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Background: Neutrophil-to-lymphocyte ratio (NLR) is a promising prognostic marker for patients undergoing hepatectomy for colorectal liver metastases (CRLM). However, its prognostic value in patients receiving neoadjuvant therapy (NAT) has not been sufficiently addressed. Methods: From 2013 to 2023, a cohort of 692 patients with CRLM receiving hepatectomy were enrolled in five centers. Clinicopathological characteristics were obtained from a prospectively maintained multi-center database. The effect of NLR (> 2 versus ≤ 2) on overall survival (OS) and recurrence-free survival was estimated by Kaplan–Meier analysis. Univariable and multivariable Cox regression analysis was applied to investigate the influence of individual clinicopathological parameters on OS. Results: In the entire cohort, the median NLR level was 2.11 (0.30–16.33). There were 307 (44.4%) patients receiving NAT followed by hepatectomy, while 385 (55.6%) patients undergoing upfront surgery. Notably, patients in the NAT group showed significantly lower NLR level than those in the upfront surgery group (1.83 versus 2.32, P < 0.001). In the upfront surgery group, high NLR was significantly associated with worse OS, independent of other factors (HR = 1.49, 95% CI 1.08–2.05, P = 0.02). In the NAT group, there was no significant difference in OS between the high NLR and low NLR group. Conclusion: The prognostic value of NLR in surgically resected CRLM is potentially influenced by NAT in the modern era. [ABSTRACT FROM AUTHOR]

Purposes: Many factors were reported to be associated with diabetic retinopathy (DR); however, their contributions remained unclear. We aimed to evaluate the prognostic and diagnostic accuracy of logistic regression and three machine learning models based on various medical records. Methods: This was a cross-sectional study. We investigated the prevalence and associations of DR among 757 participants aged 40 years or older in the 2005–2006 National Health and Nutrition Examination Survey (NHANES). We trained the models to predict if the participants had DR with 15 predictor variables. Area under the receiver operating characteristic (AUROC) and mean squared error (MSE) of each algorithm were compared in the external validation dataset using a replicate cohort from NHANES 2007–2008. Results: Among the 757 participants, 53 (7.00%) subjects had DR, the mean (standard deviation, SD) age was 57.7 (13.04), and 78.0% were male (n = 42). Logistic regression revealed that female gender (OR = 4.130, 95% CI: 1.820–9.380; P < 0.05), HbA1c (OR = 1.665, 95% CI: 1.197–2.317; P < 0.05), serum creatine level (OR = 2.952, 95% CI: 1.274–6.851; P < 0.05), and eGFR level (OR = 1.009, 95% CI: 1.000–1.014, P < 0.05) increased the risk of DR. The average performance obtained from internal validation was similar in all models (AUROC ≥ 0.945), and k-nearest neighbors (KNN) had the highest value with an AUROC of 0.984. In external validation, they remained robust or with modest reductions in discrimination with AUROC still ≥ 0.902, and KNN also performed the best with an AUROC of 0.982. Both logistic regression and machine learning models had good performance in the clinical diagnosis of DR. Conclusions: This study highlights the utility of comparing traditional logistic regression to machine learning models. We found that logistic regression performed as well as optimized machine learning methods when classifying DR patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the prognostic significance of clinicopathological characteristics in early-onset versus late-onset colorectal liver metastases (CRLM). Methods: The data of CRLM patients who underwent hepatectomy from September 2010 to September 2020 were retrospectively analyzed. According to the age of primary cancer diagnosis, patients were divided into early-onset CRLM (EOCRLM) and late-onset CRLM (LOCRLM) groups. Clinicopathological parameters were compared between the two groups. Cox regression model and Kaplan–Meier method were used to analyze the effect of clinicopathological parameters on overall survival (OS) and recurrence-free survival (RFS). Results: In total, 431 CRLM patients were identified, 130 with EOCRLM and 301 with LOCRLM. Compared with LOCRLM patients, EOCRLM patients had lower American Society of Anesthesia (ASA) grade and longer operation time (204 vs. 179 min). More aggressive features were presented in EOCRLM patients including synchronous liver metastases (76.9% vs. 61.1%) and bilobar involvement (43.8% vs. 33.2%). No significant difference in OS or RFS was found between the two groups. Multivariate analysis of EOCRLM group showed that preoperative CA19-9 level and RAS/BRAF status were predictive of OS, while bilobar involvement and preoperative CEA level were associated with RFS. In LOCRLM group, the number of CRLM, preoperative CA19-9 level, and BRAF status were associated with OS, while the number of CRLM was associated with RFS. Conclusions: The preoperative CA19-9 level, RAS/BRAF status, bilobar involvement, and preoperative CEA level were predictive of EOCRLM patient prognosis, while the number of CRLM, preoperative CA19-9 level, and BRAF status were predictive of LOCRLM patient prognosis. [ABSTRACT FROM AUTHOR]

Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process. [ABSTRACT FROM AUTHOR]