ABSTRACT
MPTP models have been developed to mimic human Parkinson's disease and serve as an indispensable tool for studying PD. Among them, subacute MPTP PD models are popular due to their short modeling period and similarity to PD pathology. However, the early pathophysiological mechanism of the model remains to be further clarified. More and more studies have shown that dysregulation of miRNAs plays an important role in the occurrence and development of neurodegenerative diseases, including PD. In this study, we identified 43 differentially expressed microRNAs (miRNAs) in the ventral midbrain of MPTP-induced subacute PD mouse by RNA sequencing. Further bioinformatics analysis revealed that these miRNAs were significantly enriched in axon guidance/neuron projection, metabolic pathways/cellular macromolecule metabolic process and PI3K/AKT signaling pathways, which were involved in the occurrence and development of early PD. Thus, targeted regulation of these miRNAs may reverse the neurodegeneration of early PD.
Subject(s)
MicroRNAs , Parkinson Disease , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Disease Models, Animal , Dopaminergic Neurons/metabolism , Humans , Mesencephalon/metabolism , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , MicroRNAs/metabolism , Parkinson Disease/metabolism , Phosphatidylinositol 3-Kinases/metabolismABSTRACT
Purpose: Accurate prediction of the progression to severe stroke in initially diagnosed nonsevere patients with acute-subacute anterior circulation nonlacuna ischemic infarction (ASACNLII) is important in making clinical decision. This study aimed to apply a machine learning method to predict if the initially diagnosed nonsevere patients with ASACNLII would progress to severe stroke by using diffusion-weighted images and clinical information on admission. Methods: This retrospective study enrolled 344 patients with ASACNLII from June 2017 to August 2020 on admission, and 108 cases progressed to severe stroke during hospitalization within 3-21 days. The entire data were randomized into a training set (n = 271) and an independent test set (n = 73). A U-Net neural network was employed for automatic segmentation and volume measurement of the ischemic lesions. Predictive models were developed and used for evaluating the progression to severe stroke using different feature sets (the volume data, the clinical data, and the combination) and machine learning methods (random forest, support vector machine, and logistic regression). Results: The U-Net showed high correlation with manual segmentation in terms of Dice coefficient of 0.806 and R 2 value of the volume measurements of 0.960 in the test set. The random forest classifier of the volume + clinical combination achieved the best area under the receiver operating characteristic curve of 0.8358 (95% CI 0.7321-0.9269), and the accuracy, sensitivity, and specificity were 0.7780 (0.7397-0.7945), 0.7695 (0.6102-0.9074), and 0.8686 (0.6923-1.0), respectively. The Shapley additive explanation diagram showed the volume variable as the most important predictor. Conclusion: The U-Net was fully automatic and showed a high correlation with manual segmentation. An integrated approach combining clinical variables and stroke lesion volumes that were derived from the advanced machine learning algorithms had high accuracy in predicting the progression to severe stroke in ASACNLII patients.
ABSTRACT
OBJECTIVES: The subtype classification of lung adenocarcinoma is important for treatment decision. This study aimed to investigate the deep learning and radiomics networks for predicting histologic subtype classification and survival of lung adenocarcinoma diagnosed through computed tomography (CT) images. METHODS: A dataset of 1222 patients with lung adenocarcinoma were retrospectively enrolled from three medical institutions. The anonymised preoperative CT images and pathological labels of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, invasive adenocarcinoma (IAC) with five predominant components were obtained. These pathological labels were divided into 2-category classification (IAC; non-IAC), 3-category and 8-category. We modeled the classification task of histological subtypes based on modified ResNet-34 deep learning network, radiomics strategies and deep radiomics combined algorithm. Then we established the prognostic models in lung adenocarcinoma patients with survival outcomes. The accuracy (ACC), area under ROC curves (AUCs) and C-index were primarily performed to evaluate the algorithms. RESULTS: This study included a training set (n = 802) and two validation cohorts (internal, n = 196; external, n = 224). The ACC of deep radiomics algorithm in internal validation achieved 0.8776, 0.8061 in the 2-category, 3-category classification, respectively. Even in 8 classifications, the AUC ranged from 0.739 to 0.940 in internal set. Further, we constructed a prognosis model that C-index was 0.892(95% CI: 0.846-0.937) in internal validation set. CONCLUSIONS: The automated deep radiomics based triage system has achieved the great performance in the subtype classification and survival predictability in patients with CT-detected lung adenocarcinoma nodules, providing the clinical guide for treatment strategies.