Purpose: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer.Currently, no effective treatment options for this condition exist. Nuclear factor erythroid 2-related factor 2 (NRF2), encoded by nuclear factor erythroid-derived 2-like 2 (NFE2L2) gene and its endogenous inhibitor, Kelch-like ECH-associated protein 1 (KEAP1), both participate in cellular defense mechanisms against oxidative stress and contribute to chemoresistance and tumor progression in numerous types of cancers. This study aimed to evaluate the expression patterns of NRF2 and KEAP1 and their prognostic value in operable TNBC. Methods: Tissue microarrays were prepared using tumor tissues collected from 203 patients with TNBC who underwent surgery. Immunohistochemical staining analyses of NRF2 and KEAP1 were performed. The expression of each immunomarker was categorized into two groups (low or high) based on the median H-score. We analyzed the association between the expression of each immunomarker and clinicopathological information to predict survival.A total of 225 TNBC samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were used to validate our results. Results: NRF2 immunoreactivity was detected in the nucleus and was associated with histologic grade and Ki-67 index, whereas KEAP1 immunoreactivity was detected in the cytoplasm and was associated with the Ki-67 index. Survival analyses showed that NRF2 and KEAP1 expressions were independent prognostic factors for overall survival (OS) (hazard ratio [HR], 2.45 and 0.30; p = 0.015 and 0.016, respectively) and disease-free survival (HR, 2.27 and 0.42; p = 0.019 and 0.022, respectively). NFE2L2 mRNA expression was an independent prognostic factor for OS (HR, 0.59; p = 0.009) in the METABRIC dataset. Conclusion High NRF2 and low KEAP1 expressions independently predicted poor survival in patients with operable TNBC. Further investigations are warranted to examine the possible therapeutic benefits of targeting the KEAP1-NRF2 pathway for TNBC treatment.

Objective: : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats. Methods: : Twenty-eight female Wistar rats (250–300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson’s trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured. Results: : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson’s trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p<0.05). Conclusion : Our results showed that the expression of genetically modified BMP-2 showed inhibition effect for bone loss in a rat model of osteoporosis.

Objective: Preoperative differentiation between inverted papilloma (IP) and its malignant transformation to squamous cell carcinoma (IP-SCC) is critical for patient management. We aimed to determine the diagnostic accuracy of conventional imaging features and histogram parameters obtained from whole tumor apparent diffusion coefficient (ADC) values to predict IP-SCC in patients with IP, using decision tree analysis. Materials and Methods: In this retrospective study, we analyzed data generated from the records of 180 consecutive patients with histopathologically diagnosed IP or IP-SCC who underwent head and neck magnetic resonance imaging, including diffusion-weighted imaging and 62 patients were included in the study. To obtain whole tumor ADC values, the region of interest was placed to cover the entire volume of the tumor. Classification and regression tree analyses were performed to determine the most significant predictors of IP-SCC among multiple covariates. The final tree was selected by cross-validation pruning based on minimal error. Results: Of 62 patients with IP, 21 (34%) had IP-SCC. The decision tree analysis revealed that the loss of convoluted cerebriform pattern and the 20th percentile cutoff of ADC were the most significant predictors of IP-SCC. With these decision trees, the sensitivity, specificity, accuracy, and C-statistics were 86% (18 out of 21; 95% confidence interval [CI], 65–95%), 100% (41 out of 41; 95% CI, 91–100%), 95% (59 out of 61; 95% CI, 87–98%), and 0.966 (95% CI, 0.912–1.000), respectively. Conclusion Decision tree analysis using conventional imaging features and histogram analysis of whole volume ADC could predict IP-SCC in patients with IP with high diagnostic accuracy.

Objective: Preoperative differentiation between inverted papilloma (IP) and its malignant transformation to squamous cell carcinoma (IP-SCC) is critical for patient management. We aimed to determine the diagnostic accuracy of conventional imaging features and histogram parameters obtained from whole tumor apparent diffusion coefficient (ADC) values to predict IP-SCC in patients with IP, using decision tree analysis. Materials and Methods: In this retrospective study, we analyzed data generated from the records of 180 consecutive patients with histopathologically diagnosed IP or IP-SCC who underwent head and neck magnetic resonance imaging, including diffusion-weighted imaging and 62 patients were included in the study. To obtain whole tumor ADC values, the region of interest was placed to cover the entire volume of the tumor. Classification and regression tree analyses were performed to determine the most significant predictors of IP-SCC among multiple covariates. The final tree was selected by cross-validation pruning based on minimal error. Results: Of 62 patients with IP, 21 (34%) had IP-SCC. The decision tree analysis revealed that the loss of convoluted cerebriform pattern and the 20th percentile cutoff of ADC were the most significant predictors of IP-SCC. With these decision trees, the sensitivity, specificity, accuracy, and C-statistics were 86% (18 out of 21; 95% confidence interval [CI], 65–95%), 100% (41 out of 41; 95% CI, 91–100%), 95% (59 out of 61; 95% CI, 87–98%), and 0.966 (95% CI, 0.912–1.000), respectively. Conclusion Decision tree analysis using conventional imaging features and histogram analysis of whole volume ADC could predict IP-SCC in patients with IP with high diagnostic accuracy.

We report a patient with severe neurological deterioration due to leptomeningeal metastases involving brain and spinal cord from anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma, managed rapidly and successfully with lorlatinib therapy. A 48-year-old male patient presented with acute mental deterioration, severe headache, and weakness of both legs. The patient’s previous medical history included cerebral metastases from ALK-positive lung adenocarcinoma, which had been successfully managed via whole brain radiation therapy and gamma knife radiosurgery one year and three months before, respectively. Physical examination revealed neck stiffness and paraparesis with motor grade I.Gadolinium-enhanced brain MRI showed newly developed leptomeningeal enhancement along cerebellar folia, and whole spine MRI revealed similar leptomeningeal metastasis along the whole spinal axis. Lorlatinib was started orally with a dose of 100 mg/day. The patient showed rapid clinical improvement after one week. The patient was alert and the headache disappeared, while the paraparesis improved to normal ambulatory status. Two months of lorlatinib treatment resulted in almost complete disappearance of previous leptomeningeal enhancement of brain and spinal cord, and absence of newly developed metastatic lesions in the central nervous system, based on MRI results. The patient had been regularly followed with ongoing lorlatinib therapy for 5 months without any systemic complications or neurological abnormality. Conclusively, lorlatinib could be a rapid and effective treatment for patients with central nervous system leptomeningeal metastases arising from ALK-positive lung cancer.

Purpose: To compare differences and changes in the parents’ awareness regarding influenza and influenza vaccination for their children according to educational intervention. Methods: This study involved 1,034 parents with children aged 6–59 months, who lived in five areas in northern Seoul and Gyeonggi Province in 2015; the study was conducted using the questionnaire survey method. Survey items included awareness regarding influenza and influenza vaccination for children and future intentions of influenza vaccination and the underlying reasons. The participants were divided into 3 groups and differences according to education (group A: no education, group B: provided education) and the changes before and after education (group C) were analyzed. Results: Differences according to education between groups A and B were seen in the recognition of high-risk of influenza in their children, effectiveness of influenza vaccination, and cost of the influenza vaccine. Changes before and after education in group C were seen in the recognition of high-risk of influenza in their children, safety of influenza vaccination, cost of the influenza vaccine, and negativity toward the influenza vaccine. Conclusions Educated parents were more aware regarding influenza and influenza vaccination for their children aged 6–59 months.

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0–83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0–4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.
Adult ; Biological Processes ; Cadmium ; Cross-Sectional Studies ; Environmental Pollutants ; Female ; Humans ; Korea ; Male ; Metals ; Methods ; Sex Characteristics ; Spectrophotometry, Atomic

PURPOSE: To evaluate the effect of combined medical treatment with anti-glaucoma eyedrops and 0.1% fluorometholone on visual acuity and refractive errors in patients complaining of blurred vision due to myopic regression after laser-assisted in-situ keratomileusis (LASIK) or laser-assisted sub-epithelial keratectomy (LASEK). METHODS: This study comprised 155 patients (155 eyes) who were diagnosed with myopic regression after LASIK or LASEK and received medical treatment from January 2015 to January 2016. The visual acuity and refractive errors were compared before and after medical treatment and evaluated to determine whether the results differ between LASIK and LASEK. RESULTS: The mean time of medical treatment was 64.1 ± 36.8 months after surgery. The responder group whose vision was improved and whose myopic error was decreased after medical treatment was comprised of 63 patients (41%). Their visual acuity in this group improved -0.21 ± 0.11 logMAR, and the amount of myopic error decreased 0.56 ± 0.32 diopters. The full responder group was 24 patients (15%), and the partial responder group was 39 patients (26%). The frequency of response to medical treatment was higher after LASIK than after LASEK, but the difference was not statistically significant. CONCLUSIONS: The combined medical treatment with anti-glaucoma eyedrops and 0.1% fluorometholone was effective in 41% of patients with regard to visual acuity improvement when used for post-LASIK or post-LASEK myopic regression. The medical treatment was effective after both LASIK and LASEK.
Fluorometholone* ; Humans ; Keratectomy, Subepithelial, Laser-Assisted* ; Keratomileusis, Laser In Situ* ; Ophthalmic Solutions* ; Refractive Errors ; Visual Acuity

OBJECTIVE: To evaluate the frequency and adequacy of statistical analyses in a general radiology journal when reporting a reliability analysis for a diagnostic test. MATERIALS AND METHODS: Sixty-three studies of diagnostic test accuracy (DTA) and 36 studies reporting reliability analyses published in the Korean Journal of Radiology between 2012 and 2016 were analyzed. Studies were judged using the methodological guidelines of the Radiological Society of North America-Quantitative Imaging Biomarkers Alliance (RSNA-QIBA), and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative. DTA studies were evaluated by nine editorial board members of the journal. Reliability studies were evaluated by study reviewers experienced with reliability analysis. RESULTS: Thirty-one (49.2%) of the 63 DTA studies did not include a reliability analysis when deemed necessary. Among the 36 reliability studies, proper statistical methods were used in all (5/5) studies dealing with dichotomous/nominal data, 46.7% (7/15) of studies dealing with ordinal data, and 95.2% (20/21) of studies dealing with continuous data. Statistical methods were described in sufficient detail regarding weighted kappa in 28.6% (2/7) of studies and regarding the model and assumptions of intraclass correlation coefficient in 35.3% (6/17) and 29.4% (5/17) of studies, respectively. Reliability parameters were used as if they were agreement parameters in 23.1% (3/13) of studies. Reproducibility and repeatability were used incorrectly in 20% (3/15) of studies. CONCLUSION: Greater attention to the importance of reporting reliability, thorough description of the related statistical methods, efforts not to neglect agreement parameters, and better use of relevant terminology is necessary.
Biomarkers ; Diagnostic Tests, Routine* ; Methods*

PURPOSE: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. MATERIALS AND METHODS: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. RESULTS: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. CONCLUSION: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.
Animals ; Anoxia ; Cell Death ; Cell Survival ; Colonic Neoplasms ; DNA Nucleotidylexotransferase ; In Vitro Techniques ; Mice ; Nanoparticles* ; Radiotherapy* ; Reactive Oxygen Species ; Silicon Dioxide