Associations Between Plasma Concentrations of Lenvatinib and Angiopoietin and Clinical Responses to Lenvatinib Therapy in Japanese Patients With Thyroid Cancer.

Background/aim: The purpose of this study was to investigate the relationships between the plasma concentration of Lenvatinib (C0), the levels of angiopoietin (Ang)-1 and Ang-2, and clinical responses to lenvatinib therapy in patients with thyroid cancer.

Patients And Methods: Lenvatinib C and Ang were measured by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively.

Results: The median decrease rates of Ang-1 and Ang-2 at 1 month after treatment from baseline were -15.

Reducing the undesirable odor of barley by cooking with superheated steam.

Superheated steam was used to cook barley and the volatile odor compounds and release of odorants from the steamed barley were analyzed. The main odor compounds in cooked barley were aldehydes (hexanal and (,)-2,4-decadienal) and acids (acetic acid and hexanoic acid). Compared to ordinary cooked barley, barley cooked by superheated steam had less odorants, and the release of odorants was reduced by almost half.

Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer.

Lenvatinib is a substrate of cytochrome P450 (CYP) 3A and ATP-binding cassette (ABC) transporters. In this study, we aimed to evaluate how CYP3A4/5 and ABC transporter polymorphisms affected the mean steady-state dose-adjusted plasma trough concentrations (C) of lenvatinib in a cohort of 40 Japanese patients with thyroid cancer. CYP3A4 20230G > A (*1G), CYP3A5 6986A > G (*3), ABCB1 1236C > T, ABCB1 2677G > T/A, ABCB1 3435C > T, ABCC2 -24C > T, and ABCG2 421C > A genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism.

Association of lenvatinib trough plasma concentrations with lenvatinib-induced toxicities in Japanese patients with thyroid cancer.

The aim of this study was to examine the association of lenvatinib-induced adverse events with the trough plasma concentration (C) in Japanese patients with thyroid cancer. Patients received lenvatinib 24 mg as an initial dose, and sequential dose reductions were conducted based on the grade of each side effect. Assessment of adverse events, assay of lenvatinib C, and analysis of clinical laboratory tests were performed at the same time of day and were retrospectively analyzed.

Dynamics of Learning in MLP: Natural Gradient and Singularity Revisited.

The dynamics of supervised learning play a main role in deep learning, which takes place in the parameter space of a multilayer perceptron (MLP). We review the history of supervised stochastic gradient learning, focusing on its singular structure and natural gradient. The parameter space includes singular regions in which parameters are not identifiable.

Characterization and Clinical Implication of Th1/Th2/Th17 Cytokines Produced from Three-Dimensionally Cultured Tumor Tissues Resected from Breast Cancer Patients.

Objectives: Several cytokines secreted from breast cancer tissues are suggested to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced from three-dimensionally cultured breast cancer tissues and related them with patient clinical profiles.

Methods: 21 tumor tissues and 9 normal tissues surgically resected from breast cancer patients were cultured in thermoreversible gelatin polymer-containing medium.

Neurodegenerative disorder FTDP-17-related tau intron 10 +16C → T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative disorder caused by mutations in the tau gene. Many mutations identified in FTDP-17 have been shown to affect tau exon 10 splicing in vitro, which presumably causes pathologic imbalances in exon 10(-) [3-repeat (3R)] and exon 10(+) [4-repeat (4R)] tau expression and leads to intracellular inclusions of hyperphosphorylated tau in patient brains. However, no reports have investigated this theory using model mice with a tau intronic mutation.

Relationship of dietary intake and lifestyle factors to health-related quality of life in the community-dwelling elderly.

Quality of life (QOL) encompasses a broad notion of health and is increasingly used to evaluate the effectiveness of health care services. The purpose of this cross-sectional study was to assess health-related quality of life (HR-QOL) in the community-dwelling elderly (mean age, 72.7±0.

Dynamics of learning in multilayer perceptrons near singularities.

The dynamical behavior of learning is known to be very slow for the multilayer perceptron, being often trapped in the "plateau." It has been recently understood that this is due to the singularity in the parameter space of perceptrons, in which trajectories of learning are drawn. The space is Riemannian from the point of view of information geometry and contains singular regions where the Riemannian metric or the Fisher information matrix degenerates.

Dynamics of learning near singularities in layered networks.

We explicitly analyze the trajectories of learning near singularities in hierarchical networks, such as multilayer perceptrons and radial basis function networks, which include permutation symmetry of hidden nodes, and show their general properties. Such symmetry induces singularities in their parameter space, where the Fisher information matrix degenerates and odd learning behaviors, especially the existence of plateaus in gradient descent learning, arise due to the geometric structure of singularity. We plot dynamic vector fields to demonstrate the universal trajectories of learning near singularities.

Indoline derivatives II: synthesis and factor Xa (FXa) inhibitory activities.

Factor Xa (FXa) is well known to play a pivotal role in blood coagulation, so FXa inhibitor is a promising drug candidate for prophylaxis and treatment of thromboembolic diseases. In the course of our research, we have found that (R)-5-[1-(acetimidoyl)piperidin-4-yloxy]-2-(7-amidinonaphthalen-2-yl)-1-(ethanesulfonyl)indoline ((R)-1) showed potent FXa inhibitory activity in vitro. However, single oral administation (RS)-1 showed high toxicity in mice.

Singularities affect dynamics of learning in neuromanifolds.

The parameter spaces of hierarchical systems such as multilayer perceptrons include singularities due to the symmetry and degeneration of hidden units. A parameter space forms a geometrical manifold, called the neuromanifold in the case of neural networks. Such a model is identified with a statistical model, and a Riemannian metric is given by the Fisher information matrix.