Since the 1975 M_(S)7.3 Haicheng earthquake,spatio-temporal variations in the gravity field have attracted much attention as potential earthquake precursors.Recent technical advances in terrestrial gravity observation...Since the 1975 M_(S)7.3 Haicheng earthquake,spatio-temporal variations in the gravity field have attracted much attention as potential earthquake precursors.Recent technical advances in terrestrial gravity observation,along with the construction of a high-precision mobile gravity network covering Chinese mainland,have positioned temporal gravity variations(GVs)as an important tool for clarifying the signal characteristics and dynamic mechanisms of crustal sources.Reportedly,crustal mass transfer,which is affected by stress state and structural environment,alters the characteristics of the regional gravity field,thus serving as an indicator for locations of moderate to strong earthquakes and a seismology-independent predictor for regions at risk for strong earthquakes.Therefore,quantitatively tracking time-varying gravity is of paramount importance to enhance the effectiveness of earthquake prediction.In this study,we divided the areas effectively covered by the terrestrial mobile gravity network in the Sichuan-Yunnan region into small grids based on the latest observational data(since 2018)from the network.Next,we calculated the 1-and 3-year GVs and gravity gradient indicators(amplitude of analytic signal,AAS;total horizontal derivative,THD;and amplitude of vertical gradient,AVG)to quantitatively characterize variations in regional time-varying gravity field.Next,we assessed the effectiveness of gravity field variations in predicting earthquakes in the Sichuan-Yunnan region using Molchan diagrams constructed for gravity signals of 13 earthquakes(M≥5.0;occurred between 2021 and 2024)within the terrestrial mobile gravity network.The results reveal a certain correspondence between gravity field variations and the locations of moderate and strong earthquakes in the Sichuan-Yunnan region.Furthermore,the 3-year AAS and AVG outperform the 3-year THD in predicting subsequent seismic events.Notably,the AAS and AVG showed large probability gains prior to the M_(S)6.8 Luding earthquake,indicating their potential for earthquake prediction.展开更多
Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and...Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center(FUSCC)for sequential high-precision proteomic profiling.Results:ARG1,NOS3,and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC.Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment.Furthermore,the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.Conclusions:The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.展开更多
Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multip...Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.展开更多
Objective:Extreme gradient boosting(XGBoost)was used to predict the 7^(th)day efficacy of the acupoint application(AP)of Chinese herbs(Xiao Zhong Zhi Tong Tie)in patients with diarrhea.Materials and Methods:We consecu...Objective:Extreme gradient boosting(XGBoost)was used to predict the 7^(th)day efficacy of the acupoint application(AP)of Chinese herbs(Xiao Zhong Zhi Tong Tie)in patients with diarrhea.Materials and Methods:We consecutively collected medical records of patients with diarrhea nationwide on the Chun Bo Wan Xiang cloud platform from August 22 to November 5,2020.Demographic and clinical data and the fecal properties were included in this study.We established the XGBoost model to predict the 7^(th)day efficacy of AP in patients with diarrhea.The XGBoost model was evaluated using the area under the receiver operating characteristic(ROC)curve(AUC).We next compared the performance of XGBoost with that of artificial neural network(ANN),ANN+boosting,ANN+bagging,and support vector machine(SVM).Results:The XGBoost model provided a prediction accuracy of 84.86%(95%confidence interval=82.74%to 86.81%)and the ROC curve analysis showed an AUC of 0.81.The top-three variables with the highest importance are age,duration of diarrhea,and region(North).Our study revealed that XGBoost was not superior to ANN,ANN+boosting,ANN+bagging,and SVM.Conclusions:The established XGBoost model for predicting the 7^(th)day efficacy of AP in patients with diarrhea exhibited good accuracy and precision,which can be used for efficacy prediction.展开更多
Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)...Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T cells.Using bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB level.We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle.By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell infiltration.Using pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI efficacy.Among the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo studies.Additionally,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy.展开更多
基金funded by the National Key R&D Program of China(Nos.2023YFE0101800 and 2023YFC 3007305)National Natural Science Foundation of China(Nos.42004069 and 42204093)Special Fund of the Institute of Geophysics,China Earthquake Administration(No.DQJB24X24).
文摘Since the 1975 M_(S)7.3 Haicheng earthquake,spatio-temporal variations in the gravity field have attracted much attention as potential earthquake precursors.Recent technical advances in terrestrial gravity observation,along with the construction of a high-precision mobile gravity network covering Chinese mainland,have positioned temporal gravity variations(GVs)as an important tool for clarifying the signal characteristics and dynamic mechanisms of crustal sources.Reportedly,crustal mass transfer,which is affected by stress state and structural environment,alters the characteristics of the regional gravity field,thus serving as an indicator for locations of moderate to strong earthquakes and a seismology-independent predictor for regions at risk for strong earthquakes.Therefore,quantitatively tracking time-varying gravity is of paramount importance to enhance the effectiveness of earthquake prediction.In this study,we divided the areas effectively covered by the terrestrial mobile gravity network in the Sichuan-Yunnan region into small grids based on the latest observational data(since 2018)from the network.Next,we calculated the 1-and 3-year GVs and gravity gradient indicators(amplitude of analytic signal,AAS;total horizontal derivative,THD;and amplitude of vertical gradient,AVG)to quantitatively characterize variations in regional time-varying gravity field.Next,we assessed the effectiveness of gravity field variations in predicting earthquakes in the Sichuan-Yunnan region using Molchan diagrams constructed for gravity signals of 13 earthquakes(M≥5.0;occurred between 2021 and 2024)within the terrestrial mobile gravity network.The results reveal a certain correspondence between gravity field variations and the locations of moderate and strong earthquakes in the Sichuan-Yunnan region.Furthermore,the 3-year AAS and AVG outperform the 3-year THD in predicting subsequent seismic events.Notably,the AAS and AVG showed large probability gains prior to the M_(S)6.8 Luding earthquake,indicating their potential for earthquake prediction.
基金supported by the National Key Research and Development Project of China(Grant No.2021YFF1201300 and 2021YFF1201302)the Shanghai Committee of Science and Technology(Grant No.24DX2800100)the Institutional Projects of SIBPT(Grant No.YZ2024-07)。
文摘Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center(FUSCC)for sequential high-precision proteomic profiling.Results:ARG1,NOS3,and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC.Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment.Furthermore,the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.Conclusions:The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.
基金This work was supported by the National Key R&D Program of China(Grant No.2018YFC1313300)the National Natural Science Foundation of China(Grant No.81572331).
文摘Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.
基金financially supported by the Fundamental Research Funds for the Central public welfare research institutes(ZZ13-024-4)。
文摘Objective:Extreme gradient boosting(XGBoost)was used to predict the 7^(th)day efficacy of the acupoint application(AP)of Chinese herbs(Xiao Zhong Zhi Tong Tie)in patients with diarrhea.Materials and Methods:We consecutively collected medical records of patients with diarrhea nationwide on the Chun Bo Wan Xiang cloud platform from August 22 to November 5,2020.Demographic and clinical data and the fecal properties were included in this study.We established the XGBoost model to predict the 7^(th)day efficacy of AP in patients with diarrhea.The XGBoost model was evaluated using the area under the receiver operating characteristic(ROC)curve(AUC).We next compared the performance of XGBoost with that of artificial neural network(ANN),ANN+boosting,ANN+bagging,and support vector machine(SVM).Results:The XGBoost model provided a prediction accuracy of 84.86%(95%confidence interval=82.74%to 86.81%)and the ROC curve analysis showed an AUC of 0.81.The top-three variables with the highest importance are age,duration of diarrhea,and region(North).Our study revealed that XGBoost was not superior to ANN,ANN+boosting,ANN+bagging,and SVM.Conclusions:The established XGBoost model for predicting the 7^(th)day efficacy of AP in patients with diarrhea exhibited good accuracy and precision,which can be used for efficacy prediction.
基金supported by the National Natural Science Foundation of China(81930065,82173128,82102921,and 82003269)the Cancer Innovation Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0004)+5 种基金the Swedish Research Council(VR-MH 2014-46602-117891-30)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-036)the Youth Teacher Cultivation Program of Sun Yat-sen UniversityGuangdong Provincial Clinical Medical Research Center for Malignant Tumors(84000-31660002)the China Postdoctoral Science Foundation(2023M744049)the Chih Kuang Scholarship for Outstanding Young Physician-Scientists of Sun Yat-sen University Cancer Center(CKS-SYSUCC-2023001)。
文摘Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T cells.Using bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB level.We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle.By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell infiltration.Using pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI efficacy.Among the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo studies.Additionally,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy.
