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The molecular mechanisms controlling the differentiation of bone marrow stromal stem cells into osteoblasts remain largely unknown. In this study, we investigated whether bone marrow stromal antigen 2 (BST2) influences differentiation toward the osteoblasts lineage. BST2 mRNA expression in human alveolar-derived bone marrow stromal cells (hAD-BMSCs) increased during differentiation into osteoblasts. hAD-BMSCs differentiation into osteoblasts and the mRNA expression of the bone-specific markers alkaline phosphatase, collagen type α 1, bone sialoprotein, osteocalcin, and osterix were reduced by BST2 knockdown using siRNA. Furthermore, BST2 knockdown in hAD-BMSCs resulted in decreased RUNX2 mRNA and protein expression. We hypothesized that BST2 is involved in differentiation of into osteoblasts via the BMP2 signaling pathway. Accordingly, we evaluated the mRNA expression levels of BMP2, BMP receptors (BMPR1 and 2), and the downstream signaling molecules SMAD1, SMAD4, and p-SMAD1/5/8 in BST2 knockdown cells. BMP2 expression following the induction of differentiation was significantly lower in BST2 knockdown cells than in cells treated with a non-targeting control siRNA. Similar results were found for the knockdown of the BMP2 receptor- BMPR1A. We also identified significantly lower expression of SMAD1, SMAD4, and p-SMAD1/5/8 in the BST2 knockdown cells than control cells. Our data provide the first evidence that BST2 is involved in the osteogenic differentiation of bone marrow stromal cells via the regulation of the BMP2 signaling pathway.

Cancer-associated fibroblasts promote tumor progression through growth facilitation, invasion, and immune evasion. This study investigated the impact of activated cancer-associated fibroblasts (aCAFs) on survival outcomes, immune response, and molecular pathways in distal bile duct (DBD) cancer. We analyzed 469 patients (418 from our cohort and 51 from The Cancer Genome Atlas) with DBD adenocarcinoma. aCAFs were evaluated using hematoxylin and eosin staining. We developed a machine learning-based survival prediction model incorporating aCAFs and clinicopathologic parameters. Additionally, we performed differential gene expression analysis, Disease Ontology analysis, gene set enrichment analysis, and in vitro drug screening of aCAFs-related genes. The presence of aCAFs significantly correlated with poor survival, advanced T and N stages, infiltrative growth pattern, lymphatic/perineural/adjacent organ invasion, and decreased tumor-infiltrating lymphocytes. aCAFs-related genes were associated with immune system functions, G protein-coupled receptor signaling, and metabolic conditions (diabetes, obesity, and abnormal C-peptide levels). In machine learning-based survival models, aCAFs emerged as a strong discriminator for survival prediction. In vitro drug screening revealed that refametinib suppressed the growth of DBD carcinoma cells expressing high levels of fibroblast activation protein-α. In conclusion, integration of machine learning and systems biology analyses identifies aCAFs as potential biomarkers for risk stratification and therapeutic targeting in DBD cancer.

Beginning in 2006, epidemics of a fatal lung injury of unknown cause in children were observed in Korea every spring. A recent study demonstrated that this type of children's interstitial lung disease (chILD) is associated with humidifier disinfectant use. To determine the clinical characteristics of this type of chILD and to assess whether the nationwide suspension of humidifier disinfectant sales in the autumn of 2011 affected its incidence. The clinical characteristics of suspected cases between 2006 and 2011 were determined by a nationwide retrospective study. The potential causal relationship with humidifier disinfectants was examined by a prospective surveillance study after humidifier disinfectant sales were suspended. In total, 138 children were diagnosed with this type of chILD, which was characterized by rapid progression, high mortality, predominance in the spring season, and a familial tendency. The annual incidence increased in 2011 and then dropped to zero in 2012. The children were on average 30.4 months old. The most frequent symptoms at admission were cough and dyspnea. As the disease progressed, the typical complication was spontaneous air leak. Eighty children (58%) died. Two years after humidifier disinfectant-sale suspension, no more new cases were found. This study suggests that humidifier disinfectant inhalation causes an idiopathic type of chILD that is characterized by spontaneous air leak, rapid progression, lack of response to treatment, and high mortality. Further safety studies must be performed on common environmental compounds, particularly those that enter the human body by an unusual route.

Background and Objectives: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography–fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. Methods: The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. Results: The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. Conclusions: Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC.

Background: This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). Methods: Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. Results: The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713–0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681–0.794) and 0.839 (95% CI, 0.738–0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590–0.917) and 0.998 (95% CI, 0.987–1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145–489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. Conclusions: Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.

This study aims to evaluate the accuracy and effectiveness of real-time personal monitoring of exposure to PM concentrations using low-cost sensors, in comparison to conventional data collection method based on fixed stations. PM2.5 data were measured every 5 min using a low-cost sensor attached to a bag carried by 47 asthmatic children living in the Seoul Metropolitan area between November 2019 and March 2020, along with the real-time GPS location, temperature, and humidity. The mobile sensor data were then matched with station-based hourly PM2.5 data using the time and location. Despite some uncertainty and inaccuracy of the sensor data, similar temporal patterns were found between the two sources of PM2.5 data on an aggregate level. However, average PM2.5 concentrations via personal monitoring tended to be lower than those from the fixed stations, particularly when the subjects were indoors, during nighttime, and located farther from the fixed station. On an individual level, a substantial discrepancy is observed between the two PM2.5 data sources while staying indoors. This study provides guidance to policymakers and researchers on improving the feasibility of personal monitoring via low-cost mobile sensors as an alternative or supplement to the conventional station-based monitoring.

Background Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. Methods We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects’ baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. Discussion Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects’ personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Inhalation of formaldehyde leads to rapid absorption by the respiratory airway, followed by metabolism by erythrocytes and the enzymes formaldehyde dehydrogenase and aldehyde dehydrogenase. [...]formaldehyde has an estimated biologic half-life of about 1–2 minutes (1). [...]inhaled formaldehyde may cause irritation and inflammation of the respiratory system (1). In addition to the cumulative irritant effect, formaldehyde as a small molecule is known to conjugate with large protein molecules in serum (such as albumin), thus provoking the formation of specific IgE antibodies, in turn leading to mast cell degranulation associated with the allergic response (9, 10). [...]formaldehyde exposure can influence the immune response, thereby increasing T-helper cell type 2 polarization through an adjuvant effect (9, 10). [...]our results demonstrated that exposure to formaldehyde in school classrooms was significantly associated with rhinitis, peripheral olfactory dysfunction, increased pharmacologically reversible nasal obstruction, small airway impairment, and elevated FeNO (Figure 1). [...]mitigation strategies for reducing exposure to formaldehyde are warranted for school environments to prevent these problems in vulnerable children.

Various studies have indicated that particulate matter <2.5 μm (PM2.5) could cause adverse health effects on pulmonary functions in susceptible groups, especially asthmatic children. Although the impact of ambient PM2.5 on children’s lower respiratory health has been well-established, information regarding the associations between indoor PM2.5 levels and respiratory symptoms in asthmatic children is relatively limited. This randomized, crossover intervention study was conducted among 26 asthmatic children’s homes located in Incheon metropolitan city, Korea. We aimed to evaluate the effects of indoor PM2.5 on children’s peak expiratory flow rate (PEFR), with a daily intervention of air purifiers with filter on, compared with those groups with filter off. Children aged between 6–12 years diagnosed with asthma were enrolled and randomly allocated into two groups. During a crossover intervention period of seven weeks, we observed that, in the filter-on group, indoor PM2.5 levels significantly decreased by up to 43%. (p < 0.001). We also found that the daily or weekly unit (1 μg/m3) increase in indoor PM2.5 levels could significantly decrease PEFR by 0.2% (95% confidence interval (CI) = 0.1 to 0.5) or PEFR by 1.2% (95% CI = 0.1 to 2.7) in asthmatic children, respectively. The use of in-home air filtration could be considered as an intervention strategy for indoor air quality control in asthmatic children’s homes.

Background: The aims of this study were to investigate the prevalence of allergic rhinitis (AR) and the accuracy of the International Study of Asthma and Allergies in Childhood (ISAAC) questions for diagnosis of AR, in Korean children. Methods: Students that participated in an allergic disease prevalence survey in 2010–2017 were evaluated (n = 18,425) using questionnaires and a skin prick test (SPT). Age−stratified (5−7, 8−10, 11−13, 14−16 years) prevalence of four rhinitis questions, accuracy of the questions for AR, and proportion of comorbidities in the AR and non-AR (NAR) groups were evaluated. Results: The proportion of students responding to the questionnaire that ever had symptoms of AR since birth, that is, the prevalence of “symptom, ever” was 47.6%. Based on the questionnaire and SPT, overall prevalence of AR and NAR were 21% and 26.5%, respectively. The sensitivity, specificity, and accuracy of “symptom, ever” were 57.5%, 58.4%, and 58.1%, respectively, and those of “diagnosis, ever”, who had ever been diagnosed with AR, were 39.8%, 76.9%, and 63.4%, respectively. Questionnaire−based asthma, atopic dermatitis, and food allergy were significantly associated with the AR group compared to the NAR group. Conclusions: Since the AR accuracy of the questionnaire is about 60%, it should be considered that the questionnaire based survey overestimates the true prevalence of AR in Korean children.