Identification and phenotypic characterization of neoantigen-specific cytotoxic CD4+ T cells in endometrial cancer.

Tumor-reactive CD4+ T cells often accumulate in the tumor microenvironment (TME) in human cancer, but their functions and roles in antitumor responses remain elusive. Here, we investigated the immunopeptidome of HLA class II-positive (HLA-II+) endometrial cancer with an inflamed TME using a proteogenomic approach. We identified HLA-II neoantigens, one of which induced polyclonal CD4+ tumor-infiltrating lymphocyte (TIL) responses.

Single-cell profiling of acral melanoma infiltrating lymphocytes reveals a suppressive tumor microenvironment.

Acral lentiginous melanoma (ALM) is the most common melanoma subtype in non-Caucasians. Despite advances in cancer immunotherapy, current immune checkpoint inhibitors remain unsatisfactory for ALM. Hence, we conducted comprehensive immune profiling using single-cell phenotyping with reactivity screening of the T cell receptors of tumor-infiltrating T lymphocytes (TILs) in ALM.

Potential radiosensitive germline biomarkers in the testes of wild mice after the Fukushima accident.

We investigated potential germline-specific radiosensitive biomarkers in the testes of large Japanese field mice (Apodemus speciosus) exposed to low-dose-rate (LDR) radiation after the Fukushima accident. Fukushima wild mice testes were analysed via RNA-sequencing to identify genes differentially expressed in the breeding and non-breeding seasons when compared to controls. Results revealed significant changes during the breeding season, with Lsp1 showing a considerable upregulation, while Ptprk and Tspear exhibited significant reductions.

Neoantigen prioritization based on antigen processing and presentation.

Somatic mutations in tumor cells give rise to mutant proteins, fragments of which are often presented by MHC and serve as neoantigens. Neoantigens are tumor-specific and not expressed in healthy tissues, making them attractive targets for T-cell-based cancer immunotherapy. On the other hand, since most somatic mutations differ from patient to patient, neoantigen-targeted immunotherapy is personalized medicine and requires their identification in each patient.

Establishment of potent TCR-T cells specific for cisplatin-resistance related tumor-associated antigen, CLSPN using codon-optimization.

Adoptive T cell therapy, using T cell receptor-engineered T (TCR-T) cells and chimeric antigen receptor T (CAR-T) cells, is a potent immunotherapy option. Bladder cancer is a prevalent urological malignancy, particularly in cases of muscle invasion and metastasis, for which systemic therapy is crucial. Immunotherapy utilizing immune checkpoint blockade has been approved for bladder cancer treatment.

HLA class II neoantigen presentation for CD4 T cell surveillance in HLA class II-negative colorectal cancer.

Neoantigen-reactive CD4 T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach.

Identification of immunogenic HLA class I and II neoantigens using surrogate immunopeptidomes.

Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE).

Disruption of insulin receptor substrate 2 (IRS2) causes non-obese type 2 diabetes with β-cell dysfunction in the golden (Syrian) hamster.

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood.

Proteogenomic identification of an immunogenic antigen derived from human endogenous retrovirus in renal cell carcinoma.

CD8+ T cells can recognize tumor antigens displayed by HLA class I molecules and eliminate tumor cells. Despite their low tumor mutation burden, immune checkpoint blockade (ICB) is often beneficial in patients with renal cell carcinoma (RCC). Here, using a proteogenomic approach, we directly and comprehensively explored the HLA class I-presenting peptidome of RCC tissues and demonstrated that the immunopeptidomes contain a small subset of peptides derived from human endogenous retroviruses (hERV).

Hypnotic prescription trends and patterns for the treatment of insomnia in Japan: analysis of a nationwide Japanese claims database.

Background: There is limited consensus regarding the optimal treatment of insomnia. The recent introduction of orexin receptor antagonists (ORA) has increased the available treatment options. However, the prescribing patterns of hypnotics in Japan have not been comprehensively assessed.

Factors Associated with Prescriptions for an Orexin Receptor Antagonist Among Japanese Patients with Insomnia: Analysis of a Nationwide Japanese Claims Database.

Background: Few studies have examined the prescribing patterns of orexin receptor antagonists (ORAs) in the real-world clinical setting in Japan.

Objective: We sought to analyze the factors associated with ORA prescriptions for patients with insomnia in Japan.

Methods: Outpatients (aged ≥ 20 to < 75 years old) prescribed one or more hypnotic for insomnia between April 1, 2018 and March 31, 2020 with continuous enrollment for ≥ 12 months were extracted from the JMDC Claims Database.

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma.

Bladder cancer is a major and fatal urological disease. Cisplatin is a key drug for the treatment of bladder cancer, especially in muscle-invasive cases. In most cases of bladder cancer, cisplatin is effective; however, resistance to cisplatin has a significant negative impact on prognosis.

Treatment patterns and satisfaction in patients with type 2 diabetes newly initiating oral monotherapy with antidiabetic drugs in Japan: results from the prospective Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND).

Introduction: To present longitudinal data from the Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND) in Japan.

Research Design And Methods: In this multicenter, prospective, observational cohort study, patients with type 2 diabetes mellitus (T2DM) newly initiated on monotherapy were followed up for 2 years. Primary outcomes included changes in treatment pattern over time, target hemoglobin A1c (HbA1c) attainment and treatment satisfaction per Oral Hypoglycaemic Agent Questionnaire (OHA-Q).

253 J at 0.2 Hz, LD pumped cryogenic helium gas cooled Yb:YAG ceramics laser.

A 253 J with 26 ns at 0.2 Hz laser performance was demonstrated using a LD pumped cryogenically cooled Yb:YAG ceramics laser amplifier. A high energy storage of 344 J was achieved with a stored energy density of 0.

Incremental medical cost of delirium in elderly patients with cognitive impairment: analysis of a nationwide administrative database in Japan.

Objectives: Delirium is a neuropsychiatric disorder that commonly occurs in elderly patients with cognitive impairment. The economic burden of delirium in Japan has not been well characterised. In this study, we assessed incremental medical costs of delirium in hospitalised elderly Japanese patients with cognitive impairment.

Clinical characteristics and drug utilisation patterns in patients with chronic cough: a retrospective cohort study using a Japanese claims database.

Background: Although unmet medical needs for better care of patients with chronic cough exist in Japan, epidemiological information about these patients and their treatments is very limited.

Objectives: To describe patient characteristics, underlying cough-related diseases and drug utilisation patterns in patients with chronic cough, and their changes over time.

Methods: This large retrospective claims database study enrolled subjects with chronic cough, identified either by a specific diagnostic cough code for chronic cough (Population 1) or by multiple cough-related diagnostic codes spanning > 8 weeks (Population 2).

Impact of refractory and unexplained chronic cough on disease burden: a qualitative study.

Background: Chronic cough lasting for > 8 weeks is a common medical condition that burdens patients. This study aimed to qualitatively describe knowledge, awareness, experiences, and subtypes of burdens (physical, social, psychological) among Japanese patients with refractory chronic cough (refractory to treatment of underlying relevant medical conditions) and unexplained chronic cough (symptoms of unexplained origin).

Methods: This non-interventional, cross-sectional study was conducted between February and March 2021 among patients (aged ≥ 20 years) with self-reported refractory or unexplained chronic cough.

Combined chemoradiotherapy and programmed cell death-ligand 1 blockade leads to changes in the circulating T-cell receptor repertoire of patients with non-small-cell lung cancer.

Combined chemoradiotherapy (CRT) and programmed cell death-ligand 1 (PD-L1) blockade is a new care standard for unresectable stage III non-small-cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy.

Characterization of Proteasome-Generated Spliced Peptides Detected by Mass Spectrometry.

CD8 T cells recognize peptides displayed by HLA class I molecules and monitor intracellular peptide pools. It is known that the proteasome splices two short peptide fragments. Recent studies using mass spectrometry (MS) and bioinformatics analysis have suggested that proteasome-generated spliced peptides (PSPs) may account for a substantial proportion of HLA class I ligands.

Super-strong magnetic field-dominated ion beam dynamics in focusing plasma devices.

High energy density physics is the field of physics dedicated to the study of matter and plasmas in extreme conditions of temperature, densities and pressures. It encompasses multiple disciplines such as material science, planetary science, laboratory and astrophysical plasma science. For the latter, high energy density states can be accompanied by extreme radiation environments and super-strong magnetic fields.

Patient characteristics associated with improvement in glycemic control following addition of an oral antidiabetic drug to DPP-4 inhibitor monotherapy in Japanese patients with type 2 diabetes mellitus (JDDM 60).

Aims: The current study evaluated patient demographics and clinical characteristics that associated with HbA1c reduction following addition of one oral antidiabetic drug (OAD) to DPP4i monotherapy.

Methods: A retrospective study was conducted using CoDiC database. Adult T2DM patients treated with sitagliptin monotherapy for ≥ 6 months and adding one OAD were extracted.

Changes in ovarian morphology and hormone concentrations associated with reproductive seasonality in wild large Japanese field mice ().

Wild large Japanese field mice () responses to cyclic seasonal changes are associated with physiological and behavioral changes. However, the detailed regulation of oogenesis in the ovary during the seasonal reproductive cycle in wild large Japanese field mice has not been studied. We assessed the dynamics and changes in ovarian morphology and hormone concentrations associated with reproductive seasonality throughout the year.

Identification of Neoantigens in Two Murine Gastric Cancer Cell Lines Leading to the Neoantigen-Based Immunotherapy.

To develop combination immunotherapies for gastric cancers, immunologically well-characterized preclinical models are crucial. Here, we leveraged two transplantable murine gastric cancer cell lines, YTN2 and YTN16, derived from the same parental line but differing in their susceptibility to immune rejection. We established their differential sensitivity to immune checkpoint inhibitors (ICI) and identified neoantigens.