Characteristics and Clinical Assessment of Elbow Pain in Youth Baseball Players.

Elbow injuries related to the throwing motion in baseball during the growth period present difficulties for early detection and may cause serious future disabilities. This study aimed to comprehensively determine the characteristics and clinical assessment of elbow pain in youth baseball players. Two hundred and sixteen young baseball players underwent elbow medical examination. Basic information and physical examination, clinical assessment, and ultrasonography results were examined. Univariate analyses were statistically performed between the pain-free (98 participants) and elbow pain (118 participants) groups. The mean age was 11.6 years, and ultrasonographic abnormalities were found on the medial side of the elbow in 37.5%. In total, 118 (54.6%) participants experienced elbow pain, with 64.4% of them complaining of elbow pain on the medial side. Players with multiple positions (≥2 positions) had a significantly higher prevalence of elbow pain. Height, weight, length of baseball experience, and positive rates of horizontal flexion and moving valgus stress tests were higher in the elbow pain group than in the pain-free group. The risk factors and clinical assessment for elbow pain are useful for the prevention and early detection of throwing elbow injuries in youth baseball players.

Variational Bayes inference for hidden Markov diagnostic classification models.

Diagnostic classification models (DCMs) can be used to track the cognitive learning states of students across multiple time points or over repeated measurements. This study developed an effective variational Bayes (VB) inference method for hidden Markov longitudinal general DCMs. The simulations performed in this study verified the validity of the proposed algorithm for satisfactorily recovering true parameters. Simulation and applied data analyses were conducted to compare the proposed VB method to Markov chain Monte Carlo (MCMC) sampling. The results revealed that the parameter estimates provided by the VB method were consistent with the MCMC method with the additional benefit of a faster estimation time. The comparative simulation also indicated differences between the two methods in terms of posterior standard deviation and coverage of 95% credible intervals. Thus, with limited computational resources and time, the proposed VB method can output estimations comparable to that of MCMC.

Interaction of BMI and respiratory status in obstructive sleep apnea, a cross-sectional COPD study.

This cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as coexisting COPD and obstructive sleep apnea (OSA). OSA was defined as a respiratory event index (REI) ≥ 5 events/h, determined using type-3 portable monitors. The mean REI was 12.8 events/h. Most participants (60.1%) had mild OSA (REI: 5-15 events/h). The REI was positively correlated with forced expiratory volume in one second (%FEV1) (r = 0.33, p < 0.001), body mass index (BMI) (r = 0.24, p = 0.005), and fat-free mass index (r = 0.31, p = 0.005), and negatively correlated with residual volume divided by total lung capacity (r = -0.27, p = 0.003). Receiver-operating characteristic curve analysis revealed an optimal BMI cutoff of 21.96 kg/m2 for predicting moderate/severe OSA. A BMI ≥ 21.96 kg/m2 was associated with OSA among participants with %FEV1 ≥ 50%, but not those with %FEV1 < 50%. This study revealed an interaction between airflow limitation and hyperinflation, nutritional status, and OSA.

Direct Estimation of Diagnostic Classification Model Attribute Mastery Profiles via a Collapsed Gibbs Sampling Algorithm.

This paper proposes a novel collapsed Gibbs sampling algorithm that marginalizes model parameters and directly samples latent attribute mastery patterns in diagnostic classification models. This estimation method makes it possible to avoid boundary problems in the estimation of model item parameters by eliminating the need to estimate such parameters. A simulation study showed the collapsed Gibbs sampling algorithm can accurately recover the true attribute mastery status in various conditions. A second simulation showed the collapsed Gibbs sampling algorithm was computationally more efficient than another MCMC sampling algorithm, implemented by JAGS. In an analysis of real data, the collapsed Gibbs sampling algorithm indicated good classification agreement with results from a previous study.

Reconsidering the structure of the questionnaire for eudaimonic well-being using wide age-range Japanese adult sample: An exploratory analysis.

BACKGROUND: An increasing amount of research is now highlighting the importance of approaching issues of happiness through eudaimonic well-being. However, the literature does not conclusively show a full understanding of the construct of eudaimonic well-being, as previous studies primarily focused on younger samples from Western countries and only a few studies have attempted to explore its psychological construct through exploratory approaches. Therefore, we conducted a survey among a wide range of age groups in Japan to capture the psychological construct of eudaimonic well-being, through an exploratory analytic approach using Questionnaire for Eudaimonic Wellbeing (QEWB). METHODS: A total of 1126 Japanese participants (580 females, 546 males) were included for analysis. Participants were divided into three age groups according to their age, including 10s to 20s (18-29 years), 30s to 40s (30-49 years) and 50s to 60s (50-69 years). After narrowing down the total number of factors by exploratory structural equation modeling (ESEM), we conducted an ESEM and bifactor ESEM with oblique goemin and oblique bi-geomin rotations for choosing and assessing the final model based on the rotated results and its interpretability. RESULTS: The results of a parallel analysis and goodness-of-fit indices obtained by ESEM indicated that the QEWB consisted of three or more factors. Both a three-to-six factor and bifactor ESEM with oblique goemin rotation showed that three-factor structure for the 30s to 40s and 50s to 60s and four-factor structure for the 10s to 20s should be chosen, respectively. "Deep and Meaningful Engagement," a factor only relevant to the 10s to 20s may be an expanded version of what original paper called the Intense Involvement in Activities, with more emphasis on the enthusiastic attitude one has towards activities. CONCLUSIONS: The structure of eudaimonic well-being may differ across cultures and ages, thus requiring further investigation in the field.

Fenofibrate inhibits TGF-ß-induced myofibroblast differentiation and activation in human lung fibroblasts in vitro.

Fenofibrate (FF), a peroxisome proliferator-activated receptor-alpha (PPAR-α) agonist and a lipid-lowering agent, can decrease experimental pulmonary fibrosis. However, the mechanisms underlying the antifibrotic effect of FF remain unknown. Hence, this study was conducted to evaluate the effects of FF on transforming growth factor-beta (TGF-ß)-induced myofibroblast differentiation and activation in lung fibroblasts. The results showed that FF inhibited alpha-smooth muscle actin (α-SMA) and connective tissue growth factor expression, collagen production, cell motility, SMAD3 phosphorylation and nuclear translocation, and metabolic reprogramming in TGF-ß-exposed cells. The inhibitory effect of FF did not decrease with the addition of a PPAR-α antagonist. Moreover, the inhibitory effect given by FF could not be reproduced with the addition of an alternative PPAR-α agonist. FF inhibited mitochondrial respiration. However, rotenone, a complex I inhibitor, did not suppress TGF-ß-induced myofibroblast differentiation. Furthermore, the TGF-ß-induced nuclear reduction of protein phosphatase, Mg2+ /Mn2+ -dependent 1A (PPM1A), a SMAD phosphatase, was inhibited by FF. These results showed that FF suppressed TGF-ß-induced myofibroblast differentiation and activation independent of PPAR-α activation and impaired mitochondrial respiration. In conclusion, this study provides information on the effects of FF on anti-TGF-ß mechanisms.

Differential effects of dexamethasone and roflumilast on asthma in mice with or without short cigarette smoke exposure.

Appropriate drug treatment for smoking asthmatics is uncertain because most smokers with asthma are less sensitive to treatment with glucocorticoids compared with non-smokers with asthma. We hypothesized that roflumilast (Rof), a selective phosphodiesterases-4 inhibitor regarded as an add-on therapy for chronic obstructive pulmonary disease, might be more effective than glucocorticoids for improving asthma in smokers. To investigate this hypothesis, we compared the therapeutic effects of dexamethasone (Dex) and Rof in a mouse model of ovalbumin-induced asthma with or without concurrent cigarette smoke (CS) exposure for 2 weeks. We found that recurrent asthma attacks increased lung tissue resistance. CS exposure in asthmatic mice decreased the central airway resistance, increased lung compliance, and attenuated airway hyper-responsiveness (AHR). CS exposure in asthmatic mice also increased the number of neutrophils and macrophages in the bronchoalveolar fluid. Treatment with Dex in asthmatic mice without CS exposure reduced airway resistance, AHR and airway eosinophilia. In asthmatic mice with CS exposure, however, Dex treatment unexpectedly increased lung tissue resistance and restored AHR that had been otherwise suppressed. Dex treatment in asthmatic mice with CS exposure inhibited eosinophilic inflammation but conversely exacerbated neutrophilic inflammation. On the other hand, treatment with Rof in asthmatic mice without CS exposure reduced airway resistance and airway eosinophilia, although the inhibitory effect of Rof on AHR was unremarkable. In asthmatic mice with CS exposure, Rof treatment did not exacerbate lung tissue resistance but modestly restored AHR, without any significant effects on airway inflammation. These results suggest that CS exposure mitigates sensitivity to both Dex and Rof. In asthmatic mice with CS exposure, Dex is still effective in reducing eosinophilic inflammation but increases lung tissue resistance, AHR and neutrophilic inflammation. Rof is ineffective in improving lung function and inflammation in asthmatic mice with CS exposure. This study did not support our initial hypothesis that Rof might be more effective than glucocorticoids for improving asthma in smokers. However, glucocorticoids may have a detrimental effect on smoking asthmatics.

A Novel Bone Substitute Based on Recombinant Type I Collagen for Reconstruction of Alveolar Cleft.

This study aimed to examine the optimal cross-link density of recombinant peptide (RCP) particles, based on human collagen type I, for bone reconstruction in human alveolar cleft. Low- (group 1), medium- (group 2), and high- (group 3) cross-linked RCP particles were prepared by altering the duration of the heat-dependent dehydration reaction. Rat palatine fissures (n = 45), analogous to human congenital bone defects, were examined to evaluate the potential of bone formation by the three different RCP particles. Microcomputed tomography images were obtained to measure bone volume and bone mineral density at 4, 8, 12, and 16 weeks post grafting. Specimens were obtained for histological analysis at 16 weeks after grafting. Additionally, alkaline phosphatase and tartrate acid phosphatase staining were performed to visualize the presence of osteoblasts and osteoclasts. At 16 weeks, bone volume, bone mineral density, and new bone area measurements in group 2 were significantly higher than in any other group. In addition, the number of osteoblasts and osteoclasts on the new bone surface in group 2 was significantly higher than in any other group. Our results demonstrated that medium cross-linking was more suitable for bone formation-and could be useful in human alveolar cleft repairs as well.

Glasgow prognostic score for prediction of chemotherapy-triggered acute exacerbation interstitial lung disease in patients with small cell lung cancer.

BACKGROUND: Predicting the incidence of chemotherapy-triggered acute exacerbation of interstitial lung disease (AE-ILD) in patients with lung cancer is important because AE-ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation-based index composed of serum levels of C-reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE-ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. METHODS: Medical records of patients who received platinum-based first-line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE-ILD and overall survival (OS) between GPS 0, 1, and 2. RESULTS: Among our cohort of 31 patients, six (19.3%) experienced chemotherapy-triggered AE-ILD. The AE-ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE-ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p < 0.001). CONCLUSIONS: Our results suggest that GPS 2 is both a predictor of risk of chemotherapy-triggered AE-ILD and a prognostic indicator in patients with ILD associated with SCLC. We propose that GPS may be used as a guide to distinguish chemotherapy-tolerant patients from those at high risk of AE-ILD.

Oil Thickening with Organoclay Enhances the Ultraviolet Absorption Ability of Sunscreen on a Skin-mimicking Substrate.

The performance of sunscreen products depends on their ultraviolet (UV) absorption ability through the film formed on the skin surface upon their application. Therefore, it is important that a uniform film is formed on the uneven skin surface for effective sunscreen performance. Because most UV filters are oil soluble, we hypothesized in this study that increasing the viscosity of the oil phase of a sunscreen product can improve the performance of the sunscreen. We first examined the association between the concentration of the oil thickener and the UV absorption ability of the sunscreen product using a skin-mimicking substrate (SMS). Among all thickeners examined (petrolatum, dextrin palmitate, silica silylate, and organoclay), organoclay and silica silylate significantly increased the UV absorbance of sunscreen on the SMS in a concentration-dependent manner. Thereafter, we examined film uniformity to elucidate the mechanism underlying the observed increase in UV absorption. The uniformity of film thickness on the SMS increased with increasing organoclay content, based on decreased standard deviations of film thickness. Our results showed that increasing the viscosity of the oil phase with organoclay resulted in the formation of a uniform film by preventing the sunscreen from flowing into the grooves when applied on the SMS, thereby increasing UV absorbance by more than two-fold that of sunscreen without organoclay. Thus, the use of thickeners, such as organoclay, increases the viscosity of the oil phase at a low shear rate after the high shear of application. This is an effective strategy for improving the overall quality and performance of sunscreen products.

Glasgow Prognostic Score predicts chemotherapy-triggered acute exacerbation-interstitial lung disease in patients with non-small cell lung cancer.

BACKGROUND: Interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy-triggered acute exacerbation (AE)-ILD. The Glasgow Prognostic Score (GPS), which is based on serum C-reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy-triggered AE-ILD and the prognosis in patients with NSCLC and pre-existing ILD. METHODS: We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent-based treatment as first-line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0-2) and compared the incidence of chemotherapy-triggered AE-ILD and OS. RESULTS: The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy-triggered AE-ILD. The median OS was at 11.5 months (95% confidence interval: 8.0-15.1). The incidence of chemotherapy-triggered AE-ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy-triggered AE-ILD and OS (P < 0.05). CONCLUSIONS: GPS assessment of patients with NSCLC and pre-existing ILD is a valuable prognostic tool for predicting chemotherapy-triggered AE-ILD and OS. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We found that GPS 2 was an independent risk factor for chemotherapy-triggered AE-ILD and prognosis in patients with ILD associated with NSCLC. WHAT THIS STUDY ADDS: GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE-ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy.

Bone formation potential of collagen type I-based recombinant peptide particles in rat calvaria defects.

INTRODUCTION: This study aimed to examine the bone-forming ability of medium-cross-linked recombinant collagen peptide (mRCP) particles developedbased on human collagen type I, contains an arginyl-glycyl-aspartic acid-rich motif, fabricated as bone filling material, compared to that of the autologous bone graft. METHODS: Calvarial bone defects were created in immunodeficient rats though a surgical procedure. The rats were divided into 2 groups: mRCP graft and tibia bone graft (bone graft). The bone formation potential of mRCP was evaluated by micro-computed tomography and hematoxylin-eosin staining at 1, 2, 3, and 4 weeks after surgery, and the data were analyzed and compared to those of the bone graft. RESULTS: The axial volume-rendered images demonstrated considerable bony bridging with the mRCP graft, but there was no significant difference in the bone volume and bone mineral density between the mRCP graft and bone graft at 4 weeks. The peripheral new bone density was significantly higher than the central new bone density and the bottom side score was significantly higher than the top side score at early stage in the regenerated bone within the bone defects. CONCLUSION: These results indicate that mRCP has a high potential of recruiting osteogenic cells, comparable to that of autologous bone chips.

Anti-cancer strategy targeting the energy metabolism of tumor cells surviving a low-nutrient acidic microenvironment.

OBJECTIVE: Tumor cells experience hypoxia, acidosis, and hypoglycemia. Metabolic adaptation to glucose shortage is essential to maintain tumor cells' survival because of their high glucose requirement. This study evaluated the hypothesis that acidosis might promote tumor survival during glucose shortage and if so, explored a novel drug targeting metabolic vulnerability to glucose shortage. METHODS: Cell survival and bioenergetics metabolism were assessed in lung cancer cell lines. Our in-house small-molecule compounds were screened to identify those that kill cancer cells under low-glucose conditions. Cytotoxicity against non-cancerous cells was also assessed. Tumor growth was evaluated in vivo using a mouse engraft model. RESULTS: Acidosis limited the cellular consumption of glucose and ATP, causing tumor cells to enter a metabolically dormant but energetically economic state, which promoted tumor cell survival during glucose deficiency. We identified ESI-09, a previously known exchange protein directly activated by cAMP (EAPC) inhibitor, as an anti-cancer compound that inhibited cancer cells under low-glucose conditions even when associated with acidosis. Bioenergetic studies showed that independent of EPAC inhibition, ESI-09 was a safer mitochondrial uncoupler than a classical uncoupler and created a futile cycle of mitochondrial respiration, leading to decreased ATP production, increased ATP dissipation, and fuel scavenging. Accordingly, ESI-09 exhibited more cytotoxic effects under low-glucose conditions than under normal glucose conditions. ESI-09 was also more effective than actively proliferating cells on quiescent glucose-restricted cells. Cisplatin showed opposite effects. ESI-09 inhibited tumor growth in lung cancer engraft mice. CONCLUSIONS: This study highlights the acidosis-induced promotion of tumor survival during glucose shortage and demonstrates that ESI-09 is a novel potent anti-cancer mitochondrial uncoupler that targets a metabolic vulnerability to glucose shortage even when associated with acidosis. The higher cytotoxicity under lower-than-normal glucose conditions suggests that ESI-09 is safer than conventional chemotherapy, can target the metabolic vulnerability of tumor cells to low-glucose stress, and is applicable to many cancer cell types.

2-Hydroxy-4-methoxybenzophenone Enhances the Suppression of Superoxide Anion Radicals Generated via UVA-induced Photosensitizing by t-Butyl Methoxydibenzoylmethane.

4-tert-Butyl-4'-methoxydibenzoylmethane (BMDM) is widely used throughout the world as a highly effective UVA absorber that can prevent the progression of photoaging in skin. However, due to its low photostability, BMDM is also known for the disadvantage of having a reduced capability to absorb UVA during prolonged exposure to sunlight. Although many studies have been carried out to overcome this disadvantage of BMDM, little attention has been paid to how the radicals generated from BMDM during UV exposure influence the skin. Therefore, the purpose of this study was twofold: One goal was to clarify the influence of radicals on human skin using cytotoxicity as a parameter. The second was to propose a solution that could reduce the radical formation while taking photostability into consideration. Using ESR spin trapping and superoxide dismutase (SOD) treatment, the radicals produced by the UV exposure of BMDM were shown to be superoxide anion radicals (•O2-). HaCaT keratinocytes exposed to UVA in the presence of BMDM showed a significant reduction in cell viability, indicating that the radicals produced from BMDM have a harmful influence on the skin. UVA exposure coincidently led to a reduction of UVA absorbance by BMDM. Interestingly, 2-hydroxy-4-methoxybenzophenone (Benzophenone-3; BP3) reduced both the radical formation and the cytotoxicity resulting from the UVA-exposure of BMDM, while also restoring its UVA absorbance. In conclusion, the results show that BMDM and BP3 is an effective combination to reduce the influence of UVA-exposed BMDM on the skin and to prevent the loss of UVA absorbance by BMDM during UV exposure.

Can DLNO/DLCO ratio offset prejudicial effects of functional heterogeneities in acinar regions?

OBJECTIVES: (1) To establish the general equation that describes relationship of DMCO/Vc versus DLNO/DLCO under conditions with no functional heterogeneities. (2) To examine the effects of functional heterogeneities, including parallel and series (stratified) heterogeneities, on DLNO/DLCO. RESULTS AND DISCUSSIONS: (1) Given that "true" θNO in pulmonary capillaries is represented by surface absorption-related θNO, relationship between DMCO/Vc and DLNO/DLCO does not differ significantly from that obtained on premise of infinite θNO. DLNO/DLCO decided physiologically may mirror morphometric DMCO/Vc actually working for gas exchange but not "total" morphometric ratio of DMCO/Vc. (2) There are three parallel heterogeneities that affect diffusing capacity (D)-related parameters. Of them, only the heterogeneity of D/VA, where VA is alveolar volume, underestimates DLCO and DLNO. DLNO/DLCO does not alleviate negative impact of D/VA heterogeneity, indicating that DMCO/Vc estimated from DLNO/DLCO does not mirror "true" morphometric DMCO/Vc in diseased lungs with D/VA maldistribution. (3) Stratified heterogeneity underrates morphometric DMCO, DMNO, and DMNO/DMCO maximally by 1.4 %, 2.8 %, and 1.4 %, respectively, under conditions similar to single-breath D measurements, suggesting that effect of stratified heterogeneity on D measures is no longer needed to be considered in normal subjects but may be in patients having lung diseases with destructive lesions of acinar structures.

What are appropriate values of relative krogh diffusion Constant of NO against CO and of theta-NO in alveolar septa?

OBJECTIVES: To propose new physical constants for NO and CO (Krogh diffusion constant ratio (KDNO/CO) and specific blood conductance for NO (θNO)) for calculating DMCO and Vc, according to Roughton-Forster's equation (Roughton and Forster, J. Appl. Physiol. 11: 290-302, 1957) from simultaneous DLNO and DLCO measurements. RESULTS AND CONCLUSIONS: (1) The Graham's law is unacceptable for determining KDNO/CO because CO does not fulfil all the conditions of an "ideal" gas. We have re-estimated KDNO/CO in a new way based on difference in molar volumes of two gases (molar volume theory). The KDNO/CO thus decided is 2.34. (2) θNO measured with rapid-reaction, constant-flow method by Carlsen and Comroe (J. Gen. Physiol. 42: 83-107, 1958) may be underestimated by about 40 % due to unstirred water layer surrounding the erythrocyte. (3) Erythrocyte θO2 can be harvested from O2 release kinetics in presence of high concentration of dithionite, which effectively removes the unstirred water layer-elicited effect. Multiplication of erythrocyte θO2 by erythrocyte KDNO/O2 equals erythrocyte θNO, the value of which is 6.2 mL/min/mmHg/(mL⋅blood). According to the concepts of Kang et al. (RESPNB. 241: 62-71, 2017) and Borland et al. (RESPNB. 241: 58-61, 2017), in vitro θNO decided from rapid-mixing experiments may mirror bulk absorption of NO by erythrocytes. (4) In pulmonary capillaries, NO uptake takes place predominantly in the surface rim of the erythrocyte. This surface absorption of NO increases the θNO 10-fold versus bulk absorption of NO to about 60 mL/min/mmHg/(mL⋅blood).

Bioresorbable Bone Graft Composed of an RGD-Enriched Recombinant Human Collagen Polypeptide Induced Neovascularization and Regeneration of Mature Bone Tissue.

Bone graft materials provide a scaffold for migrating cells for bone regeneration. One of the major challenges is to support adequate neovascularization in the graft materials and bone tissue. Vascular endothelial cells have been shown to recognize the integrin-binding Arg-Gly-Asp (RGD) sequence in natural extracellular matrix (ECM) molecules. Here, we report a bone graft material composed of an RGD-enriched recombinant polypeptide based on human type I collagen alpha 1 chain (RCPhC1) and propose a category of bone graft materials called the recombinant bone matrix. RCPhC1 demonstrated significantly increased human umbilical vein endothelial cell attachment in vitro and was further processed through freeze casting and heat crosslinking processes to generate porous granular bone graft, in which RGD sequences remained canonical. When grafted in the rat model, RCPhC1 bone graft demonstrated a uniquely increased presence of CD34+ endothelial cells within the graft material. Bone tissue was found directly in contact with the pore structure of RCPhC1 bone graft, resulting in the regeneration of large bone tissue. By contrast, the combined demineralized and decellularized bone allograft containing bone collagen in the ECM did not show vascular formation within the graft material. When applied to canine tooth extraction socket, RCPhC1 bone graft rapidly induced highly vascularized regenerating tissues, which became a mature bone with the bone marrow tissue. These results indicate that RCPhC1 bone graft is a promising material and generated highly active bone tissues, which rapidly matured.

Variational Bayes Inference Algorithm for the Saturated Diagnostic Classification Model.

Saturated diagnostic classification models (DCM) can flexibly accommodate various relationships among attributes to diagnose individual attribute mastery, and include various important DCMs as sub-models. However, the existing formulations of the saturated DCM are not better suited for deriving conditionally conjugate priors of model parameters. Because their derivation is the key in developing a variational Bayes (VB) inference algorithm, in the present study, we proposed a novel mixture formulation of saturated DCM. Based on it, we developed a VB inference algorithm of the saturated DCM that enables us to perform scalable and computationally efficient Bayesian estimation. The simulation study indicated that the proposed algorithm could recover the parameters in various conditions. It has also been demonstrated that the proposed approach is particularly suited to the case when new data become sequentially available over time, such as in computerized diagnostic testing. In addition, a real educational dataset was comparatively analyzed with the proposed VB and Markov chain Monte Carlo (MCMC) algorithms. The result demonstrated that very similar estimates were obtained between the two methods and that the proposed VB inference was much faster than MCMC. The proposed method can be a practical solution to the problem of computational load.

Liquid Phase Synthesis and Morphological Observation of BaTiO3-CoFe2O4 Nanocomposite Films.

A novel and inexpensive fabrication method of multiferroic nanocomposite films via liquid-phase formation is demonstrated in this work. Well-aligned anodized TiO2 nanotube arrays on a Ti substrate were used as the core template. The anodized TiO2 nanotube arrays were then hydrothermally treated in Ba(OH)2 aqueous solution to form BaTiO3 (BTO) nanotube arrays. The average pore diameter and thickness of the BTO nanotube arrays obtained were approximately 50~70 nm and 2~4 µm, respectively. The BTO nanotube arrays were then dip-coated with CoFe2O4 (CFO) sol with the assistance of vaccum impregnation equipment to enable the penetration of CFO sol into the tubular pores of the BTO nanotube arrays. The good distribution of CFO in the BTO nanotube arrays was confirmed by electron microscopy accompanied with elemental analysis. The good crystallinity of CFO and BTO in the nanocomposite was confirmed by X-ray diffraction, and the nanocomposite film exhibited anisotropic ferrimagnetic properties upon an in plane and out-plane applied magnetic field.

Hypercapnic tumor microenvironment confers chemoresistance to lung cancer cells by reprogramming mitochondrial metabolism in vitro.

The tumor microenvironment has previously been reported to be hypercapnic (as high as ~84 mmHg), although its effect on tumor cell behaviors is unknown. In this study, high CO2 levels, ranging from 5% to 15%, protected lung cancer cells from anticancer agents, such as cisplatin, carboplatin and etoposide, by suppressing apoptosis. The cytoprotective effect of a high CO2 level was independent of acidosis and was due to mitochondrial metabolic reprogramming that reduced mitochondrial respiration, as assessed by oxygen consumption, oxidative phosphorylation, mitochondrial membrane and oxidative potentials, eventually leading to reduced reactive oxidant species production. In contrast, high CO2 levels did not affect cisplatin-mediated DNA damage responses or the expression of Bcl-2 family proteins. Although high CO2 levels inhibited glycolysis, this inhibition was not mechanistically involved in high CO2-mediated reductions in mitochondrial respiration, because a high CO2 concentration inhibited isolated mitochondria. A cytoprotective effect of high CO2 levels on mitochondria DNA-depleted cells was not noted, lending support to our conclusion that high CO2 levels act on mitochondria to reduce the cytotoxicity of anticancer agents. High CO2-mediated cytoprotection was also noted in a 3D culture system. In conclusion, the hypercapnic tumor microenvironment reprograms mitochondrial respiratory metabolism causing chemoresistance in lung cancer cells. Thus, tumor hypercapnia may represent a novel target to improve chemosensitivity.