Background Long-read sequencing of full-length cDNAs enables the detection of structures of aberrant splicing isoforms in cancer cells. These isoforms are occasionally translated, presented by HLA molecules, and recognized as neoantigens. This study used a long-read sequencer (MinION) to construct a comprehensive catalog of aberrant splicing isoforms in non-small-cell lung cancers, by which novel isoforms and potential neoantigens are identified. Results Full-length cDNA sequencing is performed using 22 cell lines, and a total of 2021 novel splicing isoforms are identified. The protein expression of some of these isoforms is then validated by proteome analysis. Ablations of a nonsense-mediated mRNA decay (NMD) factor, UPF1, and a splicing factor, SF3B1, are found to increase the proportion of aberrant transcripts. NetMHC evaluation of the binding affinities to each type of HLA molecule reveals that some of the isoforms potentially generate neoantigen candidates. We also identify aberrant splicing isoforms in seven non-small-cell lung cancer specimens. An enzyme-linked immune absorbent spot assay indicates that approximately half the peptide candidates have the potential to activate T cell responses through their interaction with HLA molecules. Finally, we estimate the number of isoforms in The Cancer Genome Atlas (TCGA) datasets by referring to the constructed catalog and found that disruption of NMD factors is significantly correlated with the number of splicing isoforms found in the TCGA-Lung Adenocarcinoma data collection. Conclusions Our results indicate that long-read sequencing of full-length cDNAs is essential for the precise identification of aberrant transcript structures in cancer cells.

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The APASL definition was suitable for screening Japanese patients with ACLF, including those whose conditions were triggered by gastrointestinal bleeding, and the EASL-Clif Consortium criteria were useful for predicting outcome.

Aim: Factors responsible for impaired improvement of liver function despite sustained viral response after direct-acting antiviral agents therapies in cirrhotic patients with hepatitis C virus need to be elucidated.Methods: Liver function and the extent of portosystemic shunting were evaluated for 79 patients with compensated cirrhosis, in whom sustained viral response had been achieved after direct-acting antiviral agents therapies for hepatitis C virus at least 3 years earlier. Conclusions:A large size of portosystemic shunts was found to be a crucial determinant of impaired improvement of liver function, as well as of the development of portal hypertensionrelated events, even after sustained viral response in patients with compensated cirrhosis.

The significance of switching of the nucleos(t)ide analog used to treat patients with hepatitis B virus (HBV) from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) is uncertain. The subjects of this study were 159 patients with HBV who received treatment with ETV followed by TAF. Among these patients, serial changes in the HBV marker levels were monitored in 92 patients in whom the serum HBsAg levels were ≥100 IU/mL during the 48-week period immediately before and after the switching. A questionnaire survey for medication compliance was performed in 127 patients. The serum HBsAg levels (log IU/ mL) decreased by 0.041 during the ETV treatment period and by 0.068 during the TAF administration period. The degree of reduction was higher during the TAF administration period than during the ETV administration period in patients without cirrhosis (P = .030), patients with genotype B HBV (P = .014), and patients with undetectable serum HBcrAg (P = .038). Multivariate analysis revealed the HBV genotype (B vs C; odds ratio, 3.400; P = .025) and serum aspartate aminotransferase level (every 1+; 1.111; P = .015) at the time of switching as factors influencing the treatment efficacy. Thirty-six patients (28%) responded that the number of days that they forgot to take the drug decreased after the drug switching, and 77 patients (61%) reported feeling satisfied with the drug switching.Switching of the nucleos(t)ide analog used from ETV to TAF may be useful in the treatment of patients with HBV infection, as it is associated with both a decrease in the serum HBsAg level and improvement of the medication compliance.