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Additional file 2: Table S1. Community acquired pneumonia—Clinical information records. Table S2. The PCR results of identified viral pathogen in the sputum. Table S3. The PCR results of identified bacterial pathogen in the sputum. Table S4. The culture results of identified bacterial pathogen in the sputum. Table S5. The number of bacterial pathogens identified by culture in NPA, sputum, nasopharyngeal swab, etc.

Additional file 1: Figure S1. The Korean Childhood Community-Acquired Pneumonia Study Group; KoC-CAPS.

Additional file 1. ICD-10 codes that define comorbidities unrelated to diabetes.

Background and objective Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. Methods Spirometry indices (FEV1, FVC, FEV1/FVC and FEF25-75 and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z-scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z-scores were compared to the expected 0 and 1. Probabilities of falling below the lower limit of normal [LLN] (z-score: -1.64) were compared to the expected value 5scores were assessed according to low (2) BMI z-score groups. Results Mean z-scores significantly differed from 0 for FEV1/FVC in males (mean [95: 0.18 [0.08, 0.27]) and FEV1 and FVC in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5 (12.139.64, 14.77]), FVC (15.8613.06, 18.81]), and FEF25–757.315.29, 9.49]) in males and FVC (11.919.40, 14.60]) in females. FEV1 and FVC z-scores increased across low to high BMI groups, and FEV1/FVC decreased from low to high BMI groups. Conclusion GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research.

Additional file 2. ICD-10 codes that define diabetic complications and related comorbidities.

Additional file 3. Direct medical costs by diabetic complications and related comorbidities.

Background: Atherosclerosis-induced vascular disorders are major causes of death in most western countries. During the development of atherosclerotic lesions, foam cell formation is essential and formed through the expression of CD36 and the peroxisome proliferator-activated receptor gamma (PPAR-γ). Objective: To investigate whether dansameum extract (DSE) could show anti-atherosclerotic effect through down-regulating cellular redox state including CD36 and PARP-γ expression in oxidative low-density lipoprotein (oxLDL)-treated RAW264.7 cells and on differentiated foam cells in ApoE Knockout (ApoE-/-) mice. Materials and Methods: The Korean polyherbal medicine DSE was prepared from three plants in the following proportions: 40 g of Salvia miltiorrhiza root, 4 g of Amomumxanthioides fruit, and 4 g of Santalum album lignum. The immunohistochemistry and reverse transcription-polymerase chain reaction was used for analysis of protein and mRNA involved in foam cell formation. Results: We first showed that effects of DSE on foam cell formation in both oxLDL-induced RAW264.7 cells and in blood vessels from apolipoprotein E deficientApoE-/- mice with high fat diet-fed. DSE treatment significantly reduced the expression of CD36 and PPAR-γ in oxLDL-stimulated RAW264.7 cells and ApoE-/-mice, in the latter case by regulating heme oxygenase-1. Furthermore, DSE treatment also reduced cellular lipid content in vitro and in vivo experiments. Conclusion: Our data suggest that DSE may have anti-atherosclerotic properties through regulating foam cell formation. SUMMARY Dansameum extract (DSE) Regulates the expression of CD36 and peroxisome proliferator-activated receptor gamma in oxidative low-density lipoprotein-stimulated RAW264.7 Cells and ApoE Knockout (ApoE Knockout [ApoE-/-]) miceDSE Regulates Cholesterol Levels in the Serum of ApoE-deficient (ApoE-/-) miceDSE Reduced the Formation of Foam Cells by Regulating heme oxygenase-1 in ApoE-/- mice with high fat diet-fed. Abbreviations used: DSE: Dansameum extract, PPAR-γ: Peroxisome proliferator-activated receptor γ, HO-1: Heme oxygenase-1, CVD: Cardiovascular diseases

The non-small cell lung cancer (NSCLC) patients with EGFR-sensitive mutations can be therapeutically treated by EGFR-TKI such as erlotinib and gefitinib. However, about 40% of individuals harboring EGFR-TKI sensitive mutations are still resistant to EGFR-TKI. And, it has been reported that both PTEN loss and NF-κB activation contribute to intrinsic EGFR-TKI resistance in EGFR-mutant lung cancer. Transglutaminse 2 (TG2) is post-translational modification enzyme and known to induce degradation of tumor suppressors including PTEN and IκBα with peptide cross-linking activity. Because TG2 was known as a regulator of PTEN and IκBα (NF-κB inhibitor) level in cytosol, we have explored if TG2 can be another key regulator to the intrinsic resistance of EGFR-TKI in the intrinsic EGFR-TKI resistant NSCLC cell. We first found that higher TG2 expression level and lower PTEN and IκBα expression levels in the intrinsic EGFR-TKI resistant NSCLC compare with EGFR-TKI sensitive NSCLC. TG2 stably expressing EGFR-TKI sensitive NSCLC cells harboring EGFR mutations showed reduction of both PTEN and IκBα and exhibited EGFR-TKI resistance. In reverse, When TG2 is downregulated by TG2 inhibitor in H1650, intrinsic EGFR-TKI resistant NSCLC cell harboring EGFR sensitive mutation, reversed EGFR-TKI resistance via IκBα restoration. Moreover, combination treatment of TG2 inhibitor and EGFR-TKI decreased the tumor growth in mouse xenograft models of EGFR mutant NSCLCs. Therefore, we have demonstrated that TG2 elicits the intrinsic EGFR-TKI resistance via PTEN loss and activation of NF-κB pathway. These results suggest that TG2 may be a useful predictive marker and also be a target for overcoming the resistance.

Previous studies have shown that transglutaminase 2 (TG2) induces epithelial to mesenchymal transition (EMT) in various tumors. Several studies have also demonstrated the critical role of microRNAs (miRNAs) in regulating EMT of various types of tumors. However, the relationship between TG2 and miRNAs is not well understood. In the present study, we investigated if miR-205, which is known to inhibit EMT and is commonly regulated by TG2, contributes to TG2-induced EMT of human breast cancer cells. We have analyzed the expression of miR-205 in TG2-expressing and TG2-non-expressing breast cancer cells by quantitative real-time PCR (qRT-PCR) and the expression of TG2 and EMT related markers, such as ZEB1 and Vimentin, by western blotting. We also have studied the regulation of tumor metastasis by miR-205 and TG2 using matrigel invasion assays, intracardiac injection of breast cancer cells into mice and in vivo bioluminescent imaging. MiR-205 was significantly downregulated in high TG2-expressing or TG2-transfected breast cancer cells than in low TG2-expressing or mock-transfected breast cancer cells. Overexpression of miR-205 reduced the bone metastasis of MCF7/TG2-C277S cells that express transamidase-activity deficient TG2 and inhibits the invasiveness of MDA-MB-231 breast cancer cells that express TG2. Bioluminescent imaging showed that intracardiac injection of MCF7/TG2-C277S cells in mice promoted bone tumors, especially in the knee and jaw, but MCF7/TG2-C277S cells ectopically expressing miR-205 did not metastasize. The GTP binding activity, but not transamidase activity, of TG2, induces EMT in breast cancer cells by inhibiting the expression of miR-205 that suppresses EMT by downregulating the expression of ZEB1, an EMT marker. Moreover, in vivo experiments demonstrate that miR-205 down-regulation by TG2 induces bone metastasis of breast cancer cells.