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Background: In cholangiocarcinoma (CC), HER-2/neu protein overexpression has rarely been reported and the results are conflicting. The present study aimed to clarify the rates of HER-2/neu protein overexpression and gene amplification in human extrahepatic CC and to evaluate the correlation between HER-2/neu and several clinicopathologic features. Patients and methods: We investigated HER-2 gene amplification by chromogenic in situ hybridization (CISH) and HER-2/neu protein overexpression by immunohistochemistry in 55 extrahepatic CC patients who underwent curative surgery at our institution. Results: Overexpression of HER-2/neu protein (staining intensity score ≥ 2) was found in 16 out of 55 patients (29.1%). CISH revealed that HER-2 gene signals were increased in 10 out of 55 patients (18.1%). There was a positive and significant correlation between HER-2 gene amplification and HER-2/neu protein overexpression (Spearmans rho = 0.718, P < 0.01). In subgroup with lymph node metastases, HER-2 gene amplification by CISH was significant prognostic factor for survival (OR 43.6, 95% confidence interval 1.6–1219.6). Conclusions: HER-2/neu protein overexpression by HER-2 gene amplification may occur in human extrahepatic CC and constitute an independent prognostic factor in patients with lymph node metastases. In subgroup with lymph node metastases who exhibit HER-2/neu overexpression might constitute potential candidates for new adjuvant therapy, such as humanized monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Purpose: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC., Materials and Methods: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach's alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes., Results: A Cronbach's alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ)., Conclusion: The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement., Competing Interests: Byong Duk Ye has received research grants from Celltrion and Pfizer Korea; consulting fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd., Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Curacle, Daewoong Pharm, Ferring Korea, IQVIA, Janssen Korea, Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Medtronic Korea, Nano-Entek, ORGANOID SCIENCES LTD., Pfizer Korea, Samsung Bioepis, Takeda, and Takeda Korea; and speaking fees from AbbVie Korea, Celltrion, Cornerstones Health, Curacle, Daewoong Pharm, Ferring Korea, IQVIA, Janssen Korea, Pfizer Korea, and Takeda Korea. The other authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Thiopurines play an important role in the management of steroid-refractory and steroid-dependent ulcerative colitis. However, the effectiveness of the early use of thiopurines in ulcerative colitis remains controversial., Materials and Methods: In this multicenter prospective cohort (MOSAIK) study, we divided patients with ulcerative colitis into those who underwent early (within 6 mo of diagnosis) and late (6 mo after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes., Results: Overall, 333 patients with moderate-to-severe ulcerative colitis were included. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.9% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3 to 2.0); the median maintenance dose was 1.1 mg/kg (0.3 to 2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis (P=0.712). The presence of extraintestinal manifestations (hazard ratio: 4.674, 95% CI: 1.210-18.061, P=0.025) independently predicted an increased risk of clinical relapse., Conclusions: Patients with ulcerative colitis who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Wheels have been commonly used for locomotion in mobile robots and transportation systems because of their simple structure and energy efficiency. However, the performance of wheels in overcoming obstacles is limited compared with their advantages in driving on normal flat ground. Here, we present a variable-stiffness wheel inspired by the surface tension of a liquid droplet. In a liquid droplet, as the cohesive force of the outermost liquid molecules increases, the net force pulling the liquid molecules inward also increases. This leads to high surface tension, resulting in the liquid droplet reverting to a circular shape from its distorted shape induced by gravitational forces. Similarly, the shape and stiffness of a wheel were controlled by changing the traction force at the outermost smart chain block. As the tension of the wire spokes connected to each chain block increased, the wheel characteristics reflected those of a general circular-rigid wheel, which has an advantage in high-speed locomotion on normal flat ground. Conversely, the modulus of the wheel decreased as the tension of the wire spoke decreased, and the wheel was easily deformed according to the shape of obstacles. This makes the wheel suitable for overcoming obstacles without requiring complex control or sensing systems. On the basis of this mechanism, a wheel was applied to a two-wheeled wheelchair system weighing 120 kilograms, and the state transition between a circular high-modulus state and a deformable low-modulus state was realized in real time when the wheelchair was driven in an outdoor environment.

Introduction: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation., Methods: This was a prospective multicenter study conducted in 6 tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photographs of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2,161 stool pictures from 306 patients and tested on 1,047 stool images from 126 patients. The UC endoscopic index of severity was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal)., Results: The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong P = 0.458]). When rectal-sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P = 0.002)., Discussion: DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photographs are a useful monitoring tool for typical UC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: Crohn's disease [CD] has a complex polygenic aetiology with high heritability. There is ongoing effort to identify novel variants associated with susceptibility to CD through a genome-wide association study [GWAS] in large Korean populations., Methods: Genome-wide variant data from 902 Korean patients with CD and 72 179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1621 patients with CD and 4419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term., Results: We identified two novel genetic associations with the risk of CD near ZBTB38 and within the leukocyte immunoglobulin-like receptor [LILR] gene cluster [p < 5 × 10-8], with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci [QTL] for multiple LILR genes, of which LILRB2 directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants for TAP2 involved in the antigen presentation of MHC class I molecules [p = 4.11 × 10-4], showing higher CD-risk effects of the TAP2 variant in individuals carrying more risk alleles of the LILR lead variant (odds ratio [OR] = 0.941, p = 0.686 in non-carriers; OR = 1.45, p = 2.51 × 10-4 in single-copy carriers; OR = 2.38, p = 2.76 × 10-6 in two-copy carriers)., Conclusions: This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR and TAP2 loci confer a risk of CD., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Comorbidities are risk factors for poor clinical outcomes in patients with heart failure. However, no consensus has been reached on how to assess comorbidities related to clinical outcomes in patients with heart failure., Objective: The aims of this study were to review (1) how comorbidities have been assessed, (2) what chronic conditions have been identified as comorbidities and (3) the rationale for choosing the comorbidity instruments and/or specific comorbidities when exploring clinical outcomes in patients with heart failure., Methods: The clinical outcomes of interest were mortality, hospitalization, quality of life, and self-care. Three electronic databases and reference list searches were used in the search., Results: In this review, we included 39 articles using 3 different ways to assess comorbidities in the relationship with clinical outcomes: using an instrument (ie, Charlson Comorbidity Index), disease count, and including individual comorbidities. A total of 90 comorbidities were investigated in the 39 articles; however, definitions and labels for the diseases were inconsistent across the studies. More than half of the studies (n = 22) did not provide a rationale for selecting the comorbidity instruments and/or all of the specific comorbidities. Some of the rationale for choosing the instruments and/or specific comorbidities was inappropriate., Conclusions: We found several issues related to measuring comorbidities when examining clinical outcomes in patients with heart failure. Researchers need to consider these methodological issues when measuring comorbidities in patients with heart failure. Further efforts are needed to develop guidelines on how to choose proper measures for comorbidities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Recent research has demonstrated the potential of fecal microbiome analysis using machine learning (ML) in the diagnosis of inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC). This study employed the sparse partial least squares discriminant analysis (sPLS-DA) ML technique to develop a robust prediction model for distinguishing among CD, UC, and healthy controls (HCs) based on fecal microbiome data. Using data from multicenter cohorts, we conducted 16S rRNA gene sequencing of fecal samples from patients with CD ( n = 671) and UC ( n = 114) while forming an HC cohort of 1462 individuals from the Kangbuk Samsung Hospital Healthcare Screening Center. A streamlined pipeline based on HmmUFOTU was used. After a series of filtering steps, 1517 phylotypes and 1846 samples were retained for subsequent analysis. After 100 rounds of downsampling with age, sex, and sample size matching, and division into training and test sets, we constructed two binary prediction models to distinguish between IBD and HC and CD and UC using the training set. The binary prediction models exhibited high accuracy and area under the curve (for differentiating IBD from HC (mean accuracy, 0.950; AUC, 0.992) and CD from UC (mean accuracy, 0.945; AUC, 0.988)), respectively, in the test set. This study underscores the diagnostic potential of an ML model based on sPLS-DA, utilizing fecal microbiome analysis, highlighting its ability to differentiate between IBD and HC and distinguish CD from UC.

Background and Aims: Given that the majority of colorectal cancers (CRCs) develop from high-risk adenomas, identifying risk factors for high-risk adenomas is important. The relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of colorectal adenoma in young adults remains unclear. We aimed to evaluate this relationship in adults <50 (younger) and ≥50 (older) years of age., Methods: This cross-sectional study included 184 792 Korean adults (80% <50 years of age) who all underwent liver ultrasound and colonoscopy. Participants were grouped into those with and without MAFLD and classified by adenoma presence into no adenoma, low-risk adenoma, or high-risk adenoma (defined as ≥3 adenomas, any ≥10 mm, or adenoma with high-grade dysplasia/villous features)., Results: The prevalence of low- and high-risk adenomas among young and older adults was 9.6% and 0.8% and 22.3% and 4.8%, respectively. MAFLD was associated with an increased prevalence of low- and high-risk adenomas in young and older adults. Young adults with MAFLD had a 1.30 (95% CIs 1.26-1.35) and 1.40 (1.23-1.59) times higher prevalence of low- and high-risk adenomas, respectively, compared to those without MAFLD. These associations were consistent even in lean adults (BMI < 23 kg/m 2 ) and those without a family history of CRC., Conclusions: MAFLD is associated with an increased prevalence of low- and high-risk adenomas in Korean adults, regardless of age or obesity status. Whether reducing metabolic risk factors, such as MAFLD, reduces the risk of precancerous lesions and ultimately reduces the risk of early-onset CRC requires further investigation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

COPD is a heterogeneous disease, and its acute exacerbation is a major prognostic factor. We used cluster analysis to predict COPD exacerbation due to subtypes of mild-moderate airflow limitation. In all, 924 patients from the Korea COPD Subgroup Study cohort, with a forced expiratory volume (FEV1) ≥ 50% and documented age, body mass index (BMI), smoking status, smoking pack-years, COPD assessment test (CAT) score, predicted post-bronchodilator FEV1, were enrolled. Four groups, putative chronic bronchitis (n = 224), emphysema (n = 235), young smokers (n = 248), and near normal (n = 217), were identified. The chronic bronchitis group had the highest BMI, and the one with emphysema had the oldest age, lowest BMI, and highest smoking pack-years. The young smokers group had the youngest age and the highest proportion of current smokers. The near-normal group had the highest proportion of never-smokers and near-normal lung function. When compared with the near-normal group, the emphysema group had a higher risk of acute exacerbation (OR: 1.93, 95% CI: 1.29-2.88). However, multiple logistic regression showed that chronic bronchitis (OR: 2.887, 95% CI: 1.065-8.192), predicted functional residual capacity (OR: 1.023, 95% CI: 1.007-1.040), fibrinogen (OR: 1.004, 95% CI: 1.001-1.008), and gastroesophageal reflux disease were independent predictors of exacerbation (OR: 2.646, 95% CI: 1.142-6.181). The exacerbation-susceptible subtypes require more aggressive prevention strategies.

Background: The prevalence of heart failure (HF) is expected to rise due to increased survivorship and life expectancy of patients with acute heart conditions. Patients with HF and other multiple comorbid conditions are likely to have poor health outcomes. This study aimed to assimilate the current body of knowledge and to provide the pooled effect of HF patients' comorbid conditions on health outcomes., Methods: A systematic search was performed using MEDLINE, EMBASE and CINAHL databases. Observational studies evaluating the relationship between comorbid conditions and the health outcomes of HF were included. The pooled effect sizes of comorbidity on the identified health outcomes were calculated using a random effects model, and the heterogeneity was evaluated using I 2 statistics., Results: A total of 42 studies were included in this review, and a meta-analysis was performed using the results of 39 studies. In the pooled analysis, the presence of a comorbid condition showed a significant pooled effect size in relation to the prognostic health outcomes: all-cause mortality (HR 1.31; 95% CI 1.18, 1.45), all-cause readmission (HR 1.16; 95% CI 1.09, 1.23), HF-related readmission (HR 1.13; 95% CI 1.05, 1.23), and non-HF-related readmission (HR 1.17; 95% CI 1.07, 1.27). Also, comorbidity was significantly associated with health-related quality of life and self-care confidence. Furthermore, we identified a total of 32 comorbid conditions from included studies. From these, 16 individual conditions were included in the meta-analyses, and we identified 10 comorbid conditions to have negative effects on overall prognostic outcomes: DM (HR 1.16, 95% CI 1.11, 1.22), COPD (HR 1.31, 95% CI 1.23, 1.39), CKD (HR 1.18, 95% CI 1.14, 1.23, stroke (HR 1.25, 95% CI 1.17, 1.31), IHD (HR 1.17, 95% CI 1.11, 1.23), anemia (HR 1.42, 95% CI 1.14, 1.78), cancer (HR 1.17, 95% CI 1.04, 1.32), atrial fibrillation (HR 1.25, 95% CI 1.01, 1.54), dementia (HR 1.19, 95% CI 1.03, 1.36) and depression (HR 1.17, 95% CI 1.04, 1.31)., Conclusions: Comorbid conditions have significantly negative pooled effects on HF patient health outcomes, especially in regard to the prognostic health outcomes. Clinicians should carefully identify and manage these conditions when implementing HF interventions to improve prognostic outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Colorectal cancers (CRC) are classified into consensus molecular subtypes (CMS) based on gene expression profiles. The revised classification system iCMS was proposed by considering intrinsic epithelial status, microsatellite instability (MSI), and fibrosis. This study aimed to provide molecular evidence for the adenoma-carcinoma sequence concept by examining CRC and synchronous adenomas using iCMS. Epithelial CMS cell proportion was estimated using CiberSortx, an in silico cell fractionation method that included CMS cell types among the reference cell types. A random forest (RF) model estimated the posterior probabilities of CMS classes, which were compared with the CiberSortx results. Gene expression profiles of the published iCMS signature panel were retrieved from our dataset and subjected to heatmap clustering for classification. Bulk RNA sequencing data were collected from 29 adenocarcinomas and 11 adenoma samples. CiberSortx showed all CRC contained either CMS2 or CMS3 as the major epithelial cancer cell type. The RF model classified approximately half of the CRC as CMS4, whereas CMS4 was hardly detected by CiberSortx. Because they were enriched with myofibroblasts as per the CiberSortx classification, we tentatively designated them as iCMS2-F/iCMS3-F. iCMS coupled with the application of an in silico cell fractionation method can provide the molecular dissection of CRC and adenoma.

Background & Aims: The role of circulating 25-hydroxyvitamin D (25(OH)D) in the prevention of early-onset colorectal cancer (CRC) in young adults aged <50 years is uncertain. We evaluated the age-stratified associations (<50 vs ≥50 years) between circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults., Methods: Our cohort study included 236,382 participants (mean age, 38.0 [standard deviation, 9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as <10, 10 to 20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness, was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders., Results: During the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5-7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 10 5 person-years). Among young individuals aged <50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43-0.86) and 0.41 (0.27-0.63) for 25(OH)D 10 to 19 ng/mL and ≥20 ng/mL, respectively, with respect to the reference (<10 ng/mL) (P for trend <.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared with younger individuals., Conclusions: Serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed&#95;1) and the other far away (Inflamed&#95;2) from the non-inflamed samples. Inflamed&#95;1 was rich in anti-TNF durable responders (DRs), and Inflamed&#95;2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed&#95;2 than in Inflamed&#95;1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed&#95;2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

Nitrogen scanning in aryl fragments is a valuable aspect of the drug discovery process, but current strategies require time-intensive, parallel, bottom-up synthesis of each pyridyl isomer because of a lack of direct carbon-to-nitrogen (C-to-N) replacement reactions. We report a site-directable aryl C-to-N replacement reaction allowing unified access to various pyridine isomers through a nitrene-internalization process. In a two-step, one-pot procedure, aryl azides are first photochemically converted to 3 H -azepines, which then undergo an oxidatively triggered C2-selective cheletropic carbon extrusion through a spirocyclic azanorcaradiene intermediate to afford the pyridine products. Because the ipso carbon of the aryl nitrene is excised from the molecule, the reaction proceeds regioselectively without perturbation of the remainder of the substrate. Applications are demonstrated in the abbreviated synthesis of a pyridyl derivative of estrone, as well as in a prototypical nitrogen scan.

Microbial community profiling using 16S rRNA amplicon sequencing allows for taxonomic characterization of diverse microorganisms. While amplicon sequence variant (ASV) methods are increasingly favored for their fine-grained resolution of sequence variants, they often discard substantial portions of sequencing reads during quality control, particularly in datasets with large number samples. We present a streamlined pipeline that integrates FastP for read trimming, HmmUFOtu for operational taxonomic units (OTU) clustering, Vsearch for chimera checking, and Kraken2 for taxonomic assignment. To assess the pipeline's performance, we reprocessed two published stool datasets of normal Korean populations: one with 890 and the other with 1,462 independent samples. In the first dataset, HmmUFOtu retained 93.2% of over 104 million read pairs after quality trimming, discarding chimeric or unclassifiable reads, while DADA2, a commonly used ASV method, retained only 44.6% of the reads. Nonetheless, both methods yielded qualitatively similar β-diversity plots. For the second dataset, HmmUFOtu retained 89.2% of read pairs, while DADA2 retained a mere 18.4% of the reads. HmmUFOtu, being a closed-reference clustering method, facilitates merging separately processed datasets, with shared OTUs between the two datasets exhibiting a correlation coefficient of 0.92 in total abundance (log scale). While the first two dimensions of the β-diversity plot exhibited a cohesive mixture of the two datasets, the third dimension revealed the presence of a batch effect. Our comparative evaluation of ASV and OTU methods within this streamlined pipeline provides valuable insights into their performance when processing large-scale microbial 16S rRNA amplicon sequencing data. The strengths of HmmUFOtu and its potential for dataset merging are highlighted.

Pancreatic cancer(PC) is less common than other cancers; however, it has a poor prognosis. Therefore, studying novel target signaling and anticancer agents is necessary. Momordicae Semen (MS), the seed of Momordica sochinensis Spreng, mainly found in South-East Asia, including China and Bangladesh, is used to treat various diseases because of its anticancer, antioxidant, anti-inflammatory, and antibacterial properties. However, the effect of the MS extract on pancreatic cancer cells remains unknown. In this study investigated whether the MS extract exerted an anti-cancer effect by regulating c-Myc through CNOT2. Cytotoxicity and proliferation were investigated using MTT and colony formation assays. The levels of apoptotic, oncogenic, and migration-associated factors were confirmed using immunoblotting and immunofluorescence. Wound closure was analyzed using a wound healing assay. The chemical composition of the MS methanol extracts was analyzed using liquid chromatography-mass spectrometry. We confirmed that the MS extract regulated apoptotic factors and attenuated the stability of c-Myc and its sensitivity to fetal bovine serum. Furthermore, the MS extract increased apoptosis by regulating c-Myc and CNOT2 expression and enhanced the sensitivity of 5-FU in pancreatic cancer. This study showed that the MS extract is a promising new drug for PC., (© 2023. Springer Nature Limited.)

Cytosine arabinoside (AraC) is one of the main therapeutic treatments for several types of cancer, including acute myeloid leukaemia. However, after a high-dose AraC chemotherapy regime, patients develop severe neurotoxicity and cell death in the central nervous system leading to cerebellar ataxia, dysarthria, nystagmus, somnolence and drowsiness. AraC induces apoptosis in dividing cells. However, the mechanism by which it leads to neurite degeneration and cell death in mature neurons remains unclear. We hypothesise that the upregulation of the death receptor p75 NTR is responsible for AraC-mediated neurodegeneration and cell death in leukaemia patients undergoing AraC treatment. To determine the role of AraC-p75 NTR signalling in the cell death of mature neurons, we used mature cerebellar granule neurons' primary cultures from p75 NTR knockout and p75 NTRCys259 mice. Evaluation of neurite degeneration, cell death and p75 NTR signalling was done by immunohistochemistry and immunoblotting. To assess the interaction between AraC and p75 NTR , we performed cellular thermal shift and AraTM assays as well as Homo-FRET anisotropy imaging. We show that AraC induces neurite degeneration and programmed cell death of mature cerebellar granule neurons in a p75 NTR -dependent manner. Mechanistically, Proline 252 and Cysteine 256 residues facilitate AraC interaction with the transmembrane domain of p75 NTR resulting in uncoupling of p75 NTR from the NFκB survival pathway. This, in turn, exacerbates the activation of the cell death/JNK pathway by recruitment of TRAF6 to p75 NTR . Our findings identify p75 NTR as a novel molecular target to develop treatments for counteract AraC-mediated cell death of mature neurons., (© 2023. The Author(s).)

Background: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes., Methods: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation., Results: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (μg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54., Conclusion: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Although gut microbiome dysbiosis has been associated with inflammatory bowel disease (IBD), the relationship between the oral microbiota and IBD remains poorly understood. This study aimed to identify unique microbiome patterns in saliva from IBD patients and explore potential oral microbial markers for differentiating Crohn's disease (CD) and ulcerative colitis (UC). A prospective cohort study recruited IBD patients (UC: n = 175, CD: n = 127) and healthy controls (HC: n = 100) to analyze their oral microbiota using 16S rRNA gene sequencing. Machine learning models (sparse partial least squares discriminant analysis (sPLS-DA)) were trained with the sequencing data to classify CD and UC. Taxonomic classification resulted in 4041 phylotypes using Kraken2 and the SILVA reference database. After quality filtering, 398 samples (UC: n = 175, CD: n = 124, HC: n = 99) and 2711 phylotypes were included. Alpha diversity analysis revealed significantly reduced richness in the microbiome of IBD patients compared to healthy controls. The sPLS-DA model achieved high accuracy (mean accuracy: 0.908, and AUC: 0.966) in distinguishing IBD vs. HC, as well as good accuracy (0.846) and AUC (0.923) in differentiating CD vs. UC. These findings highlight distinct oral microbiome patterns in IBD and provide insights into potential diagnostic markers.

(1) Background: One of the strategies to overcome the shortage of nurses is to minimize gender inequity in nursing culture, starting from the undergraduate education program. Although the number of men entering the nursing profession has increased over the years, the portion of male nurses remains low, particularly in Asian countries. Only a few studies have been conducted to identify gender inequity in nursing, and most of these studies used qualitative study design. Therefore, it is necessary to quantitatively identify gender equity in nursing education and the influence it has on nurse job satisfaction. (2) Methods: A total of 165 male nurses participated in this study. Validated questionnaires were used to assess gender equity in nursing education programs, nurse job satisfaction, nurse job esteem, and nursing professional pride. (3) Results: The mean score of gender equity in nursing programs was 62.6, showing a positive correlation with nurse job satisfaction, nurse job esteem, and nursing professional pride. Gender equity positively predicted nurse job esteem. (4) Conclusions: The gender equity in nursing education programs has positive predictive effects on the factors that influence male nurse job satisfaction. In order to increase nurse job retention, educators should incorporate strategies to minimize gender inequity.

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported., Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment., Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients ( n  = 116)., Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n  = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model., Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers., Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment., Competing Interests: Dennis Teng is an employee of Abbvie, Inc. and may hold stock or stock options. The remaining co-authors have no competing interests to declare., (© The Author(s), 2023.)

Thermoplastic starch was blended with commercially available biodegradable polyesters of poly(butylene adipate-co-terephthalate) (PBAT) and poly(lactic acid) (PLA) for its improved performance and processability. The morphology and elemental composition of these biodegradable polymer blends were observed by scanning electron microscopy and energy dispersive X-ray spectroscopy, respectively, while their thermal properties were analyzed using thermogravimetric analysis and differential thermal calorimetry. For rheological analysis, the steady shear and dynamic oscillation tests of three samples at various temperatures were investigated using a rotational rheometer. All three samples exhibited significant shear thinning at all measured temperatures, and their shear viscosity behavior was plotted using the Carreau model. The frequency sweep tests showed that the thermoplastic starch sample exhibited a solid state at all temperatures tested, whereas both starch/PBAT and starch/PBAT/PLA blend samples exhibited viscoelastic liquid behavior after the melting temperature such that their loss modulus at low frequencies was greater than the storage modulus, and inversion occurred at high frequencies (storage modulus > loss modulus).

Reductive amination has been widely used for manufacturing carbon-nitrogen-containing building blocks. Despite its versatility, the need for a chemical reductant or harmful hydrogen gas has limited its further utilization in modern chemical applications. Here, we report electrochemical reductive amination (ERA) to pursue sustainable synthetic routes. Faradaic efficiencies of about 83% are achieved using Cu metal electrodes. In-depth electrokinetic studies reveal the rate-determining step and overall reaction nature of ERA. Through the experiments using deuterated solvent and additional proton sources, we scrutinize the origin of protons during the ERA. Furthermore, CW-EPR analysis captures the radical intermediate species, formed during the catalytic cycle, advancing mechanistic understanding of ERA process.

Purpose: The incidence of early-onset colorectal cancer (CRC) and associated mortality have been increasing. However, the potential benefits of CRC screening are largely unknown in young individuals. We aimed to evaluate the effect of CRC screening with colonoscopy on all-cause and CRC mortality among young (aged < 45 years) and older (aged ≥ 45 years) individuals., Materials and Methods: This cohort study included 528,046 Korean adults free of cancer at baseline who underwent a comprehensive health examination. The colonoscopic screening group was defined as those who reported undergoing colonoscopy for CRC screening. Mortality follow-up until December 31, 2019 was ascertained based on nationwide death certificate data from the Korea National Statistical Office., Results: Colonoscopic screening was associated with a lower risk of all-cause mortality in both young and older individuals. Multivariable-adjusted time-dependent hazard ratios (95% confidence intervals) for all-cause mortality comparing ever- to never-screening were 0.86 (0.75-0.99) for young individuals and 0.71 (0.65-0.78) for older individuals. Colonoscopic screenings were also associated with a reduced risk of CRC mortality without significant interaction by age, although this association was significant only among participants aged ≥ 45 years, with corresponding time-dependent hazard ratios of 0.47 (0.15-1.44) for young individuals and 0.52 (0.31-0.87) for those aged ≥ 45 years., Conclusion: Colonoscopic CRC screening decreased all-cause mortality among both young and older individuals, while significantly decreased CRC mortality was observed only in those aged ≥ 45 years. Screening initiation at an earlier age warrants more rigorous confirmatory studies.

Introduction: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications., Methods: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]., Results: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks., Conclusion: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications., (© 2023. The Author(s).)

Fluoxetine (Prozac™) is the only antidepressant approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in children. Despite its considerable efficacy as a selective serotonin reuptake inhibitor, the possible long-term effects of fluoxetine on brain development in children are poorly understood. In the current study, we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques ( Macaca mulatta ) one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling. We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex (DLPFC) and cingulate cortex (CC) that correlated with impulsivity in animals, suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment. Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.

Background: Heart failure (HF) is a chronic heart condition that requires patients to adapt to the disease and maintain a high degree of self-management. Patients with HF commonly feel loss of control, which has a negative effect on their compliance to self-care, health-related quality of life, and health outcomes. To promote self-care behavior and to develop healthy coping mechanisms, it is important to understand individual HF patients' perceived control, a self-generated belief that one has the ability to bring forth desired outcomes. Currently, there is no valid and reliable Korean instrument available in measuring perceived control among patients with HF., Objective: The objective of this study was to cross-culturally translate, adapt, and evaluate psychometric properties of the Korean version of Control Attitudes Scale-Revised (KCAS-R) in Korean patients with HF., Methods: The KCAS-R was developed using a translation/back-translation process and an examination of semantic and conceptual equivalence. Reliability was assessed using Cronbach α to determine internal consistency, and item-total and interitem correlations were assessed to test item homogeneity. The construct validity was examined using exploratory factor analysis, confirmatory factor analysis, and testing hypotheses for known associations with self-efficacy, self-care confidence, and self-care., Results: A convenience sample of 138 patients with HF were included for the psychometric testing of an 8-item KCAS-R. The Cronbach α for internal consistency was 0.835, and the item-total correlation was acceptable. The construct validity revealed a 2-factor structure accounting for 63.23% of the total variance. The KCAS-R was associated with higher levels of self-efficacy, self-care confidence, and self-care. In addition, patients with higher perceived control had less depression and anxiety compared with those with lower levels of perceived control., Conclusion: This study provided support for the satisfactory reliability and validity of the 8-item KCAS-R in measuring perceived control in Korean patients with HF., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD., Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019)., Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection., Conclusions: The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Timosaponin A3 (TA3), extracted from the rhizome of Anemarrhena asphodeloides Bunge, has been reported to affect various diseases, such as cancer, Alzheimer's disease, and allergies. However, the underlying molecular mechanisms and impacts are largely unknown. In the present study, we hypothesized that TA3 induces apoptosis through the inhibition of c-Myc expression via CNOT2 or MID1IP1 in HCT116. An MTT assay and colony formation assay were used to measure cell viability and proliferation. The protein expression of apoptotic markers and oncogenes was measured using immunoblotting and immunofluorescence assays. The interaction between MID1IP1 and c-Myc was confirmed by performing an immunoprecipitation assay. TA3 markedly inhibited colon cancer cell proliferation. Consistently, TA3 regulated the apoptotic proteins pro-PARP and caspase 3. TA3 inhibited the half-life of c-Myc and suppressed its expression in response to serum stimulation. In addition, TA3 enhanced the apoptotic effects of doxorubicin and 5-FU in colon cancer cells. Altogether, our results reveal a mechanism by which TA3 induces apoptosis through inhibiting c-Myc expression via CNOT2 or MID1IP1 in HCT116, which may help in the development of new therapies for colon cancer based on TA3 in the future.

Background/aims: Epidemiological data on steroid use in South Korean patients with inflammatory bowel disease (IBD) are limited. We documented the steroid use patterns in these patients, and whether physician education on appropriate steroid use affected these patterns., Methods: ACTION was an observational cohort study conducted in adults (≥19 years) with IBD. A retrospective chart review was performed at baseline (cohort 1) and 1 year after physician training (cohort 2). Eligible cases with excessive or inappropriate steroid use were identified, along with any associated risk factors., Results: Data were collected during May 2018-July 2019 from patients with Crohn's disease (CD) and ulcerative colitis (UC) in cohort 1 (n=1,685) and cohort 2 (n=1,649). At baseline, 155 patients (9.2%) had received steroids within the previous 12 months, 46 (29.7%) of whom had used steroids excessively, 16 (34.8%) of these having inappropriately used excessive steroids. Although steroid exposure was similar in cohort 1 (9.2%) and cohort 2 (9.7%), the latter comprised fewer excessive steroid users (20.0% vs. 29.7%). Severe disease was associated with excessive steroid use in cases with UC, but not with CD., Conclusions: Although, overall steroid use was relatively low in South Korean patients with IBD, one-third of steroid users used them excessively, and one-third among these used excessive steroids inappropriately. High disease activity was the main risk factor for excessive steroid use which may potentially be reduced by physician education, especially in cases with UC. Active screening to minimize excessive and inappropriate steroid use through physician education should be considered.

Background/aims: In ulcerative colitis (UC) patients, Escherichia coli Nissle 1917 (EcN) is equivalent to mesalazine for preventing disease relapse; however, evidence of the ability of EcN to increase health-related quality of life or induce remission remains scarce. We investigated the efficacy of EcN as an add-on therapy for UC., Methods: In this multicentre, double-blind, randomised, placebo-controlled study, a total of 133 UC patients were randomly assigned to receive either EcN or placebo once daily for 8 weeks. Inflammatory bowel disease questionnaire (IBDQ) scores (primary endpoint) and clinical remission and response rates (secondary endpoints) were compared (Clinical trial registration number: NCT04969679)., Results: In total, 118 patients (EcN, 58; placebo, 60) completed the study. The number of patients reaching the primary endpoint did not differ between the EcN and placebo groups (30 [51.7%] vs. 31 [51.7%]; per-protocol analysis, p = 1.0; intention-to-treat analysis, p = 0.86). However, significantly fewer patients in the EcN group exhibited a decreased IBDQ score (1 [1.7%] vs. 8 [13.3%]; per-protocol analysis, p = 0.03; intention- to-treat analysis, p = 0.02). Moreover, a significantly higher number of patients in the EcN group displayed clinical response at 4 weeks (23 [39.7%] vs. 13 [21.7%], p = 0.04) and endoscopic remission at 8 weeks (26 [46.4%] vs. 16 [27.1%], p = 0.03)., Conclusion: Although the number of patients reaching the primary endpoint did not differ between the EcN and placebo groups, EcN was found to be safe and effective in preventing the exacerbation of IBDQ scores and achieving clinical responses and endoscopic remission in patients with mild-to-moderate UC.

Background: Current guidelines recommend continuing aspirin and discontinuing clopidogrel for colon polypectomy, but evidence for endoscopic mucosal resection (EMR) is insufficient. We aimed to assess post-polypectomy bleeding (PPB) in patients receiving antiplatelet agents and underwent EMR for various polyp sizes., Methods: A single-center, prospective observational study was performed. Patients who underwent at least one EMR for polypectomy and those who received aspirin or clopidogrel were included. We compared PPB between the antiplatelet hold group (stopped antiplatelet therapy at least 5 days before the procedure) and continue group (antiplatelet therapy was maintained or stopped within 5 days before the procedure)., Results: Among patients who underwent EMR, 305 took aspirin (hold group 257, continue group 48) and 77 took clopidogrel (hold group 66, continue group 11). The mean number of polyps was four, and the mean size was 8.6 mm. There was no difference in the major PPB rate between the hold and continue groups among aspirin users (2.0% vs. 4.2%, P = 0.30), but it was significantly higher in the continue group than in the hold group among clopidogrel users (18.2% vs. 0%, P = 0.02). In patient- and polyp-based logistic regression analysis of clopidogrel users, the number of EMRs (OR 2.12, 95% CI 1.16-3.88), polyp size (OR 1.26, 95% CI 1.06-1.49), and continuing clopidogrel (OR 9.75, 95% CI 1.99-47.64) were independent risk factors for PPB., Conclusion: Continuous administration of antiplatelet agents was significantly associated with higher PPB in clopidogrel users, but not in aspirin users. Endoscopists should consider holding clopidogrel if the EMR includes polypectomy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to elucidate common and unique microbiome patterns in saliva, intestinal tissue biopsy, and stool samples from patients with Crohn's disease (CD). Saliva, tissue, and stool samples from patients with CD were prospectively collected. Quantitative and phylogenetic analyses of 16s rRNA sequencing data were performed with bioinformatical pipelines. A total of 30 patients were enrolled in this study. The composition of major microbial taxa was similar between tissue and stool samples. A total of 11 of the 20 most abundant microbiota were found in both samples. The microbial community in saliva was significantly distinct from that in tissue and stool. The major species of microbiota and their composition also differed significantly from those of tissue and stool samples. However, Streptococcus and Prevotella are common genera in saliva, tissue, and stool microbiome. The abundance of Streptococcus , Pantoea , and Actinomyces from the saliva sample group were significantly different, varying with the location of the inflammation. Saliva has a distinct microbial community compared with tissues and stools in patients with CD. Prevotella and Streptococcus , which are commonly observed in saliva, stool, and tissue, can be considered a potential biomarker related to the diagnosis or prognosis of CD.

Background/aims: This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC)., Methods: A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score., Results: A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients., Conclusions: ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

Almost half of patients show no primary or secondary response to monoclonal anti-tumor necrosis factor α (anti-TNF) antibody treatment for inflammatory bowel disease (IBD). Thus, the exact mechanisms of a non-durable response (NDR) remain inadequately defined. We used our genome-wide genotype data to impute expression values as features in training machine learning models to predict a NDR. Blood samples from various IBD cohorts were used for genotyping with the Korea Biobank Array. A total of 234 patients with Crohn's disease (CD) who received their first anti-TNF therapy were enrolled. The expression profiles of 6294 genes in whole-blood tissue imputed from the genotype data were combined with clinical parameters to train a logistic model to predict the NDR. The top two and three most significant features were genetic features ( DPY19L3 , GSTT1 , and NUCB1 ), not clinical features. The logistic regression of the NDR vs. DR status in our cohort by the imputed expression levels showed that the β coefficients were positive for DPY19L3 and GSTT1 , and negative for NUCB1 , concordant with the known eQTL information. Machine learning models using imputed gene expression features effectively predicted NDR to anti-TNF agents in patients with CD.

Background/aims: Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC., Methods: A multicenter, hospital-based, prospective study was performed using a Moderate-to-Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later., Results: In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p<0.01). Inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate also showed a negative correlation on HRQL (p<0.05). Patients whose IBDQ score improved by 16 or more (71.2%) in 1 year were younger, tended to be nonsmokers, and had a lower partial Mayo score and CRP than those whose IBDQ score did not. There was no significant association between HRQL and disease extent, treatments at diagnosis, or the highest treatment step during the 1-year period., Conclusions: Optimally controlled disease status improves HRQL in patients with moderate-to-severe UC. The partial Mayo score and inflammatory markers may be potential indicators reflecting the influence of UC on patient`s daily lives.

Background/aims: Complementary and alternative medicine (CAM) is prevalent in East Asia. However, information on CAM in East Asian patients with inflammatory bowel disease (IBD) is scarce. We aimed to profile the prevalence and pattern of CAM use among East Asian IBD patients and to identify factors associated with CAM use. We also compared physicians' perspectives on CAM., Methods: Patients with IBD from China, Japan, and South Korea were invited to complete questionnaires on CAM use. Patient demographic and clinical data were collected. Logistic regression analysis was applied for predictors of CAM use. Physicians from each country were asked about their opinion on CAM services or products., Results: Overall, 905 patients with IBD participated in this study (China 232, Japan 255, and South Korea 418). Approximately 8.6% of patients with IBD used CAM services for their disease, while 29.7% of patients sought at least 1 kind of CAM product. Current active disease and Chinese or South Korean nationality over Japanese were independent predictors of CAM use. Chinese doctors were more likely to consider CAM helpful for patients with IBD than were Japanese and South Korean doctors., Conclusions: In 8.6% and 29.7% of East Asian patients with IBD used CAM services and products, respectively, which does not differ from the prevalence in their Western counterparts. There is a significant gap regarding CAM usage among different Asian countries, not only from the patients' perspective but also from the physicians' point of view.

Background: Current post-polypectomy guidelines do not consider adenoma location. We compared the risk of metachronous colorectal neoplasia (CRN) according to adenoma location., Methods: We collected data from 9710 patients who underwent follow-up colonoscopy after adenoma removal. Patients were classified according to baseline adenoma location: distal only (n=4665), proximal only (n=3827), and both sides (n=1218)., Results: The risk of metachronous CRN in patients with proximal only adenomas was higher than that in those with distal only adenomas (adjusted hazard ratio [aHR]=1.12, 95% confidence interval [CI]=1.04-1.21), while the risk of metachronous advanced CRN (ACRN) was not different between the two groups. Among patients aged <50 years, the risk of metachronous CRN in those with proximal only non-advanced adenomas (NAAs) was higher than that in those with only distal NAAs, while among patients aged ≥ 50 years, the risk in those with proximal only advanced adenomas (AAs) was higher than that in those with distal only AAs. However, the risk of metachronous ACRN did not differ based on adenoma location in patients aged < 50 and ≥ 50 years., Conclusions: Proximal adenoma was associated with an increased risk of metachronous CRN, but not with an increased risk of metachronous ACRN, supporting the current guidelines recommending the same surveillance interval for distal and proximal adenoma without discrimination by adenoma location., (Copyright © 2021. Published by Elsevier Ltd.)

Background: This pilot study aimed to investigate the current status of e-cigarettes (ECs) use patterns among patients with chronic airway disease or chronic respiratory symptoms and the effects of ECs use on respiratory and mental health., Methods: A cross-sectional survey was conducted at the outpatient clinic of eight teaching hospitals in South Korea between November 2019 and December 2019. All adult ECs users (19 years and above) who visited the outpatient clinic as a patient with chronic airway disease or chronic respiratory symptoms were eligible to participate in this study., Results: A total of 51 subjects responded to the survey. Most of the participants were male (92.2%) and the mean age was 41.8 years. Dominant airway diseases were asthma and chronic obstructive pulmonary disease. Most of the subjects had a history of cigarette smoking, and 19 subjects were dual users of current cigarettes and ECs. Most of the subjects started ECs use due to health-related reasons. When comparing exclusive ECs users and dual users, St. George's respiratory questionnaire (SGRQ) scores, the proportion of cases with moderate to severe depressive symptoms, and average Fagerstrom test for nicotine dependence scores for ECs were higher in dual users than exclusive ECs users (mean 4.64 vs. 2.38, p = 0.006), respectively., Conclusion: Most of the subjects started ECs use due to health concerns, but dual users have more respiratory symptoms and higher nicotine dependence in this pilot study. One hypothesis that comes from these results is that greater nicotine dependence may influence behaviours, habits, and views about ECs. These preliminary observations need confirmation in a large cohort., (© 2021 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Recent strategies in cancer immunotherapy based on interleukin-2 (IL-2) are generally focused on reducing regulatory T cell (Treg) development by modifying IL-2 receptor alpha (IL-2Rα) domain. However, the clinical utility of high-dose IL-2 treatment is mainly limited by severe systemic toxicity. We find that peritumorally injectable 'BALLkine-2', recombinant human IL-2 (rIL-2) loaded porous nanoparticle, dramatically reduces systemic side effects of rIL-2 by minimizing systemic IL-2 exposure. Notably, in cynomolgus monkeys, subcutaneous (SC)-injection of BALLkine-2 not only dramatically reduces systemic circulation of rIL-2 in the blood, but also increases half-life of IL-2 compared to IV- or SC-injection of free rIL-2. Peritumorally-injected BALLkine-2 enhances intratumoral lymphocyte infiltration without inducing Treg development and more effectively synergizes with PD-1 blockade than high-dose rIL-2 administration in B16F10 melanoma model. BALLkine-2 could be a highly potent therapeutic option due to higher anti-tumor efficacy with lower and fewer doses and reduced systemic toxicity compared to systemic rIL-2., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Crohn's disease (CD) and ulcerative colitis (UC) can be difficult to differentiate. As differential diagnosis is important in establishing a long-term treatment plan for patients, we aimed to develop a machine learning model for the differential diagnosis of the two diseases using RNA sequencing (RNA-seq) data from endoscopic biopsy tissue from patients with inflammatory bowel disease ( n = 127; CD, 94; UC, 33). Biopsy samples were taken from inflammatory lesions or normal tissues. The RNA-seq dataset was processed via mapping to the human reference genome (GRCh38) and quantifying the corresponding gene models that comprised 19,596 protein-coding genes. An unsupervised learning model showed distinct clusters of four classes: CD inflammatory, CD normal, UC inflammatory, and UC normal. A supervised learning model based on partial least squares discriminant analysis was able to distinguish inflammatory CD from inflammatory UC after pruning the strong classifiers of normal CD vs. normal UC. The error rate was minimal and affected only two components: 20 and 50 genes for the first and second components, respectively. The corresponding overall error rate was 0.147. RNA-seq analysis of tissue and the two components revealed in this study may be helpful for distinguishing CD from UC.

Background: We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed., Methods: Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn's Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission., Results: Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event., Conclusions: Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although the prevalence and incidence of bronchiectasis are rising worldwide, basic epidemiologic data have not been reported in Korea. Therefore, this study was conducted to investigate epidemiological characteristics of bronchiectasis and NTM (nontuberculous mycobacteria) pulmonary diseases in Korea using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) data. The relative risks of prevalence and incidence after adjusting for demographic characteristics were evaluated by multivariate Poisson regression. The result of this study showed the prevalence and incidence rates of bronchiectasis and NTM to be epidemiologically similar to each other with a few slight differences, while the prevalence rate of bronchiectasis was not significantly different by gender, and its incidence rate was significantly lower in women than in men. Both the prevalence and incidence of NTM were significantly higher in women than in men. Both the prevalence and incidence rates of bronchiectasis and NTM were significantly lower in the age group below 40-49 years, and significantly higher in the age groups thereafter. As there were gender differences of bronchiectasis and NTM, gender-sensitive risk management should be available. In addition, since both bronchiectasis and NTM increase in prevalence and incidence after the age of 40-49, early detection and intervention strategies targeting the appropriate age group are needed.

Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alterations induced by fluoxetine treatment. Two-year fluoxetine administration to juvenile macaques revealed effects on impulsivity, sleep, social interaction, and peripheral metabolites. Here, we built upon this work by assessing residual effects of fluoxetine administration on the expression of genes and abundance of lipids and polar metabolites in the prelimbic cortex of 10 treated and 11 control macaques representing two monoamine oxidase A ( MAOA ) genotypes. Analysis of 8871 mRNA transcripts, 3608 lipids, and 1829 polar metabolites revealed substantial alterations of the brain lipid content, including significant abundance changes of 106 lipid features, accompanied by subtle changes in gene expression. Lipid alterations in the drug-treated animals were most evident for polyunsaturated fatty acids (PUFAs). A decrease in PUFAs levels was observed in all quantified lipid classes excluding sphingolipids, which do not usually contain PUFAs, suggesting systemic changes in fatty acid metabolism. Furthermore, the residual effect of the drug on lipid abundances was more pronounced in macaques carrying the MAOA-L genotype, mirroring reported behavioral effects of the treatment. We speculate that a decrease in PUFAs may be associated with adverse effects in depressive patients and could potentially account for the variation in individual response to fluoxetine in young people.

Given its highly contagious nature and an absence of a specific antiviral agent to this date, the key to controlling the spread of coronavirus disease 2019 (COVID-19) and decreasing the infection rate is adherence to preventive measures. It is essential to understand an individual's knowledge, attitudes and practices toward COVID-19 since public adherence to health guidelines relies heavily on these aspects. However, there is no validated instrument that evaluates knowledge, attitudes and practices toward COVID-19. Thus, this study aimed to develop and validate such tool. A questionnaire was developed based on international and national guidelines and a review of the literature. Initial items were evaluated by 10 experts to determine content validity. Exploratory factor analysis and reliability testing were conducted with a convenience sample of 229 nursing students. Based on the content, face validity and factor analysis, 34 items were selected. The Kaiser-Meyer-Olkin value of 0.735 indicated a highly acceptable score with a significant Bartlett's test of sphericity ( p < 0.0001). The internal consistency coefficients indicated acceptable reliability of the tool (Cronbach's α = 0.75). The KAP COVID-19 is a valid instrument that can be used to evaluate knowledge, attitudes and practices toward COVID-19.

Aim: This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea., Methods: A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method., Results: A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% ( n  = 43/77) achieved a clinical response and 18.2% ( n  = 14/77) achieved clinical remission. At week 14, 73.2% ( n  = 52/71) achieved a clinical response and 39.4% ( n  = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% ( n  = 43/105) and 49.5% ( n  = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p  = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p  = 0.785)., Conclusions: In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations., Competing Interests: Conflict of interest statement: BDY reported receiving research grants from Celltrion, Inc. and Pfizer Korea, and lecture and/or consulting fees from Abbvie Korea, Daewoong Pharma., Ferring Korea, Janssen Korea, Kangstem Biotech, LG Chem., Shire Korea, Takeda Korea, IQVIA, Takeda, Celltrion, Inc., Chong Kun Dang Pharm., Medtronic Korea, and Pfizer Korea, outside of the submitted work. KHS reported receiving lecture fees from Eisai Korea, Celltrion, Inc., and Janssen Korea, outside the submitted work. YHK reported receiving personal fees from Takeda outside the submitted work. KML reported receiving lecture and/or consulting fees from Jassen, Takeda, and Celtrion, outside the submitted work. DWL is an employee of Takeda Korea at the time of this manuscript writing. CYF is an employee of IQVIA Real World Insights at the time of this manuscript writing. IQVIA has supported Takeda and all the clinician investigators in the design, execution, data management and the development of this manuscript. All other co-authors have nothing to disclose., (© The Author(s), 2021.)

Background/aims: Infliximab (IFX) has proven effective as rescue therapy in steroid-refractory acute severe ulcerative colitis (ASUC), however, the long-term real-world data are scarce. Our study aimed to assess the long-term treatment outcomes of IFX in a real-life cohort., Methods: We established a multicenter retrospective cohort of hospitalized patients with ASUC, who met Truelove and Witt's criteria and received intravenous corticosteroid (IVCS) or IFX during index hospitalization between 2006 and 2016 in 5 university hospitals in Korea. The cohort was systematically followed up until colectomy, death or last follow-up visit., Results: A total of 296 patients were followed up for a mean of 68.9 ± 44.0 months. During index hospitalization, 49 patients were treated with IFX; as rescue therapy for IVCS failure in 37 and as first-line medical therapy for ASUC in 12. All patients treated with IFX avoided colectomy during index hospitalization. The cumulative rates of rehospitalization and colectomy were 20.4% and 6.1% at 3 months and 39.6% and 18.8% at the end of follow-up, respectively. Patients treated with IFX presented with significantly shorter colectomy-free survival than IVCS responders (P= 0.04, log-rank test). Both cytomegalovirus colitis and Clostridioides difficile infection (CDI) were the significant predictors of colectomy in the overall study cohort (hazard ratios of 6.57 and 4.61, respectively). There were no fatalities., Conclusions: Our real-world cohort study demonstrated that IFX is an effective therapeutic option in Korean patients with ASUC, irrespective of IFX indication. Aggressive vigilance for cytomegalovirus colitis and CDI is warranted for hospitalized patients with ASUC.

Background & Aims: Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19., Methods: We collected data from 46 patients (median age, 26 y; 46% men) with asymptomatic or mild COVID-19 (without fever and pneumonia) and prolonged respiratory shedding of SARS-CoV-2, quarantined from April 4, 2020, through April 24, 2020, in Korea. Respiratory specimens included upper respiratory specimens (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum), and were collected twice per week. The median interval between COVID-19 diagnosis to the start of fecal sample collection was 37 days (range, 29-41 d); 213 stool specimens were collected from 46 patients. We used real-time reverse-transcription polymerase chain reaction to detect SARS-CoV-2 in the respiratory and fecal specimens., Results: Gastrointestinal manifestations were observed in 16 of the 46 patients (35%); diarrhea was the most common (15%), followed by abdominal pain (11%), dyspepsia (11%), and nausea (2%). Virus RNA was detected in feces from 2 patients without gastrointestinal symptoms (4%). Mean cycle threshold values from the time of quarantine to the time of fecal collection tended to be lower in patients with virus detected in fecal samples than in patients without virus in fecal samples (29.91 vs 33.67 in the first week, 29.47 vs 35.71 in the fifth week, respectively). Shedding of virus into feces persisted until day 50 after diagnosis; fecal samples began to test negative before or at approximately the time that respiratory specimens also began to test negative., Conclusions: In an analysis of fecal and respiratory specimens from patients with COVID-19 in quarantine in Korea, we found that the gastrointestinal tract could be a route of transmission of SARS-CoV-2 even in patients with asymptomatic or mild disease, with no gastrointestinal symptoms. The viral load of the respiratory specimens appears be related to shedding of the virus into feces in this group of patients., (Copyright © 2021. Published by Elsevier Inc.)

Background/aims: We aimed to develop a deep learning model for the prediction of the risk of advanced colorectal neoplasia (ACRN) in asymptomatic adults, based on which colorectal cancer screening could be customized., Methods: We collected data on 26 clinical and laboratory parameters, including age, sex, smoking status, body mass index, complete blood count, blood chemistry, and tumor marker, from 70,336 first-time colonoscopy screening recipients. For reference, we used a logistic regression (LR) model with nine variables manually selected from the 26 variables. A deep neural network (DNN) model was developed using all 26 variables. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of the models were compared in a randomly split validation group., Results: In comparison with the LR model (AUC, 0.724; 95% confidence interval [CI], 0.684 to 0.765), the DNN model (AUC, 0.760; 95% CI, 0.724 to 0.795) demonstrated significantly improved performance with respect to the prediction of ACRN (p < 0.001). At a sensitivity of 90%, the specificity significantly increased with the application of the DNN model (41.0%) in comparison with the LR model (26.5%) (p < 0.001), indicating that the colonoscopy workload required to detect the same number of ACRNs could be reduced by 20%., Conclusion: The application of DNN to big clinical data could significantly improve the prediction of ACRNs in comparison with the LR model, potentially realizing further customization by utilizing large quantities and various types of biomedical information.