Liposomal formulations for enhanced lymphatic drug delivery

AbstractThe lymphatic system that extends throughout the whole body is one of useful targets for efficient drug delivery. The intestinal lymphatic drug delivery has been actively studied to date because administered drugs can avoid the first-pass metabolism in the liver, resulting in improvement of oral bioavailability. Drugs must be hydrophobic in order to be transported into the intestinal lymphatics because the lipid absorption mechanism in the intestine is involved in the lymphatic delivery. Therefore, various lipid-based drug carrier systems have been recently utilized to increase the transport of drug into the intestinal lymphatics. Lipidic molecules of the lipid-based drug delivery systems stimulate production of chylomicrons in the enterocytes, resulting in an increase in drug transport into lymphatic in the enterocytes. This review summarizes recently reported information on development of liposomal carriers for the intestinal lymphatic delivery and covers important determinants for successful lymphatic delivery

Clinical Application of Next-Generation Sequencing-Based Panel to BRAF Wild-Type Advanced Melanoma Identifies Key Oncogenic Alterations and Therapeutic Strategies

Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid cancers to discover potential therapeutic targets. Here, we describe the results of a clinical NGS panel in patients with advanced melanoma. Thirty-six tumor tissues from patients with BRAF wild-type melanoma at Seoul National University Hospital (SNUH; Seoul, Republic of Korea) were collected and deep-sequenced using the SNUH FIRST-Cancer NGS panel to assess single-nucleotide variants, small insertions/deletions, copy number variations, and structural variations to estimate tumor mutation burden (TMB). We discovered 106 oncogenic alterations and most of the patients (n = 33, 92%) harbored at least one oncogenic alteration, including 2 patients who were initially diagnosed as BRAF V600E-negative but were later confirmed to be positive. Altogether, 36 samples were classified into RAS/BRAF/NF1-mutant (n = 14, 39%) or triple wild-type (n = 22, 61%) melanoma subtypes. The estimated median TMB was 8.2 mutations per Mb, ranging from 0 to 146.67 mutations per Mb. Of the 36 patients, 25 (70%) had actionable alterations with currently developed drugs, and 7 (19.4%) were enrolled in dinical trials with an RAF inhibitor, multiple receptor tyrosine kinase inhibitor, and anti-programmed cell death-1 (PD-1) antibody. TMB tended to associate with progression-free survival (PFS) of treatment with anti-PD-1/PDL-1 antibody (HR, 0.96; 95% confidence interval, 0.92-1.00; P = 0.07). High-TMB (>= 13) group was associated with longer PFS than the low-TMB group (median 34.0 vs. 11.0 weeks, P = 0.04). Overall, the dinical use of a NGS panel in patients with advanced melanoma shows association with clinical outcomes and several therapeutic strategies.

Arithmetic PCA for Encrypted Data

Reducing the size of large dimensional data is a critical task in machine learning (ML) that often involves using principal component analysis (PCA). In privacy-preserving ML, data confidentiality is of utmost importance, and reducing data size is a crucial way to cut overall costs. This work focuses on minimizing the number of normalization processes in the PCA algorithm, which is a costly procedure in encrypted PCA. By modifying Krasulina\u27s algorithm, non-polynomial operations were eliminated, except for a single delayed normalization at the end. Our PCA algorithm demonstrated similar performance to conventional PCA algorithms in face recognition applications. We also implemented it using the CKKS (Cheon-Kim-Kim-Song) homomorphic encryption scheme and obtained the first 6 principal components of a 128$\times$128 real matrix in 7.85 minutes using 8 threads

Copy Number Deletion Has Little Impact on Gene Expression Levels in Racehorses

Copy number variations (CNVs), important genetic factors for study of human diseases, may have as large of an effect on phenotype as do single nucleotide polymorphisms. Indeed, it is widely accepted that CNVs are associated with differential disease susceptibility. However, the relationships between CNVs and gene expression have not been characterized in the horse. In this study, we investigated the effects of copy number deletion in the blood and muscle transcriptomes of Thoroughbred racing horses. We identified a total of 1,246 CNVs of deletion polymorphisms using DNA re-sequencing data from 18 Thoroughbred racing horses. To discover the tendencies between CNV status and gene expression levels, we extracted CNVs of four Thoroughbred racing horses of which RNA sequencing was available. We found that 252 pairs of CNVs and genes were associated in the four horse samples. We did not observe a clear and consistent relationship between the deletion status of CNVs and gene expression levels before and after exercise in blood and muscle. However, we found some pairs of CNVs and associated genes that indicated relationships with gene expression levels: a positive relationship with genes responsible for membrane structure or cytoskeleton and a negative relationship with genes involved in disease. This study will lead to conceptual advances in understanding the relationship between CNVs and global gene expression in the horse