Background This study was to evaluate the predictors of xerostomia and Grade 3 xerostomia in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving radical radiotherapy and establish prediction models for xerostomia and Grade 3 xerostomia based on the predictors. Methods Totally, 365 patients with locoregionally advanced NPC who underwent radical radiotherapy were randomly divided into the training set (n = 255) and the testing set (n = 110) at a ratio of 7:3. All variables were included in the least absolute shrinkage and selection operator regression to screen out the potential predictors for xerostomia as well as the Grade 3 xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The random forest (RF), a decision tree classifier (DTC), and extreme-gradient boosting (XGB) models were constructed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC) and accuracy were analyzed to evaluate the predictive performance of the models. Results In the RF model for predicting xerostomia, the sensitivity was 1.000 (95%CI 1.000–1.000), the PPV was 0.990 (95%CI 0.975–1.000), the NPV was 1.000 (95%CI 1.000–1.000), the AUC was 0.999 (95%CI 0.997–1.000) and the accuracy was 0.992 (95%CI 0.981–1.000) in the training set. The sensitivity was 0.933 (95%CI 0.880–0.985), the PPV was 0.933 (95%CI 0.880–0.985), and the AUC was 0.915 (95%CI 0.860–0.970) in the testing set. Hypertension, age, total radiotherapy dose, dose at 50% of the left parotid volume, mean dose to right parotid gland, mean dose to oral cavity, and course of induction chemotherapy were important variables associated with the risk of xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The AUC of DTC model for predicting xerostomia was 0.769 (95%CI 0.666–0.872) in the testing set. The AUC of the XGB model for predicting xerostomia was 0.834 (0.753–0.916) in the testing set. The RF model showed the good predictive ability with the AUC of 0.986 (95%CI 0.972–1.000) in the training set, and 0.766 (95%CI 0.626–0.905) in the testing set for identifying patients who at high risk of Grade 3 xerostomia in those with high risk of xerostomia. Conclusions An RF model for predicting xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy and an RF model for predicting Grade 3 xerostomia in those with high risk of xerostomia showed good predictive ability.
Background: The COVID-19 pandemic has currently developed into a worldwide threat to humankind. Importantly, patients with severe COVID-19 are believed to have a higher mortality risk than those with mild conditions. However, despite the urgent need to develop novel therapeutic strategies, the biological features and pathogenic mechanisms of severe COVID-19 are poorly understood.Methods: Here, peripheral blood mononuclear cells (PBMCs) from four patients with severe COVID-19, four patients with mild COVID-19, and four healthy controls were examined by RNA sequencing (RNA-Seq). We conducted gene expression analysis and Venn diagrams to detect specific differentially expressed genes (DEGs) in patients with severe disease compared with those with mild conditions. Gene Ontology (GO) enrichment analysis was performed to identify the significant biological processes, and protein–protein interaction networks were constructed to extract hub genes. These hub genes were then subjected to regulatory signatures and protein–chemical interaction analysis for certain regulatory checkpoints and identification of potent chemical agents. Finally, to demonstrate the cell type-specific expression of these genes, we performed single-cell RNA-Seq analyses using an online platform.Results: A total of 144 DEGs were specifically expressed in severe COVID-19, and GO enrichment analysis revealed a significant association of these specific DEGs with autophagy. Hub genes such as MVB12A, CHMP6, STAM, and VPS37B were then found to be most significantly involved in the biological processes of autophagy at the transcriptome level. In addition, six transcription factors, including SRF, YY1, CREB1, PPARG, NFIC, and GATA2, as well as miRNAs, namely, hsa-mir-1-3p, and potent chemical agents such as copper sulfate and cobalt chloride, may cooperate in regulating the autophagy hub genes. Furthermore, classical monocytes may play a central role in severe COVID-19.Conclusion: We suggest that autophagy plays a crucial role in severe COVID-19. This study might facilitate a more profound knowledge of the biological characteristics and progression of COVID-19 and the development of novel therapeutic approaches to achieve a breakthrough in the current COVID-19 pandemic.
Background. Hypoxia plays a significant role in the pathogenesis of pancreatic cancer, but the effect of hypoxia-related genes in pancreatic cancer remains to be elucidated. This study aimed to identify hypoxia-related genes related to pancreatic cancer and construct a prognostic signature. Methods. Pancreatic cancer datasets were retrieved from TCGA database. Cox regression analyses were used to identify hypoxia-related genes and construct a prognostic signature. Datasets from International Cancer Genome Consortium and GEO databases were used as validated cohorts. The CIBERSORT method was applied to estimate the fractions of immune cell types. DNA methylation and protein levels of the genes in pancreatic cancer were examined. Results. Three hypoxia-related genes (TES, LDHA, and ANXA2) were identified as associated with patient survival and selected to construct a prognostic signature. Patients were divided into high- and low-risk groups based on the signature. Those in the high-risk group showed worse survival than those in the low-risk group. The signature was shown to be involved in the HIF-1 signaling pathway. The time-dependent ROC analyses of three independent validated cohorts further revealed that this signature had a better prognostic value in the prediction of the survival of pancreatic cancer patients. Immune cells analysis for three datasets demonstrated that high-risk signature was significantly associated with macrophages and T cells. DNA methylation and protein levels of the three genes validated their aberrant expression in pancreatic cancer. Conclusions. Our research provided a novel and reliable prognostic signature that composes of three hypoxia-related genes to estimate the prognosis of pancreatic cancer.
Purpose The most common and potentially fatal side effect of thoracic radiation therapy is radiation pneumonitis (RP). Due to the lack of effective treatments, predicting radiation pneumonitis is crucial. This study aimed to develop a dynamic nomogram to accurately predict symptomatic pneumonitis (RP ≥ 2) following thoracic radiotherapy for lung cancer patients. Methods Data from patients with pathologically diagnosed lung cancer at our hospital between January 2017 and June 2022 were retrospectively analyzed. Risk factors for radiation pneumonitis were identified through multivariate logistic regression analysis and utilized to construct a dynamic nomogram. The predictive performance of the nomogram was validated using a bootstrapped concordance index and calibration plots. Results Age, smoking index, chemotherapy, and whole lung V5/V10/MLD were identified as significant factors contributing to the accurate prediction of symptomatic pneumonitis. A dynamic nomogram for symptomatic pneumonitis was developed using these risk factors. The area under the curve was 0.920 (95% confidence interval 0.90–0.94). The nomogram demonstrated a bootstrapped concordance index of 0.892 (95% confidence interval 0.83–0.95) and was well calibrated. Furthermore, the threshold values for high risk and low risk were determined to be 150 using the receiver operating curve. Conclusions The developed dynamic nomogram offers an accurate and convenient tool for clinical application in predicting the risk of symptomatic pneumonitis in patients with lung cancer undergoing thoracic radiation.
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