Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial.

Background: The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy.

Methods: This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery.

Glioblastoma with high O6-methyl-guanine DNA methyltransferase expression are more immunologically active than tumors with low expression.

Background: Glioblastoma (GBM) is a highly lethal brain tumor. The effectiveness of temozolomide (TMZ) treatment in GBM is linked to the methylation status of O6-methyl-guanine DNA methyltransferase () promoter. Patients with unmethylated promoter have limited treatment options available.

Alterations in Intratumoral Immune Response before and during Early-On Nivolumab Treatment for Unresectable Advanced or Recurrent Gastric Cancer.

We investigated the tumor immune response in gastric cancer patients receiving third-line nivolumab monotherapy to identify immune-related biomarkers for better patient selection. Nineteen patients (10 males, median age 67 years) who received nivolumab as a third- or later-line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients.

Immuno-genomic analysis reveals eosinophilic feature and favorable prognosis of female non-smoking esophageal squamous cell carcinomas.

Most of esophageal squamous cell carcinoma (ESCC) develop in smoking males in Japan, but the genomic etiology and immunological characteristics of rare non-smoking female ECSS remain unclear. To elucidate the genomic and immunological features of ESCC in non-smoking females, we analyzed whole-genome or transcriptome sequencing data from 94 ESCCs, including 20 rare non-smoking female cases. In addition, 31,611 immune cells were extracted from four ESCC tissues and subject to single-cell RNA-seq.

Managing a case of Breus' mole with severe fetal growth restriction via sequential ultrasonographic imaging and MRI.

A Breus' mole is a massive subchorionic thrombohematoma that arises below the chorionic plate on the fetal side of the placenta. It requires careful perinatal management because of the associated high incidence of severe fetal growth restriction and intrauterine fetal demise. However, the mechanism of its development remains unclear, and there are no reports examining the continuous changes in the hematomas.

Epicardial fat and Stage B heart failure among overweight/obese and normal weight individuals with diabetes mellitus.

Purpose: Although up to 20% of people with type 2 diabetes (DM) have normal BMI (< 25 kg/m), it remains unclear whether there is a difference in the development of cardiac dysfunction between those with normal and higher BMI. Furthermore, little is known about the relationship of visceral fat with BMI or fitness in asymptomatic patients with DM.

Methods: We prospectively enrolled asymptomatic patients with DM and divided into two groups: BMI ≥ 25kg/m (overweight/obese group) versus < 25kg/m(normal-weight group).

Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial.

Aims/hypothesis: Type 2 diabetes in people in the healthy weight BMI category (<25 kg/m), herein defined as 'normal-weight type 2 diabetes', is associated with sarcopenia (low muscle mass). Given this unique body composition, the optimal exercise regimen for this population is unknown.

Methods: We conducted a parallel-group RCT in individuals with type 2 diabetes (age 18-80 years, HbA 47.

Clinical and Echocardiographic Diversity Associated With Physical Fitness in the Project Baseline Health Study: Implications for Heart Failure Staging.

Background: Clinical and echocardiographic features may carry diverse information about the development of heart failure (HF). Therefore, we determined heterogeneity in clinical and echocardiographic phenotypes and its association with exercise capacity.

Methods: In 2036 community-dwelling individuals, we defined echocardiographic profiles of left and right heart remodeling and dysfunction.

Defining left ventricular remodeling using lean body mass allometry: a UK Biobank study.

Purpose: The geometric patterns of ventricular remodeling are determined using indexed left ventricular mass (LVM), end-diastolic volume (LVEDV) and concentricity, most often measured using the mass-to-volume ratio (MVR). The aims of this study were to validate lean body mass (LBM)-based allometric coefficients for scaling and to determine an index of concentricity that is independent of both volume and LBM.

Methods: Participants from the UK Biobank who underwent both CMR and dual-energy X-ray absorptiometry (DXA) during 2014-2015 were considered (n = 5064).

Effectiveness of a Community-Based Structured Physical Activity Program for Adults With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: The efficacy of physical activity interventions among individuals with type 2 diabetes has been established; however, practical approaches to translate and extend these findings into community settings have not been well explored.

Objective: To test the effectiveness of providing varying frequencies of weekly structured exercise sessions to improve diabetes control.

Design, Setting, And Participants: The IMPACT (Initiate and Maintain Physical Activity in Communities Trial) study was a controlled randomized clinical trial (randomization occurred from October 2016 to April 2019) that included a 6-month, structured exercise intervention either once or thrice weekly vs usual care (UC; advice only).

Immunotherapies targeting neoantigens are effective in PD-1 blockade-resistant tumors.

Only a small fraction of tumor-infiltrating lymphocytes can specifically recognize and attack cancer cells in PD-1/PD-L1 blockade therapy. Here, we investigate approaches to expand the neoantigen-specific CD8 T cells to overcome the difficulties in treating PD-1/PD-L1 blockade-resistant tumors. Mutation-associated neoepitopes of murine nonsmall cell lung cancer ASB-XIV were estimated by whole-exome and RNA sequencing and predicted by MHC-I binding affinity (FPKM >1) in silico.

Novel missense COL2A1 variant in a fetus with achondrogenesis type II.

Achondrogenesis type II (ACG2) is a lethal skeletal disorder caused by pathogenic variants in COL2A1. We present a fetus with cystic hygroma and severe shortening of the limbs at 14 weeks of gestation. We performed postnatal genetic analysis of the parents and fetus to diagnose the disease.

Association of left ventricular diastolic function with coronary artery calcium score: A Project Baseline Health Study.

Background: Coronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear.

Methods: In the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography.

Principal component analysis of early immune cell dynamics during pembrolizumab treatment of advanced urothelial carcinoma.

Immune checkpoint inhibitors have been approved as second-line therapy for patients with advanced urothelial carcinoma (UC). However, which patients will obtain clinical benefit remains to be determined. To identify predictive biomarkers for the pembrolizumab (PEM) response early during treatment, the present study investigated 31 patients with chemotherapy-resistant recurrent or metastatic UC who received 200 mg PEM intravenously every 3 weeks.

Clinical outcomes in pregnant women with coronavirus disease 2019 in a perinatal medical centre in Japan: a retrospective study of the first 1 year of the pandemic.

In this retrospective study, we analysed clinical and demographic data from the medical records of 31 pregnant women with coronavirus disease 2019 (COVID-19) who were treated at our hospital between April 2020 and April 2021. The most common symptom was a fever; ∼10% of patients were asymptomatic. One patient with rapidly worsening pneumonia needed a Caesarean Section at 30 weeks and was admitted for intensive care.

Selection of RNA-based evaluation methods for tumor microenvironment by comparing with histochemical and flow cytometric analyses in gastric cancer.

Understanding the tumor microenvironment (TME) and anti-tumor immune responses in gastric cancer are required for precision immune-oncology. Taking advantage of next-generation sequencing technology, the feasibility and reliability of transcriptome-based TME analysis were investigated. TME of 30 surgically resected gastric cancer tissues was analyzed by RNA-Seq, immunohistochemistry (IHC) and flow cytometry (FCM).

Association between effector-type regulatory T cells and immune checkpoint expression on CD8 T cells in malignant ascites from epithelial ovarian cancer.

Background: Regulatory T cells (Tregs) play an important role in the antitumor immune response in epithelial ovarian cancer (EOC). To understand the immune-inhibitory networks of EOC, we addressed the association between Tregs and immune checkpoint expression on T cells in the tumor microenvironment of EOC.

Methods: A total of 41 patients with stage IIIC and IV EOC were included in the analysis.

Evaluation of diastole by echocardiography for detecting early cardiac dysfunction: an outcome study.

Aims: Timely detection of subclinical left ventricular diastolic dysfunction (LVDDF) is of importance for precise risk stratification of asymptomatic subjects. Here, we evaluated the prevalence of LVDDF and its prognostic significance in the general population using two grading approaches: the 2016 ASE/EACVI recommendations and population-derived, age-specific criteria.

Methods And Results: We randomly recruited 1407 community-dwelling participants (mean age, 51.

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.

Two distinct phenotypes of immunologically hot gastric cancer subtypes.

An in-depth understanding of the tumor microenvironment (TME) is required for the development of improved combination immunotherapies for gastric cancer. Recently, we classified these cancers into four main types defined by their immunological attributes, namely Hot 1, Hot 2, Intermediate and Cold. Of these, the T cell-inflamed "Hot" tumors were further divided into Hot 1 and Hot 2 with different clinical outcomes.

Neoantigen Dendritic Cell Vaccination Combined with Anti-CD38 and CpG Elicits Anti-Tumor Immunity against the Immune Checkpoint Therapy-Resistant Murine Lung Cancer Cell Line LLC1.

An important factor associated with primary resistance to immune-checkpoint therapies (ICT) is a "cold" tumor microenvironment (TME), characterized by the absence of T cell infiltration and a non-inflammatory milieu. Whole-exome and RNA sequencing to predict neoantigen expression was performed on the LLC1 cell line which forms "cold" tumors in mice. Dendritic cell (DC)-based vaccination strategies were developed using candidate neoantigen long peptides (LPs).

Modification of improved-genome editing via oviductal nucleic acids delivery (i-GONAD)-mediated knock-in in rats.

Background: Improved genome-editing via oviductal nucleic acids delivery (i-GONAD) is a new technology that facilitates in situ genome-editing of mammalian zygotes exiting the oviductal lumen. The i-GONAD technology has been developed for use in mice, rats, and hamsters; however, oligonucleotide (ODN)-based knock-in (KI) is more inefficient in rats than mice. To improve the efficiency of i-GONAD in rats we examined KI efficiency using three guide RNAs (gRNA), crRNA1, crRNA2 and crRNA3.