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Abstract A-kinase anchoring protein 12 (AKAP12) is a key scaffolding protein that regulates cellular signaling by anchoring protein kinase A (PKA) and other signaling molecules. While recent studies suggest an important role for AKAP12 in the brain, including cognitive functions, its role in middle-aged mice and potential sex differences are not fully understood. Therefore, this study investigated the effects of AKAP12 on cognitive and exploratory behavior in middle-aged mice, focusing on sex differences. Cognitive function was assessed using the spontaneous Y-maze test and the novel object recognition test (NORT). No significant sex differences in cognitive function were found in middle-aged C57BL/6J mice; however, female mice showed greater exploratory behavior during the NORT. In addition, both middle-aged male and female Akap12 knockout (KO) mice performed similarly to wild-type (WT) mice in the Y-maze test, but had lower discrimination indices in the NORT, suggesting a potential role for AKAP12 in short-term memory. Notably, exploratory behavior was suppressed in female Akap12 KO mice compared to WT mice, whereas male Akap12 KO mice did not show this effect. There were no significant differences in movement distance and velocity during the Y-maze test and NORT between WT and KO mice of either sex. These results indicate that AKAP12 affects cognitive function and exploratory behavior in middle-aged mice and that these effects differ between sexes.

Background/Aims: The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor β (TGF-β), interleukin (IL)-1β, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: The messenger RNA expressions of TGF-β, IL-1β, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-β, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-β, IL-1β, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions: Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions (ClinicalTrials.gov, NCT05653011).

Abstract This study evaluates the diagnostic efficacy of automated machine learning (AutoGluon) with automated feature engineering and selection (autofeat), focusing on clinical manifestations, and a model integrating both clinical manifestations and CT findings in adult patients with ambiguous computed tomography (CT) results for acute appendicitis (AA). This evaluation was compared with conventional single machine learning models such as logistic regression(LR) and established scoring systems such as the Adult Appendicitis Score(AAS) to address the gap in diagnostic approaches for uncertain AA cases. In this retrospective analysis of 303 adult patients with indeterminate CT findings, the cohort was divided into appendicitis (n = 115) and non-appendicitis (n = 188) groups. AutoGluon and autofeat were used for AA prediction. The AutoGluon-clinical model relied solely on clinical data, whereas the AutoGluon-clinical-CT model included both clinical and CT data. The area under the receiver operating characteristic curve (AUROC) and other metrics for the test dataset, namely accuracy, sensitivity, specificity, PPV, NPV, and F1 score, were used to compare AutoGluon models with single machine learning models and the AAS. The single ML models in this study were LR, LASSO regression, ridge regression, support vector machine, decision tree, random forest, and extreme gradient boosting. Feature importance values were extracted using the “feature_importance” attribute from AutoGluon. The AutoGluon-clinical model demonstrated an AUROC of 0.785 (95% CI 0.691–0.890), and the ridge regression model with only clinical data revealed an AUROC of 0.755 (95% CI 0.649–0.861). The AutoGluon-clinical-CT model (AUROC 0.886 with 95% CI 0.820–0.951) performed better than the ridge model using clinical and CT data (AUROC 0.852 with 95% CI 0.774–0.930, p = 0.029). A new feature, exp(-(duration from pain to CT)3 + rebound tenderness), was identified (importance = 0.049, p = 0.001). AutoML (AutoGluon) and autoFE (autofeat) enhanced the diagnosis of uncertain AA cases, particularly when combining CT and clinical findings. This study suggests the potential of integrating AutoML and autoFE in clinical settings to improve diagnostic strategies and patient outcomes and make more efficient use of healthcare resources. Moreover, this research supports further exploration of machine learning in diagnostic processes.

Abstract Background Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive. Methods In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. Results We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy. Conclusions Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

A-kinase anchor protein 12 (AKAP12), a scaffold protein, has been implicated in the central nervous system, including blood-brain barrier (BBB) function. Although its expression level in the corpus callosum is higher than in other brain regions, such as the cerebral cortex, the role of AKAP12 in the corpus callosum remains unclear. In this study, we investigate the impact of AKAP12 deficiency by transcriptome analysis using RNA-sequencing (RNA-seq) on the corpus callosum of AKAP12 knockout (KO) mice. We observed minimal changes, with only 13 genes showing differential expression, including Akap12 itself. Notably, Klf2 and Sgk1 , genes potentially involved in BBB function, were downregulated in AKAP12 KO mice and expressed in vascular cells similar to Akap12 . These changes in gene expression may affect important biological pathways that may be associated with neurological disorders. Our findings provide an additional data set for future research on the role of AKAP12 in the central nervous system.

Background Bipolar disorder, a chronic mental health condition characterised by fluctuations in mood, energy and functionality, affects millions of individuals worldwide. Its management requires a comprehensive approach, and, as such, treatment guidelines have a pivotal role in guiding clinicians to alleviate symptoms, prevent relapse and enhance overall patient well-being. However, the treatment landscape is far from homogenous, with significant variations existing across different countries. Aims This study aimed to explore and compare treatment guidelines for bipolar disorder in various regions, shedding light on the factors that influence therapeutic approaches and thus offering insights that could contribute to the ongoing refinement of evidence-based practices in management. Method The study explores various international treatment guidelines for bipolar disorder that have been updated after 2014. Guidelines from the UK, Canada, Australia/New Zealand, South Korea and the International College of Neuropsychopharmacology are scrutinised to identify factors contributing to the observed differences among them. Results The variations in recommended drugs across guidelines arise from the approaches employed in guideline development – whether relying on expert consensus or meta-analysis results. Timing disparities in conducting these analyses and the selection of studies also exert influence. Moreover, differences in metabolic enzymes among diverse races and the health policies implemented by individual nations play a significant part in shaping these differences. Conclusion The primary hindrance to consistent treatment conclusions lies in the scarcity of high-quality research results, leading to variations in guidelines. Enhancing evidence-based recommendations necessitates the undertaking of large-scale studies dedicated to assessing treatments for bipolar disorder.

Abstract Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer. This study aims to investigate genomic and clinicopathological characteristics of EBVaGC according to the histological pattern. We retrospectively collected 18 specimens of surgically resected EBVaGCs. Whole-exome sequencing was performed for all cases. Moreover, PD-L1 expression and tumor-infiltrating lymphocyte (TIL) percentage were investigated. Among 18 EBVaGCs, 10 cases were of intestinal histology, 3 were of poorly cohesive histology, and the remaining 5 were of gastric carcinoma with lymphoid stroma histology. Whole-exome sequencing revealed that EBVaGCs with intestinal histology harbored pathogenic mutations known to frequently occur in tubular or papillary adenocarcinoma, including TP53, KRAS, FBXW7, MUC6, ERBB2, CTNNB1, and ERBB2 amplifications. One patient with poorly cohesive carcinoma histology harbored a CDH1 mutation. Patients with EBVaGCs with intestinal or poorly cohesive carcinoma histology frequently harbored driver mutations other than PIK3CA, whereas those with EBVaGCs with gastric carcinoma with lymphoid stroma histology lacked other driver mutations. Moreover, the histological pattern of EBVaGCs was significantly associated with the levels of TILs (P = 0.005) and combined positive score (P = 0.027). In conclusion, patients with EBVaGCs with different histological patterns exhibited distinct genetic alteration, PD-L1 expression, and degree of TILs.

Abstract Background Transplantation of mitochondria is increasingly explored as a novel therapy in central nervous system (CNS) injury and disease. However, there are limitations in safety and efficacy because mitochondria are vulnerable in extracellular environments and damaged mitochondria can induce unfavorable danger signals. Methods Mitochondrial O-GlcNAc-modification was amplified by recombinant O-GlcNAc transferase (OGT) and UDP-GlcNAc. O-GlcNAcylated mitochondrial proteins were identified by mass spectrometry and the antiglycation ability of O-GlcNAcylated DJ1 was determined by loss-of-function via mutagenesis. Therapeutic efficacy of O-GlcNAcylated mitochondria was assessed in a mouse model of transient focal cerebral ischemia-reperfusion. To explore translational potential, we evaluated O-GlcNAcylated DJ1 in CSF collected from patients with subarachnoid hemorrhagic stroke (SAH). Results We show that isolated mitochondria are susceptible to advanced glycation end product (AGE) modification, and these glycated mitochondria induce the receptor for advanced glycation end product (RAGE)-mediated autophagy and oxidative stress when transferred into neurons. However, modifying mitochondria with O-GlcNAcylation counteracts glycation, diminishes RAGE-mediated effects, and improves viability of mitochondria recipient neurons. In a mouse model of stroke, treatment with extracellular mitochondria modified by O-GlcNAcylation reduces neuronal injury and improves neurologic deficits. In cerebrospinal fluid (CSF) samples from SAH patients, levels of O-GlcNAcylation in extracellular mitochondria correlate with better clinical outcomes. Conclusions These findings suggest that AGE-modification in extracellular mitochondria may induce danger signals, but O-GlcNAcylation can prevent glycation and improve the therapeutic efficacy of transplanted mitochondria in the CNS.

Background Severe burns cause pathophysiological processes that result in mortality. A laboratory biomarker, red cell distribution width (RDW), is known as a predictor of mortality in critically-ill patients. We examined the association between RDW and postoperative mortality in severe burn patients. Methods We retrospectively analyzed medical data of 731 severely burned patients who underwent surgery under general anesthesia. We evaluated whether preoperative RDW value can predict 3-month mortality after burn surgery using receiver operating characteristic (ROC) curve analysis, logistic regression, and Cox proportional-hazards regression analysis. Mortality was also analyzed according to preoperative RDW values and incidence of postoperative acute kidney injury (AKI). Results The 3-month mortality rate after burn surgery was 27.1% (198/731). The area under the ROC curve of preoperative RDW to predict mortality after burn surgery was 0.701 (95% confidence interval [CI], 0.667–0.734; P < 0.001) with a cut-off point of 12.9. The adjusted hazard ratio in patients with RDW > 12.9 was 1.238 (95% CI, 1.138–1.347; P < 0.001). Subgroup analysis showed that the survival rate was 88.8% for the non-AKI group with RDW ≤ 12.9 and 17.6% for the AKI group with RDW > 12.9. Preoperative RDW was considered an independent risk factor for mortality (odds ratio, 1.679; 95% CI, 1.378–2.046; P < 0.001). Conclusions Preoperative RDW may predict 3-month postoperative mortality in patients with severe burns, while preoperative RDW > 12.9 and postoperative AKI may further increase mortality after burn surgery.

Fluxapyroxad, a persistent fungicide in soil, was investigated for differences in residue dissipation in Chinese cabbage and spring scallion through the application methods of soil, foliar, and systemic treatment. Soil application of 0.4% granule fluxapyroxad resulted in residues up to 0.09 mg kg−1 in the scallion, while it did not contribute to the residues in the harvested cabbage. The 50% dissipation time (DT50) of fluxapyroxad in the scallion was 6.8 days. The residues from systemic treatment were highly correlated with foliar application in both the cabbage and the scallion, and the initial residue and DT50 values were similar for foliar and systemic treatments. In comparing the residues from the systemic treatments between the two crops, the initial residue was 3.11 and 0.22 mg kg−1 in the cabbage and the scallion after the systemic treatment, respectively. The DT50 values were 2.6 and 12.2 days in the cabbage and the scallion, respectively. The theoretical dilution effect due to crop growth was higher for the cabbage (4-fold) than for the scallion (1.2-fold), and the half-lives of fluxapyroxad without considering the dilution effect were 6.4 days in the cabbage and 17.8 days in the scallion. Thus, the residue difference was drastically reduced after 14 days from the last treatment.

Abstract Background The deep learning-based nodule detection (DLD) system improves nodule detection performance of observers on chest radiographs (CXRs). However, its performance in different pulmonary nodule (PN) locations remains unknown. Methods We divided the CXR intrathoracic region into non-danger zone (NDZ) and danger zone (DZ). The DZ included the lung apices, paramediastinal areas, and retrodiaphragmatic areas, where nodules could be missed. We used a dataset of 300 CXRs (100 normal and 200 abnormal images with 216 PNs [107 NDZ and 109 DZ nodules]). Eight observers (two thoracic radiologists [TRs], two non-thoracic radiologists [NTRs], and four radiology residents [RRs]) interpreted each radiograph with and without the DLD system. The metric of lesion localization fraction (LLF; the number of correctly localized lesions divided by the total number of true lesions) was used to evaluate the diagnostic performance according to the nodule location. Results The DLD system demonstrated a lower LLF for the detection of DZ nodules (64.2) than that of NDZ nodules (83.2, p = 0.008). For DZ nodule detection, the LLF of the DLD system (64.2) was lower than that of TRs (81.7, p

Tilia mandshurica trees with rust symptoms have consistently been noticed during disease surveys in Korea since 2006. Based on the morphological examination and molecular sequence analysis of the internal transcribed spacer and large subunit of ribosomal DNA, Pucciniastrum tiliae was identified as the causal fungus of rust disease. This is the first report of P. tiliae infection on T. mandshurica in Korea.

In Korea, Cornus controversa and C. florida are known as hosts of Erysiphe pulchra from section Microspharea of the genus Erysiphe. However, recent molecular-phylogenetic analyses on the internal transcribed spacer regions and large subunit gene of the rDNA revealed that the Erysiphe powdery mildew on C. controversa in Japan is in fact E. cornicola. To assess the taxonomic status of Erysiphe–C. controversa association in Korea, isolates collected since 1987 were investigated and consequently identified as E. cornicola based on molecular–phylogenetic analyses and new morphological traits. To our knowledge, this is the first study to confirm the presence of this powdery mildew in Korea.

Abstract Background Remimazolam is a new anesthetic drug developed and is an ultra-short-acting agent with rapid onset and offset. The pharmacology of this drug seems to be ideal for short surgeries eligible for I-gel insertion. Therefore, this study aimed to determine the optimal bolus dose of remimazolam for I-gel insertion when co-administered with remifentanil without neuromuscular blocking agents (NMBAs). Methods Patients aged 19–65 years with American Society of Anesthesiologists physical status I or II scheduled for general anesthesia were enrolled. The first dose of remimazolam was 0.15 mg/kg and remifentanil was co-administered at an effect-site concentration (Ce) of 3.0 ng/mL. The dose of remimazolam for the following patient was decreased or increased by 0.05 mg/kg depending on the success or failure of I-gel insertion in the previous patient. Results The remimazolam bolus dose required for successful I-gel insertion in 50% of adult patients using modified Dixon’s up-and-down method with remifentanil Ce 3.0 ng/mL and no NMBAs was 0.280 ± 0.048 mg/kg. Isotonic regression analysis showed that the 50% and 95% effective doses were 0.244 (83% confidence interval [CI] 0.213–0.313) mg/kg and 0.444 (95% CI 0.436–0.448) mg/kg, respectively. The mean time to loss of consciousness (Modified Observer’s Assessment of Alertness/Sedation score

Abstract Background Despite the dynamic treatment landscape for EGFR mutant-positive metastatic non-small cell lung cancer (EGFRm+ mNSCLC), most of the earlier studies have focused on US or Western populations. Objective The objective of this study was to explore real-world treatment patterns and outcomes of South Korean patients with EGFRm+ mNSCLC. Methods Retrospective chart review of adult patients with EGFRm+ mNSCLC who received systemic treatment between January-2019 and June-2019. Results A total of 162 patients were included from 21 hospitals, with a median follow-up of 15.6 months. Median age was 65.0 years, 22% had central nervous system metastasis, and 57% and 38% had exon 19 deletion and exon 21 L858R, respectively. Among 144 patients (89%) who received first-line EGFR-tyrosine kinase inhibitor, afatinib was most the common (44%), followed by gefitinib (28%) and erlotinib (13%). First-line chemotherapy was more common when an EGFR-mutation was detected after versus before first-line treatment initiation (31% vs 5%). Discontinuation of first-line treatment was mostly due to disease-progression (81%) and toxicity (7%). Among 58 (78%) patients who received second-line treatment, osimertinib was the most common (40%). Most (60%) patients reported ≥1 Grade ≥3 adverse event during first-line treatment. Following initiation of first-line treatment, physician visits and chest X-rays were the most frequent healthcare utilisation events. Rates of emergency-room visits and hospitalization were 12% and 16%, respectively, with a mean length-of-stay of 10.4 days. At 12 months, overall survival rate was 95%, and numerically worse for patients with exon 21 versus 19 mutations. Conclusions Characteristics and clinical outcomes of Korean patients with EGFRm+ mNSCLC in real-world practice were comparable to those observed in clinical trials. As osimertinib was not reimbursed for first-line treatment before study completion, further investigation is warranted to explore evolving treatment practice.

Background Remimazolam is a new ultra short-acting benzodiazepine originally developed as an improved version of midazolam. Recent studies have demonstrated non-inferiority of remimazolam to propofol in general anesthesia. However, to date, few studies have investigated the induction bolus dose of remimazolam required to achieve general anesthesia. We aimed to determine the 95% effective dose (ED95) of remimazolam bolus required to achieve loss of consciousness (LOC) and the appropriate doses for different age groups. Methods Patients aged 20–79 years with the American Society of Anesthesiologists physical status of I or II were enrolled in this study. A total of 120 patients were included representing young, middle-aged, and elderly groups. Loss of eyelash reflex and verbal response after the administration of remimazolam was considered successful LOC. The ED95 of remimazolam was determined using a biased coin up-and-down design with sequential allocation and the isotonic regression method. Results The ED95 of remimazolam for induction of general anesthesia was 0.367 mg/kg (95% CI [0.277, 0.392]) in the young group, 0.369 mg/kg (95% CI [0.266, 0.394]) in the middle-aged group, and 0.249 mg/kg (95% CI [0.199, 0.288]) in the elderly group. During the study period, none of the patients required rescue medications for hypotension or bradycardia. Conclusions This study investigated the ED95 of remimazolam bolus for anesthesia induction. The precise dosing of the ED95 can help maintain hemodynamic stability during the induction of anesthesia.

Abstract Early diagnosis and treatment are critical for improving the survival of patients with lung cancer, which is the leading cause of cancer-related deaths worldwide. In this study, we investigated whether the metabolomics analysis of exhaled breath condensate (EBC) from patients with lung cancer can provide biomarkers that can be used for noninvasive screening for lung cancer diagnosis. EBC samples obtained from patients with lung cancer (n = 20) and healthy individuals (n = 5) were subjected to high-resolution metabolomics (HRM) using liquid chromatography–mass spectrometry (LC–MS). Univariate analysis, with a false discovery rate (FDR), q = 0.05, and hierarchical clustering analysis were performed to discover significantly different metabolites between the healthy controls and patients with lung cancer. This was followed by the identification of the metabolites using the METLIN database. Pathway analysis based on the identified metabolites revealed that arachidonic acid (AA) metabolism was the most significantly affected pathway. Finally, 5-hydroxyicosatetraenoic acid (HETE) (m/z 343.2233, [M + Na]+), a metabolite involved in AA metabolism, was found to be significantly higher in patients with lung cancer than in healthy counterparts. Our finding suggested that the HRM of EBC samples is a useful approach for identifying biomarkers for noninvasive screening for lung cancer diagnosis.

Some insertion sequence (IS) elements were actively transposed using oxidative stress conditions, including gamma irradiation and hydrogen peroxide treatment, in Deinococcus geothermalis, a radiation-resistant bacterium. D. geothermalis wild-type (WT), sigma factor gene-disrupted (∆dgeo_0606), and LysR gene-disrupted (∆dgeo_1692) mutants were examined for IS induction that resulted in non-pigmented colonies after gamma irradiation (5 kGy) exposure. The loss of pigmentation occurred because dgeo_0524, which encodes a phytoene desaturase in the carotenoid pathway, was disrupted by the transposition of IS elements. The types and loci of the IS elements were identified as ISDge2 and ISDge6 in the ∆dgeo_0606 mutant and ISDge5 and ISDge7 in the ∆dgeo_1692 mutant, but were not identified in the WT strain. Furthermore, 80 and 100 mM H2O2 treatments induced different transpositions of IS elements in ∆dgeo_0606 (ISDge5, ISDge6, and ISDge7) and WT (ISDge6). However, no IS transposition was observed in the ∆dgeo_1692 mutant. The complementary strain of the ∆dgeo_0606 mutation showed recovery effects in the viability assay; however, the growth-delayed curve did not return because the neighboring gene dgeo_0607 was overexpressed, probably acting as an anti-sigma factor. The expression levels of certain transposases, recognized as pivotal contributors to IS transposition, did not precisely correlate with active transposition in varying oxidation environments. Nevertheless, these findings suggest that specific IS elements integrated into dgeo_0524 in a target-gene-deficient and oxidation-source-dependent manner.

Abstract In ischemic stroke patients undergoing endovascular treatment (EVT), we aimed to test the hypothesis that cerebral microbleeds (CMBs) are associated with clinical outcomes, while estimating the mediating effects of hemorrhagic transformation (HT), small-vessel disease burden (white matter hyperintensities, WMH), and procedural success. From a multicenter EVT registry, patients who underwent pretreatment MR imaging were analyzed. They were trichotomized according to presence of CMBs (none vs. 1–4 vs. ≥ 5). The association between CMB burden and 3-month mRS was evaluated using multivariable ordinal logistic regression, and mediation analyses were conducted to estimate percent mediation. Of 577 patients, CMBs were present in 91 (15.8%); 67 (11.6%) had 1–4 CMBs, and 24 (4.2%) had ≥ 5. Increases in CMBs were associated with hemorrhagic complications (β = 0.27 [0.06–0.047], p = 0.010) in multivariable analysis. The CMB effect on outcome was partially mediated by post-procedural HT degree (percent mediation, 14% [0–42]), WMH (23% [7–57]) and lower rates of successful reperfusion (6% [0–25]). In conclusion, the influence of CMBs on clinical outcomes is mediated by small-vessel disease burden, post-procedural HT, and lower reperfusion rates, listed in order of percent mediation size.

Collybiopsis is a genus of the gymnopoid/marasmioid complex of the family Omphalotaceae. The classification system of Collybiopsis has recently undergone large changes through molecular approaches. The new classification system has not been applied for Collybiopsis in the Republic of Korea, and general research on this genus was also lacking. In this study, we analyzed the Collybiopsis species in the Republic of Korea by assessing all gymnopoid/marasmioid specimens collected nationwide for ten years by combining morphological approaches and multilocus (ITS + nrLSU) phylogenetic analysis. We thus confirmed that 16 species of Collybiopsis are present in the Republic of Korea, including two previously unreported species (Co. nonnulla and Co. dichroa) and seven new species (Co. albicantipes sp. nov., Co. clavicystidiata sp. nov., Co. fulva sp. nov., Co. orientisubnuda sp. nov., Co. subumbilicata sp. nov., Co. undulata sp. nov., and Co. vellerea sp. nov.). A thorough examination of the Collybiopsis suggested that it is difficult to distinguish or identify the species based on morphological characteristics only; a combined molecular approach is needed for accurate identification. The Collybiopsis database of the Republic of Korea is updated, and information on the new species is provided. Five new combinations from Marasmiellus to Collybiopsis are also proposed (Co. istanbulensis comb. nov., Co. koreana comb. nov., Co. omphalodes comb. nov., Co. pseudomphalodes comb. nov., and Co. ramuliciola comb. nov.).

Purpose Sphingosine kinase is a lipid kinase that phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). S1P regulates pancreatic islet β-cell endoplasmic reticulum stress and proliferation. Type 1 and type 2 diabetes share some key pathogenic processes. In this study, we investigated whether secretion of insulin and production of S1P is altered in alloxan and glucose-treated cells from the rat pancreatic β-cell line RIN-5F. Methods RIN-5F cells were treated with 2 mM alloxan and 20 mM glucose for 6 hours or 24 hours before being evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting. Results Insulin secretion and expression was higher in RIN-5F cells treated with glucose compared to control cells. In contrast, alloxan treatment did not affect insulin secretion and expression in RIN-5F cells. Interestingly, compared with normal control levels, S1P/EDG-5 was increased in both alloxan and glucose-treated pancreatic β cell than normal control. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibition strongly decreased the expression of insulin and S1P in glucose- or alloxan-treated RIN-5F cells. Conclusions We observe that production of S1P is increased in both diabetic cell models. In addition, MAPK/ERK signaling regulates secretion of insulin and S1P expression in pancreatic β-cells. Based on the literature and our findings, S1P may be a promising agent for the treatment of insulin-related disorders.

Abstract Dupilumab is a dual inhibitor of interleukin-4 and interleukin-13 and is mainly used to treat moderate-to-severe atopic dermatitis. Post-marketing safety data related to dupilumab have been accumulated, and it has been found that ocular surface diseases are closely associated with dupilumab treatment. The aim of this study was to detect dupilumab-related signals and to determine the safety characteristics of dupilumab with respect to eye disorders using real-world big data. Data on dupilumab use until December 29, 2019 were collected. The data were mined by calculating three indices: proportional reporting ratios, reporting odds ratios, and information components. The detected signals were classified using the primary system organ class in MedDRA terminology. Among 21,161,249 reports for all drugs, 20,548 reports were recorded for dupilumab. A total of 246 signals in the preferred terms were detected for dupilumab. Among the 246 positive signals obtained, 61 signals were related to eye disorders, which accounted for the largest percentage (24.8%), and 38 signals were anatomically related to the ocular surface. Dupilumab may cause extensive eye disorders; however, the underlying mechanisms and risk factors remain unclear. Our findings may facilitate broad safety screening of dupilumab-related eye disorders using real-world big data.

BackgroundThe mechanical and physiological properties of the arterial wall might affect the behavior of spontaneous cervicocephalic arterial dissections (CCAD). We aimed to determine the effects of endothelial function and arterial stiffness on the clinical characteristics and outcomes of CCAD using brachial flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (PWV).MethodsFrom a single-center database, we identified patients admitted from April 2011 to December 2021 with a diagnosis of CCAD who underwent both FMD and PWV. FMD was classified as normal and decreased according to institutional thresholds. PWV was categorized into tertiles. Comparative and multivariable analyses were performed to determine the effects of FMD and PWV values on major clinical outcomes.ResultsA total of 146 patients (age: 47 ± 11 years; men: 77.4%) were included. The main presentation was ischemic stroke in 76.7% of the patients, while 23.3% presented with headache or other symptoms. Healing of the dissection was observed in 55.8%. In multivariable analysis, Normal FMD levels (vs. decreased; adjusted OR: 4.52, 95% CI [1.95 −10.52]) were associated with spontaneous healing of the dissection. Highest PWV tertile (vs. lowest; adjusted OR: 17.05, 95% CI [3.07–94.82]) was associated with ischemic presentation. There was a higher ischemic stroke recurrence in the 3rd PWV tertile, and more frequent aneurysmal enlargement in the lowest PWV tertile, but their frequency was low, precluding multivariable analysis.ConclusionIn spontaneous CCAD, preserved endothelial function was associated with spontaneous arterial healing. Arterial stiffness is associated with ischemic presentation.

Malakoplakia is a rare chronic granulomatous disease found in the genitourinary tract, mainly. It is considered to be related to immunosuppression and/or infectious processes. We would like to present an operative case of cecal malakoplakia in a patient with a history of surgical resection and chemotherapy for cervical cancer. A 74-year-old female patient visited our hospital for 1-year follow-up after operation and chemo-radiotherapy for cervical cancer. An infiltrative mass of 6 cm, between the cecal base and the right psoas muscle, was observed on computed tomography. An ileocectomy was performed for diagnosis. Histopathologic examination revealed cecal malakoplakia. After surgery, based on previous reports, antibiotics therapy was added. Then the patient was discharged and treated in the outpatient clinic. To our knowledge, a rare case has been described of cecal malakoplakia during observation after surgery and chemo-radiotherapy for cervical cancer. Malakoplakia is known to be related to immunosuppressive condition. Therefore, our case suggests that close observation should be made in patients on immunosuppressive condition, such as chemotherapy.

Abstract Aims/Introduction It is not clear whether survival in kidney transplant recipients with pre‐transplant diabetes has improved over the past decades. We compared the rates of mortality and major adverse cardiovascular events (MACE) after renal transplantation in patients with and without pre‐transplant diabetes. Furthermore, we investigated whether transplant era and recipient age affected the association between diabetes status and adverse events. Materials and Methods This retrospective cohort study included 691 patients who underwent renal transplantation between 1994 and 2016 at a single tertiary center. We compared the incidences of post‐transplant mortality and four‐point MACE in patients with and without pre‐transplant diabetes using Kaplan–Meier analysis and the Cox proportional hazard model, and assessed the interactions between diabetes status and transplant era and recipient age. Results Of 691 kidney recipients, 143 (20.7%) had pre‐transplant diabetes. The mean follow‐up duration was 94.5 months. Kaplan–Meier analysis showed that patients with pre‐transplant diabetes had higher incidences of post‐transplant mortality and four‐point MACE compared with those without pre‐transplant diabetes (log–rank test, P

Background/Aims: This study aimed to characterize the changes in the gut microbiota of irritable bowel syndrome (IBS) patients and to investigate the consequent alterations in bacterial functions. Methods: We performed 16S rRNA metagenomic sequencing and a phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analyses using fecal samples from control (n=12) and diarrhea-dominant IBS patients (n=7). Results: The samples were clustered by the principal coordinates analysis depending on the presence of IBS (p=0.003). In the IBS patients, the abundances of Acidaminococcaceae, Sutterellaceae, and Desulfovibrionaceae were significantly increased, while those of Enterococcaceae, Leuconostocaceae, Clostridiaceae, Peptostreptococcaceae, and Lachnospiraceae were significantly decreased. The PICRUSt results indicated that two orthologues involved in secondary bile acid biosynthesis were significantly decreased in IBS patients. Modules involved in multidrug resistance, lipopolysaccharide biosynthesis, the reductive citrate cycle, and the citrate cycle were significantly increased in the IBS patients. In contrast, modules involved in cationic antimicrobial peptide resistance, and some transport systems were more abundant in controls than in IBS patients. Conclusions: Changes in the gut microbiota composition in IBS patients lead to alterations in bacterial functions, such as bile acid transformation and the induction of inflammation, which is a known pathophysiological mechanism of IBS.

Background/Aims: Helicobacter pylori (Hp) suppresses gastric acid secretion by repressing the expression of the H+, K+-adenosine triphosphatase (H+, K+-ATPase) and stimulating interleukin-1 (IL-1β; encoded by IL-1B). This study was aimed at evaluating the expression of the H+, K+-ATPase and IL-1β after Hp eradication. Methods: Two hundred twentyone subjects were categorized as Hp-negative (n=84) or Hppositive (n=137) according to the results of Hp tests (histology, CLO test, culturing, and serology). The mRNA expression levels of IL-1B and ATP4A (the gene encoding the α-subunit of H+, K+-ATPase) were measured in biopsy specimens from the gastric corpus using real-time polymerase chain reaction. Results: The Hp-positive group had significantly higher IL-1B mRNA levels than the whole Hp-negative group and the intestinal metaplasia (IM)-negative subgroup. After Hp eradication, the difference between the Hp-negative and Hperadicated groups disappeared, including in the IM-negative subgroup. The IL-1B mRNA level did not significantly change from the baseline level. Within the gastric cancer (GC)/dysplasia subgroup, the IL-1B mRNA levels at 1, 2, 3-4, and ≥5 years after Hp eradication were significantly lower than the baseline level. The difference in ATP4A mRNA levels between the Hp-negative and Hp-positive groups was not significant at baseline, and the changes in the ATP4A mRNA levels after Hp eradication compared to the baseline levels in the whole group and subgroups stratified by the presence of IM and GC/dysplasia were not significant. Conclusions: Infection with Hp has an effect on the level of IL-1B mRNA in IM-negative subjects. The continuous reduction in the IL-1B mRNA level in patients with GC/dysplasia after Hp eradication contributes to the prevention of metachronous GC after Hp eradication.

Background Surgeries in patients with coronavirus disease 2019 (COVID-19) put medical staff at a high risk of infection. We report the anesthetic management and infection control of a mechanically ventilated COVID-19 patient who underwent exploratory laparotomy for suspected duodenal ulcer perforation. Case A 73-year-old man, mechanically ventilated for confirmed COVID-19, showed clinical and radiographic signs of a perforated duodenal ulcer, and he was transferred under sedation and intubation to a negative-pressure operating room. The operating and assistant staff wore personal protective equipment. High-efficiency particulate absorbing filters were inserted into the expiratory circuits of the anesthesia machine and portable ventilator. No participating staff contracted COVID-19, although the patient later died due to pneumonia. Conclusions This report can contribute to establishing clinical guidelines for the surgical management and operation room setting of COVID-19 patients.

Abstract Background In acute large anterior circulation infarct patients with large core volume, we evaluated the role of optic nerve sheath diameter (ONSD) change rates in prediction of malignant progression. Methods We performed a retrospective observational study including patients with anterior circulation acute ischemic stroke with large ischemic cores from January 2010 to October 2017. Primary outcome was defined as undergoing decompressive surgery or death due to severe cerebral edema, and termed malignant progression. Patients were divided into malignant progressors and nonprogressors. Malignant progression was divided into early progression that occurred before D1 CT, and late progression that occurred afterwards. Retrospective analysis of changes in mean ONSD/eyeball transverse diameter (ETD) ratio, and midline shifting (MLS) were evaluated on serial computed tomography (CT). Through analysis of CT at baseline, postprocedure, and at D1, the predictive ability of time based change in ONSD/ETD ratio in predicting malignant progression was evaluated. Results A total of 58 patients were included. Nineteen (32.8%) were classified as malignant; 12 early, and 7 late progressions. In analysis of CTpostprocedure, A 1 mm/hr. rate of change in MLS during the CTbaseline-CTpostprocedure time phase lead to a 6.7 fold increased odds of early malignant progression (p

Background Before publication of the new classification system named the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) in 2018, there was no standard classification for salivary gland lesions obtained by fine-needle aspiration (FNA). We therefore aimed to evaluate the diagnostic utility of this system by retrospectively reviewing FNA samples using the MSRSGC and to determine their risk of developing into neoplasms and becoming malignant. Methods Retrospective slide review and classification of salivary gland FNAs obtained over a 6-year period (2013–2018) at a single center were performed by two pathologists. The risks of neoplasm and malignancy for each category also were calculated. Results This study surveyed 374 FNAs (371 patients) performed over a six-year period and selected 148 cases that included documented surgical follow-up (39.6%). Among the surgically treated cases, the distributions of FNA categories were as follows: non-diagnostic (ND; 16.9%), non-neoplastic (NN; 2.7%), atypia of undetermined significance (AUS; 3.4%), benign (BN; 54.7%), salivary gland neoplasm of uncertain malignant potential (SUMP; 10.1%), suspicious for malignancy (SM; 6.8%), and malignant (M; 5.4%). The risk of malignancy (ROM) was 24.0% for ND, 0% for NN, 40.0% for AUS, 2.5% for BN, 46.7% for SUMP, 100% for SM, and 87.5% for M. The overall diagnostic accuracy was 95.9% (142/148 cases). Conclusions The newly proposed MSRSGC appears to be a reliable system for classification of salivary gland lesions according to the associated ROM.

Species of Laccaria (Hydnangiaceae, Agaricales, and Basidiomycota) are well-known ectomycorrhizal symbionts of a broad range of hosts. Laccaria species are characterized by brown, orange, or purple colored basidiocarps, and globose or oblong, echinulate and multinucleate basidiospores. While some Laccaria species are easily identified at the species level using only the morphological characteristics, others are hard to distinguish at the species level due to small differences in morphology. Heretofore, ten Laccaria species have been reported in Korea. While studying the fungal diversity in the National Parks of Korea, two new Laccaria species were discovered. Species identification was done based on molecular analyses (ITS, 28S rDNA, rpb2, and tef1), then were confirmed by their corresponding morphologies. The two newly discovered Laccaria species are proposed here as Laccaria macrobasidia and Laccaria griseolilacina. The unique morphological characters of L. macrobasidia that distinguish it from its closely related species are orange-brown colored basidiocarp, long basidia and the absence of cheilocystidia. L. griseolilacina is characterized by a light grayish lavender-colored pileus and the absence of cheilocystidia. Two new species are described and illustrated in the present paper.

Abstract Background With increasing number of patients undergoing spine surgery, the spinal epidural hemorrhage (SEH) has become a growing concern. However, current studies on SEH rely on case reports or observations from a single center. Our study attempted to demonstrate the incidence rate and risk factors of SEH using a national dataset. Methods A total of 17,549 spine surgery cases from the Health Insurance Review and Assessment Service National Inpatient Sample of 2014 were analyzed. After evaluating the incidence of SEH based on severe cases requiring reoperation, a univariate comparison was performed. Variables found to be significant were included in a multivariable analysis model to determine the risk factors. Results The incidence of SEH was found to be 1.15% in Korean population, and there were no severe SEH cases. Our analysis confirmed the previous findings that lumbar surgery, intraoperative blood loss, prolonged surgical time, high blood pressure, use of nonsteroidal anti-inflammatory drugs, and concurrent bleeding factors are the risk factors of SEH. Anterior approach showed a protective effect. The use of anticoagulant demonstrated no statistical significance. Conclusion Although severe SEH cases were not detected, the incidence of SEH was similar to that reported in literature. Given that SEH is a rare complication of spine surgery and constitutes an important research area that needs to be studied further, our study makes a meaningful contribution based on a rigorous national level sample for the first time and provides the academic circle and health professionals with a reliable evidence of improved clinical outcomes in such cases.

Retracted on the 7th of July, 2020 by the Journal’s Editor-in-Chief request dated July 3th 2020. The type of retraction – plagiarism. The Editor-in-Chief of the journal was asked to retract this article because of plagiarism. The request came from the author of the article, which was published 8 months before the retracted article was published in “Banks and Bank Systems” journal. The author(s) insisted that the article completely repeated his own, i.e. contained a high level of plagiarism that could not be corrected. Editorial staff carried out an investigation into plagiarism in the article published. When the manuscript was submitted to the Journals for consideration, the authors signed the Cover letter and attested to the fact that their manuscript is an original research and has not been published before. After that, the manuscript was accepted for consideration by the Managing Editor and was tested for plagiarism using the iThenticate program. Plagiarism was not detected. Later, after the article complaint and the statement of plagiarism, we used all the sources and resources provided by the complainant, the article was re-tested for plagiarism, and plagiarism was established According to the results of the investigation, the editorial board decided to retract the article on July 7, 2020. The authors were notified of such a decision.

Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare, benign lymphoproliferative disease, which is characterized by nonclonal lymphoproliferation. PNLH is usually asymptomatic and usually detected incidentally on imaging studies. Common imaging findings include a solitary nodule, multiple nodules, or focal consolidation. Atypically, PNLH may present with persistent subsolid nodules, mimicking adenocarcinoma. Here, we report a rare case of PNLH presenting as multifocal subsolid nodules in both lower lobes. During follow-up, persistency and growth of the subsolid nodules suggested the possibility of malignancy. Wedge resection was performed bilaterally, and PNLH was confirmed on pathological examination.

Brain damage induces systemic inflammation, but insights and implication of this induction is still unclear. Here the authors show, using rat and mouse focal cerebral ischemia models, that the damaged brain signals via the VEGF-C/VEFGR3 axis to activate inflammatory responses in the draining cervical lymph nodes to induce systemic inflammation.

Background In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC). Methods Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases. Results The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAFV600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27). Conclusions The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.

Helicobacter pylori infection changes gastric microbiota profiles. However, it is not clear whether H. pylori eradication can restore the healthy gastric microbiota. Moreover, there has been no study regarding the changes in gastric microbiota with aging. The objective of this study was to investigate the changes in gastric corpus microbiota with age and following H. pylori eradication. Changes in corpus mucosa-associated microbiota were evaluated in 43 individuals with endoscopic follow-up > 1 year, including 8 H. pylori-uninfected and 15 H. pylori-infected subjects with no atrophy/metaplasia by histology and pepsinogen I/II ratio > 4.0; 17 H. pylori-infected subjects with atrophy/metaplasia and pepsinogen I/II ratio < 2.5; and 3 subjects with atrophy/metaplasia, no evidence of active H. pylori infection, negative for anti-H. pylori immunoglobulin G (IgG) antibody testing, and no previous history of H. pylori eradication. Successful H. pylori eradication was achieved in 21 patients. The gastric microbiota was characterized using an Illumina MiSeq platform targeting 16S ribosomal DNA (rDNA). The mean follow-up duration was 57.4 months (range, 12–145 months), and median follow-up visit was 1 (range, 1–3). Relative abundance of Lactobacillales and Streptococcus was increased with atrophy/metaplasia. In H. pylori-uninfected subjects (n = 8), an increase in Proteobacteria (Enhydrobacter, Comamonadaceae, Sphingobium); a decrease in Firmicutes (Streptococcus, Veillonella), Fusobacteria (Fusobacterium), Nocardioidaceae, Rothia, and Prevotella; and a decrease in microbial diversity were observed during the follow-up (p trend < 0.05). In 10 of 21 subjects (47.6%), H. pylori eradication induced restoration of microbial diversity; however, a predominance of Acinetobacter with a decrease in microbial diversity occurred in 11 subjects (52.3%). The presence of atrophy/metaplasia at baseline and higher neutrophil infiltration in the corpus were associated with the restoration of gastric microbiota after successful eradication, whereas a higher relative abundance of Acinetobacter at baseline was associated with the predominance of Acinetobacter after H. pylori eradication (p < 0.05). To conclude, in H. pylori-uninfected stomach, relative abundance of Proteobacteria increases, relative abundance of Firmicutes and Fusobacteria decreases, and microbial diversity decreases with aging. H. pylori eradication does not always restore gastric microbiota; in some individuals, gastric colonization by Acinetobacter species occurs after anti-Helicobacter treatment.

Topical corticosteroids (TCs) are widely used to treat dermatological conditions such as eczema and psoriasis. It can be a safe and effective treatment when used appropriately. However, misguided information and corticosteroid phobia appear to contribute to inadequate adherence to therapy, leading to unsatisfactory treatment outcomes. Therefore, community pharmacists (CPs) are in a prime position to inform patients about the appropriate use of medicine. The aim of this study was to examine how the knowledge and perceptions of CPs, as well as other factors, associate CPs' patient counseling practice around the use of TCs. A structured, validated questionnaire was distributed to CPs in the Republic of Korea, and additional focus group discussions were implemented to obtain a deeper understanding of the survey findings. We analyzed the survey results by applying a modified knowledge-perception-practice model. In addition, we used path analysis to validate the model and assessed how knowledge level and perceptions of barriers affect CPs' counseling behavior. We ran a multiple regression to identify factors that associate CPs' practice levels. A total of 1018 surveys were analyzed. In general, respondents had sufficient knowledge to provide appropriate patient counseling on TC use. An increase in knowledge level positively associated the quality of practice, and more knowledge increased the perception of barriers that negatively associated patient counseling. Location in rural areas and pharmacists' perception of counseling barriers negatively associated the quality of practice. A higher level of knowledge, training in ADEs, higher proportion of OTC TC sales, and increased time for counseling positively associated the quality of practice. Therefore, minimizing barriers such as negative perceptions is very important in facilitating CPs' counseling practice around TC use.

Reactive oxygen species modulator 1 (romo1) causes cell hyperplasia and promotes cancer cell invasion. Based recent studies, the overexpression of romo1 is associated with lymphatic metastasis and poor prognosis in lung cancer. We aimed to evaluate associations between romo1 expression and lymph node metastasis in non-small cell lung cancer (NSCLC). Clinical data and pathological results were retrospectively reviewed for 98 subjects diagnosed with NSCLC and who underwent surgical biopsy between 1994 and 2009. A total 98 tumor specimens were analyzed. The romo1 H score was correlated with stage and was significantly higher in subjects with lymph node metastasis than in those without metastasis (173 vs 116; P < 0.05). The area (%) of grade 1 expression was significantly smaller (19.5 vs 37.0; P = 0.005) and the area of grade 3 expression was significantly larger (27.9 vs 6.00; P < 0.001) in subjects with lymph node metastasis than in those without metastasis. In stage I patients, disease free survival (DFS) (191 ± 18.8 vs. 75.6 ± 22.4 months, P = 0.004) was significantly longer in the low romo1 group than in the high romo1 group. A multivariate analysis showed a significant association between high romo1 expression and poor DFS (hazard ratio 5.59, 95 confidence interval, 1.54-20.3, P = 0.009). These findings support the prognostic value of romo1 in NSCLC, especially in stage I.

Purpose Preterm infants frequently require red blood cell (RBC) transfusions in neonatal intensive care units (NICU). Storage RBCs undergo many changes during storage periods. We aimed to compare the hemoglobin (Hb) correction effect according to the period of RBC storage and investigate the factors influencing Hb correction. Methods This retrospective study reviewed the medical records of 289 patients who received RBC transfusion more than once in the NICU of Kosin University Gospel Hospital between February 2006 and March 2016. The subjects were classified into two storage groups: short-term (≤7 days, n=88) and long-term (>7 days, n=201), according to the period of RBC storage. We checked Hb levels by complete blood cell count tests conducted within 2 days before and 5 to 9 days after the first transfusion. We compared the Hb difference between the two groups and analyzed the factors influencing Hb correction. Results Excluding the use of an invasive ventilator, there was no significant difference between the two groups in terms of clinical characteristics. There was no significant difference in the Hb correction effect between the two groups (P=0.537). Birth weight greater than 1,500 g, higher weight at transfusion, and larger volume of transfusion were significant prognostic factors affecting greater changes in Hb. In addition, surgeryexperience, higher Hb level at transfusion, and additional blood tests were found to be significantly associated with less changes in Hb. Conclusion The RBC storage period did not affect the Hb correction effect. The Hb correction effect may be diminished in infants with lower birth weight and lower weight at transfusion under unstable clinical conditions.

Listeriosis is a rare foodborne infection caused by Listeria monocytogenes. It is 12–20 times more prevalent in pregnant women compared to the general population, with a 20–40% mortality rate in neonates. Early treatment with appropriate antimicrobial agents is critical for pregnancy outcomes; however, the infection is difficult to control because the nonspecific clinical manifestations and rarity of the disease often preclude early diagnosis. We encountered 2 cases of pregnancy-associated listeriosis that occurred at 29 and 37 weeks of gestation. Both neonates were delivered by emergent cesarean section due to fetal condition, and one of the preterm infants died immediately after birth. Pregnancy-associated listeriosis should be considered in the management of unexplained fever or inflammatory conditions in pregnant women.

Background/AimsMale predominance has been observed in the erosive reflux disease (ERD), but reverse finding in nonerosive reflux disease (NERD). This suggests sex-specific medicine approach is needed but its mechanism is remained to be elucidated. We aimed to compare clinical characteristics and mRNA expression levels of tight junction-related proteins between male and female gastroesophageal reflux disease (GERD).Methods : Sixteen healthy controls, 45 ERD, and 14 NERD patients received upper endoscopies and completed questionnaires. Quantitative real-time polymerase chain reactions of occludin (OCLN), zonal occludens (ZO) 1, claudin-1 (CLDN1) and claudin-4 (CLDN4), and neurokinin 1 receptor (NK1R) were performed in the distal esophageal mucosal specimen. These results were analyzed by sex.Results : Female GERD patients were affected more by reflux symptoms than males. The impairment of overall quality of life was more prominent in female patients with reflux symptoms than male patients (5.6±0.2 vs 4.9±0.6, p=0.009). The levels of OCLN mRNA expression were significantly lower in the male ERD group. On the other hand, those of CLDN1, CLDN4, and NK1R except ZO-1 were significantly higher in the male ERD group.Conclusion : sWe demonstrated that female ERD/NERD patients were affected more by GERD and male ERD patients showed significant changes of tight junction protein mRNA expression levels.

Liver fibrosis: Reversing the damage A scaffolding protein that modulates cell signaling pathways contributes to reverse liver scarring. Liver fibrosis is caused by a build-up of scar tissue that interferes with liver function. However, the damage is reversed when the cause of injury is removed. Kyu-Won Kim at Seoul National University, South Korea, and colleagues examined the levels of A-Kinase Anchoring Protein 12 (AKAP12), a scaffolding protein that regulates the subcellular location of signaling proteins, in mouse and human livers. Levels of AKAP12 were reduced in fibrotic livers but restored when fibrosis was reversed. Mice lacking AKAP12 were unable to effectively repair the damage caused by fibrosis. Genetic analyses suggest that AKAP12 stimulates signaling through the adenosine 3′,5′-cyclic monophosphate (cAMP) pathway, which can inhibit fibrosis. These findings highlight a key role for AKAP12 in accelerating liver recovery.

We present a patient diagnosed with skin sarcoidosis, breast cancer, pulmonary tuberculosis, and peritoneal sarcoidosis with a past history of colorectal cancer. During stage work up for breast cancer, suspicious lesions on peritoneum were observed in imaging studies. Considering our patient’s history and imaging findings, we initially suspected peritoneal carcinomatosis. However, the peritoneal lesion was diagnosed as sarcoidosis in laparoscopic biopsy. This case demonstrates that abdominal sarcoidosis might be considered as a differential diagnosis when there is a lesion suspected of being peritoneal carcinomatosis with nontypical clinical presentations.

Neuroblastoma is one of the commonest and deadliest solid tumours of childhood, and is thought to result from disrupted differentiation of the developing sympathoadrenergic lineage of the neural crest. Neuroblastoma exhibits intra- and intertumoural heterogeneity, with high risk tumours characterised by poor differentiation, which can be attributable to MYCN-mediated repression of genes involved in neuronal differentiation. MYCN is known to co-operate with oncogenic signalling pathways such as Alk, Akt and MEK/ERK signalling, and, together with c-MYC has been shown to be activated by Wnt signalling in various tissues. However, our previous work demonstrated that Wnt3a/Rspo2 treatment of some neuroblastoma cell lines can, paradoxically, decrease c-MYC and MYCN proteins. This prompted us to define the neuroblastoma-specific Wnt3a/Rspo2-driven transcriptome using RNA sequencing, and characterise the accompanying changes in cell biology. Here we report the identification of ninety Wnt target genes, and show that Wnt signalling is upstream of numerous transcription factors and signalling pathways in neuroblastoma. Using live-cell imaging, we show that Wnt signalling can drive differentiation of SK-N-BE(2)-C and SH-SY5Y cell-lines, but, conversely, proliferation of SK-N-AS cells. We show that cell-lines that differentiate show induction of pro-differentiation BMP4 and EPAS1 proteins, which is not apparent in the SK-N-AS cells. In contrast, SK-N-AS cells show increased CCND1, phosphorylated RB and E2F1 in response to Wnt3a/Rspo2, consistent with their proliferative response, and these proteins are not increased in differentiating lines. By meta-analysis of the expression of our 90 genes in primary tumour gene expression databases, we demonstrate discrete expression patterns of our Wnt genes in patient cohorts with different prognosis. Furthermore our analysis reveals interconnectivity within subsets of our Wnt genes, with one subset comprised of novel putative drivers of neuronal differentiation repressed by MYCN. Assessment of β-catenin immunohistochemistry shows high levels of β-catenin in tumours with better differentiation, further supporting a role for canonical Wnt signalling in neuroblastoma differentiation.

BackgroundThe aim of this retrospective study was to compare the clinical performance of the modified Marsh model for propofol between underweight and normal-weight patients with Crohn's disease.MethodsThe medical records of 50 patients who underwent elective surgery for Crohn's disease were reviewed retrospectively. Propofol and remifentanil were administered using target effect-site concentration (Ce)-controlled infusion with the modified Marsh and Minto models. Target Ce values of propofol were adjusted within a range of 2.5–3 µg/ml to maintain a bispectral index (BIS) value of less than 60 during anesthesia maintenance. Dosages of anesthetic agents administered during surgery were compared between underweight and normal-weight patients. The infusion profiles of patients were applied as inputs to calculate the Ce values in the Schnider model.ResultsThe total midazolam and remifentanil dosages required for underweight patients were higher than those required for normal-weight patients to maintain BIS values at less than 60 within a target propofol Ce range of 2.5–3 µg/ml. Simulation results suggested that the Schnider model may be an appropriate pharmacokinetic model for target-controlled infusion in underweight patients, as the clearance was consistently higher in the Schnider model than the modified Marsh model, particularly in underweight patients.ConclusionsThe modified Marsh model might cause inadvertent propofol underdosing in underweight patients. Future studies are necessary to compare the predictive performance of the modified Marsh and Schnider pharmacokinetic models in underweight patients.

Background/AimsConcerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea.Methods : Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction restriction fragment length polymorphism.Results : After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism.Conclusion : sThis study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).

ObjectiveThe current paradigm in the treatment of patients with non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a diagnostic lobectomy rather than complete thyroidectomy and postoperative radioiodine treatment. Consequently, preoperative diagnosis of NIFTP is considered to be important.MethodsWe performed the comprehensive analysis for diagnosis of preoperative 20 NIFTPs in comparison with 41 invasive encapsulated follicular papillary thyroid carcinomas (I-EFVPTCs) using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and molecular analysis for BRAF and RAS mutations.ResultsK-TIRADS 3 was identified as the most common sonographic diagnosis in both NIFTP and I-EFVPTC. Unlike I-EFVPTC, K-TIRADS 5 was not identified in NIFTP. AUS/FLUS was the most common cytopathological diagnosis and none of the cases were classified as malignant category in both groups, although the difference in distribution was not significant between the groups. BRAF mutation was not found in NIFTP but was present in 9.8% of cases in I-EFVPTC. The frequency of RAS mutation in I-EFVPTCs was twice as high as that of NIFTP. Wild-type BRAF and RAS in NIFTP was significantly higher than I-EFVPTC.ConclusionThe existence of overlapping features between the groups was evident, hence conclusive distinction between radiology, cytology and molecular analysis could not be achieved. Apparently, the diagnosis of NIFTP based on comprehensive analysis was not confirmable but could perceive or at least favor the diagnosis of NIFTP.