In recent years,artificial intelligence(AI)has demonstrated remarkable advancements in the field of cardiovascular disease(CVD),particularly in the analysis of electrocardiograms(ECGs).Due to its widespread use,low co...In recent years,artificial intelligence(AI)has demonstrated remarkable advancements in the field of cardiovascular disease(CVD),particularly in the analysis of electrocardiograms(ECGs).Due to its widespread use,low cost,and high efficiency,the ECG has long been regarded as a cornerstone of cardiological examinations and remains the most widely utilized diagnostic tool in cardiology.The integration of AI,especially deep learning(DL)technologies based on convolutional neural networks(CNNs),into ECG analysis,has shown immense potential across several cardiological subfields.Deep learning methods have provided robust support for the rapid interpretation of ECGs,enabling the fine-grained analysis of ECG waveform changes with diagnostic accuracy comparable to that of expert cardiologists.Additionally,CNN-based models have proven capable of capturing subtle ECG changes that are often undetectable by traditional methods,accurately predicting complex conditions such as atrial fibrillation,left and right ventricular dysfunction,hypertrophic cardiomyopathy,acute coronary syndrome,and aortic stenosis.This highlights the broad application potential of AI in the diagnosis of cardiovascular diseases.However,despite their extensive applications,CNN models also face significant limitations,primarily related to the reliability of the acquired data,the opacity of the“black box”processes,and the associated medical,legal,and ethical challenges.Addressing these limitations and seeking viable solutions remain critical challenges in modern medicine.展开更多
Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational res...Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype(CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using crossplatform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas. We provide a data-driven, pan-gastrointestinal stratification of individual samples based on CIMP status and we investigate correlations with oncogenic alterations, including somatic mutations and epigenetic silencing of tumor suppressor genes. Besides known events in CIMP such as BRAF V600 E mutation, CDKN2 A silencing or MLH1 inactivation, we discuss the potential role of emerging actors such as Wnt pathway deregulation through truncating mutations in RNF43 and epigenetic silencing of WIF1. Our results highlight the existence of molecular similarities that are superimposed over a larger backbone of tissue-specific features and can be exploited to reduce heterogeneity of response in clinical trials.展开更多
ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia.However,the neural mechanisms underlying this association are unknown.Given that ZNF804A upregulates the expression of COMT,we hypothesi...ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia.However,the neural mechanisms underlying this association are unknown.Given that ZNF804A upregulates the expression of COMT,we hypothesized that ZNF804 A may influence brain activity by interacting with COMT.Here,we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants.Amplitudes of low-frequency fluctuations(ALFFs)were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680.The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 x COMT rs4680 interaction,manifesting as a U-shaped modulation,presumably by dopamine signaling.Significant main effects were also found.These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT,and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.展开更多
The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines （ENAMEL） Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research （NI...The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines （ENAMEL） Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research （NIDCR）. Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.展开更多
Central nervous system(CNS)neurons typically fail to regenerate their axons after injury leading to neurological impairment.Axonal regeneration is a highly energy-demanding cellular program that requires local mitocho...Central nervous system(CNS)neurons typically fail to regenerate their axons after injury leading to neurological impairment.Axonal regeneration is a highly energy-demanding cellular program that requires local mitochondria to supply most energy within injured axons.Recent emerging lines of evidence have started to reveal that injury-triggered acute mitochondrial damage and local energy crisis contribute to the intrinsic energetic restriction that accounts for axon regeneration failure in the CNS.Characterizing and reprogramming bioenergetic signaling and mitochondrial maintenance after axon injury-ischemia is fundamental for developing therapeutic strategies that can restore local energy metabolism and thus facilitate axon regeneration.Therefore,establishing reliable and reproduc-ible neuronal model platforms is critical for assessing axonal energetic metabolism and regeneration capacity after injury-ischemia.In this focused methodology article,we discuss recent advances in applying cutting-edge microflu-idic chamber devices in combination with state-of-the-art live-neuron imaging tools to monitor axonal regeneration,mitochondrial transport,bioenergetic metabolism,and local protein synthesis in response to injury-ischemic stress in mature CNS neurons.展开更多
文摘In recent years,artificial intelligence(AI)has demonstrated remarkable advancements in the field of cardiovascular disease(CVD),particularly in the analysis of electrocardiograms(ECGs).Due to its widespread use,low cost,and high efficiency,the ECG has long been regarded as a cornerstone of cardiological examinations and remains the most widely utilized diagnostic tool in cardiology.The integration of AI,especially deep learning(DL)technologies based on convolutional neural networks(CNNs),into ECG analysis,has shown immense potential across several cardiological subfields.Deep learning methods have provided robust support for the rapid interpretation of ECGs,enabling the fine-grained analysis of ECG waveform changes with diagnostic accuracy comparable to that of expert cardiologists.Additionally,CNN-based models have proven capable of capturing subtle ECG changes that are often undetectable by traditional methods,accurately predicting complex conditions such as atrial fibrillation,left and right ventricular dysfunction,hypertrophic cardiomyopathy,acute coronary syndrome,and aortic stenosis.This highlights the broad application potential of AI in the diagnosis of cardiovascular diseases.However,despite their extensive applications,CNN models also face significant limitations,primarily related to the reliability of the acquired data,the opacity of the“black box”processes,and the associated medical,legal,and ethical challenges.Addressing these limitations and seeking viable solutions remain critical challenges in modern medicine.
基金funded by the Intramural program of the National Human Genome Research Institute,the National Institutes of Health
文摘Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype(CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using crossplatform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas. We provide a data-driven, pan-gastrointestinal stratification of individual samples based on CIMP status and we investigate correlations with oncogenic alterations, including somatic mutations and epigenetic silencing of tumor suppressor genes. Besides known events in CIMP such as BRAF V600 E mutation, CDKN2 A silencing or MLH1 inactivation, we discuss the potential role of emerging actors such as Wnt pathway deregulation through truncating mutations in RNF43 and epigenetic silencing of WIF1. Our results highlight the existence of molecular similarities that are superimposed over a larger backbone of tissue-specific features and can be exploited to reduce heterogeneity of response in clinical trials.
基金supported by the National Basic Research Development Program of China (2016YFC0906400, 2016YFC1306900 and 2016YFC0904300)the National Natural Science Foundation of China (81571311 and 81571331)+4 种基金the National Science Fund for Distinguished Young Scholars of China (81725005)the National High Tech Development Project (863 Project) of China (2015AA020513)the Science and Technology Project of Liaoning Province, China (2015225018)the Educational Foundation (Pandeng Scholarship) of Liaoning Province, Chinathe support of Department of Radiology and Psychiatry, First Affiliated Hospital of China Medical University
文摘ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia.However,the neural mechanisms underlying this association are unknown.Given that ZNF804A upregulates the expression of COMT,we hypothesized that ZNF804 A may influence brain activity by interacting with COMT.Here,we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants.Amplitudes of low-frequency fluctuations(ALFFs)were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680.The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 x COMT rs4680 interaction,manifesting as a U-shaped modulation,presumably by dopamine signaling.Significant main effects were also found.These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT,and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.
文摘The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines （ENAMEL） Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research （NIDCR）. Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.
基金This work was supported by grants from the“Young Talent Support Plan”of Xi’an Jiaotong University(71211222010704)to N.Huangthe Intramural Research Program of NINDS,NIH(ZIA NS003029 and ZIA NS002946)to Z.-H.Sheng.
文摘Central nervous system(CNS)neurons typically fail to regenerate their axons after injury leading to neurological impairment.Axonal regeneration is a highly energy-demanding cellular program that requires local mitochondria to supply most energy within injured axons.Recent emerging lines of evidence have started to reveal that injury-triggered acute mitochondrial damage and local energy crisis contribute to the intrinsic energetic restriction that accounts for axon regeneration failure in the CNS.Characterizing and reprogramming bioenergetic signaling and mitochondrial maintenance after axon injury-ischemia is fundamental for developing therapeutic strategies that can restore local energy metabolism and thus facilitate axon regeneration.Therefore,establishing reliable and reproduc-ible neuronal model platforms is critical for assessing axonal energetic metabolism and regeneration capacity after injury-ischemia.In this focused methodology article,we discuss recent advances in applying cutting-edge microflu-idic chamber devices in combination with state-of-the-art live-neuron imaging tools to monitor axonal regeneration,mitochondrial transport,bioenergetic metabolism,and local protein synthesis in response to injury-ischemic stress in mature CNS neurons.
