Accurate prediction for the prognosis of patients with pancreatic cancer (PC) is a emerge task nowadays. We aimed to develop survival models for postoperative PC patients, based on a novel algorithm, random survival forest (RSF), traditional Cox regression and neural networks (Deepsurv), using the Surveillance, Epidemiology, and End Results Program (SEER) database. A total of 3988 patients were included in this study. Eight clinicopathological features were selected using least absolute shrinkage and selection operator (LASSO) regression analysis and were utilized to develop the RSF model. The model was evaluated based on three dimensions: discrimination, calibration, and clinical benefit. It found that the RSF model predicted the cancer-specific survival (CSS) of the postoperative PC patients with a c-index of 0.723, which was higher than the models built by Cox regression (0.670) and Deepsurv (0.700). The Brier scores at 1, 3, and 5 years (0.188, 0.177, and 0.131) of the RSF model demonstrated the model’s favorable calibration and the decision curve analysis illustrated the model’s value of clinical implement. Moreover, the roles of the key variables were visualized in the Shapley Additive Explanations plotting. Lastly, the prediction model demonstrates value in risk stratification and individual prognosis. In this study, a high-performance prediction model for PC postoperative prognosis was developed, based on RSF The model presented significant strengths in the risk stratification and individual prognosis prediction.

Defects in the posttranscriptional modifications of mitochondrial tRNAs have been linked to human diseases, but their pathophysiology remains elusive. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNAIle 4295A>G mutation affecting a highly conserved adenosine at position 37, 3′ adjacent to the tRNA’s anticodon. Primer extension and methylation activity assays revealed that the m.4295A>G mutation introduced a tRNA methyltransferase 5 (TRMT5)-catalyzed m1G37 modification of tRNAIle. Molecular dynamics simulations suggested that the m.4295A>G mutation affected tRNAIle structure and function, supported by increased melting temperature, conformational changes and instability of mutated tRNA. An in vitro processing experiment revealed that the m.4295A>G mutation reduced the 5′ end processing efficiency of tRNAIle precursors, catalyzed by RNase P. We demonstrated that cybrid cell lines carrying the m.4295A>G mutation exhibited significant alterations in aminoacylation and steady-state levels of tRNAIle. The aberrant tRNA metabolism resulted in the impairment of mitochondrial translation, respiratory deficiency, decreasing membrane potentials and ATP production, increasing production of reactive oxygen species and promoting autophagy. These demonstrated the pleiotropic effects of m.4295A>G mutation on tRNAIle and mitochondrial functions. Our findings highlighted the essential role of deficient posttranscriptional modifications in the structure and function of tRNA and their pathogenic consequence of deafness.

BackgroundMachine learning (ML) algorithms are widely applied in building models of medicine due to their powerful studying and generalizing ability. This study aims to explore different ML models for early identification of severe acute pancreatitis (SAP) among patients hospitalized for acute pancreatitis.MethodsThis retrospective study enrolled patients with acute pancreatitis (AP) from multiple centers. Data from the First Affiliated Hospital and Changshu No. 1 Hospital of Soochow University were adopted for training and internal validation, and data from the Second Affiliated Hospital of Soochow University were adopted for external validation from January 2017 to December 2021. The diagnosis of AP and SAP was based on the 2012 revised Atlanta classification of acute pancreatitis. Models were built using traditional logistic regression (LR) and automated machine learning (AutoML) analysis with five types of algorithms. The performance of models was evaluated by the receiver operating characteristic (ROC) curve, the calibration curve, and the decision curve analysis (DCA) based on LR and feature importance, SHapley Additive exPlanation (SHAP) Plot, and Local Interpretable Model Agnostic Explanation (LIME) based on AutoML.ResultsA total of 1,012 patients were included in this study to develop the AutoML models in the training/validation dataset. An independent dataset of 212 patients was used to test the models. The model developed by the gradient boost machine (GBM) outperformed other models with an area under the ROC curve (AUC) of 0.937 in the validation set and an AUC of 0.945 in the test set. Furthermore, the GBM model achieved the highest sensitivity value of 0.583 among these AutoML models. The model developed by eXtreme Gradient Boosting (XGBoost) achieved the highest specificity value of 0.980 and the highest accuracy of 0.958 in the test set.ConclusionsThe AutoML model based on the GBM algorithm for early prediction of SAP showed evident clinical practicability.

Background This study aims to explore a deep learning (DL) algorithm for developing a prognostic model and perform survival analyses in SBT patients. Methods The demographic and clinical features of patients with SBTs were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We randomly split the samples into the training set and the validation set at 7:3. Cox proportional hazards (Cox-PH) analysis and the DeepSurv algorithm were used to develop models. The performance of the Cox-PH and DeepSurv models was evaluated using receiver operating characteristic curves, calibration curves, C-statistics and decision-curve analysis (DCA). A Kaplan–Meier (K–M) survival analysis was performed for further explanation on prognostic effect of the Cox-PH model. Results The multivariate analysis demonstrated that seven variables were associated with cancer-specific survival (CSS) (all p < 0.05). The DeepSurv model showed better performance than the Cox-PH model (C-index: 0.871 vs. 0.866). The calibration curves and DCA revealed that the two models had good discrimination and calibration. Moreover, patients with ileac malignancy and N2 stage disease were not responding to surgery according to the K–M analysis. Conclusions This study reported a DeepSurv model that performed well in CSS in SBT patients. It might offer insights into future research to explore more DL algorithms in cohort studies.