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Germinal centers (GCs) are the site of antibody affinity maturation, a fundamental immunological process that increases the potency of antibodies and thereby their ability to protect against infection. GC biology is highly dynamic in both time and space, making it ideally suited for intravital imaging. Using multiphoton laser scanning microscopy (MPLSM), the field has gained insight into the molecular, cellular, and structural changes and movements that coordinate affinity maturation in real time in their native environment. On the other hand, several limitations of MPLSM have had to be overcome to allow full appreciation of GC events taking place across different timescales. Here, we review the technical advances afforded by intravital imaging and their contributions to our understanding of GC biology.

Managerial career concerns could affect firm efficiency through financial reporting quality, but this important link has received relatively little attention in the literature. The present study examines this link by developing a model that has the following elements. A risk-neutral manager provides effort to increase the market value of the firm and to favorably influence the market assessment of the manager’s ability. Depending on the magnitude of career concerns, the manager either under- or overinvests effort relative to an efficiency-maximizing level. The analysis identifies conditions un-der which higher-quality reporting induces the manager to invest more effort. Under these condi-tions, the model is extended to a setting in which the manager also chooses the quality of financial reporting at some cost. In doing so, the manager seeks to reduce distortion in their effort invest-ment. The equilibrium reporting quality and effort investment are determined by a trade-off be-tween them. In the presence of high uncertainty about the firm’s future cash flows, if the manager’s career concerns exceed a threshold, the manager underinvests in reporting quality and overinvests effort. The empirical implication is a negative relation between managerial career concerns and fi-nancial reporting quality. To a large extent, this is consistent with findings in prior empirical studies. Thus, the present study offers a theoretical explanation for the empirical findings as an equilibrium outcome.

This paper investigates the intragroup flows of brand royalties within large Korean business groups, known as chaebols. We find that business group member firms pay a greater amount of brand royalties when the associated business groups adopt a holding company governance structure, consistent with the bitter denunciation that chaebols transfer wealth from member firms to holding companies over which they have direct control. However, member firms pay a smaller amount of brand royalties when their related party transactions (RPTs) are monitored by a designated RPTs committee on the board of directors. The results suggest that the monitoring of RPTs is effective in mitigating the alleged unethical wealth transfer via brand royalties of large business groups.

The pairwise maximum entropy model (MEM) for resting state functional MRI (rsfMRI) has been used to generate energy landscape of brain states and to explore nonlinear brain state dynamics. Researches using MEM, however, has mostly been restricted to fixed‐effect group‐level analyses, using concatenated time series across individuals, due to the need for large samples in the parameter estimation of MEM. To mitigate the small sample problem in analyzing energy landscapes for individuals, we propose a Bayesian estimation of individual MEM using variational Bayes approximation (BMEM). We evaluated the performances of BMEM with respect to sample sizes and prior information using simulation. BMEM showed advantages over conventional maximum likelihood estimation in reliably estimating model parameters for individuals with small sample data, particularly utilizing the empirical priors derived from group data. We then analyzed individual rsfMRI of the Human Connectome Project to show the usefulness of MEM in differentiating individuals and in exploring neural correlates for human behavior. MEM and its energy landscape properties showed high subject specificity comparable to that of functional connectivity. Canonical correlation analysis identified canonical variables for MEM highly associated with cognitive scores. Inter‐individual variations of cognitive scores were also reflected in energy landscape properties such as energies, occupation times, and basin sizes at local minima. We conclude that BMEM provides an efficient method to characterize dynamic properties of individuals using energy landscape analysis of individual brain states., We propose a Bayesian maximum entropy model estimation (BMEM) to characterize nonlinear brain state dynamics in each individual. BMEM showed advantages over conventional maximum likelihood estimation in reliably estimating model parameters for individuals with small sample data. BMEM and its energy landscape properties showed high subject specificity.

With pervasive pension funding deficits, Korean firms have been under pressure to improve their funding levels. We examine whether firms have incentives to set obligation‐decreasing pension assumptions when they have large pension deficits (pension obligations in excess of plan assets) and when they make insufficient contributions to external pension funds. We find that firms report larger actuarial gains (or smaller actuarial losses) associated with the remeasurement of pension liabilities when their pension funding ratio (the ratio of the fair value of plan assets to defined benefit obligations) is lower and when contributions to plan assets relative to pension service costs are smaller. Next, upon the introduction of a minimum pension funding guideline, we find that the effect of the funding ratio and contributions to pension funds on actuarial gains and losses is more pronounced for firms whose funding ratios are slightly below the minimum funding ratio than it is for firms whose funding ratios exceed or fall short of the minimum by a large margin. Our results indicate that firms opportunistically exercise discretion regarding corporate pension accounting under International Financial Reporting Standards to comply with pension funding regulations, thereby reducing perceived pension deficits.

The articulator is a prerequisite device for the analysis of occlusion and prosthodontic treatment, and it is required to simulate patient jaw movements. This article describes the technique to obtain sagittal condylar inclination (SCI) using cone beam computed tomography (CBCT) data and intraoral scan of the protrusive interocclusal position. The SCI can be used on a virtual articulator in a computer-aided design software, and it can assist in the fabrication of prosthesis which is harmonious with the mandibular movement of individual patient.

BACKGROUND The role of testosterone as a prognostic factor for castration-resistant prostate cancer treated with docetaxel in Japan was investigated. METHODS A total of 164 patients with castration-resistant prostate cancer who received docetaxel treatment at Chiba University Hospital and an affiliated hospital were retrospectively analyzed. Testosterone and other clinical factors at the start of docetaxel treatment were evaluated with respect to overall survival and progression-free survival. RESULTS Of the 164 patients, 69 had high-volume tumors. The median prostatic-specific antigen was 27.0 ng/mL. The median testosterone was 13.0 ng/dL. The rates of bone and visceral metastases were 80.1% and 8.8%, respectively. For progression-free survival, testosterone ≥13 ng/dL was an independent prognostic factor only on univariate analysis (hazard ratio, 1.81; P = .0108). For overall survival, testosterone ≥ 1.3 ng/dL (hazard ratio, 3.37; P

Background Acute chest syndrome (ACS) is a leading cause of morbidity and mortality among children with sickle cell disease (SCD). Preventing hypoxemia by optimizing lung aeration during sleep remains a challenge. Objectives To explore safety, feasibility, and tolerability of noninvasive, bi-level positive airway pressure ventilation (BiPAP) as preventative, supportive care for hospitalized, medically stable children with SCD on a general pediatric inpatient unit. Methods Retrospective chart review of patients ≤22 years of age with SCD admitted to the general pediatric inpatient unit from February 1, 2017 to March 1, 2020 for whom BiPAP was recommended as supportive care. Hospitalizations were excluded if patients were admitted to the pediatric intensive care unit (PICU), required BiPAP for respiratory failure, or used BiPAP at home for obstructive sleep apnea. Results Twenty-three patients had 53 hospitalizations in which BiPAP was recommended. Fifty-two (98%) hospitalizations included acute SCD pain. Indications for BiPAP included prior ACS (94%), chest or back pain (79%), and/or oxygen desaturation (66%). On 17 occasions, patients already had mild to moderate ACS but were stable when BiPAP was recommended. BiPAP was used successfully during 75% of hospitalizations for a median of two nights. There were no adverse effects associated with BiPAP. PICU transfer for respiratory support occurred during three hospitalizations. In 26 hospitalizations of children at risk for ACS who tolerated BiPAP, 23 (88%) did not develop ACS. Conclusions BiPAP is safe, feasible, and well tolerated as supportive care for hospitalized children with SCD. Next steps include an intervention trial to further assess the efficacy of BiPAP on ACS prevention.

The purpose of this study is to evaluate the efficacy of bone regeneration and volume maintenance of the three-dimensional (3D) structured biphasic calcium phosphate (BCP) block with porous hexahedron channels in a rabbit calvarial model. In this work, four circular defects (diameter: 8 mm) in calvarium of rabbits were randomly assigned to (1) negative control (control), (2) 3D hexahedron channel structured BCP block, (3) deproteinized bovine bone mineral particle, and (4) deproteinized porcine bone mineral particle. Animals were euthanized at 2 (n = 5) and 8 weeks (n = 5). Outcome measures included micro-computed tomography (CT) and histomorphometrical analysis. Results indicated that in micro-CT, BCP group showed the highest new bone volume with significant difference compared to control (p = 0.008) at 8 weeks. Histomorphometrically, total augmented area of BCP group was the highest with significant difference compared to control (p = 0.008) at 8 weeks. BCP group also maintained total volume of the original defect without collapsing. BCP block with 3D hexahedron channel structure seems to have favorable osteogenic and volume maintaining ability and highly porous structure might attribute to new bone formation. Further studies regarding the optimal internal structure and porosity of the BCP block bone substitute are needed. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2254-2262, 2019.

This study examined the validity and reliability of the Korean version of the Generalized Anxiety Disorder-7 (GAD-7) scale. The GAD-7 was standardized with data from 112 patients at a psychiatric outpatient clinic. The GAD-7 revealed high internal consistency, good test-retest reliability, and convergent validity. The ROC analysis resulted in poor sensitivity and specificity for detecting anxiety disorders in a psychiatric setting. The GAD-7 may not be useful in diagnosing anxiety disorders in a psychiatric setting, even though it appears to be a reliable, efficient, and valid measurement tool for evaluating anxiety symptoms.

Objective With the recognition of epilepsy as a network disease that disrupts the organizing ability of resting-state brain networks, vagus nerve stimulation (VNS) may control epileptic seizures through modulation of functional connectivity. We evaluated preoperative 2-deoxy-2[18 F]fluoro-D-glucose (FDG) positron emission tomography (PET) in VNS-implanted pediatric patients with refractory epilepsy to analyze the metabolic connectivity of patients and its prognostic role in seizure control. Methods Preoperative PET data of 66 VNS pediatric patients who were followed up for a minimum of 1 year after the procedure were collected for the study. Retrospective review of the patients' charts was performed, and five patients with inappropriate PET data or major health issues were excluded. We conducted an independent component analysis of FDG-PET to extract spatial metabolic components and their activities, which were used to perform cross-sectional metabolic network analysis. We divided the patients into VNS-effective and VNS-ineffective groups (VNS-effective group, ≥50% seizure reduction; VNS-ineffective group, Results Thirty-four (55.7%) patients showed >50% seizure reduction from baseline frequency 1 year after VNS. A significant difference in metabolic connectivity evaluated by preoperative FDG-PET was noted between groups. Relative changes in glucose metabolism were strongly connected among the areas of brainstem, cingulate gyrus, cerebellum, bilateral insula, and putamen in patients with Significance This study shows that seizure outcome of VNS may be influenced by metabolic connectivity, which can be obtained from preoperative PET imaging. This study of metabolic connectivity analysis may contribute in further understanding of the mechanism of VNS in intractable seizures.

Defect-specific bone regeneration using 3-dimensional (3D) printing of block bone has been developed. Polycaprolactone (PCL) is biocompatible polymer that can be used as 3D scaffold. The aim of this study is to assess the biocompatibility and osteogenic efficacy of 3D printed PCL scaffold and to evaluate the effectiveness of β-tricalcium phosphate (β-TCP) addition in PCL scaffold. In this work, four circular defects (diameter: 8 mm) in rabbit calvarium were randomly assigned to (1) negative control (control), (2) PCL block (PCL), (3) PCL mixed with 10 wt% β-TCP (PCL/β-TCP), and (4) PCL/β-TCP plus collagen membrane (PCL/β-TCP + M). Animals were euthanized at 2 (n = 5) and 8 weeks (n = 5). Results indicated that in micro-CT, PCL/β-TCP + M showed the highest total augmented volume and new bone volume at 8 weeks, but there was no significant difference among four groups. Histomorphometrically, PCL, PCL/β-TCP, and PCL/β-TCP + M showed the significantly higher total augmented area compared to the control. PCL/β-TCP + M showed the highest new bone area but not statistically higher than the control. New bone formation deep inside the scaffold was observed only in β-TCP added scaffold. PCL showed high biocompatibility with great volume maintenance. Addition of β-TCP to PCL seemed to increase hydrophilicity and osteoconductivity. Developments in 3D-printed PCL material are expected. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1254-1263, 2019.

Overexpression of GRP78 in a variety of cancers such as glioblastoma, leukemia, lung, prostate, breast, gastric, and colon makes it a prime target for anticancer drug development. Present study reports GRP78-based design of novel anticancer agents using in-silico methods. As a first step toward the work, the interactions between GRP78 and 15 known ligands were modeled by docking simulation. The docked complex, GRP78-13, superior to other compounds with respect to its experimental activity and energy descriptors, was deduced into a structure-based pharmacophore. This hypothesis was applied as a screening filter to Asinex and Chemdiv databases. Finally, 23 hits were tested in vitro. Among these, VH1019 and VH1011 induced a concentration-dependent strong broad antiproliferative effect in glioma (U87-MG), breast cancer (MCF-7), and prostate cancer (DU-145) cell lines as compared to nontumorigenic control, neonatal foreskin fibroblast (HFF-1). These compounds showed preferential growth inhibition of cancer cells over normal cells. The acetohydrazide derivative VH1019 was identified as a potential new chemotype for GRP78 inhibitors with an IC50 of 12.7 μM in MCF-7.