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Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1‐/‐ mice. Further, we show that A1‐reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV‐infected IFNAR1‐/‐ mice also induced neuronal cell death through the activation of A1‐reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluate the effectiveness and safety of a topical emollient in treating mild-to-moderate atopic dermatitis (AD) in adolescents and adults. The study involved 100 participants and lasted for 24 weeks. The results showed that the group using the emollient had significant improvements in various measures compared to the placebo group. No safety concerns were reported. However, the study had limitations and further research is needed to explore other aspects of AD and the effects of the emollient. Overall, the emollient shows promise as a therapeutic option for long-term care of AD patients. [Extracted from the article]

Background: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. Methods: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1–19.9, and ≥20. Results: During a median follow‐up of 119 months, 232 recipients (12.5%) experienced death‐censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death‐censored graft loss independent of recipient characteristics (LKDPI 1–19.9: HR 1.389, 95% CI 1.036–1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50–2.998). High LKDPI score was also significantly associated with increased risk of biopsy‐proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. Conclusion: High LKDPI scores were associated with an increased risk of death‐censored graft loss, biopsy‐proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort. [ABSTRACT FROM AUTHOR]

Background: A typical stroke MRI protocol includes perfusion‐weighted imaging (PWI) and MR angiography (MRA), requiring a second dose of contrast agent. A deep learning method to acquire both PWI and MRA with single dose can resolve this issue. Purpose: To acquire both PWI and MRA simultaneously using deep learning approaches. Study type: Retrospective. Subjects: A total of 60 patients (30–73 years old, 31 females) with ischemic symptoms due to occlusion or ≥50% stenosis (measured relative to proximal artery diameter) of the internal carotid artery, middle cerebral artery, or anterior cerebral artery. The 51/1/8 patient data were used as training/validation/test. Field Strength/Sequence: A 3 T, time‐resolved angiography with stochastic trajectory (contrast‐enhanced MRA) and echo planar imaging (dynamic susceptibility contrast MRI, DSC‐MRI). Assessment: We investigated eight different U‐Net architectures with different encoder/decoder sizes and with/without an adversarial network to generate perfusion maps from contrast‐enhanced MRA. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), mean transit time (MTT), and time‐to‐max (Tmax) were mapped from DSC‐MRI and used as ground truth to train the networks and to generate the perfusion maps from the contrast‐enhanced MRA input. Statistical Tests: Normalized root mean square error, structural similarity (SSIM), peak signal‐to‐noise ratio (pSNR), DICE, and FID scores were calculated between the perfusion maps from DSC‐MRI and contrast‐enhanced MRA. One‐tailed t‐test was performed to check the significance of the improvements between networks. P values < 0.05 were considered significant. Results: The four perfusion maps were successfully extracted using the deep learning networks. U‐net with multiple decoders and enhanced encoders showed the best performance (pSNR 24.7 ± 3.2 and SSIM 0.89 ± 0.08 for rCBV). DICE score in hypo‐perfused area showed strong agreement between the generated perfusion maps and the ground truth (highest DICE: 0.95 ± 0.04). Data Conclusion: With the proposed approach, dynamic angiography MRI may provide vessel architecture and perfusion‐relevant parameters simultaneously from a single scan. Evidence Level: 3 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Cancer‐associated fibroblasts (CAFs) in the tumor microenvironment have been associated with tumor progression in breast cancer. Although crosstalk between breast cancer cells and CAFs has been studied, the effect of CAFs on non‐neoplastic breast epithelial cells is not fully understood to date. Here, we investigated the effect of CAFs on aggressive phenotypes in non‐neoplastic MCF10A breast epithelial cells. CAFs induced epithelial‐to‐mesenchymal transition (EMT) and invasive phenotype in MCF10A cells. S100A8, a potential prognostic marker in several cancers, was markedly increased in MCF10A cells by CAFs. S100A8 was crucial for CAFs‐induced invasive phenotype of MCF10A cells. Among cytokines increased by CAFs, interleukin (IL)‐8 induced S100A8 through transcription factors p65 NF‐κB and C/EBPβ. In a xenograft mouse model with MCF10A cells and CAFs, tumor was not developed, suggesting that coinjection with CAFs may not be sufficient for in vivo tumorigenicity of MCF10A cells. Xenograft mouse tumor models with MDA‐MB‐231 breast carcinoma cells provided an in vivo evidence for the effect of CAFs on breast cancer progression as well as a crucial role of IL‐8 in tumor growth and S100A8 expression in vivo. Using a tissue microarray of human breast cancer, we showed that S100A8 expression was correlated with poor outcomes. S100A8 expression was more frequently detected in cancer‐adjacent normal human breast tissues than in normal breast tissues. Together, this study elucidated a novel mechanism for the acquisition of invasive phenotype of non‐neoplastic breast cells induced by CAFs, suggesting that targeting IL‐8 and S100A8 may be an effective strategy against breast cancer. [ABSTRACT FROM AUTHOR]

Although entrepreneurial orientation (EO) at the firm‐level is often conceptualized as a direct antecedent of performance, the findings of previous studies lending support to this association are inconsistent. Consequently, drawing on the attraction/selection/attrition and institutional theories and employing the moderated mediation analysis approach, this study conceptualizes the individual perception of a firm's EO or individual entrepreneurial orientation (IEO). It examines the direct and indirect effects of IEO on individual outcomes measured in terms of performance expectation, job involvement, and organizational commitment. More specifically, it examines whether these effects are mediated by value congruence and moderated by the institutional entrepreneurial environment to understand these inconsistent findings better. Using a sample of 398 environmentally concerned small and medium‐sized enterprises (SMEs) in South Korea, partial least squares structural equation modeling (PLS‐SEM), and the PROCESS macro were employed to analyzed the research model. This study finds that value congruence mediates the association between IEO and performance expectation, job involvement, and organizational commitment. The moderated mediation model analysis also suggests that the mediating role of value congruence increases as the level of the institutional entrepreneurial environment increases. These findings offer useful theoretical and managerial implications of the IEO on individual outcomes. [ABSTRACT FROM AUTHOR]

Several carcinomas including gastric cancer have been reported to contain Epstein‐Barr virus (EBV) infection. EBV‐associated gastric cancer (EBVaGC) is classified as one of four molecular subtypes of gastric cancer by The Cancer Genome Atlas (TCGA) group with increased immune‐related signatures. Identification of EBV‐dependent pathways with significant biological roles is needed for EBVaGC. To compare the biological changes between AGS gastric epithelial cells and EBV‐infected AGS (AGS‐EBV) cells, proliferation assay, CCK‐8 assay, invasion assay, cell cycle analysis, RT‐PCR, Western blot and ELISA were performed. BI836845, a humanized insulin‐like growth factor (IGF) ligand‐neutralizing antibody, was used for IGF‐related signalling pathway inhibition. AGS‐EBV cells showed slower proliferating rate and higher sensitivity to BI836845 compared to AGS cells. Moreover, invasiveness of AGS‐EBV was increased than that of AGS, and BI836845 treatment significantly decreased the invasiveness of AGS‐EBV. Although no apoptosis was detected, entry into the S phase of the cell cycle was delayed in BI836845‐treated AGS‐EBV cells. In conclusion, AGS‐EBV cells seem to modulate their proliferation and invasion through the IGF signalling pathway. Inhibition of the IGF signalling pathway therefore could be a potential therapeutic strategy for EBVaGC. [ABSTRACT FROM AUTHOR]

Receptor tyrosine kinase MET (c‐MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c‐MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET‐related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty‐nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET‐related molecules. Four c‐MET inhibitors were tested to elucidate the dependency on MET pathway in the 49 GC cell lines. Six of 49 cell lines were MET amplified with overexpression of c‐MET and p‐MET. The variants of MET were not associated with c‐MET expression or amplification. Hs746T showed an exon 14 deletion in conjunction with MET amplification. The cell lines were divided into 6 MET amplified, 2 c‐MET overexpressed, 2 hepatocyte growth factor (HGF) overexpressed, and 39 MET‐negative subgroups. Except tivantinib, the c‐MET inhibitors showed higher inhibition (%) in MET amplified than in MET nonamplified cell lines that MET amplified cell lines showed MET pathway dependency. However, the c‐MET overexpressed and HGF overexpressed cell lines showed moderate dependency on MET pathway. Well‐characterized cell lines are very important in studying drug development. Our 49 GC cell lines had various characteristics of MET and MET‐related molecules and MET pathway dependency. These provide a promising platform for development of various RTK inhibitors including c‐MET inhibitors. [ABSTRACT FROM AUTHOR]

Abstract: This study was to investigate a hierarchical prognostic model using clinicopathological factors and 18F‐fludeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) for recurrence‐free survival (RFS) in patients with early breast cancer who underwent surgery without neoadjuvant chemotherapy. A total of 524 patients with early breast cancer were included. The Cox proportional hazards model was used with clinicopathological variables and maximum standardized uptake value (SUVmax) on PET/CT. After classification and regression tree (CART) modeling, RFS curves were estimated using the Kaplan–Meier method and differences in each risk layer were assessed using the log‐rank test. During a median follow‐up of 46.2 months, 31 (5.9%) patients experienced recurrence. The CART model identified four risk layers: group 1 (SUVmax ≤6.75 and tumor size ≤2.0 cm); group 2 (SUVmax ≤6.75 and Luminal A [LumA] or TN tumor >2.0 cm); group 3 (SUVmax ≤6.75 and Luminal B [LumB] or human epidermal growth factor receptor 2 [HER2]‐enriched] tumor >2.0 cm); group 4 (SUVmax >6.75). Five‐year RFS was as follows: 95.9% (group 1), 98% (group 2), 82.8% (group 3), and 85.4% (group 4). Group 3 or group 4 showed worse prognosis than group 1 or group 2 (group 1 vs. group 3: P = 0.040; group 1 vs. group 4: P < 0.001; group 2 vs. group 3: P = 0.016; group 2 vs. group 4: P < 0.001). High SUVmax (>6.75) in primary breast cancer was an independent factor for poor RFS. In patients with low SUVmax, LumB or HER2‐enriched tumor >2 cm was also prognostic for poor RFS, similar to high SUVmax. [ABSTRACT FROM AUTHOR]

Objective Thyroid core needle biopsy (CNB) is increasingly being used as a tool for evaluating thyroid nodules; thus, standardization of its diagnostic terminology is called for. We aimed to analyse the pathologic reporting system of thyroid CNB based on the recently proposed protocol by the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group and evaluate its usefulness. Design/Methods A total of 1998 consecutive cases of thyroid CNBs were reviewed and divided into six categories according to the protocol. Malignancy rate in each category and the diagnostic performance of thyroid CNB were calculated using 705 resected cases. Results Thyroid CNB yielded 132 nondiagnostic (6.6%), 791 benign (39.6%), 328 indeterminate (16.4%), 227 follicular neoplasm (11.4%), 69 suspicious for malignancy (3.5%) and 451 malignant lesions (22.6%). In resected specimens, all of the cases designated as suspicious for malignancy and malignant categories in CNB were proven to be true malignant lesions. Lesions diagnosed with follicular neoplasm in CNB were identified as malignant lesions in 57.0%. Malignancy rate was significantly higher in indeterminate lesions with nuclear atypia compared to those with architectural atypia (80.0% vs 28.2%). When CNB diagnoses of indeterminate lesions or higher categories were considered positive, the sensitivity and positive predictive value for final malignant diagnoses were 99.2% and 81.3%, respectively. Conclusions CNB is an accurate method of evaluating thyroid nodules and can serve as an alternative to fine needle aspiration when it is used and reported according to standardized diagnostic categories. [ABSTRACT FROM AUTHOR]

This paper revisits the long-run determinants of house prices, and analyzes the house price dynamics using Korean data taking into account the close relationship between house prices and household debt. The results of cointegrating regression indicate that the major portion of the rise in house prices in Korea over the last 15 years can be explained by changes in macro variables such as household income, the demographic structure, the user cost of home ownership and the housing stock supply. The results also confirm that house prices are, indeed, closely linked to the steep increase in household debt seen over this period. Estimation of an error correction model shows that the extent of convergence of actual house prices to their long-run equilibrium path has weakened somewhat since the global financial crisis while the speed of convergence has slowed, indicating structural changes in the Korean housing market. Finally, a forecast for house prices over the next several years suggests that they are unlikely to rise as sharply as they did in the 2000s, given the likely changes in the macro-financial environment, and that their future path will be closely associated with that of the household debt-to-income ratio. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer ( NSCLC) frequently metastasizes to bone, which is associated with significant morbidity and a dismal prognosis. RUNX3 functions as a tumour suppressor in lung cancer and loss of expression occurs more frequently in invasive lung adenocarcinoma than in pre-invasive lesions. Here, we show that RUNX3 and RUNX3-regulated chemokines are linked to NSCLC-mediated bone resorption. Notably, the receptor activator of nuclear factor- κB ligand ( RANKL)/osteoprotegerin ( OPG) ratio, an index of osteoclastogenic stimulation, was significantly increased in human osteoblastic cells treated with conditioned media derived from RUNX3-knockdown NSCLC cells. We aimed to identify RUNX3-regulated factors that modify the osteoblastic RANKL/ OPG ratio and found that RUNX3 knockdown led to CCL5 up-regulation and down-regulation of CCL19 and CXCL11 in NSCLC cells. Tumour size was noticeably increased and more severe osteolytic lesions were induced in the calvaria and tibiae of mice that received RUNX3-knockdown cells. In response to RUNX3 knockdown, serum and tissue levels of CCL5 increased, whereas CCL19 and CXCL11 decreased. Furthermore, CCL5 increased the proliferation, migration, and invasion of lung cancer cells in a dose-dependent manner; however, CCL19 and CXCL11 did not show any significant effects. The RANKL/ OPG ratio in osteoblastic cells was increased by CCL5 but reduced by CCL19 and CXCL11. CCL5 promoted osteoclast differentiation, but CCL19 and CXCL11 reduced osteoclastogenesis in RANKL-treated bone marrow macrophages. These findings suggest that RUNX3 and related chemokines are useful markers for the prediction and/or treatment of NSCLC-induced bone destruction. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

ABSTRACT Silk fibroin (SF) nanofiber scaffold containing microalgae Spirulina extract were prepared by electrospinning and the performance and functionality of the scaffold were evaluated. The viscosity and conductivity of the dope solution of Spirulina containing SF were examined for electrospinability and we found that the morphological structure of SF nanofiber is affected by the concentration of Spirulina extract added. The platelet adhesion and coagulation time test confirmed that the Spirulina containing SF nanofiber scaffold had excellent ability to prevent blood clotting or antithrombogenicity that is comparable to heparin. Low cytotoxicity and excellent cell adhesion and proliferation were also observed for Sprulina containing SF nanofiber scaffold by methylthiazolyldiphenyl-tetrazolium bromide assay and confocal fluorescence microscope using fibroblast and human umbilical vein endothelial cells. Based on these results, we believe SF nanofiber scaffold containing Spirulina extract has the potential to be used as tissue engineering scaffold that requires high hemocompatibility. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 307-318, 2014. [ABSTRACT FROM AUTHOR]

This study compared crosslinked dextrans in hydroxylpropyl methycellulose (DiHMs, pH 5 or 7) with polymethylmethacrylate in bovine collagen (PMMA) and hyaluronic acid (HA) fillers on soft tissue augmentation and safety in rats. HA tended to maintain its size throughout the experimental period but was moveable and friable because of a lack of thick fibroconnective tissue formation. Although, PMMA induced moderately thick fibroconnective tissue formation, its size was decreased markedly from 3-week postimplantation (PI) and became the smallest at 24-month PI. DiHM (pH 7) elicited strong fibrous encapsulation around the filler. Its size decreased slowly but was still considerably maintained at 24-month PI. In contrast, the rate of the DiHM (pH 5) size decrease was slower than that of PMMA, faster DiHM (pH 7), but comparable to HA. Immunohistochemically, types I and III collagens were deposited inside and outside DiHMs (pH 5 and 7). DiHMs (pH 5 and 7), PMMA, and HA showed no adverse reactions. These results suggest that DiHM (pH 7) assures efficacy and safety and is a good candidate for soft tissue augmentation in both humans and animals. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 131-140, 2014. [ABSTRACT FROM AUTHOR]

The development of liver fibrosis from chronic inflammation can involve epithelial-mesenchymal transition (EMT). Severe liver fibrosis can progress to cirrhosis, and further to hepatocellular carcinoma. Because the tetraspanin transmembrane 4 L6 family member 5 (TM4SF5) induces EMT and is highly expressed in hepatocellular carcinoma, it is of interest to investigate whether TM4SF5 expression is correlated with EMT processes during the development of fibrotic liver features. Using hepatic cells in vitro and a CCl4-mediated mouse liver in vivo model, we examined whether TM4SF5 is expressed during liver fibrosis mediated by CCl4 administration and whether treatment with anti-TM4SF5 reagent blocks the fibrotic liver features. Here, we found that TM4SF5 expression was induced by the transforming growth factor (TGF)β1 and epidermal growth factor signaling pathways in hepatocytes in vitro. In the CCl4-mediated mouse liver model, TM4SF5 was expressed during the liver fibrosis mediated by CCl4 administration and correlated with α-smooth muscle actin expression, collagen I deposition, and TGFβ1 and epidermal growth factor receptor signaling activation in fibrotic septa regions. Interestingly, treatment with anti-TM4SF5 reagent blocked the TM4SF5-mediated liver fibrotic features: the formation of fibrotic septa with α-smooth muscle actin expression and collagen I deposition was attenuated by treatment with anti-TM4SF5 reagent. These results suggest that TM4SF5 expression mediated by TGFβ1 and growth factor can facilitate fibrotic processes during chronic liver injuries. TM4SF5 is thus a candidate target for prevention of liver fibrosis following chronic liver injury. [ABSTRACT FROM AUTHOR]

Background: Mitochondria are the main sites for fatty acid oxidation and play a central role in lipotoxicity and nonalcoholic steatohepatitis. Aims: We investigated whether carnitine prevents free fatty acid ( FFA)-induced lipotoxicity in vitro and in vivo. Methods: HepG2 cells were incubated with FFA, along with carnitine and carnitine complexes. Mitochondrial β-oxidation, transmembrane potential, intracellular ATP levels and changes in mitochondrial copy number and morphology were analysed. Otsuka Long-Evans Tokushima Fatty and Long-Evans Tokushima Otsuka rats were segregated into three experimental groups and fed for 8 weeks with (i) normal chow, (ii) a methionine choline-deficient ( MCD) diet or (iii) an l-carnitine-supplemented MCD diet. Results: Carnitine prevented FFA-induced apoptosis (16% vs. 3%, P < 0.05). FFA treatment resulted in swollen mitochondria with increased inner matrix density and loss of cristae. However, mitochondria co-treated with carnitine had normal ultrastructure. The mitochondrial DNA copy number was higher in the carnitine treatment group than in the palmitic acid treatment group (375 vs. 221 copies, P < 0.05). The carnitine group showed higher mitochondrial β-oxidation than did the control and palmitic acid treatment groups (597 vs. 432 and 395 ccpm, P < 0.05). Carnitine treatment increased the mRNA expression of carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor-γ, and carnitine-lipoic acid further augmented the mRNA expression. In the in vivo model, carnitine-treated rats showed lower alanine transaminase levels and lesser lobular inflammation than did the MCD-treated rats. Conclusions: Carnitine and carnitine-lipoic acid prevent lipotoxicity by increasing mitochondrial β-oxidation and reducing intracellular oxidative stress. [ABSTRACT FROM AUTHOR]

The stereotype content model (SCM) proposes potentially universal principles of societal stereotypes and their relation to social structure. Here, the SCM reveals theoretically grounded, cross-cultural, cross-groups similarities and one difference across 10 non-US nations. Seven European (individualist) and three East Asian (collectivist) nations (N = 1; 028) support three hypothesized cross-cultural similarities: (a) perceived warmth and competence reliably differentiate societal group stereotypes; (b) many out-groups receive ambivalent stereotypes (high on one dimension; low on the other); and (c) high status groups stereotypically are competent, whereas competitive groups stereotypically lack warmth. Data uncover one consequential cross-cultural difference: (d) the more collectivist cultures do not locate reference groups (in-groups and societal prototype groups) in the most positive cluster (high-competence/high-warmth), unlike individualist cultures. This demonstrates out-group derogation without obvious reference-group favouritism. The SCM can serve as a pancultural tool for predicting group stereotypes from structural relations with other groups in society, and comparing across societies. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron involvement. Mutations in the human Cu/Zn superoxide dismutase (SOD1) gene are found in some cases of familial ALS. Many studies have reported SOD1 mutation-related neurodegeneration. However, whether or not a mutant SOD1 affects neural development has not been demonstrated. We developed motor neuron-neuroblastoma hybrid cells that expressed a mutant (G93A) or the wild type (WT) SOD1. Cells were differentiated by dibutyryl cAMP and aphidicolin. The mutant showed a defect in neurite outgrowth and had decreased viability. Cytochrome c released and nuclear fragmentation were observed. Western blot analysis showed that the amount of neurofilament and microtubule associated proteins-2 (MAP-2) decreased during differentiation. These results suggest that the defect in neurite outgrowth of mutant SOD1 cells is a cytoskeletal defect and is associated with neuronal death. [Copyright &y& Elsevier]

Topoisomerase IV is involved in topological changes in the bacterial genome using the free energy from ATP hydrolysis. Its functions are the decatenation of daughter chromosomes following replication by DNA relaxation and double-strand DNA breakage. In this study, the N-terminal fragment of the topoisomerase IV ParE subunit from Xanthomonas oryzae pv. oryzae was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.15 Å resolution using a synchrotron-radiation source. The crystal belonged to space group P42212, with unit-cell parameters a = b = 105.30, c = 133.76 Å. The asymmetric unit contains one molecule, with a corresponding VM of 4.21 Å3 Da−1 and a solvent content of 69.6%. [ABSTRACT FROM AUTHOR]

Objectives: There is little evidence on interrelationships between physical activity, sedentary behaviors, and health‐related quality of life (HRQOL) among adolescents with congenital heart disease (CHD). We hypothesized that exercise capacity would have a mediating effect on the associations of either physical activity or sedentary behavior with HRQOL. Methods: Adolescents with complex CHD (n = 111) were consecutively recruited from an outpatient clinic in a general hospital in South Korea. Physical activity and sedentary behavior were assessed using the global physical activity questionnaire. Exercise capacity was directly measured by peak oxygen uptake using a symptom‐limited maximal treadmill exercise test. HRQOL was evaluated by both adolescents and their parents using the Pediatric Quality of Life Inventory questionnaire. Results: The self‐reported and parent proxy‐reported HRQOL were positively associated with physical activity (ß = 0.16, P =.003; ß = 0.12, P =.049) and exercise capacity (ß = 0.63, P < .001; ß = 0.66, P < .001), but not with sedentary behavior in adjusted regression models. When both variables were entered in the same regression models, only exercise capacity remained significantly associated with the self‐reported (ß = 0.50, P =.008) and parent proxy‐reported HRQOL (ß = 0.62, P =.003). Exercise capacity acted as a full mediator variable on the relationship between physical activity and HRQOL (P < .05 for both). Conclusions: The present findings suggest that exercise capacity mediates the association between physical activity and HRQOL, highlighting the importance of improving exercise capacity to potentially enhance HRQOL in adolescents with complex CHD. [ABSTRACT FROM AUTHOR]