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Many optically active 2-azaspirocyclic structures have frequently been found in biologically active natural products. In particular, Nitraria alkaloids, (+)-nitramine, (+)-isonitramine, (-)-isonitramine, and (-)-sibirine, have stereogenicity on their quaternary carbon of the 2-azaspiro[5,5]undecane-7-ol structure. To synthesize Nitraria alkaloids, we developed a new enantioselective synthetic method for chiral α-quaternary lactams via the α-alkylation of α-tert-butoxycarbonyl lactams. α-Alkylation of α-tert-butoxycarboxylactams in the circumstances of phase-transfer catalytic (PTC) system (solid KOH, toluene, and -40 °C) by virtue of the catalytic action of (S,S)-NAS bromide (5 mol %) furnished the corresponding α-alkyl-α-tert-butoxycarbonyl lactams in very high chemical (

To develop a simplified MRI-based model to predict the risk for positive surgical margins (PSMs) after radical prostatectomy (RP) in patients with prostate cancer (PCa). Consecutive patients who underwent RP for PCa were retrospectively identified from a tertiary referral hospital. Patients who underwent RP between January 2014 and June 2014 were assigned as derivation cohort (n = 330) and those between January 2018 and February 2018 were assigned as validation cohort (n = 100). MRI-based predictors associated with PSM were assessed: tumor size, tumor-capsule contact length, the Prostate Imaging Reporting and Data System (PI-RADS) category, tumor location (tumor contact to the apex or posterolateral side near the neurovascular bundle), apical depth, and prostate volume. A prediction model was developed by using multivariable logistic regression, and then it was transformed into a scoring system. The prediction and calibration performance of this scoring system was evaluated using the C statistics and Hosmer-Lemeshow goodness-of-fit test. A total of 121 (36.7%) and 32 (32.0%) of patients in the derivation and validation cohorts had PSMs after RP. The scoring system consisted of the following variables: tumor-capsule contact length, PI-RADS category, tumor located at the apex and/or posterolateral side. This scoring system provided good prediction performance for PSM in the derivation (C statistics, 0.80 [95% CI: 0.76, 0.85]) and validation (C statistics, 0.77 [95% CI: 0.68, 0.87]) cohorts, and also showed good calibration in both cohorts (p = 0.83 and 0.86, respectively). An MRI-based scoring system can help estimate the risk of PSM after RP. • An MRI-based scoring system served as a tool to estimate the risk of positive surgical margin (C statistics, 0.80 and 0.77 in the derivation and validation cohorts, respectively) after radical prostatectomy. • Tumor with contact to the apex or posterolateral aspect, the tumor contact length to capsule, and higher PI-RADS category were independent predictors for the presence of positive resection margins after radical prostatectomy in men with prostate cancer. • High-risk patients as determined by the scoring system demonstrated adverse post-surgical outcomes compared with low- or intermediate-risk patients, in regard to longer length (mean length, 13.0 mm versus 3.9 mm in low risk or 6.2 mm in intermediate risk; p ≤ 0.001) and higher Gleason grade at the margin (grades 4 and 5 in 69.4% and 20.4% versus 16.7% and 16.7% in low risk or 46.7% and 5.4% in intermediate risk; p < 0.001).

Background: This study compared the treatment outcomes of patients with multidrug-resistant tuberculosis (MDRTB) before and after the implementation of public-private mix (PPM). Factors affecting treatment success were also investigated. Methods: Data from culture-confirmed pulmonary MDR-TB patients who commenced MDR-TB treatment at Pusan National University Hospital between January 2003 and December 2017 were retrospectively reviewed. Patients were divided into two groups in terms of PPM status: pre-PPM period, patients who commenced MDR-TB treatment between 2003 and 2010; and post-PPM period, patients treated between 2011 and 2017. Results: A total of 176 patients were included (64 and 112 in the pre- and post-PPM periods, respectively). 36.9% of the patients were resistant to a fluoroquinolone or a second-line injectable drug, or both. The overall treatment success rate was 72.7%. The success rate of post-PPM patients was higher than that of pre-PPM patients (79.5% vs. 60.9%, p=0.008). Also, loss to follow-up was lower in the post-PPM period (5.4% vs. 15.6%, p=0.023). In multivariate regression analysis, age ≥65 years, body mass index ≤18.5 kg/m2, previous TB treatment, bilateral lung involvement, and extensively drug-resistant (XDR)- or pre-XDR-TB were associated with poorer treatment outcomes. However, the use of bedaquiline or delamanid for ≥1 month increased the treatment success. Conclusion: The treatment success rate in MDR-TB patients was higher in the post-PPM period than in the pre-PPM period, particularly because of the low rate of loss to follow-up. To ensure comprehensive patient-centered PPM in South Korea, investment and other support must be adequate.

Although obesity is associated with numerous diseases, the risks of disease may depend on metabolic health. Associations between the gut microbiota, obesity, and metabolic syndrome have been reported, but differences in microbiomes according to metabolic health in the obese population have not been explored in previous studies. Here, we investigated the composition of gut microbiota according to metabolic health status in obese and overweight subjects. A total of 747 overweight or obese adults were categorized by metabolic health status, and their fecal microbiota were profiled using 16S ribosomal RNA gene sequencing. We classified these adults into a metabolically healthy group (MH, N = 317) without any components of metabolic syndrome or a metabolically unhealthy group (MU, N = 430) defined as having at least one metabolic abnormality. The phylogenetic and non-phylogenetic alpha diversity for gut microbiota were lower in the MU group than the MH group, and there were significant differences in gut microbiota bacterial composition between the two groups. We found that the genus Oscillospira and the family Coriobacteriaceae were associated with good metabolic health in the overweight and obese populations. This is the first report to describe gut microbial diversity and composition in metabolically healthy and unhealthy overweight and obese individuals. Modulation of the gut microbiome may help prevent metabolic abnormalities in the obese population.

To determine the concordance of dynamic contrast-enhanced (DCE) imaging findings with clinico-pathologic characteristics and their prognostic impact for predicting biochemical recurrence (BCR) in patients who underwent radical prostatectomy (RP) for prostate cancer.This retrospective study included patients who underwent MRI within 1 year after RP between November 2019 and October 2020. DCE findings and their concordance with the presence and location of positive surgical margin (PSM) were assessed using RP specimens. Kaplan-Meier and logistic regression analyses were used to evaluate the prognostic impact of DCE findings for BCR.Among the 272 men (mean age ± standard deviation, 66.6 ± 7.4 years), focal nodular enhancement was more frequently observed in those with PSM compared to those with negative margin (85.4% versus 14.6%; p0.001). The sites of focal nodular enhancement were 72.9% (35/48) concordant with the PSM locations. Focal nodular enhancement was associated with a higher Gleason score, higher preoperative PSA (≥ 10 ng/mL), higher Gleason grade at the surgical margin, and non-limited margin involvement (p = 0.002, 0.006, 0.032, and 0.001, respectively). In patients without BCR at the time of MRI, focal nodular enhancement was associated with a shorter time to BCR (p0.001) and a significant factor predicting 1-year BCR in both univariate (odds ratio = 8.4 [95% CI: 2.5-28.3]; p = 0.001) and multivariate (odds ratio = 5.49 [1.56-19.3]; p = 0.008) analyses.Focal nodular enhancement on post-prostatectomy MRI was associated with adverse clinico-pathologic characteristics of high risk for recurrence and can be a predictor for 1-year BCR in patients undergoing RP.• Focal nodular enhancement (PI-RR DCE score ≥ 4) was 72.9% (35/48) concordant with the site of positive resection margin by radiologic-histologic correlation. • Focal nodular enhancement (PI-RR DCE score ≥ 4) was associated with higher Gleason score ( ≥ 8), preoperative PSA (10 ng/mL), and Gleason grade 4 or 5 at the surgical margin and non-limited margin involvement (p ≤ 0.032). • In patients without BCR at the time of MRI, focal nodular enhancement was a significant factor predicting 1-year BCR (odds ratio = 5.49; 95% CI: 1.56-19.3; p = 0.008).

Background Prostate-specific membrane antigen (PSMA) is increasingly recognized as an excellent target for prostate cancer imaging and therapy. Finding compounds with a high target-to-nontarget ratio are an important challenge in the development of positron emission tomography (PET) imaging agents. In this study, we attempted to find a suitable compound from a simply-synthesized compound library. Method 18 F-labeling was achieved in a two-step synthesis consisting of [18 F]fluorination of azido sulfonates followed by copper(I)-catalyzed click ligation. In vitro binding experiment and in vivo studies were carried out using isogenic PSMA+ PC3-PIP and PSMA- PC3-flu cells and 22RV1 cells. [125 I]MIP-1095 was used to measure the binding affinities of compounds through a competitive binding assay, and [18 F]DCFPyL was used for a comparative assessment of compounds. Radiation dosimetry data were obtained using OLINDA/EXM software. Results Nine novel PSMA ligands were synthesized by the combination of three azido compounds and three terminal acetylene-containing Glu-urea-Lys compounds. Among them, compound 6f having a pyridine moiety showed a high binding affinity of 6.51 ± 0.19 nM (Ki ). 18 F-labeled compounds were obtained at moderate yields within 70 to 75 minutes (including high-performance liquid chromatography purification). Compound [18 F]6c had the lowest log P of -2.693. MicroPET/computed tomography (CT) images were acquired from 22RV1 cell xenograft mice after injecting [18 F]6c, [18 F]6f, and [18 F]6i. Additional microPET/CT experiments of [18 F]6c and [18 F]6f were performed using PSMA+ PC3-PIP and PSMA- PC3-flu cell-bearing mice. [18 F]6c was selected for further studies because it was found to have high uptake in tumors and rapid renal clearance, resulting in great tumor-to-nontumor ratios and distinct tumor images with very low background activity. Human dosimetry estimation of [18 F]6c using OLINDA/EXM software was calculated, resulting in an effective dose of 4.35 × 10-3 mSv/MBq. Conclusions [18 F]6c showed significant tumor uptake, a high tumor-to-nontumor ratio, and good radiation dosimetry results, suggesting further development as a potential diagnostic PET agent for prostate cancer.

Burkholderia cepacia is an opportunistic pathogen that infects patients with debilitating underlying diseases. This study investigated the production of outer membrane vesicles (OMVs) by B. cepacia cultured with sub-minimum inhibitory concentrations (MICs) of antibiotics and examined their pathogenic roles both in vitro and in vivo. B. cepacia ATCC 25416 produced more OMVs under antibiotic stress conditions than controls. OMVs isolated from B. cepacia cultured in Luria-Bertani (LB) broth (OMVs/LB) induced cytotoxicity and the expression of pro-inflammatory cytokine genes in A549 cells in a dose-dependent manner. Host cell cytotoxicity and pro-inflammatory responses were significantly higher in A549 cells treated with B. cepacia OMVs cultured with 1/4 MIC of ceftazidime (OMVs/CAZ) than in the cells treated with OMVs/LB, OMVs cultured with 1/4 MIC of trimethoprim/sulfamethoxazole (OMVs/SXT), or OMVs cultured with 1/4 MIC of meropenem. Intratracheal injection of B. cepacia OMVs also induced histopathology in vivo in mouse lungs. Expressions of IL-1β and TNF-α genes were significantly up-regulatedin the lungs of mice treated with OMVs/CAZ compared to mice administered other OMVs; the expression of the GRO-α gene, however, was significantly up-regulated in OMVs/SXT. In conclusion, OMVs produced by B. cepacia under different antibiotic stress conditions induce different host responses that may contribute to the pathogenesis of B. cepacia.

To investigate whether the detection of clinically significant prostate cancer (csPCa) and the added value of focal saturation biopsy and systematic biopsy (SBx) differ according to index lesion size, and to compare the current guidelines for csPCa detection.This retrospective study included consecutive men who underwent MRI and subsequent SBx and MRI-targeted biopsy (TBx) for a suspicious lesion between April 2019 and February 2020. Lesion visibility on transrectal ultrasound (US) and added value of focal saturation biopsy and SBx were compared according to index lesion size using chi-square and McNemar tests. csPCa detection rates and the proportion of biopsy-indicated men were compared among four biopsy strategies based on current guidelines.Of 313 men evaluated (median age, 65; interquartile range 60‒71), csPCa was detected in 110 (35%). In lesions 10 mm, greater US invisibility (42.7% of lesions 10 mm versus 20.0% of lesions ≥ 10 mm; p 0.001) and higher added value of focal saturation biopsy and SBx (11.1% and 17.1% in lesions 10 mm versus 4.2% and 6.3% in lesions ≥ 10 mm) were observed, compared with lesions ≥ 10 mm. Consideration of prostate-specific antigen (PSA) density 0.15 ng/mL/mL as a cutoff in unsuspicious MRI led to a 14% reduction (44/313) in men who needed biopsy.Determination of the biopsy strategy in terms of the need for focal saturation biopsy or SBx should be made considering lesion size. The use of PSA density in non-suspicious MRI can lead to a reduction in biopsy-indicated men.

Alzheimer’s disease (AD) is the most common dementia in late life memory related issues. It is estimated that worldwide 46.8 million people suffer from dementia. The hypoxia inducible factor (HIF) ...

In recent years, pharmacophore modeling and molecular docking approaches have been extensively used to characterize the structural requirements and explore the conformational space of a ligand in the binding pocket of the selected target protein. Herein, we report a pharmacophore modeling and molecular docking of 45 compounds comprising of the indole scaffold as vitamin D receptor (VDR) inhibitors. Based on the selected best hypothesis (DRRRR.61), an atom-based three-dimensional quantitative structure-activity relationships model was developed to rationalize the structural requirement of biological activity modulating components. The developed model predicted the binding affinity for the training set and test set with R2 (training) = 0.8869 and R2 (test) = 0.8139, respectively. Furthermore, molecular docking and dynamics simulation were performed to understand the underpinning of binding interaction and stability of selected VDR inhibitors in the binding pocket. In conclusion, the results presented here, in the form of functional and structural data, agreed well with the proposed pharmacophores and provide further insights into the development of novel VDR inhibitors with better activity.

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy.

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability (davg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer.

Metal-free consecutive C(sp2)-X (X = Cl, Br, S, N) bond formations of N-aryl amines (cyclic, fused, carbamate, and aminium radicals) were achieved under mild conditions using [bis(trifluoroacetoxy)iodo]benzene (PIFA) and simple nonharmful sodium salts. This direct and selective C(sp2)-H functionalization showed excellent functional group compatibility, cost effectiveness, and late-stage applicability for the synthesis of biologically active natural products. Two mechanisms were proposed to explain the ortho- or para-preference, as well as the accelerating effect of CH3NO2.

Introduction To reduce the rate of falls in the rehabilitation ward, fall prevention program was developed and educated for physical and occupational therapists, which increased the attitude towards falls and knowledge towards fall prevention activities. Method Participants of this study include 17 therapists currently employed at a university-affiliated hospital located in Gyeongg-do, South Korea. Systematic protocol for fall prevention with the emphasis in the roles of rehabilitation teams was developed. This standardized protocol consists of educating therapists with adequate assistive device use, safe ambulation techniques, and client-centered transfer techniques. The therapists then record the paitent's status related to fall prevention and or risks, which is then shared with other medical professionals including registered nurses and medical doctors. Paper-based questionnaires regarding 9 questions on attitude towards falls and 12 questions on knowledge towards fall prevention activities were done by the participants after the education of systematic protocol. The rate of falls was then compared with the change of attitudes in participants. Rate of falls was calculated by dividing the number of fall by the patient bed days and multiplying by 1000. Result After the education of fall prevention program, the mean score of attitude towards falls significantly increased (t=-3.99, p=0.001). The mean score of knowledge towards fall prevention activities significantly increased (t=-4.79, p Conclusion In order to effectively convey the fall prevention education program, the multidisciplinary approach showed promising results in this study. Implications for future research include translation of this program to the community, such as long term care facility.

Background Acinetobacter baumannii is an important opportunistic pathogen responsible for various nosocomial infections. The BfmRS two-component system plays a role in pathogenesis and antimicrobial resistance of A. baumannii via regulation of bacterial envelope structures. This study investigated the role of the sensor kinase, BfmS, in localization of outer membrane protein A (OmpA) in the outer membrane and production of outer membrane vesicles (OMVs) using wild-type A. baumannii ATCC 17978, ΔbfmS mutant, and bfmS-complemented strains. Results The ΔbfmS mutant showed hypermucoid phenotype in the culture plates, growth retardation under static culture conditions, and reduced susceptibility to aztreonam and colistin compared to the wild-type strain. The ΔbfmS mutant produced less OmpA in the outer membrane but released more OmpA via OMVs than the wild-type strain, even though expression of ompA and its protein production were not different between the two strains. The ΔbfmS mutant produced 2.35 times more OMV particles and 4.46 times more OMV proteins than the wild-type stain. The ΔbfmS mutant OMVs were more cytotoxic towards A549 cells than wild-type strain OMVs. Conclusions The present study demonstrates that BfmS controls production of OMVs in A. baumannii. Moreover, BfmS negatively regulates antimicrobial resistance of A. baumannii and OMV-mediated host cell cytotoxicity. Our results indicate that BfmS negatively controls the pathogenic traits of A. baumannii via cell envelope structures and OMV production.

Non-small cell lung cancers (NSCLCs) harboring uncommon epidermal growth factor receptor (EGFR) mutations are heterogeneous and show variable prevalence and clinical responses to EGFR tyrosine kinase inhibitors. We investigated the characteristics of uncommon EGFR mutations and the clinical efficacy of afatinib in patients with NSCLC harboring uncommon EGFR mutations.In this multicenter, retrospective study, we analyzed patients with NSCLC with uncommon EGFR mutations in 16 South Korean institutes. Mutations were categorized according to their incidence: 1) major uncommon mutations (G719X and L861Q), 2) compound mutations, and 3) minor uncommon mutations (exon 20 insertion, S768I, and de novo T790M).Of 703 patients with EGFR-mutant NSCLC, 64 (9.1%) had uncommon EGFR mutations. Afatinib demonstrated activity against tumors harboring major uncommon mutations [median time of treatment (TOT): 20.3 months, 95% confidence interval (CI)=15.1-25.5; overall survival (OS): 30.6 months, 95% CI=26.3-34.8] and compound mutations (median TOT: 12.3 months, 95% CI=7.7-17.0; OS: 29.1 months, 95% CI=20.4-37.7) but not against tumors harboring minor uncommon mutations (median TOT: 3.8 months, 95% CI=1.7-6.0; OS: 8.5 months, 95% CI=5.2-11.7). The S768I mutation was present in 14 patients (1.99%). The median TOT and OS were not significantly different between S768I mutations and resistant exon 20 mutations.Afatinib is effective in patients with NSCLC harboring major uncommon and compound EGFR mutations.

A person high in neuroticism is more likely to experience anxiety, stress, worry, fear, anger, and depression. Previous studies have shown that the gut microbiota can influence personality and mental disorders, including stress, anxiety, and depression, through the gut–brain axis. Here, we investigated the correlations between the sub-facet of neuroticism and gut microbiota using the Revised NEO Personality Inventory and the 16S rRNA gene sequencing data 784 adults. We found that the high anxiety and vulnerability group showed significantly lower richness in microbial diversity than a group with low anxiety and vulnerability. In beta diversity, there was a significant difference between the low and high groups of anxiety, self-consciousness, impulsiveness, and vulnerability. In taxonomic compositions, Haemophilus belonging to Gammaproteobacteria was correlated with the Neuroticism domain as well as N1 anxiety and N6 vulnerability facets. The high N1 anxiety and N6 vulnerability group was correlated with a low abundance of Christensenellaceae belonging to Firmicutes Clostridia. High N4 self-consciousness was correlated with a low abundance of Alistipes and Sudoligranulum. N5 impulsiveness was correlated with a low abundance of Oscillospirales. Our findings will contribute to uncovering the potential link between the gut microbiota and neuroticism, and the elucidation of the correlations of the microbiome–gut–brain axis with behavioral changes and psychiatric cases in the general population.

BACKGROUND Deep learning-based reconstruction (DLR) can potentially improve image quality by reduction of noise, thereby enabling fast acquisition of magnetic resonance imaging (MRI). However, a systematic evaluation of image quality and diagnostic performance of MRI using short acquisition time with DLR has rarely been investigated in men with prostate cancer. PURPOSE To assess the image quality and diagnostic performance of MRI using short acquisition time with DLR for the evaluation of extraprostatic extension (EPE). STUDY TYPE Retrospective. POPULATION One hundred and nine men. FIELD STRENGTH/SEQUENCE 3 T; turbo spin echo T2-weighted images (T2WI), echo-planar diffusion-weighted, and spoiled gradient echo dynamic contrast-enhanced images. ASSESSMENT To compare image quality, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and subjective analysis using Likert scales on three T2WIs (MRI using conventional acquisition time, MRI using short acquisition time [fast MRI], and fast MRI with DLR) were performed. The diagnostic performance for EPE was evaluated by three independent readers. STATISTICAL TESTS SNR, CNR, and image quality scores across the three imaging protocols were compared using Friedman tests. The diagnostic performance for EPE was assessed using the area under receiver operating characteristic curves (AUCs). P

Accumulating evidence shows that nut consumption beneficially affects health outcomes. The purpose of this study was to investigate the association between the intake of nuts, focusing on their mineral contents, and the risk of hypertension in nationally representative samples in Korea. A cross-sectional study was conducted among 12,113 subjects (4762 men and 7351 women) aged 19–64 years using raw data from KNHANES 2016–2019. Daily intake of 20 nuts and 9 minerals from nuts was assessed using the 24-h recall method. The risk of hypertension according to the median mineral intake from nuts and nuts themselves was assessed using logistic regression analysis with adjustment for potential confounders. The average daily nut intake was 4.34 g for females and 3.78 g males. Among nut intake, chestnuts represented the highest value at 0.95 g/day, followed by peanuts (0.72 g/day), almonds (0.62 g/day), sesame seeds (0.62 g/day), perilla seeds (0.33 g/day), and walnuts (0.32 g/day). The daily intake of minerals from nuts was significantly higher in the nut-overmedian (OM) group than in the nut-undermedian (UM) group. Regarding mineral intake from nuts, each mineral-UM group showed higher odds of hypertension than the mineral-OM group in women, but not in men. After adjustment for potential confounders, an inverse association between nut consumption, including minerals obtained from nuts, and hypertension prevalence, especially in women, was observed. Based on our results, it is suggested that incorporation of nuts into a daily diet may yield beneficial effects and lower the risk of hypertension in adult Korean women.

This study aims to demonstrate the need for learner-corpus-informed applications and proposes methods of application that promote the proper use of Korean topic and nominative markers. This study extracted 3004 pieces of error from the error-annotated corpus of theKorean Learners’ Corpus,the largest Korean learner corpus to date. A detailed examination of the above data was conducted to subdivide the types of substitution errors related to the topic and nominative markers, and to analyze the error rate according to the type of error and level of proficiency. The statistical data revealed no consistent correlation between the error rate and proficiency level. Furthermore, based on the proportion of error types by proficiency level, this study proposes the use of common mistake boxes with real errors; these errors are generally committed by learners of all proficiency levels and are not presumed problematic by grammarians or intuition-based teachers. These boxes can, therefore, be utilized as a practical tool for inclusion in pedagogical materials, such as learner’s dictionaries and textbooks.

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Objectives Immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor-1 and its ligand have achieved impressive success in treating patients with advanced-stage non-small cell lung cancer (NSCLC) after failed first-line cytotoxic chemotherapy. However, knowledge on clinical biomarkers that could help select patients who will respond well to second-line ICI therapy is limited. Patients and methods Medical records of patients with NSCLC treated with first-line platinum-based chemotherapy and subsequent second-line ICI were collected from 6 medical centers between January 2018 and June 2020. Clinical information, pathologic variables, and radiologic findings of the data collected were reviewed. The patients were followed up until the date of the last visit, the death of any cause, or the end of data recording (December 31, 2020). Results A total of 181 patients with NSCLC were treated with second-line ICI following first-line platinum-based doublet chemotherapy. The median progression-free survival was 2.0 months (interquartile range, 1.0 to 5.5 mo), and the median overall survival was 12.0 months (interquartile range, 6.0 to 20.0 mo). Low body mass index (BMI) was independently associated with progression-free survival (odds ratio [OR], 0.826; 95% confidence interval [CI], 0.723-0.945; P=0.005). Similarly, a low BMI (OR, 0.839; 95% CI, 0.740-0.952; P=0.005) and a high number of metastatic organs (OR, 1.682; 95% CI, 1.156-2.448; P=0.007) were independently associated with the overall survival after second-line ICI therapy. Conclusion BMI and the number of metastatic sites were significantly associated with second-line ICI therapy outcomes in patients with NSCLC receiving first-line platinum-based chemotherapy.

The British Thoracic Society guidelines recommend observation for patients with asymptomatic malignant pleural effusion (MPE). However, asymptomatic MPE can become symptomatic. This study examined the clinical course of asymptomatic MPE in patients with non-small cell lung cancer (NSCLC), including the incidence and timing of symptom development of asymptomatic MPE and the associated factors. Retrospective data of 4822 NSCLC patients between January 2012 and December 2017 were reviewed. Symptom development of asymptomatic MPE was defined as the development of symptoms requiring additional treatment, such as insertion of a chest tube, within 1 year in patients who lacked MPE symptoms at the time of diagnosis. Clinical information, pathological parameters, and radiological characteristics were reviewed. Patient data up to 1 year from the initial diagnosis were reviewed. Of 113 patients with asymptomatic MPE, 46 (41%) became symptomatic within 1 year despite appropriate anticancer treatment. The median time to symptom development was 4 months, and 38 patients (83%) developed symptoms within 6 months. Multivariate logistic regression showed that female sex (odds ratio [OR], 0.256; 95% confidence interval [CI], 0.101–0.649; P = .004) and the depth of pleural effusion on initial computed tomography (CT) (OR, 0.957; 95% CI, 0.932–0.982; P = .001) were independently associated with symptom development of asymptomatic MPE. A fraction of 41% of patients with asymptomatic MPE became symptomatic within 1 year. Female sex and larger MPE on initial CT were independently associated with symptom development of asymptomatic MPE.

Purpose Colistin resistance in gram-negative bacteria from humans and livestock has been increasingly reported worldwide. The aim of this study was to investigate the underlying mechanisms of chromosome-mediated colistin resistance in Escherichia coli isolates from livestock in Korea. Materials and methods Thirty mcr-1-negative isolates were selected from a collection of colistin-resistant E. coli isolates collected from livestock in 2005 and 2015 in Korea. Amino acid alterations in PmrAB, PhoPQ, MgrB, and PmrD were investigated. Colistin-resistant derivatives were produced by serial passage of colistin-susceptible E. coli isolates in colistin-containing media. Results Thirty colistin-resistant mcr-negative E. coli isolates were classified into 26 sequence types. Twenty-two isolates carried diverse amino acid alterations in PmrB, PhoP, PhoQ, MgrB, and/or PmrD, whereas no mutation in any of these genes was found in the remaining eight isolates. Sixteen out of the 22 isolates shared a total of nine polymorphic positions that were found in colistin-susceptible E. coli strains. Colistin-resistant derivatives from two colistin-susceptible isolates showed the same genetic alterations that were observed in colistin-resistant clinical isolates. Conclusion Our results suggest that the mechanism underlying chromosome-mediated colistin resistance remain to be discovered in E. coli. Selective pressure of colistin in vitro induced the same genetic mutations associated with colistin resistance in vivo. Efforts to reduce colistin consumption in livestock should be redoubled, to prevent the occurrence of colistin-resistant E. coli strains.

Background/aims Matrix-assisted laser desorption/ionization time-of-f light mass spectrometry (MALDI-TOF MS) is a new diagnostic tool for microorganism identification. The clinical usefulness of this approach has not been widely examined in Korea. This retrospective pre-post-intervention quasi-experimental study examined the effect of MALDI-TOF MS on patients with multidrug-resistant (MDR) bacteremia in the intensive care unit (ICU). Methods All consecutive patients with MDR bacteremia in the ICU of a tertiary care hospital between March 2011 and February 2013 and between March 2014 and February 2016 were enrolled. MALDI-TOF MS was introduced between these periods. In the pre-intervention and intervention groups, microorganisms were identified by conventional means and by MALDI-TOF MS, respectively. The groups were compared in terms of time from venipuncture to microorganism identification and antimicrobial susceptibility test results. Results In total, 187 patients (mean age, 61.0 years; 56.7% male) were enrolled. Of these, 97 and 90 were in the pre-intervention and intervention groups, respectively. The intervention group had a significantly shorter time from venipuncture to microorganism identification and antimicrobial susceptibility test results (82.5 ± 21.6 hours vs. 92.3 ± 40.4 hours, p = 0.038). The antibiotics were adjusted in 52 patients (26 each in the pre-intervention and intervention groups) based on these results. These groups did not differ in terms of time from venipuncture to antibiotic adjustment, and multivariate regression analysis showed that MALDI-TOF MS-based microorganism identification was not associated with 28-day mortality. Conclusion Our study showed that MALDI-TOF MS accelerated microorganism identification in patients with MDR bacteremia, but did not inf luence 28-day mortality.

Background The presence of EGFR mutation in patients with advanced non-small cell lung cancer (NSCLC) plays an important role in determining the appropriate treatment, response, and survival. Therefore, this study attempted to predict the prognosis of NSCLC patients using data from quantitative mutation measurements. Methods The data of patients with advanced NSCLC who underwent EGFR mutation testing using the peptide nucleic acid (PNA) mediated clamping method at the Pusan National University Hospital from October 2015 to December 2017 were retrospectively analyzed. The efficiency of PNA clamping was determined by measuring the threshold cycle (Ct ) value. The ΔCt -1 value (standard Ct value minus sample Ct value) was calculated to quantify EGFR mutation. Results During the study period, 71 patients were treated with EGFR-tyrosine kinase inhibitors. The cutoff point for the ΔCt -1 value derived from the receiver operating characteristic curve was 5.32. A survival benefit was observed in the group with an ΔCt -1 value > 5.32 or with a common EGFR mutation type compared to the group with an ΔCt -1 value Conclusion EGFR mutation testing using PNA clamping may predict patient survival, especially in patients with common EGFR mutations, such as exon 19 deletion or L858R. A higher ΔCt -1 value correlates with better survival.