Background: There is currently a lack of model for predicting the occurrence of venous thromboembolism (VTE) in patients with lung cancer. Machine learning (ML) techniques are being increasingly adapted for use in the medical field because of their capabilities of intelligent analysis and scalability. This study aimed to develop and validate ML models to predict the incidence of VTE among lung cancer patients.Methods: Data of lung cancer patients from a Grade 3A cancer hospital in China with and without VTE were included. Patient characteristics and clinical predictors related to VTE were collected. The primary endpoint was the diagnosis of VTE during index hospitalization. We calculated and compared the area under the receiver operating characteristic curve (AUROC) using the selected best-performed model (Random Forest model) through multiple model comparison, as well as investigated feature contributions during the training process with both permutation importance scores and the impurity-based feature importance scores in random forest model.Results: In total, 3,398 patients were included in our study, 125 of whom experienced VTE during their hospital stay. The ROC curve and precision–recall curve (PRC) for Random Forest Model showed an AUROC of 0.91 (95% CI: 0.893–0.926) and an AUPRC of 0.43 (95% CI: 0.363–0.500). For the simplified model, five most relevant features were selected: Karnofsky Performance Status (KPS), a history of VTE, recombinant human endostatin, EGFR-TKI, and platelet count. We re-trained a random forest classifier with results of the AUROC of 0.87 (95% CI: 0.802–0.917) and AUPRC of 0.30 (95% CI: 0.265–0.358), respectively.Conclusion: According to the study results, there was no conspicuous decrease in the model’s performance when use fewer features to predict, we concluded that our simplified model would be more applicable in real-life clinical settings. The developed model using ML algorithms in our study has the potential to improve the early detection and prediction of the incidence of VTE in patients with lung cancer.

The widespread use of immune checkpoint inhibitors (ICIs) has demonstrated significant survival benefits for cancer patients and also carry the risk of immune-related adverse events (irAEs). ICIs-associated myocarditis is a rare and serious adverse event with a high mortality rate. Here, we explored the mechanism underlying ICIs-associated myocarditis. Using the peripheral blood of patients with ICIs therapy and ICIs treated mice with transplanted tumors, we dissect the immune cell subsets and inflammatory factors associated with myocarditis. Compared to the control group, patients with myocarditis after ICIs therapy showed an increase in NK cells and myeloid cells in peripheral blood, while T cells significantly decreased. Among T cells, there was an imbalance of CD4/CD8 ratio in the peripheral blood of myocarditis patients, with a significant decrease in central memory CD4+ T (CD4+ T_CM) cells. RNA-Seq revealed that CD4+ T_CM cells in myocarditis patients were an immunosuppressive cell subset, which highly express the immunosuppressive factor IL4I1. To elucidate the potential mechanism of the decrease in CD4+ T_CM cells, protein array was performed and revealed that several inflammatory factors gradually increased with the severity of myocarditis in the myocarditis group, such as IL-1B/CXCL13/CXCL9, while the myocardial protective factor IL-15 decreased. Correlation analysis indicated a positive correlation between IL-15 and CD4+ T_CM cells, with high expression of IL-15 receptor IL15RA. Furthermore, in vivo studies using an anti-PDL1 antibody in a mouse tumor model indicated a reduction in CD4+ T_CM cells and an increase in CD8+ T_EMRA cells, alongside evidence of cardiac fibrosis. Conversely, combining anti-PDL1 antibody treatment with IL-15 led to a resurgence of CD4+ T_CM cells, a reduction in CD8+ T_EMRA cells, and a mitigated risk of cardiac fibrosis. Our data highlight CD4+ T_CM cells as a crucial role in cardiac protection during ICIs therapy. IL-15, IL4I1 and CD4+ T_CM cells can serve as therapeutic targets to reduce ICIs-associated myocarditis in cancer patients.

Background: Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for various malignancies. However, research indicates blocking the immune checkpoint pathway may exacerbate atherosclerotic lesions.Objectives: We aimed to investigate whether ICI therapy increases the risk of arterial thromboembolic events (ATEs).Methods: A retrospective cohort study was conducted on patients with histologically confirmed cancer at our institution between 2018 and 2021, using the propensity score matching method. The primary endpoint was ATEs occurrence, comprising acute coronary syndrome, stroke/transient ischemic attack, and peripheral arterial thromboembolism. Subgroup analyses assessed whether the ICI treatment effect on ATEs varied over time by limiting the maximum follow‐up duration. Logistic regression analysis identified ATE risk factors in ICI‐treated patients.Results: Overall, the ICI group (n = 2877) demonstrated an ATEs risk 2.01 times higher than the non‐ICI group (RR, 2.01 [95% CI (1.61–2.51)]; p < 0.001). Subgroup analysis revealed no significant increase in ATEs risk for ICI‐treated patients within 1 year (Limited to a max 9‐month follow‐up, p = 0.075). However, ATEs risk in the ICI group rose by 41% at 1 year (p = 0.010) and 97% at 4 years (p ≤ 0.001). Age, diabetes, hypertension, peripheral atherosclerosis, atrial fibrillation, chronic ischemic heart disease, distant cancer metastasis, and ICI treatment cycles contributed to ATEs risk elevation in ICI‐treated patients.Conclusion: ICI‐treated patients may exhibit a higher risk of ATEs, especially after 1 year of treatment.

Background: Venous thromboembolism (VTE) is a potential complication among lymphoma patients. We evaluated the incidence rate and predictors of VTE in lymphoma patients undergoing chemotherapy.Methods: The present study retrospectively studied 1,069 patients with lymphoma who were treated with chemotherapy from 2018 to 2020. We investigated clinical predictors of VTE among all patients. The follow-up results were obtained via telephone communication and from inpatient and outpatient records.Results: A total of 1,069 patients underwent chemotherapy for lymphoma. During a mean follow-up of 23.1 months, 52 (4.9%) patients developed VTE. According to a multivariate analysis, the five variables found to be independently associated with VTE were male sex (HR 2.273, 95% CI 1.197–4.316, p = 0.012), age >64-years-old (HR 2.256, 95% CI 1.017–5.005, p = 0.045), the number of cycles of chemotherapy (HR 4.579, 95% CI 1.173–17.883, p = 0.029), platelet count ≥350 × 10⁹/L (HR 2.533, 95% CI 1.187–5.406, p = 0.016), and D-dimer >0.5 mg/L (HR 4.367, 95% CI 2.124–8.981, p < 0.001).Conclusion: This population-based study confirms the risk factors for VTE among patients with lymphoma who underwent chemotherapy and confirms that targeted thromboprophylaxis may reduce the burden of VTE in this population.

Optimizing cellulase biosynthesis in Bacillus subtilis is crucial for enhancing enzymatic yield in lignocellulosic biomass conversion. However, the regulatory mechanisms linking intracellular NAD(H/⁺) levels to cellulase production remain elusive. In this study, we systematically screened 13 genes associated with NAD⁺ biosynthesis and NADH regeneration in B. subtilis Z2. Employing a modular engineering strategy with four distinct modules, we directed metabolic flux to enhance NAD⁺ biosynthesis and NADH regeneration. Key genes (ycel, nadV, nadM, mdh, and sucB) were identified, and their co-expression in B. subtilis Z2 resulted in a 13.09-fold increase in intracellular NADH levels and a consequential 2.24- and 2.04-fold enhancement in the filter paper-hydrolyzing (FPase [representing total cellulase]) activity and carboxymethylcellulose (CMCase [representing endoglucanase]) activity, respectively. Experimental validations, including antagonist LaCl₃ treatment and spcF gene deletion, unequivocally established the calcium signaling pathway’s role in regulating cellulase gene overexpression in response to elevated intracellular NAD(H/⁺) levels.