Therapeutic proteins have increasingly been used in modern medical applications, but their effectiveness is limited by factors such as stability and blood circulation time. Recently, there has been significant research into covalently linking polyethylene glycol polymer chains (PEG) to proteins, known as PEGylation, to mitigate these issues. In this work, an atomistic molecular dynamics study of N-terminal conjugated PEG-BSA (bovine serum albumin) was conducted with varying PEG molecular weights (2, 5, 10, and 20 kDa) to probe PEG-BSA interactions and evaluate the effect of polymer length on dynamics. It was found that the affinity of PEG toward the protein surface increased as a function of PEG molecular weight and that a certain weight (around 10 kDa) was required to promote protein–polymer interactions. Additionally, preferential interactions were monitored through formed contacts and hotspots were identified. PEG chains coordinating in looplike conformations were found near lysine residues. Also, it was found that hydrophobic interactions played an important role in promoting PEG-BSA interactions as the PEG molecular weight increased. The results provide insight into underlying mechanisms behind transitions in PEG conformations and will aid in future design of effective PEGylated drug molecules.

The choroid layer is a vascular layer in human retina and its main function is to provide oxygen and support to the retina. Various studies have shown that the thickness of the choroid layer is correlated with the diagnosis of several ophthalmic diseases. For example, diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. Despite contemporary advances, automatic segmentation of the choroid layer remains a challenging task due to low contrast, inhomogeneous intensity, inconsistent texture and ambiguous boundaries between the choroid and sclera in Optical Coherence Tomography (OCT) images. The majority of currently implemented methods manually or semi-automatically segment out the region of interest. While many fully automatic methods exist in the context of choroid layer segmentation, more effective and accurate automatic methods are required in order to employ these methods in the clinical sector. This paper proposed and implemented an automatic method for choroid layer segmentation in OCT images using deep learning and a series of morphological operations. The aim of this research was to segment out Bruch’s Membrane (BM) and choroid layer to calculate the thickness map. BM was segmented using a series of morphological operations, whereas the choroid layer was segmented using a deep learning approach as more image statistics were required to segment accurately. Several evaluation metrics were used to test and compare the proposed method against other existing methodologies. Experimental results showed that the proposed method greatly reduced the error rate when compared with the other state-of-the-art methods.

Macromolecules such as proteins conjugated to polyethylene glycol (PEG) have been employed in therapeutic drug applications, and recent research has emphasized the potential of varying polymer architectures and conjugation strategies to achieve improved efficacy. In this study, we performed atomistic molecular dynamics simulations of bovine serum albumin (BSA) conjugated to 5 kDa PEG polymers in an array of schemes, including varied numbers of attached chains, grafting density, and nonlinear architectures. Nonlinear architectures included U-shaped PEG, Y-shaped PEG, and poly(oligoethylene glycol methacrylate) (POEGMA). Buried surface area calculations and polymer volume map analyses revealed that volume exclusion behaviors of the high grafting density conjugate promoted additional protein–polymer interactions when compared to simply increasing numbers of conjugated chains uniformly across the protein surface. Investigation of nonlinear polymer architectures showed that stable polymer-lysine loop-like conformations seen in previous conjugate designs were more variable in prevalence, especially in POEGMA, which contained short oligomer PEG chains. The findings of this comprehensive study of alternate PEGylation schemes of BSA provide critical insight into molecular patterns of interaction within bioconjugates and highlight their importance in the future of controlled modification of conjugate system parameters.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

e16306 Background: Duodenal adenocarcinoma (DA) is a rare malignancy with poor outcomes. Tumor markers are used to assess disease response and to monitor for recurrence. Specifically, CA-19-9 and CEA have been validated for use in pancreatic cancer and colorectal cancer, respectively. However, these tumor markers have never been validated in patients with DA. We aim to assess the association of these biomarkers with clinical outcomes in patients with DA. Methods: This is a retrospective cohort study. After obtaining IRB approval (IRB202102705), we accessed the University of Florida medical records of patient treated for DA from January 1, 2006, until December 31, 2021. CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal CA 19-9 < = 35 U/ml; CEA < = 3 ng/ml). Analysis was conducted using Kaplan Meyer curves, log-rank test and Cox proportional hazards model. Results: A total of 68 patients were included in the final analysis. Median age was 67 years and median follow-up was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. Patients with an elevated CA 19-9 had a median overall survival (OS) of 8.5 months vs. 27.4 months in patients with normal levels (HR 1.67; 95%CI 0.94–2.99; p = 0.081). Patients with an elevated CEA had a median OS of 13.4 months vs. 16.8 months in patients with normal level normal levels (HR 1.43; 95%CI 0.81–2.52; p value = 0.221). In a sensitivity analysis, a concomitant elevation of both tumoral markers was significantly associated with worsened OS (HR 1.9; 95%CI 1.05–3.06; p = 0.035). Conclusions: In patients with duodenal adenocarcinoma, elevation of both CA 19-9 and CEA was associated with a statistically significant worse overall survival. CA 19-9 level had a higher prognostic impact on OS than CEA levels. To our knowledge, this is the first study to evaluate the role of CA 19-9 and CEA in patients with DA. Further research is required for validation.[Table: see text]