Search

Purpose: The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP).Methods: The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart.Results: PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups.Conclusion: Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years.

[Purpose] Research on the interaction between renal and lung functions has been conducted; however, studies on the general adult population are limited. This study aimed to investigate the association between serum creatinine levels and pulmonary function in Korean adults.[Methods] From the 2016–2019 Korean National Health and Nutrition Examination Survey, we recruited 11,380 participants who were 40 years or older for this study. Serum creatinine levels were divided into three groups: low, normal, and high. Pulmonary function was divided into three groups: normal, restrictive, and obstructive. The odds ratios for abnormal pulmonary function patterns were calculated using weighted multinomial logistic regression analysis.[Results] The odds ratios were 0.97 for low vs. normal (0.40–2.33) and 2.00 for high vs. normal (1.18–3.38) for the restrictive pattern, and 0.12 for low vs. normal (0.02–0.49) and 1.74 for high vs. normal (0.90–3.35) for the obstructive pattern after being adjusted for age, sex, smoking status, alcohol consumption, regular exercise, body mass index, diabetes mellitus, hypertension, cardiovascular disease, total energy, and total proteins.[Conclusion] High serum creatinine levels were associated with an increased odds ratio for restrictive and obstructive pulmonary function patterns. The odds ratio of the restrictive pattern was higher than that of the obstructive pattern. Screening for abnormal pulmonary function in individuals with high serum creatinine levels may be useful to ensure that there is no abnormal pulmonary function before the onset of potential pulmonary problems. Thus, this study highlights the relationship between renal and pulmonary function using serum creatine levels, which can be easily tested in the primary medical environment of the general population.

Purpose: The purpose of this study was to examine the relationship between coronavirus disease 2019 (COVID-19)-related knowledge, preventive behaviors, risk perception, nursing professional values, and COVID-19 psychological distress among nursing students, and to identify factors associated with senior nursing students’ COVID-19 psychological distress.Methods: This descriptive cross-sectional study included fourth-year nursing students (n=183). Data were collected using a structured questionnaire between May and June 2022. Data were analyzed using descriptive statistics, the independent t-test, one-way analysis of variance, the Scheffé test, Pearson’s correlation coefficients, and multiple linear regression analysis, using SPSS version 27.0 for Windows.Results: COVID-19 risk perception (β=.39, ppp=.004), and COVID-19 preventive behavior (β=-.16, p=.023). These variables accounted for approximately 27% of the variance in COVID-19-related psychological distress.Conclusion: Nursing educators should work to develop interventions to reduce nursing students’ COVID-19-related psychological distress and should consider COVID-19 knowledge, COVID-19 risk perception, and COVID-19 preventive behavior. Furthermore, plans should be developed to enhance students’ satisfaction with the nursing major by improving the clinical practicum suited to their needs.

In recent years, general education has grown more sharply than ever in the number of dedicated organizations and professors in universities. The “Korea Association of General Education” has grown rapidly into an organization with more than 2,000 members, and its academic achievement has grown so rapidly that the IF (Impact Factor) of the Korean Journal of General Education ranked 1st in the major category of ‘Complex Studies’ and ranked 7th among all academic journals.The National Research Foundation of Korea's is used as a coordinate for establishing academic status in Korea and as a criterion for distributing shares of the national R&D budget for research support projects. The organizational size of the Korea Association of General Education and the academic level of its journal definitely deserves a higher ranking than the ‘Medium Classification’ in the , which is hierarchically divided into “Large Classification, Medium Classification, Small Classification and Detail Classification.” However, in reality, it is located in ‘Detail Classification’, which is the lowest rank under the name of ‘Basic and General Education’. This classification system does not sufficiently reflect the academic characteristics of general education. As a result, it is difficult to receive an appropriate evaluation in terms of academic research activities and research support. Over the past decade, the Korean Association for General Education, the National Council for General Education, and the Korea National Institute for General Education have continuously made many attempts to correct such contradictions.This study summarized the past efforts into a history of Korean general education and sought where and how we should relocate general education in the in order to live up to the spirit of the era of the 4th Industrial Revolution. In the era of the 4th Industrial Revolution, which calls for fostering convergence talents, a renaissance of general education designed for a fusion of the academic fields, is expected, instead of one that promotes specialization. If the placement of general education in the is a matter falls under the knowledge category, the subsequent classification method is determined by how, in our times, we can conceptualize general education. In order to study the category and concept of general education, it is necessary to establish a new academic field called ‘General Studies’.This study proposes to set the academic status of ‘General Studies’ in the in the following three ways. The first option is to take the spirit of the 4th Industrial Revolution and upgrade it to the ‘Large Classification’. The second option is to position it as a division of various basic studies in humanities and sciences, because ‘General Studies’ encompasses “almost all knowledge that humans need to know.” The third option is to adjust it to the middle classification under the Large Classification of ‘Complex Studies’. Ultimately, the resetting of the is to secure the identity and independence of general education. This study is meaningful in that it specifically presented three options for the and that it is a preemptive preparation for future institutional discussions on the classification of academic research fields.

Purpose: Based on the World Health Organization framework on reproductive health, this descriptive correlational study investigated the factors affecting reproductive health-promoting behaviors of married women, with a focus on family values and reproductive health knowledge.Methods: A cross-sectional survey was conducted on 170 married women between the ages of 25 and 49 years living in Daegu, Korea. The general and reproductive health characteristics, family values, and reproductive health knowledge of married women were identified, as well as factors affecting reproductive health-promoting behaviors. A questionnaire survey was administered to investigate the impact of various factors on reproductive health-promoting behaviors.Results: Positive correlations were shown for family values (r=.78, p

Evaluation indicators of general education represent the value and identity of general education. University members can clearly understand general education through evaluation indicators. Evaluation indicators serve as standards for establishing and implementing educational policies. Universities support general education according to the evaluation indicators. From this point of view, this study conducted a questionnaire survey to diagnose problems with the general education evaluation indicators of the Basic Competency Assessment for Universities. A survey was conducted targeting 127 universities that joined the Korean Council for University General Education. The total number of respondents was 51. The summary of the survey results is as follows. First, 70% of respondents said that it was reasonable to evaluate general education as ‘operation and improvement of curriculum’. But about 50% of the respondents were negative about evaluating the general curriculum as ‘core competency’ as a diagnostic factor. Second, more than 70% of respondents said that the standard of the general education standard model of the Korea National Institute for General Education, which was established theoretically and academically, was not applied to the current evaluation indicators. So it is necessary to improve the inclusiveness of general education evaluation indicators. Third, about 50% of the respondents were negative about the relevance of the evaluation indicators as a driving force for improving the quality of general education. Fourth, 70% of the respondents thought that the basis for applying core competencies as evaluation indicators for general education was not sufficient. Therefore, they think that evaluation criteria should be designed according to the essential characteristics of general education. Finally, many respondents said that the essential components of the evaluation indicators should include the organization and operation of the general education curriculum, the operating system for improving general education, and the organization and manpower necessary for supporting general education. This study examined the validity of competency-based general education, focusing on general education experts. As a result, it provided clear evidence for developing and designing evaluation indicators for the development and improvement of practical general education in universities. In particular, the Ministry of Education should go through a public deliberation process to improve the acceptance of evaluation results. Therefore, we proposed that the concept of competency should be established first and then the validity of competency-based general education should be reviewed.

Purpose: This study investigated the effects of depression and social support on quality of life in family caregivers of cancer patients undergoing chemotherapy at an outpatient department.Methods: This study had a crosssectional, correlational design using a structured questionnaire. Data were collected from October to December 2019 at a hematology-oncology outpatient department. In total, 148 family caregivers participated in this study. The collected data were analyzed using descriptive statistics, independent t-test, one-way analysis of variance, Pearson correlation coefficients, and multiple regression with SPSS for Windows version 27.0.Results: The quality of life showed statistically significant differences according to the educational level (t=-3.02, p=.003), family monthly income (t=-4.22, p

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as

Background: Postsurgical hypocalcemia is the most common and troublesome consequence of thyroidectomy. We investigated the potential role of routine calcium or vitamin D supplementation in preventing postsurgical hypocalcemia. Methods: We searched MEDLINE and Embase for English-language publications using the keywords “calcium,” “vitamin D,” and “thyroid cancer.” The primary outcome was any postoperative hypocalcemia, and the secondary outcome was symptomatic hypocalcemia. Results: Four studies that included 381 patients were eligible for this meta-analysis. A random-effects model showed no significant difference in the occurrence of hypocalcemia between calcium/vitamin D treatment and placebo/no treatment. However, the occurrence of symptomatic hypocalcemia was lower in patients with calcium/vitamin D treatment. In the combined results, preoperative calcium and vitamin D supplementation were associated with a reduced incidence of symptomatic hypocalcemia. Conclusions: Our findings support the use of preoperative calcium and vitamin D supplementation in conjunction with routine postsurgical supplementation for patients after total thyroidectomy.

Purpose: This descriptive study aimed to identify the factors influencing caring behaviors and anxiety during surgery recognized by patients undergoing surgery with regional anesthesia. Methods: The subjects were 147 hospitalized patients who underwent surgery with regional anesthesia from July to September 2017. Data were collected through structured questionnaires and medical records at three orthopedics and women’s hospitals and one university hospital located in city A. The collected data were analyzed for frequency and percentage, mean and standard deviation, the independent t-test, one-way analysis of variance, correlation analysis, and stepwise multiple regression using the SPSS 27.0 program. Results: The factors influencing anxiety during surgery were caring behaviors (β=-.39, ppp=.007), in descending order of influence, and the explanatory power was approximately 21%. Conclusion: Health care staff’s caring behaviors were the factor with the strongest influence on anxiety during surgery in patients undergoing surgery with regional anesthesia. Therefore, in order to alleviate anxiety during surgery, it is necessary to study the effect of developing and applying an intervention program for caring behaviors.

Purpose: This study aimed to develop the Korean Health Behavior for Dementia Prevention Scale (K-HBDP) and test its validity and reliability. Methods: In this methodological study, the K-HBDP scale was administered to 216 community-dwelling older adults (aged 65 or older) in 2020 in seven cities of western Korea using convenience sampling. Item analysis, construct validity, item convergent and discriminant validity, criterion validity, and internal consistency reliability were evaluated using SPSS for Windows 27.0. Results: The scale includes 23 items and five subscales: cognitive social activities, healthcare management, lifestyle, smoking and drinking, and eating habits, and the cumulative variance explained by the factors was 66.8%. Cronbach’s ⍺ for internal consistency of the total scale was .90 and ranged from .65 to .89 for all subscales. Item convergent and discriminant validity of the K-HBDP were confirmed. Criterion validity was demonstrated with the Health Promoting Lifestyle Profile-II. Conclusion: The findings suggest that K-HBDP scale can be used to measure healthy activities to prevent dementia in older adults. The use of this tool is expected to help develop interventions, educational materials, and training programs to improve nursing practice.

For the EL CVn candidate 1SWASPJ181417.43+481117.0 (WASP 1814+48), we secured the first spectroscopic observations between 2015 April and 2021 March. Using the echelle spectra, the radial velocities (RVs) of the primary star were measured with its atmospheric parameters of $T_{\rm eff,1}=7770\pm130$ K and $v_1$$\sin$$i=47\pm6$ km s$^{-1}$. We fitted our single-lined RVs and the TESS light curve simultaneously. From the binary modeling, we determined the following fundamental parameters for each component: $M_1=1.659\pm0.048$ $M_\odot$, $R_1=1.945\pm0.027$ $R_\odot$, and $L_1=12.35\pm0.90$ $L_\odot$ for WASP 1814+48 A, and $M_2=0.172\pm0.005$ $M_\odot$, $R_2=0.194\pm0.005$ $R_\odot$, and $L_2=0.69\pm0.07$ $L_\odot$ for WASP 1814+48 B. The surface gravity of $\log g_2=5.098\pm0.026$ obtained from $M_2$ and $R_2$ is concurrent with 5.097$\pm$0.025 computed directly from the observable quantities. WASP 1814+48 B is well-matched with the 0.176 M$_\odot$ white dwarf (WD) evolutionary model for $Z=0.01$. The metallicity and our Galactic kinematics indicate that the program target is a thin-disk star. The whole light residuals after removal of the binary trend were analyzed and found to oscillate at a total of 52 frequencies. Among these, most of the low frequencies below 24 day$^{-1}$ are aliases and orbital harmonics. The five significant frequencies between 32 and 36 day$^{-1}$ are the pulsation modes of WASP 1814+48 A located in the $\delta$ Sct domain on ZAMS, and the high frequencies of 128$-$288 day$^{-1}$ arise from WASP 1814+48 B in the pre-He WD instability strip. Our results reveal that WASP 1814+48 is the fifth EL CVn star that is composed of a $\delta$ Sct-type primary and a pre-ELMV (extremely low-mass pre-He WD variable)., Comment: 16 pages, including 7 figures and 6 tables, accepted for publication in MNRAS

PURPOSE: Although the prevalence of periodontal disease in adults over the age of 50 is rapidly increasing, the association between serum lipid levels and periodontal disease in Korean adults over the age of 50 still remains to investigate. Thus, the aim was to determine the effect of serum lipid levels on periodontal disease in older adults over the age of 50 using data from the seventh Korea National Health and Nutrition Examination Survey.METHODS: The study used the data of 809 adults aged ≥50 years targeted in the 7th Korea National Health and Nutrition Examination Survey, 2016-2018. Levels of total cholesterol, triglyceride, high density- lipoprotein (HDL-cholesterol), and low density-lipoprotein (LDL-cholesterol) and periodontal conditions were measured. Complex-sample chi square test and linear regression were used to analyze the relationship serum lipid levels with periodontal disease.RESULTS: The results of chi square tests showed that the prevalence of periodontal disease among the elderly ≥50 years were statistically significant differences according to gender, age, education level, marital status, and smoking status. After adjusting for all confounding factors, HDL-cholesterol alleviated periodontal disease, while LDL-cholesterol exacerbates periodontal disease. However, total cholesterol and triglycerides were not connected with periodontal disease.CONCLUSIONS: Therefore, controlling HDL and LDL cholesterol levels through physical exercise could be a preventative measure for periodontal disease.

Recombinant interleukin-33 (IL-33) inhibits tumor growth, but the detailed immunological mechanism is still unknown. IL-33-mediated tumor suppression did not occur in Batf3−/− mice, indicating that conventional type 1 dendritic cells (cDC1s) play a key role in IL-33-mediated antitumor immunity. A population of CD103+ cDC1s, which were barely detectable in the spleens of normal mice, increased significantly in the spleens of IL-33-treated mice. The newly emerged splenic CD103+ cDC1s were distinct from conventional splenic cDC1s based on their spleen residency, robust effector T-cell priming ability, and surface expression of FCGR3. DCs and DC precursors did not express Suppressor of Tumorigenicity 2 (ST2). However, recombinant IL-33 induced spleen-resident FCGR3+CD103+ cDC1s, which were found to be differentiated from DC precursors by bystander ST2+ immune cells. Through immune cell fractionation and depletion assays, we found that IL-33-primed ST2+ basophils play a crucial role in the development of FCGR3+CD103+ cDC1s by secreting IL-33-driven extrinsic factors. Recombinant GM-CSF also induced the population of CD103+ cDC1s, but the population neither expressed FCGR3 nor induced any discernable antitumor immunity. The population of FCGR3+CD103+ cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs (FL-BMDCs) when IL-33 was added in a pre-DC stage of culture. FL-BMDCs generated in the presence of IL-33 (FL-33-DCs) offered more potent tumor immunotherapy than control Flt3L-BMDCs (FL-DCs). Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors. Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.

Purpose: To report the first case of a 53-year-old male patient diagnosed with central Horner syndrome, associated with vertebral artery dissection, which has never been reported in Korea to date.Case summary: A 53-year-old male patient presented with conjunctival hyperemia in the left eye for over 4 months, with a past history of acute subarachnoid hemorrhage and ruptured dissecting aneurysm in the left vertebral artery. On slit-lamp examination, mild ptosis of the upper eyelid and conjunctival hyperemia were noted in his left eye. The left pupil was smaller than the right without afferent pupillary defects in either eye. Anisocoria was greater in the dark, and dilation lag was noted in the left pupil. On systemic examination, he complained of numbness in the right upper and lower extremities and symptoms of leaning to the left when walking. After instillation of 0.5% apraclonidine, the anisocoria was reversed, and ptosis and conjunctival hyperemia disappeared. Magnetic resonance images revealed chronic infarction in the left lateral medulla, and he was diagnosed with central Horner syndrome associated with Wallenberg syndrome.Conclusions: We present the first case in Korea of central Horner syndrome associated with lateral medullary infarction caused by vertebral artery dissection.

To evaluate the safety and effectiveness of recombinant human follicle-stimulating hormone (rhFSH [Follitrope™]) in infertile women undergoing in vitro fertilization (IVF). To identify predictors of ovarian response that induce optimal clinical outcomes. This multicenter prospective study enrolled infertile women who were scheduled to undergo IVF after ovarian stimulation with rhFSH (Follitrope™) following the gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocol. Predictive factors for ovarian response were identified in the GnRH antagonist group based on the number of oocytes retrieved. A total of 516 infertile women were enrolled, among whom 136 (except one who withdrew before administration) received rhFSH using the GnRH agonist protocol and 379 using the antagonist protocol. The mean number of oocytes retrieved was 13.4 in the GnRH agonist group and 13.6 in the GnRH antagonist group. The clinical pregnancy rates were 32.3% (30/93) and 39.9% (115/288) in the GnRH agonist and antagonist groups, respectively. The incidence of ovarian hyperstimulation syndrome was 1.8% and 3.4% in the GnRH agonist and antagonist groups, respectively. No other significant safety risks associated with rhFSH administration were identified. Body mass index, basal serum FSH and anti-Müllerian hormone levels, and antral follicle count were identified as predictors of ovarian response by multiple regression with backward elimination, and the final regression model accounted for 26.5% of the response variability. In real-world practice, rhFSH (Follitrope™) is safe and effective in inducing ovarian stimulation in infertile women. Patient characteristics identified as predictors can be considered to be highly related to optimal clinical outcomes.

Legends for Supplementary Figures

Purpose:The plasticity of innate lymphoid cells (ILCs) has been reported in vitro and in the microenvironment of the intestine. However, whether ILC plasticity contributes to regulation of the tumor microenvironment remains unknown. In this study, we explored plasticity of ILCs in human lung cancer.Experimental Design:We analyzed immune subsets and cytokine expression in lung cancers freshly obtained from 80 patients and explored conversion of ILC1 into ILC3 in coculture with lung cancer cells. Prognostic effects of converted ILC3 and related pathway were evaluated by retrospective cohort composed of 875 patients with lung cancer.Results:Low percentages of ILC1, and high percentages of ILC3 were found in pulmonary squamous cell carcinomas (SqCC) but not adenocarcinomas (ADC). In non–small-cell lung cancers, the percentage of ILC3 was associated with IL23 expression in tumor cells but not immune cells. In cocultures, tumor cells of SqCCs converted ILC1 into ILC3 by producing IL23, thus promoting IL17-mediated tumor cell proliferation. Consistently, among IL17+ immune cells, the percentages of ILCs were higher in SqCCs than ADCs. Furthermore, the numbers of CD3−RORγt+ ILC3, IL17 expression level, and IL23- or IL17RA-expressing tumor cells were associated with short survival of patients with SqCC but not ADC.Conclusions:Conversion from ILC1 into ILC3 by IL23-producing SqCCs promotes IL17-mediated tumor progression, resulting in a poor prognosis.

Supplementary Figures S1-S9 S1: The representative case showing CD90 expression. Morphology and character of hepatic stellate cell lines. S2: The expression change of KRT19 following S3I-201, TPA, U0126, and SCH772984. The transfection efficiency of HCC cell lines. S3: The HGF concentrations in conditioned media from hTERT-HSC, LX-2, and primary human hepatic stellate cells. Western blot analysis of hepatocellular carcinoma cell lines, showing expression of phospho-MET, MET, phsopho-ERK1/2, and KRT19. mRNA and protein expression of KRT19 in HepG2 and SNU475 cells, following transient expression of MET. S4: Morphologic changes in HepG2 and SNU423 induced by conditioned media (CM) from inducible HGF knockdown stable cell lines established from hTERT-HSC: shHGF-1 and shHGF-2. mRNA expression levels of KRT19 and morphologic changes in HepG2 and SNU423, following CM treatment combined with hepatocyte growth factor (HGF) neutralizing antibody. S5: The gene knock-down efficiencies of two pooled siRNAs targeting JUN, JUND, FOSL1, or FOSL2. The gene knock-down efficiencies of siRNAs targeting JUN or FOSL1. S6: Expression of HGF in hepatic stellate cell line of hTERT-HSC, and HCC cell lines of HepG2 and SNU423. Distribution of HGF and MET expression in HepG2 cells, at various time points after conditioned media (CM) treatment. S7: S7. Increased KRT19 expression and nuclear translocation of ERK1/2, phospho-ERK1/2, FOSL1, phospho-FOSL1 after the conditioned media treatment in HepG2. Rapid decline in phosphor-MET levels after removal of conditioned media. S8: Schematic representation of regulatory mechanism of KRT19 gene by cancer-associated fibroblast (CAF) derived HGF via MET-ERK1/2- AP1 and SP1 axis. S9: Conservation of AP1 and SP1 binding sites in KRT19 promoter.

Supplementary Materials and Methods

Keratin (KRT) 19 is a poor prognostic marker for hepatocellular carcinoma (HCC); however, regulatory mechanisms underlying its expression remain unclear. We have previously reported the presence of fibrous tumor stroma in KRT19-positive HCC, suggesting that cross-talk between cancer-associated fibroblasts (CAF) and tumor epithelial cells could regulate KRT19 expression. This was investigated in this study using an in vitro model of paracrine interaction between HCC cell lines (HepG2, SNU423) and hepatic stellate cells (HSC), a major source of hepatic myofibroblasts. HSCs upregulated transcription and translation of KRT19 in HCC cells via paracrine interactions. Mechanistically, hepatocyte growth factor (HGF) from HSCs activated c-MET and the MEK–ERK1/2 pathway, which upregulated KRT19 expression in HCC cells. Furthermore, AP1 (JUN/FOSL1) and SP1, downstream transcriptional activators of ERK1/2, activated KRT19 expression in HCC cells. In clinical specimens of human HCC (n = 339), HGF and KRT19 protein expression correlated with CAF levels. In addition, HGF or MET protein expression was associated with FOSL1 and KRT19 expression and was found to be a poor prognostic factor. Analysis of data from The Cancer Genome Atlas also revealed KRT19 expression was closely associated with CAF and MET-mediated signaling activities. These results provide insights into the molecular background of KRT19-positive HCC that display an aggressive phenotype.Significance: These findings reveal KRT19 expression in hepatocellular carcinoma is regulated by cross-talk between cancer-associated fibroblasts and HCC cells, illuminating new therapeutic targets for this aggressive disease. Cancer Res; 78(7); 1619–31. ©2018 AACR.

Supplementary Figures and Table

Supplementary materials and methods about the generation of conditioned media and ELISA, quantitative real time PCR, western blot analysis and phospho-receptor tyrosine kinase array, plasmids, siRNA, and transfection, dual luciferase assay, oligo pull-down and ChIP, immunofluorescence staining. Supplementary tables S1-S10. S1: Clinicopathologic characteristics of hepatocellular carcinoma cohort (n=339). S2: List of antibodies used for the immunohistochemistry. S3: Criteria for qualitative immunohistochemistry analysis. S4: Criteria for semiquantitative immunohistochemistry analysis. S5: Primer sequences for PCR reaction. S6: List of antibodies. S7: shRNA/siRNA target sequence for gene knockdown. S8: Clinicopathologic characteristics of hepatocellular carcinoma with HGF or MET expression. S9: Univariate and multivariate analyses of disease-specific survival. S10: Univariate and multivariate analyses of disease-free survival.

PurposeThis study examines how the locus of agency of brands' artificial intelligence (AI)–powered voice assistants (VAs) could lead to brand loyalty through perceived control, flow and consumer happiness under the moderating influences of brand image and voice congruity.Design/methodology/approachThis study conducted a 2 (locus of agency: high vs. low) by 2 (brand image-voice congruity: congruent vs. incongruent) between-subjects experimental design. MANOVA, ANOVA and structural equation modeling (SEM) were conducted to test the hypothesized model.FindingsANOVA results revealed that human-centric (vs. machine-centric) agency led to higher perceived control. The interaction effect was significant, indicating the importance of congruency between brand image and VAs' voices. SEM results confirmed that perceived control predicted brand loyalty fully mediated by flow experience and consumer happiness.Originality/valueThis study provides evidence that the positive technology paradigm could carve out a new path in existing literature on AI-powered devices by showing the potential of a smart device as a tool for improving consumer–brand relationships and enriching consumers' well-being.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. Methods We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. Results In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. Conclusions Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

The standard treatment for allergic-airway inflammation, which is the dominant asthma endotype, is a steroid. However, steroid-refractory asthma is a significant problem. Innate-lymphoid cells (ILCs) produce type-2 cytokines as Th2 cells and play critical roles in asthma pathogenesis. Limited evidence from the asthma-mouse models and human studies suggests that ILC2s may participate in steroid-resistant asthma. Here, we showed that lung ILC2s, but not Th2 cells, can develop steroid resistance that maintains their survival, cytokine production, and pathogenic activities during steroid treatment. Such steroid-resistant ILC2s are associated with the presence of multiple ILC2-stimulating cytokines and the emergence of multipotent IL-5+IL-13+IL-17A+ ILC2s, and the Janus-kinase (JAK) 3/signal-transducer-and-activator-of-transcription (STAT) 3,5, and 6 pathway participates in the acquisition of steroid-resistant ILC2s. JAK3-inhibitor treatment significantly reduced the survival, proliferation, and cytokine production of multipotent ILC2s in vitro ameliorated ILC2-dependent Alternaria-induced asthma. Moreover, JAK3-inhibitor combined with a steroid strongly inhibited steroid-resistant asthma. Therefore, sustained asthmatic conditions may induce multipotent ILC2s that promote steroid-resistant asthma, and combining JAK3-inhibitor with steroid may be a treatment option for steroid-refractory asthma.

Invariant natural-killer T (iNKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this iniNKT cells is very limited. It is also not clear whether such metabolic regulation ofiNKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediatedde novofatty-acid synthesis is required for the survival ofiNKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lungiNKT cells from WT mice that were developing asthma.Cd4-CreAcc1fl/flmice failed to develop OVA-induced and HDM-induced asthma. Moreover,iNKT cell-deficient mice that were reconstituted with ACC1-deficientiNKT cells failed to develop asthma, unlike when WTiNKT cells were transferred. ACC1 deficiency iniNKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR)γ, but increased glycolytic capacity that promotediNKT-cell death. Furthermore, circulatingiNKT cells from allergic-asthma patients expressed higherACC1andPPARGlevels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus,de novofatty-acid synthesis preventsiNKT-cell deathviaan ACC1-FABP-PPARγ axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma.

Purpose This study aims to investigate the relationships between customer perceptions of luxury companies’ brand pages (i.e. brand page value and self-expressive brands) and customers’ affective (i.e. brand page satisfaction and brand love) and behavioral (i.e. word-of-mouth [WOM] and attitudinal loyalty intentions) responses. Design/methodology/approach Structural equation modeling was used to analyze the data of 290 social media users in the USA who followed at least one luxury brand on social media. Findings The results demonstrated that consumers’ brand page satisfaction, influenced by the brand page’s information and entertainment value, was related to brand love and WOM intentions. Meanwhile, brand love – defined as emotional devotion to a brand – was influenced by self-expressive brands and was positively related to both WOM and attitudinal loyalty intentions. Originality/value This study identifies a set of customer perceptions that drive consumers’ affective and behavioral responses and that can be used to guide luxury brands to best use their brand pages on social media. By developing and testing a dual-impact model consisting of brand page satisfaction and brand love, this study provides practical directions for luxury brand managers and marketers who wish to transform their followers into both brand advocates who elevate the brand through WOM communications and loyal customers who are committed to affiliating with and supporting the brand.