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Mixed refrigerant (MR) Cascade Refrigeration Systems are widely employed in industries requiring both extremely low temperatures and large cooling capacity, such as semiconductors and displays. The composition of the MR has a significant impact on the performance of the cascade refrigeration systems, so optimizing the MR composition is essential. The current studies mainly focus on optimization that changes only the composition ratio with a limited number of refrigerants. Therefore, there may be a configuration and composition ratio that can improve the performance of the system more than existing methods. This study presents the need to find the optimal combination and number of MRs before determining the performance of MRs according to changes in composition. The proposed method selects five types of refrigerants that meet the conditions, then classifies cases according to the number of refrigerants in MR and analyzes the performance of each MR at various HTC evaporation temperatures based on energy and exergy through cycle simulation for each case. The proposed method showed COP up to 14.85 % higher than the conventional method, so it is expected to contribute to improving system performance by finding the optimal refrigerant combination and number before optimizing the composition of the MR.

This study investigates the implementation of a cryogenic chiller utilizing a mixed-refrigerant cascade refrigeration cycle (MRCRC). In this setup, R-404A is employed in the high-temperature circuit (HTC), while a mixture of refrigerants is utilized in the low-temperature circuit (LTC). Unlike a conventional MRCRC that operates without a receiver to maintain the composition ratio, this research explores the impact of receiver installation on system performance. Experiments were conducted with and without a receiver to assess performance improvements and device behavior. With a fixed refrigerant charge of 4 kg, the suction and discharge pressures of the LTC compressor remained low and stable after the receiver’s installation. The addition of a receiver significantly reduced the cooling time, with further reductions observed as the refrigerant charge increased. The system achieved evaporative heat capacities of 0.59, 1.76, and 2 kW for refrigerant charges of 4, 7, and 9 kg, respectively. Notably, at the maximum refrigerant charge of 11 kg, the evaporative heat capacity peaked at 3.3 kW. These findings indicate that incorporating a receiver is crucial for enhancing the cooling performance of cryogenic coolers using mixed refrigerants and stabilizing device operation. This contrasts with previous studies that omitted receivers due to concerns over potential alterations in the composition ratio of the mixed refrigerant.

Recent advancements in cryogenic etching, characterized by high aspect ratios and etching rates, address the growing demand for enhanced performance and reduced power consumption in electronics. To precisely maintain the temperature under high loads, the cascade mixed-refrigerant cycle (CMRC) is predominantly used. However, most refrigerants currently used in semiconductor cryogenic etching have high global warming potential (GWP). This study introduces a −100 °C chiller using a mixed refrigerant (MR) with a GWP of 150 or less, aiming to comply with stricter environmental standards and contribute to environmental preservation. The optimal configuration for the CMRC was determined based on a previously established methodology for selecting the best MR configuration. Comprehensive analyses—energy, exergy, environmental, and exergoeconomic—were conducted on the data obtained using Matlab simulations to evaluate the feasibility of replacing conventional refrigerants. The results reveal that using eco-friendly MRs increases the coefficient of performance by 52%, enabling a reduction in compressor size due to significantly decreased discharge volumes. The exergy analysis indicated a 16.41% improvement in efficiency and a substantial decrease in exergy destruction. The environmental analysis demonstrated that eco-friendly MRs could reduce carbon emissions by 60%. Economically, the evaporator and condenser accounted for over 70% of the total exergy costs in all cases, with a 52.44% reduction in exergy costs when using eco-friendly MRs. This study highlights the potential for eco-friendly refrigerants to be integrated into semiconductor cryogenic etching processes, responding effectively to environmental regulations in the cryogenic sector.

Relapsing polychondritis (RP) is a rare, progressive immune-mediated systemic inflammatory disease of unknown etiology, characterized by recurrent inflammation of cartilaginous structures. Approximately 30% of RP cases are associated with other autoimmune diseases. However, the co-occurrence of RP and Crohn disease (CD) has rarely been reported. Herein, we present a 35-year-old woman diagnosed with RP and CD, who was refractory to initial conventional medications, including azathioprine and glucocorticoid, but who subsequently responded to infliximab (IFX). For both diseases, remission was sustained with IFX. There has been no previous report regarding the successful treatment of co-existing RP and CD with IFX.

Pedagogical strategies for nurturing group creativity in school mathematics have remained largely unexplored despite their significance. In this study, we explored the use of role playing in mathematical modeling activities for nurturing group creativity in a 9th-grade mathematics class in Korea. We described the theoretical bases and types of roles that nurture group creativity while examining the effects of role playing and the factors that seem to promote it. The data of this study included lesson observations, samples of student work, and interviews with 20 participating students and their teachers. The interactions of the five groups of students were compared and analyzed. The results suggest that role playing contributes to nurturing group creativity by inducing interactions and improving creative synergies. The factors that seem to promote role playing are students' understanding of role playing, a comfortable environment, the thought evaluator's role-playing effectiveness, and the need to make a mathematical decision. Based on these findings, we recommend that creativity researchers build on these findings to further explore how group creativity can be enhanced in mathematical modeling through role playing.

Abstract Although happiness or subjective well-being (SWB) has drawn much attention from researchers, the precise neural structural correlates of SWB are generally unknown. In the present study, we aimed to investigate the associations between gray matter (GM) volumes, white matter (WM) microstructures, and SWB in healthy individuals, mainly young adults using multimodal T1 and diffusion tensor imaging studies. We enrolled 70 healthy individuals using magnetic resonance imaging. We measured their SWB using the Concise Measure of Subjective Well-Being. Voxel-wise statistical analysis of GM volumes was performed using voxel-based morphometry, while fractional anisotropy (FA) values were analyzed using tract-based spatial statistics. In healthy individuals, higher levels of SWB were significantly correlated with increased GM volumes of the anterior insula and decreased FA values in clusters of the body of the corpus callosum, precuneus WM, and fornix cres/stria terminalis. A correlational analysis revealed that GM volumes and FA values in these significant regions were significantly correlated with severity of psychological symptoms such as depression, anxiety, and quality of life. Our findings indicate that GM volumes and WM microstructures in these regions may contribute to SWB, and could be the neural basis for psychological symptom severity as well as quality of life in healthy individuals.

Abstract The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which are resistant to various antibiotics. Combination therapies using natural compounds with antibiotics have been found to have synergistic effects against several pathogens. Synergistic natural compounds can potentiate the effects of polymyxins for the treatment of Acinetobacter baumannii infection. Out of 120 types of plant extracts, only Silene armeria extract (SAE) showed a synergistic effect with polymyxin B (PMB) in our fractional inhibitory concentration and time-kill analyses. The survival rate of G. mellonella infected with A. baumannii ATCC 17978 increased following the synergistic treatment. Interestingly, the addition of osmolytes, such as trehalose, canceled the synergistic effect of SAE with PMB; however, the underlying mechanism remains unclear. Quadrupole time-of-flight liquid chromatography-mass spectrometry revealed 6-bromo-2-naphthol (6B2N) to be a major active compound that exhibited synergistic effects with PMB. Pretreatment with 6B2N made A. baumannii cells more susceptible to PMB exposure in a time- and concentration-dependent manner, indicating that 6B2N exhibits consequential synergistic action with PMB. Moreover, the exposure of 6B2N-treated cells to PMB led to higher membrane leakage and permeability. The present findings provide a promising approach for utilizing plant extracts as adjuvants to reduce the toxicity of PMB in A. baumannii infection.

Background: This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin. Methods: In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135). Results: At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (--0.47%; 95% confidence interval, -0.61 to -0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, high-density lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%). Conclusion: Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin. [ABSTRACT FROM AUTHOR]

Abstract Background Instances of customers bullying employees at the workplace are increasing with the development of the service industry. Korea has established a worker protection system to prevent negative effects of customer bullying on workers’ health. This study identified the latent profile types of protection against customer bullying in workplaces, and determined their predictors. Methods Data were collected over 28 days, from March 2 to 30, 2020. This study identified whether protection against customer bullying is implemented for workers in person-to-person services, the change effected by this protection, and worker monitoring scope. Data from 1,537 out of 1,550 participants were analyzed, excluding the missing values. Latent profile types were identified using Mplus 8.5 for data analysis, and the multinomial logistic regression analysis was performed to review the predictors. Results The results are as follows. There were four types of latent profile types: lagging, medium, relative preventive type, and excellent type. Variables predicting these types included age, gender, service period, position, occupational category, worker monitoring scope, decrease in the number of customers causing problems, decrease in disputes with customers, and worker satisfaction. Conclusions First, a system to prevent customer bullying must be adopted in the service industry. Second, there must be a way to improve trust between customers and workers when protective measures are being adopted. Third, managers must establish a system that can both protect workers against bullying and provide customer satisfaction.

Abstract Background Few studies have annotated the whole mitochondrial DNA (mtDNA) genome associated with drug responses in Asian populations. This study aimed to characterize mtDNA genetic profiles, especially the distribution and frequency of well-known genetic biomarkers associated with diseases and drug-induced toxicity in a Korean population. Method Whole mitochondrial genome was sequenced for 118 Korean subjects by using a next-generation sequencing approach. The bioinformatic pipeline was constructed for variant calling, haplogroup classification and annotation of mitochondrial mutation. Results A total of 681 variants was identified among all subjects. The MT-TRNP gene and displacement loop showed the highest numbers of variants (113 and 74 variants, respectively). The m.16189T > C allele, which is known to reduce the mtDNA copy number in human cells was detected in 25.4% of subjects. The variants (m.2706A > G, m.3010A > G, and m.1095T > C), which are associated with drug-induced toxicity, were observed with the frequency of 99.15%, 30.51%, and 0.08%, respectively. The m.2150T > A, a genotype associated with highly disruptive effects on mitochondrial ribosomes, was identified in five subjects. The D and M groups were the most dominant groups with the frequency of 34.74% and 16.1%, respectively. Conclusions Our finding was consistent with Korean Genome Project and well reflected the unique profile of mitochondrial haplogroup distribution. It was the first study to annotate the whole mitochondrial genome with drug-induced toxicity to predict the ADRs event in clinical implementation for Korean subjects. This approach could be extended for further study for validation of the potential ethnic-specific mitochondrial genetic biomarkers in the Korean population.

Abstract Aims/Introduction The benefits of once‐daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established. Materials and Methods This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once‐daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated. Results The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C‐peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P

Background To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM). Methods In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without nocturnal hypoglycemia at week 12. Results Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014). Conclusion The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

Abstract Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety.

Acinetobacter baumannii, a major nosocomial pathogen, survives in diverse hospital environments, and its multidrug resistance is a major concern. The ppGpp-dependent stringent response mediates the reprogramming of genes with diverse functions in several bacteria. We investigated whether ppGpp is involved in A. baumannii’s pathogenesis by examining biofilm formation, surface motility, adhesion, invasion, and mouse infection studies. Transcriptome analysis of early stationary phase cultures revealed 498 differentially-expressed genes (≥ 2-fold change) in a ppGpp-deficient A. baumannii strain; 220 and 278 genes were up and downregulated, respectively. Csu operon expression, important in pilus biosynthesis during early biofilm formation, was significantly reduced in the ppGpp-deficient strain. Our findings suggest that ppGpp signaling influences A. baumannii biofilm formation, surface motility, adherence, and virulence. We showed the association between ppGpp and pathogenicity in A. baumannii for the first time; ppGpp may be a novel antivirulence target in A. baumannii.

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%–10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2–3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1–2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.

Abstract Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-β, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P

Purpose The ‘DSD Pathways’ study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions—classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS).Participants Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a ‘strength-of-evidence’ score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation.Findings to date Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores

Actinomycosis is an inflammatory disease with various clinical presentations including inflammation and formation of masses. There are several reports suggesting the infiltrative mass-like nature of actinomycosis that is misunderstood as a tumor. A 39-year-old male clinically presented with a fungating mass-like lesion during colonoscopy for healthcare screening. Biopsy was performed for the lesion, and chronic inflammation was diagnosed. Abdominal computed tomography (CT) suggested severe edematous changes in the appendix with an appendicolith, suspected chronic inflammation, and wall thickening of the cecal base, but malignancy could not be definitively ruled out. The patient underwent a laparoscopic single-port cecectomy based on the possibility of cecal cancer. The final biopsy was diagnosed as actinomycosis, and the patient was prescribed antibiotics and showed no recurrence in the follow-up CT scan. We present this rare case of mass-like appendiceal actinomycosis treated with the single-port laparoscopic method.

Abstract TiO2 is the most widely used material for the electron transport layers (ETLs) because it is characterized by proper band alignment with light absorbers, adequate optical transmittance, and high electron mobility. There are two thermodynamically stable crystal phases of TiO2: anatase and rutile. However, understanding which phase is more effective as the ETL is still required. In this paper, we demonstrate the different effects of using epitaxial anatase TiO2 and epitaxial rutile TiO2 (both grown using pulsed laser deposition) as the ETL material on the electrical and optical properties. Epitaxial Nb-doped TiO2 layers were used as the common electrode material for the both epitaxial ETLs for which the crystalline structural analysis revealed high crystalline qualities and good coherency for both phases. By analyzing the recombination kinetics, the anatase phase shows a preferable performance in comparison with the rutile phase, although both epitaxial phases show remarkably reduced extrinsic recombination properties, such as trap-assisted recombination. This study demonstrates not only a better electron transporting performance of anatase phase but also reduced extrinsic recombination through epitaxy growth.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn. [ABSTRACT FROM AUTHOR]

Abstract Lactobacillus reuteri AN417 is a newly characterized probiotic strain. The activity of AN417 against oral pathogenic bacteria is unknown. We investigated the antibacterial activity of cell-free L. reuteri AN417 culture supernatant (LRS) against three oral pathogens: Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans. P. gingivalis and F. nucleatum have been implicated in periodontal disease, whereas S. mutans causes dental caries. Exposing these oral pathogenic bacteria to LRS significantly reduced their growth rates, intracellular ATP levels, cell viability, and time-to-kill. The minimal inhibitory volume of LRS was 10% (v/v) against P. gingivalis, 20% (v/v) for F. nucleatum, and 30% (v/v) for S. mutans. LRS significantly reduced the integrity of biofilms and significantly suppressed the expression of various genes involved in P. gingivalis biofilm formation. The L. reuteri AN417 genome lacked genes encoding reuterin, reuteran, and reutericyclin, which are major antibacterial compounds produced in L. reuteri strains. LRS treated with lipase and α-amylase displayed decreased antibacterial activity against oral pathogens. These data suggest that the antibacterial substances in LRS are carbohydrates and/or fatty acid metabolites. Our results demonstrate that LRS has antimicrobial activity against dental pathogenic bacteria, highlighting its potential utility for the prevention and treatment of P. gingivalis periodontal disease.

Abstract Background This study was focused on the measurement of anticancer properties of six medicinal plants from western Nepal in three cell lines; HeLa, Hep3B, and HCT116, and anti-inflammatory properties in RAW 264.7 cell line through NO, PGE2, and TNF-α production. In addition, the phytochemical screening, total phenolic, flavonoid content, and antioxidant properties were evaluated. Results The qualitative phytochemical analysis revealed the presence of different secondary metabolite and range of total phenolic and total flavonoid content. The highest antioxidant activities were observed in Bergenia pacumbis against both DPPH (IC50 = 25.97 ± 0.19 μg/mL) and ABTS (IC50 = 14.49 ± 0.40 μg/mL). Furthermore, the highest antiproliferative effect against cervical, liver, and colon cancer cell lines were observed in Melia azedarach as IC50 values of 10.50, 5.30, and 1.57 μg/mL respectively, while the strongest anti-metastatic potential on liver cancer cell line was found in Pleurospermum benthamii. In addition, P. benthamii showed the most potent anti-inflammatory effect in RAW264.7 murine macrophage cells. Conclusion This study provided the evidence for M. azedarach and P. benthamii to have great anticancer potential and finding builds the enough scientific backgrounds in future to isolate and purify the bioactive compounds for further applications.

The Korean guidelines for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers were previously developed under co-work with the Korean College of Helicobacter and Upper Gastrointestinal Research and Korean Society of Gastroenterology at 2009. On the other hand, the previous guidelines were based mainly on a literature review and expert opinions. Therefore, the guidelines need to be revised. In this study, a guideline development committee for drug-induced peptic ulcers was organized under the Korean College of Helicobacter and Upper Gastrointestinal Research in 2017. Nine statements were developed, including four for NSAID, three for aspirin and other antiplatelet agents, and two for anticoagulants through de novo processes based on evidence-based medicine, such as a literature search, meta-analysis, and the consensus was established using the modified Delphi method. The primary target of this guideline was adult patients taking long-term NSAIDs, aspirin, or other antiplatelet agent and anticoagulants. The revised guidelines reflect the consensus of expert opinions and are intended to assist relevant clinicians in the management and prevention of drug-induced peptic ulcers and associated conditions.

Abstract Background Dupilumab is a receptor antagonist binding to the alpha subunit of the interleukin-4 receptor. Through binding to it, dupilumab inhibits signaling of both IL-4 and IL-13, the representative Th2 biomarkers. Recently, in addition to the treatment effects for atopic dermatitis (AD), there is an emerging adverse event as facial erythema. Case presentation A twenty-seven-year-old female patient developed erythema and desquamation on the face and neck after dupilumab administration. She had AD on her arms, legs, and trunk before the treatment but there was no atopic clinical feature in her face and neck. With the treatment of dupilumab, her skin lesions of the body have improved from the beginning of the treatment. In the patch test, including dupilumab, there was no specific finding other than the 1+ response to neomycin on day 2. In the intradermal test to dupilumab, a positive result was observed 15 min later, but negative both days 1 and 2. The blood examination showed an elevation of both ANA as 1:80 and anti-phospholipid antibodies (Anti-cardiolipin IgM, IgG, and Anti- beta 2 GPI IgG). She was diagnosed with Systemic lupus erythematosus (SLE) based on diagnostic criteria by a rheumatologist. Conclusion Dupilumab is an emerging therapeutic agent for AD, and treatment cases are increasing in Korea. However, there are several adverse events during the treatment of dupilumab. Herein, we report the unexpected adverse event during the treatment of dupilumab in SLE patients.

Von Hippel-Lindau (VHL) disease is a rare inherited cancer predisposition syndrome characterized by benign and malignant tumors in multiple organs, especially cerebellar hemangioblastomas, retinal angiomas, renal-cell carcinoma, and pheochromocytomas. Clinically, VHL disease also presents an increased risk for developing multiple visceral cysts in the pancreas, liver, and kidneys. Regular surveillance for VHL disease-associated tumors after early diagnosis is necessary for better outcomes in VHL disease. An 11-year-old girl was admitted with prolonged fever lasting for more than 10 days and cervical lymphadenopathy. She did not have a family history of cysts or malignancy. Initial blood tests showed mild leukopenia and moderate elevation in aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, but with normal amylase and lipase. Hepatobiliary ultrasonography and magnetic resonance cholangiopancreatography were done and revealed multiple cysts involving the whole pancreas with cyst sizes up to 1.6 cm, indicating VHL disease. Direct sequencing of the VHL gene showed a heterozygous duplication at codon 384 (c.384dup), which is predicted to cause a frameshift of the reading frame (p.Leu129Serfs*3). This was a novel pathogenic variant VHL gene. We carried out the surveillance protocol for VHL disease-associated tumors, and found a hemangioblastoma in the medulla of the brainstem. We are reporting an 11-year-old female patient of VHL disease with brainstem hemangioblastoma who could be suspected and diagnosed of VHL disease in asymptomatic state due to incidentally found multiple pancreatic cysts.

ABSTRACT: In Korea, 4 big layer companies that possess one grandparent and 3 parent stocks are in charge of 100% of the layer chicken industry. In this study, we investigated the antimicrobial resistance of commensal 578 E. coli isolated from 20 flocks of 4-layer breeder farms (A, B, C, and D), moreover, compared the characteristics of their resistance and virulence genes. Isolates from farms B and D showed significantly higher resistance to the β-lactam antimicrobials (amoxicillin, ampicillin, and 1st-, 2nd-, and 3rd-generation cephalosporins). However, resistance to ciprofloxacin, nalidixic acid, and tetracycline was significantly higher in the isolates from farm A (P < 0.05). Interestingly, the isolates from farm C showed significantly lower resistance to most antimicrobials tested in this study. The isolates from farms B, C, and D showed the high multiple resistance to the 3 antimicrobial classes. Furthermore, the isolates from farm A showed the highest multiple resistance against the 5 classes. Among the 412 β-lactam-resistant isolates, 123 (29.9%) carried blaTEM-1, but the distribution was significantly different among the farms from 17.5% to 51.4% (P < 0.05). Similarly, the most prevalent tetracycline resistance gene in the isolates from farms B, C, and D was tetA (50.0–77.0%); however, the isolates from farm A showed the highest prevalence in tetB (70.6%). The distribution of quinolone (qnrB, qnrD, and qnrS) and sulfonamide (su12)-resistant genes were also significantly different among the farms but that of chloramphenicol (catA1)- and aminoglycoside (aac [3]-II, and aac [6′]-Ib)-resistant genes possessed no significant difference among the farms. Moreover, the isolates from farm C showed significantly higher prevalence in virulence genes (iroN, ompT, hlyF, and iss) than the other 3 farms (P < 0.05). Furthermore, the phenotypic and genotypic characteristics of E. coli isolates were significantly different among the farms, and improved management protocols are required to control of horizontal and vertical transmission of avian disease, including the dissemination of resistant bacteria in breeder flocks.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is still rapidly spreading as of March 2022. An accurate and rapid molecular diagnosis is essential to determine the exact number of confirmed cases. Currently, the viral transport medium (VTM) required for testing is in short supply due to a sharp increase in the laboratory tests performed, and alternative VTMs are needed to alleviate the shortage. Guanidine thiocyanate-based media reportedly inactivate SARS-CoV-2 and are compatible with quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays, but the compatibility and the viral detection capacity have not been fully validated. To evaluate the guanidine thiocyanate-based Gene Transport Medium (GeneTM) as an alternative VTM, we prepared 39 SARS-CoV-2-positive and 7 SARS-CoV-2-negative samples in GeneTM, eNAT™, and phosphate-buffered saline (PBS). The cycle threshold (Ct) values of three SARS-CoV-2 targets (the S, RdRP, and N genes) were analyzed using RT-qPCR testing. The comparison of Ct values from the positive samples showed a high correlation (R2= 0.95–0.96) between GeneTM and eNAT™, indicating a comparable viral detection capacity. The delta Ct values of the SARS-CoV-2 genes in each transport medium were maintained for 14 days at cold (4°C) or room (25°C) temperatures, suggesting viral samples were stably preserved in the transport media for 14 days. Together, GeneTM is a potential alternative VTM with comparable RT-qPCR performance and stability to those of standard media.

Gastroesophageal reflux disease (GERD) is diagnosed according to the medical history or in response to proton pump inhibitor therapy. However, the need for further testing is always appropriate. The decisive evidence for the current diagnosis of GERD is severe erosive esophagitis of Los Angeles grade C or D, long-segment Barrett’s mucosa or peptic strictures seen on endoscopy or an acid exposure time >6% on ambulatory pH or pH impedance monitoring. If ambulatory reflux monitoring correlates between reflux and the symptoms, then the diagnosis and treatment are certain. If it is difficult to clearly diagnose this malady as seen upon endoscopy and ph/pH impedance monitoring, then this review recommends the biopsy findings, motor evaluation and novel impedance metrics. Novel impedance metrics include the baseline impedance and the post reflux swallow-induced peristaltic wave index. Therefore, making a future GERD diagnosis should focus on defining the patient's phenotype. The phenotype is determined by the level of reflux exposure, clearance efficacy, anatomy of the esophageal gastric junction, and the psychological state of the patient. The purpose of this review is to clarify the diagnostic guideline for GERD according to several test methods.

BackgroundConflicting results have been reported on the efficacy of insulin degludec/insulin aspart (IDegAsp) compared to basal insulin in type 2 diabetes. We investigated the effects of changing basal insulin to IDegAsp on glycemic control and sought to identify factors related to those effects.MethodsIn this retrospective study of patients from three referral hospitals, patients with type 2 diabetes using basal insulin with hemoglobin A1c (HbA1c) levels less than 11.0% were enrolled. Basal insulin was replaced with IDegAsp, and data were analyzed from 3 months before to 3 months after the replacement.ResultsEighty patients were recruited (52.5% male; mean age, 67.0±9.8 years; mean duration of diabetes, 18.9±8.5 years; mean HbA1c, 8.7%±1.0%). HbA1c levels increased during 3 months of basal insulin use, but significantly decreased after changing to IDegAsp (8.28%±1.10%, P=0.0001). The reduction was significant at 6 months in 35 patients whose longer-term data were available. Patients with a measured fasting plasma glucose (m-FPG) lower than their predicted FPG (p-FPG) by regression from HbA1c showed a significant HbA1c reduction caused by the change to IDegAsp, even without a significantly increased insulin dose. However, patients whose m-FPG was higher than their p-FPG did not experience a significant HbA1c reduction, despite a significantly increased insulin dose. Furthermore, the HbA1c reduction caused by IDegAsp was significant in patients with low fasting C-peptide levels and high insulin doses.ConclusionWe observed a significant glucose-lowering effect by replacing basal insulin with IDegAsp, especially in patients with a lower m-FPG than p-FPG.

Background: Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. Methods: Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. Results: PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. Conclusion: This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi. [ABSTRACT FROM AUTHOR]

Background/Aims Endoscopic ultrasonography (EUS) is the most efficient imaging modality for gastric subepithelial tumors (SETs). However, abdominopelvic computed tomography (APCT) has other advantages in evaluating the characteristics, local extension, or invasion of SETs to adjacent organs. This study aimed to compare the diagnostic ability of EUS and APCT based on surgical histopathology results. Methods We retrospectively reviewed data from 53 patients who underwent both EUS and APCT before laparoscopic wedge resection for gastric SETs from January 2010 to December 2017 at a single institution. On the basis of histopathology results, we assessed the diagnostic ability of the 2 tests. Results The overall accuracy of EUS and APCT was 64.2% and 50.9%, respectively. In particular, the accuracy of EUS vs. APCT for the diagnosis of gastrointestinal stromal tumors (GISTs), leiomyomas, and ectopic pancreas was 83.9% vs. 74.2%, 37.5% vs. 0.0%, and 57.1% vs. 14.3%, respectively. Most of the incorrect diagnoses with EUS involved hypoechoic lesions originating in the fourth echolayer, with the most common misdiagnosed lesions being GISTs mistaken for leiomyomas and vice versa. Conclusions APCT showed a lower overall accuracy than EUS; however, APCT remains a useful modality for malignant/potentially malignant gastric SETs.

We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had undergone continuous treatment with immunosuppressants. First, he complained of partial spasm from the left thigh to the left upper limb. Magnetic resonance imaging revealed multifocal enhancing nodules in the cortical and subcortical area of both cerebral hemispheres, which were suggestive of brain metastases. However, the patient developed fever with stuporous mentality and an open biopsy was performed immediately. Microscopically, numerous amoebic trophozoites, measuring 20 to 25 µm in size, with nuclei containing one to four nucleoli and some scattered cysts having a double-layered wall were noted in the background of hemorrhagic necrosis. Based on the microscopic findings, amoebic encephalitis caused by Balamuthia mandrillaris was diagnosed. The patient died on the 10th day after being admitted at the hospital. The diagnosis of amoebic encephalitis in the early stage is difficult for clinicians. Moreover, most cases undergo rapid deterioration, resulting in fatal consequences. In this report, we present the first case of B. mandrillaris amoebic encephalitis with fatal progression in a Korean patient.

Achalasia is a motility disorder of the esophagus characterized by absence of peristalsis and failure of relaxation of lower esophagus sphincter. The introduction of high resolution manometry (HRM) and per-oral endoscopic myotomy (POEM) has made a new chapter in diagnosis and treatment of achalasia. HRM allows classify according to the subtype of achalasia, and help predict prognosis and therapeutic response. POEM is a minimally invasive, effective option for treating achalasia. The management of achalasia required tailored application of various therapies such as botox injection, pneumatic balloon dilatation, POEM, or Heller’s myotomy. In this review, we state the important aspects of diagnosis as well as management of achalasia.

Abstract Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.

Cyclophilin A (CypA), which has peptidyl–prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression of several diseases, including inflammatory diseases, coronavirus infection, and cancer, by activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA and CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, therapeutic resistance, and the stem-like properties of cancer cells and is related to the poor prognosis of patients with cancer. This review aims to understand the biology and interaction of CypA and CD147 and to review the roles of the CypA/CD147 interaction in cancer pathology and the therapeutic potential of targeting the CypA/CD147 axis. To validate the clinical significance of the CypA/CD147 interaction, we analyzed the expression levels of PPIA and BSG genes encoding CypA and CD147, respectively, in a wide range of tumor types using The Cancer Genome Atlas (TCGA) database. We observed a significant association between PPIA/BSG overexpression and poor prognosis, such as a low survival rate and high cancer stage, in several tumor types. Furthermore, the expression of PPIA and BSG was positively correlated in many cancers. Therefore, this review supports the hypothesis that targeting the CypA/CD147 interaction may improve treatment outcomes for patients with cancer.

Renal artery injury is a rare complication in blunt trauma, but can cause devascularization of the kidney, leading to renal failure. It requires early diagnosis and management. The treatment of renal artery injury still remains controversial, but recent studies have reported the successful treatment outcome with endovascular stent placement. Nevertheless, there is no standard treatment strategy in cases of pediatric patients. We report a case of a 16-year-old girl with right renal artery occlusion associated with a grade IV liver laceration. She was treated with only balloon angioplasty, and the kidney showed marked improvement of parenchymal perfusion with normalized renal function. Treatment with only balloon angioplasty can be a treatment option in pediatric patients with renal artery injury.