluted area(Liujiaxia,LJX),and Tree Sparrows(Passer montanus)as study species to explore the response of female extrapair mate choice and genetic benefits from EPP to heavy metal pollution in socially monogamous birds.The relatedness between social mates and extra-pair mates was investigated.Additionally,we compared the body size and heterozygosity of extra-pair offspring(EPO),within-pair offspring(WPO),social males and extra-pair males from the two Tree Sparrow populations.We found that at BY,female Tree Sparrows tended to choose extra-pair males with larger body size and lower genetic similarity,thereby producing higher heterozygosity and larger body size of EPO compared with those of WPO.However,no similar phenomenon was observed in the Tree Sparrow population from LJX.In addition,there was a significant interaction between population and paternity in the analyses of the fitness-related traits,suggesting that environmental variation could affect female genetic benefits from EPP.This study confirmed the existence of presumed interactions between environmental pollution and EPP within the natural population of socially monogamous Tree Sparrows.Our findings shed lights on the possible effects of long-term environmental stress on mating system in wild birds.
基金the National Natural Science Foundation of China(Grant Nos.42188101,42025404,41974186,42174188,and 42204160)the National Key R&D Program of China(Grant No.2022YFF0503700)+2 种基金the B-type Strategic Priority Program of the Chinese Academy of Sciences(Grant No.XDB41000000)the Fundamental Research Funds for the Central Universities(Grant Nos.2042022kf1016 and 2042023kf1025)the China Postdoctoral Science Foundation(Grant No.2022M722447)。
文摘The energy spectrum of energetic electrons is a key factor representing the dynamic variations of Earth’s Van Allen radiation belts.Increased measurements have indicated that the commonly used Maxwellian and Kappa distributions are inadequate for capturing the realistic spectral distributions of radiation belt electrons.Here we adopt the Kappa-type(KT)distribution as the fitting function and perform a statistical analysis to investigate the radiation belt electron flux spectra observed by the Van Allen Probes.By calculating the optimal values of the key KT distribution parameters(i.e.,κandθ2)from the observed spectral shapes,we fit the radiation belt electron fluxes at different L-shells under different geomagnetic conditions.In this manner,we obtain typical values of the KT distribution parameters,which are statistically feasible for modeling the radiation belt electron flux profiles during either geomagnetically quiet or active periods.A comparison of the KT distribution model results with those using the Maxwellian or Kappa distribution reveals the advantage of the KT distribution for studying the overall properties of the radiation belt electron spectral distribution,which has important implications for deepening the current understanding of the radiation belt electron dynamics under evolving geomagnetic conditions.
基金National Natural Science Foundation of China under Grant No.51878508。
文摘Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.
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.
文摘Microsoft Excel is essential for the End-User Approach (EUA), offering versatility in data organization, analysis, and visualization, as well as widespread accessibility. It fosters collaboration and informed decision-making across diverse domains. Conversely, Python is indispensable for professional programming due to its versatility, readability, extensive libraries, and robust community support. It enables efficient development, advanced data analysis, data mining, and automation, catering to diverse industries and applications. However, one primary issue when using Microsoft Excel with Python libraries is compatibility and interoperability. While Excel is a widely used tool for data storage and analysis, it may not seamlessly integrate with Python libraries, leading to challenges in reading and writing data, especially in complex or large datasets. Additionally, manipulating Excel files with Python may not always preserve formatting or formulas accurately, potentially affecting data integrity. Moreover, dependency on Excel’s graphical user interface (GUI) for automation can limit scalability and reproducibility compared to Python’s scripting capabilities. This paper covers the integration solution of empowering non-programmers to leverage Python’s capabilities within the familiar Excel environment. This enables users to perform advanced data analysis and automation tasks without requiring extensive programming knowledge. Based on Soliciting feedback from non-programmers who have tested the integration solution, the case study shows how the solution evaluates the ease of implementation, performance, and compatibility of Python with Excel versions.
基金Ministry of Higher Education of Malaysia under theResearch GrantLRGS/1/2019/UKM-UKM/5/2 and Princess Nourah bint Abdulrahman University for financing this researcher through Supporting Project Number(PNURSP2024R235),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Due to the overwhelming characteristics of the Internet of Things(IoT)and its adoption in approximately every aspect of our lives,the concept of individual devices’privacy has gained prominent attention from both customers,i.e.,people,and industries as wearable devices collect sensitive information about patients(both admitted and outdoor)in smart healthcare infrastructures.In addition to privacy,outliers or noise are among the crucial issues,which are directly correlated with IoT infrastructures,as most member devices are resource-limited and could generate or transmit false data that is required to be refined before processing,i.e.,transmitting.Therefore,the development of privacy-preserving information fusion techniques is highly encouraged,especially those designed for smart IoT-enabled domains.In this paper,we are going to present an effective hybrid approach that can refine raw data values captured by the respectivemember device before transmission while preserving its privacy through the utilization of the differential privacy technique in IoT infrastructures.Sliding window,i.e.,δi based dynamic programming methodology,is implemented at the device level to ensure precise and accurate detection of outliers or noisy data,and refine it prior to activation of the respective transmission activity.Additionally,an appropriate privacy budget has been selected,which is enough to ensure the privacy of every individualmodule,i.e.,a wearable device such as a smartwatch attached to the patient’s body.In contrast,the end module,i.e.,the server in this case,can extract important information with approximately the maximum level of accuracy.Moreover,refined data has been processed by adding an appropriate nose through the Laplace mechanism to make it useless or meaningless for the adversary modules in the IoT.The proposed hybrid approach is trusted from both the device’s privacy and the integrity of the transmitted information perspectives.Simulation and analytical results have proved that the proposed privacy-preserving information fusion technique for wearable devices is an ideal solution for resource-constrained infrastructures such as IoT and the Internet ofMedical Things,where both device privacy and information integrity are important.Finally,the proposed hybrid approach is proven against well-known intruder attacks,especially those related to the privacy of the respective device in IoT infrastructures.
基金supported by the National Natural Science Foundation of China(32072358 and 32272507)the National Key R&D Program of China(2021YFD1401000)+1 种基金the earmarked fund for CARS-03,the Natural Science Basic Research Project in Shaanxi Province of China(2020JZ-15)National“111 Project”of China(BP0719026)。
文摘Wheat stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is one of the most destructive fungal diseases of wheat,and seriously threatens safe production of the crop worldwide.In China,new races historically appeared and rapidly developed to be predominant races and have resulted in ineffectiveness and replacement of wheat resistance cultivars as well as massive reduction in yield.In the present study,the relative parasitic fitness of the two newlyemerged Yr5-virulent races(TSA-6 and TSA-9)were compared with those of four currently predominant Chinese races(CYR31,CYR32,CYR33,and CYR34)based on evaluation on 10 Chinese wheat cultivars.As a result,there were significant differences in the relative parasitic fitness parameters among overall tested races based on multiple comparison(LSD)analysis(P<0.05).The principal component analysis(PCA)of overall parasitic fitness parameters indicated that the sporulation ability,infection and spore survivability,expansion capacity,and potential pathogenicity were the most important parasitic fitness attributes of the tested races.Based on the establishment of extracted three principal components and a comprehensive factor score mathematical models,evaluations of the parasitic fitness attributes of tested races showed that the level of relative parasitic fitness of the tested six races was:CYR32(1.15)>TSA-9(0.95)>TSA-6(0.92)>CYR34(0.29)>CYR31(–1.54)>CYR33(–1.77).The results indicated that two Yr5-virulent races TSA-9 and TSA-6 possessed relative parasitic fitness higher than races CYR34,CYR31,and CYR33,but lower than race CYR32,and have potential risks in developing to be predominant races.Therefore,continual monitoring of both Yr5-virulent races,and their variants is needed.The use of wheat cultivars(lines)with Yr5 resistance gene singly in wheat breeding is essential for being avoided,and is suggested to combine with other effective stripe rust resistance genes.
基金the Ethics Committee of Beijing Sport University(No.2019113H).
文摘BACKGROUND Flight cadets need to have good physical fitness to cope with the challenges of flying missions.The continuous development of science and technology has led to the constant upgrading of fighter jets and the improvement of their performance,which has resulted in new and higher requirements for the physical fitness of flight personnel.The traditional physical training mode,method,and assessment have been used for many years and do not meet current fitness needs.AIM To investigate the impact of a 12-wk comprehensive anti-G fitness training program on the aerobic capacity of aviation cadets and to evaluate its effectiveness.METHODS Fifty-five cadets were randomly assigned to control and experimental groups using a randomized,single-blind design.The control group maintained their existing training regimen,while the experimental group participated in a 12-wk comprehensive training intervention.The training program comprised strength training twice per week,high-intensity interval training three times per week,and supplemental nutritional and psychological support.Maximal oxygen uptake(VO2max),lower limb strength,and hemoglobin levels were measured at baseline,at 6 wk and 12 wk post-intervention.RESULTS Repeated measures analysis of variance revealed significant differences of both VO2max and relative VO2 in both groups across time points(P<0.05).However,no significant time-group interaction was observed(P>0.05).Paired t-tests comparing baseline and 12-wk results showed that VO2max and relative VO2 were significantly higher in the experimental group than the control group(P<0.05).This suggests that the training program effectively enhanced the aerobic capacity of the experimental group.Key indicators of aerobic capacity,bilateral lower limb strength and hemoglobin levels,were also significantly different over time and between groups(P<0.05).No significant differences were noted in heart-rate metrics(P>0.05).CONCLUSION A 12-wk comprehensive anti-G fitness training program significantly improved the aerobic capacity of aviation cadets,thereby enhancing their overall capacity and laying a physiological foundation for enduring high-G flights.
基金Natural Science Foundation of Gansu Province,No.21JR1RA186and the Health Industry Research Program of Gansu Province,No.GSWSKY2021-043.
文摘Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.