Aortic stenosis(AS)is the most common valvular heart disease,with a prevalence of over 4%among octogenarians.[1]The prevalence of autopsy-confirmed wild-type transthyretin cardiac amyloidosis(ATTRwt-CA)increases with ...Aortic stenosis(AS)is the most common valvular heart disease,with a prevalence of over 4%among octogenarians.[1]The prevalence of autopsy-confirmed wild-type transthyretin cardiac amyloidosis(ATTRwt-CA)increases with age,accounting for 25%of patients aged 85 years and older in Europe and 12%of patients older than 80 years in Japan.[2,3]Recent studies have reported that ATTRwt-CA coexists in 11%-16%of older patients with AS undergoing transcatheter aortic valve replacement(TAVR).[1,4,5]In a metaanalysis by Ho et al.,[6]the prevalence rates of cardiac amyloidosis,predominantly ATTRwt-CA,in patients with AS and those referred for TAVR or surgical aortic valve replacement(SAVR)were 14.4%and 15.2%,respectively.Conversely,the prevalence of AS in patients with cardiac amyloidosis is 8.7%.Owing to the high surgical risk in patients with both AS and ATTRwt-CA,TAVR may be preferred over SAVR.展开更多
Objective:Accurate detection of PIK3CA mutations is essential for guiding PI3K-targeted therapies in breast cancer,yet sequencing is not universally accessible,and single-modality prediction models have limited perfor...Objective:Accurate detection of PIK3CA mutations is essential for guiding PI3K-targeted therapies in breast cancer,yet sequencing is not universally accessible,and single-modality prediction models have limited performance.This study developed a multimodal deep learning framework integrating whole-slide imaging(WSI)and structured clinical data to improve mutation prediction.Methods:A total of 1,047 patients from TCGA and 166 patients from 3 external centers were included.The histopathology model used a transformer-based pretrained encoder(H-optimus-0)and a clustering-constrained attention multiple instance learning(CLAM-SB MIL)classifier to generate WSI-level representations.The clinical model incorporated engineered clinical variables and an extreme gradient boosting(XGBoost)model.A decision-level late fusion strategy(Multimodal PIK3CA Model,MPM)combined probabilistic outputs from both branches.Performance was evaluated with the area under the curve(AUC)and secondary metrics.Interpretability was assessed via attention heatmaps and shapley additive explanations(SHAP)analysis.Results:MPM outperformed single-modality models.It achieved an AUC of 0.745 on TCGA and maintained stable performance across external cohorts(0.695,0.690,and 0.680).SHAP analysis identified molecular subtype as the most influential clinical feature,whereas attention maps highlighted mutation-associated morphological regions.Conclusions:The developed multimodal framework effectively integrates complementary morphological and clinical information,and provides a robust and generalizable method for predicting PIK3CA mutation status.Strong multicenter adaptability and biological interpretability support its potential use as a clinical decision-support tool and an accessible alternative to molecular testing.展开更多
We report the results of the experiment on synthesizing ^(287,288)Mc isotopes (Z=115) using the fusionevaporation reaction ^(243)Am(^(48)Ca,4n,3n)^(287,288)Mc at the Spectrometer for Heavy Atoms and Nuclear Structure-...We report the results of the experiment on synthesizing ^(287,288)Mc isotopes (Z=115) using the fusionevaporation reaction ^(243)Am(^(48)Ca,4n,3n)^(287,288)Mc at the Spectrometer for Heavy Atoms and Nuclear Structure-2(SHANS2),a gas-filled recoil separator located at the China Accelerator Facility for Superheavy Elements(CAFE2).In total,20 decay chains are attributed to ^(288)Mc and 1 decay chain is assigned to ^(287)Mc.The measured oa-decay properties of ^(287,288)Mc as well as its descendants are consistent with the known data.No additional decay chains originating from the 2n or 5n reaction channels were detected.The excitation function of the ^(243)Am(^(48)Ca,3n)^(288)Mc reaction was measured at the cross-section level of picobarn,which indicates the promising capability for the study of heavy and superheavy nuclei at the facility.展开更多
Ischemia-reperfusion(I/R)injury induces region-specific neuronal vulnerability within the hippocampus,with the cornu ammonis 1(CA1)subfield particularly prone to delayed neuronal death.While intrinsic neuronal factors...Ischemia-reperfusion(I/R)injury induces region-specific neuronal vulnerability within the hippocampus,with the cornu ammonis 1(CA1)subfield particularly prone to delayed neuronal death.While intrinsic neuronal factors have been implicated,emerging evidence highlights the decisive contribution of astrocyte endfeet(AEF)—specialized perivascular structures that regulate ion and water homeostasis,glutamate clearance,and blood–brain barrier(BBB)stability.This review synthesizes structural and molecular alterations of AEF across the CA1-CA3 subfields following I/R and their correlation with neuronal fate.In CA1,AEF undergo early-onset swelling and detachment from the vascular basal lamina due to dysfunction of critical proteins such as aquaporin-4(AQP4)and Kir4.1.These changes impair glutamate uptake,metabolic support,and potassium buffering,contributing to neuronal hyperexcitability and degeneration.In contrast,AEF in CA3 preserves polarity and functional coupling of AQP4 and Kir4.1,conferring regional resilience.At the signaling level,AEF disruption activates mitogen-activated protein kinase(MAPK)/c-Jun N-terminal kinase(JNK)pathways,promotes reactive oxygen species(ROS)accumulation,and induces inducible nitric oxide synthase(iNOS)-mediated inflammation,amplifying neurotoxicity.Furthermore,subfield-specific astrocytic transcriptional profiles modulate inflammatory responses and gliovascular interactions.By reframing AEF not as passive scaffolds but as active regulators of neuronal survival,this review provides novel insight into the astrocyte-dependent mechanisms of hippocampal vulnerability.Therapeutic strategies that preserve AEF structure and function may offer targeted protection against delayed neuronal death in ischemic brain injury.展开更多
文摘Aortic stenosis(AS)is the most common valvular heart disease,with a prevalence of over 4%among octogenarians.[1]The prevalence of autopsy-confirmed wild-type transthyretin cardiac amyloidosis(ATTRwt-CA)increases with age,accounting for 25%of patients aged 85 years and older in Europe and 12%of patients older than 80 years in Japan.[2,3]Recent studies have reported that ATTRwt-CA coexists in 11%-16%of older patients with AS undergoing transcatheter aortic valve replacement(TAVR).[1,4,5]In a metaanalysis by Ho et al.,[6]the prevalence rates of cardiac amyloidosis,predominantly ATTRwt-CA,in patients with AS and those referred for TAVR or surgical aortic valve replacement(SAVR)were 14.4%and 15.2%,respectively.Conversely,the prevalence of AS in patients with cardiac amyloidosis is 8.7%.Owing to the high surgical risk in patients with both AS and ATTRwt-CA,TAVR may be preferred over SAVR.
基金financially supported by the Hebei Natural Science Foundation(Grant No.H2024206504)the Medical Science Research Project of Hebei(Grant No.20260484,20260530)the Fundamental Research Funds for the Central Universities(Grant No.20822041J4123).
文摘Objective:Accurate detection of PIK3CA mutations is essential for guiding PI3K-targeted therapies in breast cancer,yet sequencing is not universally accessible,and single-modality prediction models have limited performance.This study developed a multimodal deep learning framework integrating whole-slide imaging(WSI)and structured clinical data to improve mutation prediction.Methods:A total of 1,047 patients from TCGA and 166 patients from 3 external centers were included.The histopathology model used a transformer-based pretrained encoder(H-optimus-0)and a clustering-constrained attention multiple instance learning(CLAM-SB MIL)classifier to generate WSI-level representations.The clinical model incorporated engineered clinical variables and an extreme gradient boosting(XGBoost)model.A decision-level late fusion strategy(Multimodal PIK3CA Model,MPM)combined probabilistic outputs from both branches.Performance was evaluated with the area under the curve(AUC)and secondary metrics.Interpretability was assessed via attention heatmaps and shapley additive explanations(SHAP)analysis.Results:MPM outperformed single-modality models.It achieved an AUC of 0.745 on TCGA and maintained stable performance across external cohorts(0.695,0.690,and 0.680).SHAP analysis identified molecular subtype as the most influential clinical feature,whereas attention maps highlighted mutation-associated morphological regions.Conclusions:The developed multimodal framework effectively integrates complementary morphological and clinical information,and provides a robust and generalizable method for predicting PIK3CA mutation status.Strong multicenter adaptability and biological interpretability support its potential use as a clinical decision-support tool and an accessible alternative to molecular testing.
基金supported in part by the National Key R&D Program of China (Contract Nos.2023YFA1606500,2024YFE0109800,and 2024YFE0110400)Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB34010000)+5 种基金the Gansu Key Project of Science and Technology (Grant No.23ZDGA014)the Guangdong Major Project of Basic and Applied Basic Research (Grant No.2021B0301030006)the National Natural Science Foundation of China (Grant Nos.12105328,W2412040,12475126,12422507,12035011,12375118,12435008,and W2412043)the Chinese Academy of Sciences Project for Young Scientists in Basic Research(Grant No.YSBR-002)the Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant Nos.2020409 and 2023439)the Russian Science Foundation (Grant No.25-42-00003)。
文摘We report the results of the experiment on synthesizing ^(287,288)Mc isotopes (Z=115) using the fusionevaporation reaction ^(243)Am(^(48)Ca,4n,3n)^(287,288)Mc at the Spectrometer for Heavy Atoms and Nuclear Structure-2(SHANS2),a gas-filled recoil separator located at the China Accelerator Facility for Superheavy Elements(CAFE2).In total,20 decay chains are attributed to ^(288)Mc and 1 decay chain is assigned to ^(287)Mc.The measured oa-decay properties of ^(287,288)Mc as well as its descendants are consistent with the known data.No additional decay chains originating from the 2n or 5n reaction channels were detected.The excitation function of the ^(243)Am(^(48)Ca,3n)^(288)Mc reaction was measured at the cross-section level of picobarn,which indicates the promising capability for the study of heavy and superheavy nuclei at the facility.
文摘Ischemia-reperfusion(I/R)injury induces region-specific neuronal vulnerability within the hippocampus,with the cornu ammonis 1(CA1)subfield particularly prone to delayed neuronal death.While intrinsic neuronal factors have been implicated,emerging evidence highlights the decisive contribution of astrocyte endfeet(AEF)—specialized perivascular structures that regulate ion and water homeostasis,glutamate clearance,and blood–brain barrier(BBB)stability.This review synthesizes structural and molecular alterations of AEF across the CA1-CA3 subfields following I/R and their correlation with neuronal fate.In CA1,AEF undergo early-onset swelling and detachment from the vascular basal lamina due to dysfunction of critical proteins such as aquaporin-4(AQP4)and Kir4.1.These changes impair glutamate uptake,metabolic support,and potassium buffering,contributing to neuronal hyperexcitability and degeneration.In contrast,AEF in CA3 preserves polarity and functional coupling of AQP4 and Kir4.1,conferring regional resilience.At the signaling level,AEF disruption activates mitogen-activated protein kinase(MAPK)/c-Jun N-terminal kinase(JNK)pathways,promotes reactive oxygen species(ROS)accumulation,and induces inducible nitric oxide synthase(iNOS)-mediated inflammation,amplifying neurotoxicity.Furthermore,subfield-specific astrocytic transcriptional profiles modulate inflammatory responses and gliovascular interactions.By reframing AEF not as passive scaffolds but as active regulators of neuronal survival,this review provides novel insight into the astrocyte-dependent mechanisms of hippocampal vulnerability.Therapeutic strategies that preserve AEF structure and function may offer targeted protection against delayed neuronal death in ischemic brain injury.
