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Background The endogenous secretory receptor for advanced glycation end products (esRAGE) is a soluble isoform produced by alternative splicing of the RAGE gene. The isoform has anti-inflammatory properties due to its inhibition of the RAGE/ligand interaction and is reduced in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the association of esRAGE serum and bronchoalveolar lavage fluid (BALF) levels with progression of IPF. Methods This study included 79 IPF patients and 90 healthy controls. IPF and control serum esRAGE levels were compared, and the correlation between serum and BALF esRAGE levels was analyzed in 57 IPF patient samples. We also investigated the relationship of esRAGE serum and BALF levels with prognoses and lung function parameters in patients with IPF. Results Serum esRAGE levels in IPF patients were significantly lower than those in healthy controls (162.0 ± 102.4 ng/ml and 200.7 ± 107.3 ng/ml, p = 0.009), although the baseline characteristics of age and smoking history were not matched. Serum levels of esRAGE were correlated with BALF esRAGE levels (rs = 0.317). The BALF esRAGE levels were also correlated with diffusion capacity for carbon monoxide (rs = 0.406). A Kaplan-Meier curve analysis and univariate/multivariate Cox hazard proportion analysis revealed that lower levels of esRAGE in blood and BALF were significantly associated with poorer prognoses in patients with IPF. Conclusions Decreased esRAGE levels in BALF and blood were associated with poor prognoses in patients with IPF. These results suggest that esRAGE could be related to the pathophysiology of IPF and serum esRAGE could be a potential prognostic marker of IPF.

In this paper, we present the data-driven fluid flow simulations using the deep CNN (Convolutional Neural Network) with the parametric softsign activation functions. To simulate the fluid flow problems, the particle-method approach based on SPH (Smoothed Particle Hydrodynamics) is used herein. The GPU-implementation consists mainly of the search for neighboring particles in the locally uniform grid cell using hash function. We construct significantly the deep CNN architectures with novel activation functions, so-called parametric softsign. Numerical results demonstrate the workability and validity of the present approach through the dam-breaking fluid flow simulations with free surface.

Severe leukopenia, thrombocytopenia, and bi-cytopenia due to nivolumab have been reported. In this report, we present the first case of nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma. A 56-year-old Japanese man with lung adenocarcinoma received nivolumab therapy as second-line treatment. After 3 cycles of this therapy, although computed tomography (CT) showed a reduced tumor size, laboratory findings revealed pancytopenia and a bone marrow biopsy showed a severely hypoplastic marrow. The pancytopenia was diagnosed as an adverse effect of nivolumab; filgrastim (75 μg/day), steroid-pulse therapy (intravenous methylprednisolone: 500 mg/day), and subsequently intravenous prednisolone (50 mg/day) were administered. Furthermore, intravenous administration of immunoglobulins was also performed. However, these treatments were ineffective. He was further diagnosed with fungal pneumonia and a catheter-related bloodstream infection. Anti-bacterial chemotherapy was administered. Two months after hospitalization, the neutrophil count improved to 1000/μL, but multiple red blood cell and platelet transfusions were needed. Therefore, further chemotherapy for lung adenocarcinoma could not be initiated, and the patient died due to progression of lung cancer 118 days after the onset of pancytopenia. The possibility of severe pancytopenia as an immune-related adverse event should be considered as a mandatory prerequisite for nivolumab therapy.

BackgroundA significant number of children with asthma show remission in adulthood. Although these adults are often diagnosed with COPD in later life, the effect of clinically remitted childhood asthma on the decline in lung function during adulthood is uncertain. We examined whether clinical remission of childhood asthma was associated with an accelerated decline in lung function in apparently nonasthmatic adults.Methods3584 participants (mean (range) age 48.1 (35–65) years) who did not have adulthood asthma and other lung diseases and had normal lung function at the baseline visit were included. They were categorised as those with remitted childhood asthma (n=121) and healthy controls (n=3463) according to their self-reported childhood asthma history. Spirometry was performed at baseline and follow-up visits.ResultsThe mean follow-up was 5.3 years. Multivariate regression analysis showed that remitted childhood asthma and smoking were independently associated with a rapid decline in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Smoking was an independent predictor of a rapid decline in FEV1/FVC. The annual decline in FEV1 and FVC was significantly greater in participants with remitted childhood asthma than in healthy controls, and the differences remained significant after adjusting for the propensity score.ConclusionsA history of clinically remitted childhood asthma is an independent risk factor for accelerated decline in lung function in adults. Remitted childhood asthma and smoking may additively accelerate the development of obstructive lung disease.

In this paper, we present the application of the GPU-based particle simulations to droplet-falling impact problem including free surfaces with surface tension and drag force. The particle approach is based on the MPS (Moving Particle Semi-implicit) method using logarithmic weighting functions. We adopt the inter-particle potential force model with a potential coefficient as a surface tension model. The GPU-implementation consists mainly of the search for neighboring particles in the locally uniform grid cell using hash function and solving the Poisson equation with respect to the pressure fields. Numerical results demonstrate the workability and validity of the present approach through the droplet-falling impact with surface tension and drag force.

Pemetrexedis a key drug in the first and second -line therapy for non-small-cell lung cancer. It exhibits an increased area under the plasma drug concentration-time curve, and it has a prolonged half -life when administered to patients with reduced renal function, resulting in a high frequency of neutropenia. Accordingly, pemetrexed is administered to these patients with caution. Herein, we retrospectively investigated the background characteristics of patients with a creatinine clearance rate (Ccr) of45 mL/min, who experienced severe adverse events due to pemetrexed. Thirty-eight patients with a Ccr of45 mL/min were administered pemetrexed. Of these patients, 13 (34%) developed severe adverse events (≥Grade 3) such as neutropenia, thrombocytopenia, and nausea. Multiple logistic regression analysis revealed that a Ccr of30 mL/min (p= 0.033) and the concomitant use of non-steroidal anti-inflammatory drugs (p=0.012) were significant risk factors for adverse events. Therefore, whenever possible, pemetrexed administration should be avoided in patients with a Ccr of30 mL/ min and in those receiving concomitant non-steroidal anti-inflammatory drugs.

The application of a finite element scheme to full three-dimensional (3D) incompressible viscous flow around a circular cylinder is presented in this paper. The scheme is based on the Petrov-Galerkin weak formulation using exponential weighting functions and on the second-order accurate Adams-Bashforth strategy as a time integration. As a typical example of the problems, flow around a circular cylinder involving an interesting phenomenon of the drag crisis is performed numerically. Numerical results demonstrate the workability and the validity of the present approach.

The application of a finite element scheme to three-dimensional Rayleigh-Benard convection in a horizontal fluid layer heated from below is presented. The scheme is based on the Petrov-Galerkin weak formulation using exponential weighting functions. The incompressible Navier-Stokes equations and energy equation with the Boussinesq approximation are numerically integrated in time by using a fractional step strategy with second-order accurate Adams-Bashforth scheme for both convection and diffusion terms. Numerical results obtained are compared through the Rayleigh-Benard convection of air for Rayleigh numbers up to 87300 with the experimental data and other existing numerical data, and demonstrate the workability and validity of the present approach.

In previous papers, we proposed finite element schemes based on the Petrov-Galerkin weak formulation using exponential weighting functions for solving accurately, and in a stable manner, the flow field of an incompressible viscous fluid. In this paper, we present the Petrov-Galerkin finite element scheme for turbulent flow fields based on large eddy simulation using the standard Smagorinsky model with the Van Driest damping function. The filtered incompressible Navier-Stokes equations are numerically integrated in time by using a fractional step strategy with second-order accurate Adams-Bashforth explicit differencing for both convection an diffusion terms. In order to evaluate more accurately a mass matrix, the well-known multi-pass algorithm was also adopted in this study. Numerical results obtained are compared through flow around a rectangular cylinder at Re = 22,000 with the experimental data and other existing numerical data.

Smoking is a major cause of cardiovascular risk factor. It is an independent risk factor for the onset and development of atherosclerotic vascular disease. Inflammation--and/or oxidative stress-induced vascular wall damage, particularly endothelial dysfunction, can be influenced by smoking. Endothelial dysfunction is an initiating event in atherogenesis, as well as a major factor in causing acute cardiovascular events. This review focuses on the mechanisms by which smoking causes aortic wall damage and subsequently induces clinical manifestation. Smoking cessation plays an important role in the management of atherosclerotic vascular disease.

A finite element scheme based on the Petrov-Galerkin weak formulation using exponential weighting functions for solving accurately, and in a stable manner, the flow field of an incompressible viscous fluid has been proposed in our previous works. In this paper, we present the Petrov-Galerkin finite element scheme for turbulent flow field. The incompressible Navier-Stokes equations are numerically integrated in time by using a fractional step strategy with second-order accurate Adams-Bashforth explicit differencing for both convection and diffusion terms. Numerical results obtained herein are compared through turbulent flow around a square cylinder at Re = 22,000 with the experimental data and other existing numerical ones.Copyright © 2003 by ASME