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Abstract In our search for novel small molecules activating procaspase-3, we have designed and synthesized two series of novel (E)-N'-arylidene-2-(2-oxoindolin-1-yl)acetohydrazides (4) and (Z)-2-(5-substituted-2-oxoindolin-1-yl)-N'-(2-oxoindolin-3-ylidene)acetohydrazides (5). Cytotoxic evaluation revealed that the compounds showed notable cytotoxicity toward three human cancer cell lines: colon cancer SW620, prostate cancer PC-3, and lung cancer NCI-H23. Especially, six compounds, including 4f–h and 4n–p, exhibited cytotoxicity equal or superior to positive control PAC-1, the first procaspase-3 activating compound. The most potent compound 4o was three- to five-fold more cytotoxic than PAC-1 in three cancer cell lines tested. Analysis of compounds effects on cell cycle and apoptosis demonstrated that the representative compounds 4f, 4h, 4n, 4o and 4p (especially 4o) accumulated U937 cells in S phase and substantially induced late cellular apoptosis. The results show that compound 4o would serve as a template for further design and development of novel anticancer agents.

Secoisolariciresinol diglucoside (SDG), the most abundant lignan in flaxseed, is metabolized by the ruminal microbiota into enterolignans, which are strong antioxidants. Enterolactone (EL), the main mammalian enterolignan produced in the rumen, is transferred into physiological fluids, with potentially human health benefits with respect to menopausal symptoms, hormone-dependent cancers, cardiovascular diseases, osteoporosis and diabetes. However, no information exists to our knowledge on bacterial taxa that play a role in converting plant lignans into EL in ruminants. In order to investigate this, eight rumen cannulated cows were used in a double 4 × 4 Latin square design and fed with four treatments: control with no flax meal (FM), or 5%, 10% and 15% FM (on a dry matter basis). Concentration of EL in the rumen increased linearly with increasing FM inclusion. Total rumen bacterial 16S rRNA concentration obtained using Q-PCR did not differ among treatments. PCR-T-RFLP based dendrograms revealed no global clustering based on diet indicating between animal variation. PCR-DGGE showed a clustering by diet effect within four cows that had similar basal ruminal microbiota. DNA extracted from bands present following feeding 15% FM and absent with no FM supplementation were sequenced and it showed that many genera, in particular Prevotella spp., contributed to the metabolism of lignans. A subsequent in vitro study using selected pure cultures of ruminal bacteria incubated with SDG indicated that 11 ruminal bacteria were able to convert SDG into secoisolariciresinol (SECO), with Prevotella spp. being the main converters. These data suggest that Prevotella spp. is one genus playing an important role in the conversion of plant lignans to human health beneficial antioxidants in the rumen.

The supralittoral environment, at the transition between sea and land, is characterized by harsh conditions for life. Nonetheless, evolution of terrestrial isopods (Oniscidea), the only group of Crustacea fully adapted to live on land, appears to have involved a transitional step within the supralittoral. The two most basal oniscidean lineages (Ligiidae and Tylidae) have representatives that successfully colonized the supralittoral. One of them is the genus Tylos, which is found exclusively in supralittoral sandy beaches from tropical and subtropical coasts around the world. Comprehensive phylogenetic hypotheses for this genus are lacking, which are necessary for understanding the evolution and biogeography of a lineage that successfully diversified in the harsh sea-land interface. Herein, we studied the phylogenetic relationships among 17 of the 21 currently recognized species of the genus Tylos, based on sequences from four mitochondrial genes (Cytochrome Oxidase I, Cytochrome b, 16S rDNA, and 12S rDNA). Maximum Likelihood and Bayesian phylogenetic analyses identified several lineages with deep divergences and discrete geographic distributions. Phylogenetic and distributional patterns of Tylos provide important clues on the biogeography and evolution of this group. Large divergences among the most basal clades are consistent with ancient splits. Due to the biological characteristics of Tylos, which likely prevent dispersal of these isopods across vast oceanic scales, we argue that tectonic events rather than trans-oceanic dispersal explain the distribution of Tylos in different continents. Overwater dispersal, however, likely enabled range expansions within some basins, and explains the colonization of volcanic oceanic islands. Present-day distributions were also likely influenced by sea level and climate changes. High levels of allopatric cryptic genetic differentiation are observed in different regions of the world, implying that the dispersal abilities of Tylos isopods are more limited than previously thought. Our results indicate that a taxonomic revision of this group is necessary.

BackgroundExtensively drug-resistant Acinetobacter baumannii (XDR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Although solid organ transplant (SOT) recipients are particularly susceptible to XDR-Ab infections, studies in this population are limited. Our objectives were to determine the epidemiology, clinical characteristics and outcomes of XDR-Ab infections among SOT patients.MethodsA retrospective study of SOT recipients at our center who were colonized or infected with XDR-Ab between November 2006 and December 2011 was conducted. Among infected patients, the primary outcome was survival at 28 days. Secondary outcomes included survival at 90 days and clinical success at 28 days, and XDR-Ab infection recurrence.ResultsXDR-Ab was isolated from 69 SOT patients, of whom 41% (28) and 59% (41) were colonized and infected, respectively. Infections were significantly more common among cardiothoracic than abdominal transplant recipients (p=0.0004). Ninety-eight percent (40/41) of patients had respiratory tract infections, most commonly ventilator-associated pneumonia (VAP; 88% [36/41]). Survival rates at 28 and 90 days were 54% (22/41) and 46% (19/41), respectively. Treatment with a colistin-carbapenem regimen was an independent predictor of 28-day survival (p=0.01; odds ratio=7.88 [95% CI: 1.60-38.76]). Clinical success at 28 days was achieved in 49% (18/37) of patients who received antimicrobial therapy, but 44% (8/18) of successes were associated with infection recurrence within 3 months. Colistin resistance emerged in 18% (2/11) and 100% (3/3) of patients treated with colistin-carbapenem and colistin-tigecycline, respectively (p=0.03).ConclusionsXDR-Ab causes VAP and other respiratory infections following SOT that are associated with significant recurrence and mortality rates. Cardiothoracic transplant recipients are at greatest risk. Results from this retrospective study suggest that colistin-carbapenem combinations may result in improved clinical responses and survival compared to other regimens and may also limit the emergence of colistin resistance.

Abstract Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Objectives: The use of qualitative healthcare services or its discrepancy between different income levels of the type 2 diabetes (T2D) patients has seldom been studied concurrently. The present study is unique that regarding T2D patients of early stages of diagnosis. Aimed to assess the utilization of qualitative healthcare services and influence of income levels on the inequality of care among newly diagnosed patients with T2D. Methods: A retrospective cohort study of 7590 patients was conducted by the National Health Insurance Service National Sample Cohort 2.0 from 2002 to 2015. Insured employee in 2013 with no history of T2D between 2002 and 2012 were included. The standard of diabetes care includes hemoglobin A1c (HbAlc; 4 times/y), eyes (once/y) and lipid abnormalities (once/y). Multivariate logistic regression analysis was performed to examine the difference between income levels and inequality of care. Results: From years 1 to 3, rates of appropriate screening fell from 16.9% to 14.1% (HbA1c), 15.8% to 14.5% (eye), and 59.2% to 33.2% (lipid abnormalities). Relative to income class 5 (the highest-income group), HbA1 screening was significantly less common in class 2 (year 2: odds ratio [OR], 0.78; 95% confidence interval [CI], 0.61 to 0.99; year 3: OR, 0.79; 95% CI, 0.69 to 0.91). In year 1, lipid screening was less common in class 1 (OR, 0.84; 95% CI, 0.73 to 0.98) than in class 5, a trend that continued in year 2. Eye screening rates were consistently lower in class 1 than in class 5 (year 1: OR, 0.73; 95% CI, 0.60 to 0.89; year 2: OR, 0.63; 95% CI, 0.50 to 0.78; year 3: OR, 0.81; 95% CI, 0.67 to 0.99). Conclusions: Newly diagnosed T2D patients have shown low rate of HbA1c and screening for diabetic-related complications and experienced inequality in relation to receiving qualitative diabetes care by income levels.

Abstract Cerebrospinal fluid (CSF) plays an important role in brain tumors, including medulloblastoma (MBL). Recent advancements in mass spectrometry systems and ‘Omics’ data analysis methods enable unbiased, high proteome depth research. We conducted proteomic profiling of the total CSF in MBL patients with the purpose of finding a potential diagnostic biomarker for MBL. We quantified 1112 proteins per CSF sample. Feature selection identified four elevated soluble proteins (SPTBN1, HSP90AA1, TKT, and NME1-NME2) in MBL CSF. Validation with ELISA confirmed that TKT was significantly elevated in MBL. Additionally, TKT-positive extracellular vesicles were significantly enriched in MBL CSF and correlated with the burden of leptomeningeal seeding. Our results provide insights into the proteomics data of the total CSF of MBL patients. Furthermore, we identified the significance of TKT within the total CSF and its presence within circulating EVs in the CSF. We suggest that TKT may serve as a biomarker for MBL.

Abstract Obesity is the one of the most important components of metabolic syndrome. Because obesity related hypertension accounts for two thirds of essential hypertension, managing obesity and metabolic syndrome is a crucial task in the management of hypertension. However, the current non-pharmacological therapies have limitations for achieving or maintaining ideal body weight. Recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated excellent weight control effects, accompanied by corresponding reductions in blood pressure. GLP1-RAs have shown cardiovascular and renal protective effects in cardiovascular outcome trials both in primary and secondary prevention. In this document, the Korean Society of Hypertension intends to remark the current clinical results of GLP1-RAs and recommend the government and health-policy makers to define obesity as a disease and to establish forward-looking policies for GLP1-RA treatment for obesity treatment, including active reimbursement policies.

Abstract Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan–Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024–1.692; P

Abstract Objectives Wilson disease (WD) is a rare genetic disease affecting copper metabolism and the biliary tract’s copper excretion. Lifelong medication is necessary to prevent liver failure, neurological complications, and death. Although D-penicillamine (DPA), trientine, and zinc are used to treat WD, there is limited research on the long-term outcomes of these drugs, especially in children. This study aimed to evaluate the efficacy and safety of DPA, trientine, and zinc in patients diagnosed with WD during childhood. Methods Ninety out of 92 patients were included in the analysis, excluding two patients who underwent liver transplantation without drug treatment due to an acute liver failure diagnosis. Treatment outcomes and reasons for discontinuation of therapy in 148 treatment blocks (37 DPA, 50 trientine, and 61 zinc) were analyzed using Kaplan–Meier analysis. Results The median age at diagnosis was 8.3 years. There was a statistically significant difference in drug changes due to treatment ineffectiveness among the three drugs: trientine (22/50, 44%), zinc (15/61, 25%), and DPA (2/37, 5%) (all p

Abstract KCNQ4 is a voltage-gated K+ channel was reported to distribute over the basolateral surface of type 1 vestibular hair cell and/or inner surface of calyx and heminode of the vestibular nerve connected to the type 1 vestibular hair cells of the inner ear. However, the precise localization of KCNQ4 is still controversial and little is known about the vestibular phenotypes caused by KCNQ4 dysfunction or the specific role of KCNQ4 in the vestibular organs. To investigate the role of KCNQ4 in the vestibular organ, 6-g hypergravity stimulation for 24 h, which represents excessive mechanical stimulation of the sensory epithelium, was applied to p.W277S Kcnq4 transgenic mice. KCNQ4 was detected on the inner surface of calyx of the vestibular afferent in transmission electron microscope images with immunogold labelling. Vestibular function decrease was more severe in the Kcnq4 p.W277S/p.W277S mice than in the Kcnq4 +/+ and Kcnq4 +/p.W277S mice after the stimulation. The vestibular function loss was resulted from the loss of type 1 vestibular hair cells, which was possibly caused by increased depolarization duration. Retigabine, a KCNQ activator, prevented hypergravity-induced vestibular dysfunction and hair cell loss. Patients with KCNQ4 mutations also showed abnormal clinical vestibular function tests. These findings suggest that KCNQ4 plays an essential role in calyx and afferent of type 1 vestibular hair cell preserving vestibular function against excessive mechanical stimulation.

Abstract Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

Chikungunya fever, a viral illness transmitted to humans through the bites of infected mosquitoes, presents with symptoms such as high fever, severe myalgia, headache, arthralgia, rash, and vomiting. This disease predominantly manifests in Southeast Asia, Africa, and Central and South America, with a limited occurrence in Northeast Asia. To date, no such a documented case has been reported in South Korea. Herein, we present the first adolescent case of chikungunya fever in South Korea following a travel to Bali, Indonesia.

Abstract Lumbar sympathetic ganglion neurolysis (LSGN) has been used for long-term pain relief in patients with complex regional pain syndrome (CRPS). However, the actual effect duration of LSGN has not been accurately measured. This prospective observational study measured the effect duration of LSGN in CRPS patients and investigated the relationship between temperature change and pain relief. After performing LSGN, the skin temperatures of both the maximum pain site and the plantar area in the affected and unaffected limbs were measured by infrared thermography, and pain intensity was assessed before and at 2 weeks, 1 month, and 3 months. The median time to return to baseline temperature was calculated using survival analysis. The skin temperature increased significantly at all-time points relative to baseline in both regions (maximum pain site: 1.4 °C ± 1.0 °C, plantar region: 1.28 °C ± 0.8 °C, all P

Abstract Background Dizziness and vertigo rank among the top 10 reasons for emergency and clinical referrals to neurologists. Chronic dizziness and imbalance not only reduce quality of life, but also increase mortality. While the Mediterranean diet has long been considered beneficial for human and planetary health, its effects on chronic dizziness or imbalance are understudied. We investigated the associations of adherence to the Mediterranean diet with chronic dizziness and imbalance. Methods This study used data from the Korea National Health and Nutrition Examination Survey 2019–2021 and included 4,183 adults aged 40 years and older with complete information from diet, dizziness, and neurotology questionnaires. The alternate Mediterranean diet score (aMed) for nine food groups was calculated from 24-hour dietary recall data. Based on questionnaire responses, chronic dizziness was categorized as either isolated or chronic dizziness with imbalance, characterized by a cluster of difficulties maintaining a standing position, walking, or falling. Results In a multivariable-adjusted model, the prevalence of chronic imbalance was lower in the top aMed tertile than in the bottom tertile (OR 0.37; 95% CI, 0.18–0.74; p-trend = 0.01). Among the individual aMed components, the intake of whole grains and nuts exhibited an inverse relationship with chronic imbalance (OR 0.50; 95% CI, 0.27–0.93 for whole grains; OR 0.55; 95% CI, 0.31–1.01 for nuts). The aMed score was not associated with isolated chronic dizziness. Conclusions Greater adherence to the Mediterranean diet may reduce chronic imbalance, particularly with an adequate intake of whole grains and nuts.

Objectives The existing evidence for the impacts of continuity of care (COC) in patients with chronic obstructive pulmonary disease (COPD) is low to moderate. This study aimed to investigate the associations between relational COC within primary care and COPD-related hospitalisations using a robust methodology.Design Population-based cohort study.Setting National Health Insurance Service database, South Korea.Participants 92 977 adults (≥40 years) with COPD newly diagnosed between 2015 and 2016 were included. The propensity score (PS) matching approach was used. PSs were calculated from a multivariable logistic regression that included eight baseline characteristics.Exposure COC within primary care.Main outcome measures The primary outcome was the incidence of COPD-related hospitalisations. Cox proportional hazard models were used to estimate HRs and 95% CIs.Results Out of 92 977 patients, 66 677 of whom were cared for continuously by primary doctors (the continuity group), while 26 300 were not (the non-continuity group). During a 4-year follow-up period, 2094 patients (2.25%) were hospitalised; 874 (1.31%) from the continuity group and 1220 (4.64%) from the non-continuity group. After adjusting for confounding covariates, patients in the non-continuity group exhibited a significantly higher risk of hospital admission (adjusted HR (aHR) 2.43 (95% CI 2.22 to 2.66)). This risk was marginally reduced to 2.21 (95% CI 1.99 to 2.46) after PS matching. The risk of emergency department (ED) visits, systemic corticosteroid use and costs were higher for patients in the non-continuity group (aHR 2.32 (95% CI 2.04 to 2.63), adjusted OR 1.25 (95% CI 1.19 to 1.31) and expβ=1.89 (95% CI 1.82 to 1.97), respectively). These findings remained consistent across the PS-matched cohort, as well as in the sensitivity and subgroup analyses.Conclusions In patients with COPD aged over 40, increased continuity of primary care was found to be associated with less hospitalisation, fewer ED visits and lower healthcare expenditure.

Pavlovian fear conditioning research suggests that the interaction between the dorsal periaqueductal gray (dPAG) and basolateral amygdala (BLA) acts as a prediction error mechanism in the formation of associative fear memories. However, their roles in responding to naturalistic predatory threats, characterized by less explicit cues and the absence of reiterative trial-and-error learning events, remain unexplored. In this study, we conducted single-unit recordings in rats during an ‘approach food-avoid predator’ task, focusing on the responsiveness of dPAG and BLA neurons to a rapidly approaching robot predator. Optogenetic stimulation of the dPAG triggered fleeing behaviors and increased BLA activity in naive rats. Notably, BLA neurons activated by dPAG stimulation displayed immediate responses to the robot, demonstrating heightened synchronous activity compared to BLA neurons that did not respond to dPAG stimulation. Additionally, the use of anterograde and retrograde tracer injections into the dPAG and BLA, respectively, coupled with c-Fos activation in response to predatory threats, indicates that the midline thalamus may play an intermediary role in innate antipredatory-defensive functioning.

Background Spinal anesthesia-induced hypotension (SAH) frequently occurs in older patients, many of whom have mild left ventricular (LV) diastolic dysfunction, often asymptomatic at rest. This study investigated the association between preoperative echocardiographic measurements and SAH in older patients with mild LV diastolic dysfunction. Methods We conducted a retrospective observational study using data from electronic medical records. The patients ≥ 65 years old who underwent spinal anesthesia for urologic surgery between January 2016 and December 2017 and whose preoperative echocardiography within 6 months before surgery revealed grade I LV diastolic dysfunction were recruited. SAH was investigated using the anesthesia records. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results A total of 163 patients were analyzed. SAH and significant SAH developed in 55 (33.7%) patients. The mitral inflow E velocity was an independent risk factor for SAH (odds ratio [OR], 0.886; 95% confidence interval [CI], 0.845–0.929; P < 0.001). The area under the ROC curve for mitral inflow E velocity to predict SAH was 0.819 (95% CI, 0.752–0.875; P < 0.001). If mitral inflow E velocity was ≤ 60 cm/s, SAH was predicted with a sensitivity of 83.6% and specificity of 70.4%. Conclusions The preoperative mitral inflow E velocity demonstrated the greatest predictability of SAH in older patients with mild LV diastolic dysfunction. This may assist in identifying patients at high risk of SAH and guiding preventive strategies in the future.

Purpose This study aimed to describe the process of developing a validated pediatric nursing simulation scenario template using the real-time Delphi method. Methods A panel of 13 pediatric nursing experts participated in a real-time Delphi survey conducted over two rounds. Initially, 83 items were included in the questionnaire focusing on the structure and content of the simulation scenario template. Data analysis involved calculating the content validity ratio (CVR) and the coefficient of variation to assess item validity and stability. Results Through iterative rounds of the Delphi survey, a consensus was reached among the experts, resulting in the development of a pediatric nursing simulation scenario template comprising 41 items across nine parts. The CVR values ranged from 0.85 to 1.0, indicating a high consensus among experts regarding the inclusion of all items in the template. Conclusion This study presents a novel approach for developing a pediatric nursing simulation scenario template using real-time Delphi methods. The real-time Delphi method facilitated the development of a comprehensive and scientifically grounded pediatric nursing simulation scenario template. Our template aligns with the International Nursing Association for Clinical Simulation and Learning standards, and provides valuable guidance for educators in designing effective simulation scenarios, contributing to enhanced learning outcomes and better preparation for pediatric clinical practice. However, consideration of cultural and contextual adaptations is necessary, and further research should explore alternative consensus criteria.

Abstract Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

Abstract We aimed to investigate the changes in cupping in chiasmal lesion optic neuropathy (chON) compared to baseline optic disc and glaucoma. We used a novel study design to enroll patients who had fundus photographs incidentally taken during routine health check-ups prior to the onset of optic neuropathy. In 31 eyes (21 patients) with chON and 33 eyes (30 patients) with glaucoma, we investigated the change in cup-to-disc (C/D) area from the baseline to overt cupping using flicker analysis. Compared to the baseline, 23 eyes (74.2%) had increased cup size and 3 (9.7%) had vascular configuration changes in the chONgroup; in contrast, all glaucoma eyes exhibited changes in cup size and vascular configuration. The increase in C/D area ratio was significantly smaller in chON (0.04 ± 0.04) compared to glaucoma (0.10 ± 0.04, P

Purpose This study aimed to assess the survival rate (SR) and death risk for associated pulmonary arterial hypertension (aPAH; 10th revision of the International Statistical Classification of Diseases [ICD-10], I27.2) in Koreans. Methods The data were collected from the Korean National Health Insurance Service from 2006 through 2017 (n= 15,448). We analyzed the SR using the Kaplan-Meier method and carried out Cox proportional hazards analyses. Results Patients’ mean age upon aPAH diagnosis was 60.1±24.0 years, and 60.7% of the patients were female. The 10-year SR of aPAH was 46.3% (95% confidence interval, 45.0 to 47.6). The factors associated with an increase in the adjusted death risk included age of 0 to 9 years, advancing age, male sex, lower income level, and comorbidities including diabetes mellitus, myocardial infarction, heart failure, hemorrhagic stroke, chronic kidney disease, malignant neoplasm, hereditary hemorrhagic telangiectasia, and systemic lupus erythematosus. Conclusion The 10-year SR of aPAH was over 46%. The risk of death from aPAH was significantly higher with advancing age, sex, lower income level, and comorbidities.

Abstract Loss of myelin in the brain may lead to cognitive decline in Alzheimer's disease (AD). The ratio of T1 weighted/T2 weighted (T1w/T2w) on magnetic resonance imaging has been used as a proxy for myelin content in the brain. Using this approach, we investigated the correlation between the white matter (WM) T1w/T2w ratio and both cognitive scores and disease progression in AD. A total of 93 participants who were cognitively unimpaired or diagnosed with mild cognitive impairment or AD dementia were recruited between March 2021 and November 2022. All participants were assessed using neuropsychological tests, and a subset of the participants was assessed every 1 year to monitor disease progression. We observed significant positive associations between the WM T1w/T2w ratio and executive function within the fornix, sagittal stratum, anterior internal capsule, and body of the corpus callosum (False discovery rate [FDR]-corrected P-value

Abstract This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P

Background/Aims Epicardial adipose tissue (EAT) shares pathophysiological properties with other visceral fats and potentially triggers local inflammation. However, the association of EAT with cardiovascular disease (CVD) is still debatable. The study aimed to observe the changes and associations in EAT and risk factors over time, as well as to investigate whether EAT was associated with CVD. Methods A total of 762 participants from Seoul National University Hospital (SNUH) and SNUH Gangnam Center were included in this study. EAT was measured using coronary computed tomography angiography. Results Baseline EAT level was positively associated with body mass index (BMI), calcium score, atherosclerotic cardiovascular disease (ASCVD) 10-year risk score, glucose, triglycerides (TG)/high-density lipoprotein (HDL), but not with total cholesterol, low-density lipoprotein (LDL). At follow-up, EAT levels increased in all groups, with low EAT groups demonstrating a significant increase in EAT per year. Change in EAT was associated with a change in BMI, TG/HDL, and glucose, while changes in LDL, calcium score, and ASCVD 10-year risk score were not associated. Although calcium score and ASCVD 10-year risk score were associated with CVD events, baseline information of EAT, baseline EAT/body surface area, or EAT change was not available. Conclusions Metabolic risks, e.g., BMI, TG/HDL, and glucose, were associated with EAT change per year, whereas classical CVD risks, e.g., LDL, calcium score, and ASCVD 10-year risk score, were not. The actual CVD event was not associated with EAT volume, warranting future studies combining qualitative assessments with quantitative ones.

Abstract Previous studies have reported the association between myocardial infarction (MI) and air pollution (AP). However, limited information is available regarding the long-term effects of AP on the relative incidence rates of ST-elevation MI (STEMI) and Non-ST-elevation MI (NSTEMI). We investigated the association between long-term exposure to AP and the incidence of STEMI. Between January 2006 and December 2015, a total of 45,619 eligible patients with Acute Myocardial Infarction (AMI) were enrolled in the Korea Acute MI Registry (KAMIR) and KAMIR-National Institutes of Health. Mixed-effect regression models were used to examine the association between the annual average ambient AP before MI onset and the incidence of STEMI, and to evaluate the association of AP with the incidence of in-hospital cardiogenic shock. After mixed-effect regression model analysis, particulate matter (PM) 10 µm or less in diameter (PM10) was associated with increased incidence of STEMI compared with NSTEMI (odds ratio [OR] 1.009, 95% Confidence Interval [CI] 1.002–1.016; p = 0.012). For in-hospital cardiogenic shock complication, PM10 and SO2 were associated with increased risk, PM10 (OR 1.033, 95% CI 1.018–1.050; p

BackgroundUp to 50% of antibiotic prescriptions for upper respiratory infections (URIs) are inappropriate. Clinical decision support (CDS) systems to mitigate unnecessary antibiotic prescriptions have been implemented into electronic health records, but their use by providers has been limited. ObjectiveAs a delegation protocol, we adapted a validated electronic health record–integrated clinical prediction rule (iCPR) CDS-based intervention for registered nurses (RNs), consisting of triage to identify patients with low-acuity URI followed by CDS-guided RN visits. It was implemented in February 2022 as a randomized controlled stepped-wedge trial in 43 primary and urgent care practices within 4 academic health systems in New York, Wisconsin, and Utah. While issues were pragmatically addressed as they arose, a systematic assessment of the barriers to implementation is needed to better understand and address these barriers. MethodsWe performed a retrospective case study, collecting quantitative and qualitative data regarding clinical workflows and triage-template use from expert interviews, study surveys, routine check-ins with practice personnel, and chart reviews over the first year of implementation of the iCPR intervention. Guided by the updated CFIR (Consolidated Framework for Implementation Research), we characterized the initial barriers to implementing a URI iCPR intervention for RNs in ambulatory care. CFIR constructs were coded as missing, neutral, weak, or strong implementation factors. ResultsBarriers were identified within all implementation domains. The strongest barriers were found in the outer setting, with those factors trickling down to impact the inner setting. Local conditions driven by COVID-19 served as one of the strongest barriers, impacting attitudes among practice staff and ultimately contributing to a work infrastructure characterized by staff changes, RN shortages and turnover, and competing responsibilities. Policies and laws regarding scope of practice of RNs varied by state and institutional application of those laws, with some allowing more clinical autonomy for RNs. This necessitated different study procedures at each study site to meet practice requirements, increasing innovation complexity. Similarly, institutional policies led to varying levels of compatibility with existing triage, rooming, and documentation workflows. These workflow conflicts were compounded by limited available resources, as well as an implementation climate of optional participation, few participation incentives, and thus low relative priority compared to other clinical duties. ConclusionsBoth between and within health care systems, significant variability existed in workflows for patient intake and triage. Even in a relatively straightforward clinical workflow, workflow and cultural differences appreciably impacted intervention adoption. Takeaways from this study can be applied to other RN delegation protocol implementations of new and innovative CDS tools within existing workflows to support integration and improve uptake. When implementing a system-wide clinical care intervention, considerations must be made for variability in culture and workflows at the state, health system, practice, and individual levels. Trial RegistrationClinicalTrials.gov NCT04255303; https://clinicaltrials.gov/ct2/show/NCT04255303

Abstract This study aimed to identify somatic mutations in nontumor cells (NSMs) in normal prostate and benign prostatic hyperplasia (BPH) and to determine their relatedness to prostate cancer (PCA). From 22 PCA patients, two prostates were sampled for 3-dimensional mapping (50 normal, 46 BPH and 1 PCA samples), and 20 prostates were trio-sampled (two normal or BPH samples and one PCA sample) and analyzed by whole-genome sequencing. Normal and BPH tissues harbored several driver NSMs and copy number alterations (CNAs), including in FOXA1, but the variations exhibited low incidence, rare recurrence, and rare overlap with PCAs. CNAs, structural variants, and mutation signatures were similar between normal and BPH samples, while BPHs harbored a higher mutation burden, shorter telomere length, larger clone size, and more private NSMs than normal prostates. We identified peripheral-zonal dominance and right-side asymmetry in NSMs, but the asymmetry was heterogeneous between samples. In one normal prostate, private oncogenic RAS-signaling NSMs were detected, suggesting convergence in clonal maintenance. Early embryonic mutations exhibited two distinct distributions, characterized as layered and mixed patterns. Our study identified that the BPH genome differed from the normal prostate genome but was still closer to the normal genome than to the PCA genome, suggesting that BPH might be more related to aging or environmental stress than to tumorigenic processes.

Abstract We aimed to investigate the age-related glaucoma progression rates in myopic normal tension glaucoma (NTG). In this long-term retrospective cohort (7.2 ± 3.5 years), we grouped patients based on their age at initial presentation: group A (age

Abstract To determine the increased risk of major adverse cardiovascular events (MACE) in patients with systemic lupus erythematosus (SLE) compared to the general population in Korea. Using data from the National Health Insurance Service database spanning 2008 to 2018, incident SLE patients aged 18 years and above were selected along with a 1:4 age- and sex-matched control group. The crude incidence rate (IR) of MACE was calculated as the number of events per 1000 person-years and the IR ratio (IRR) for MACE was adjusted using generalized estimating equations. Subgroup analysis was conducted to evaluate the risk differences of overall MACE and its composites based on age and sex stratification. The study included 8568 SLE patients and 34,272 controls. The cumulative IR of MACE per 1000 person-years in SLE patients and controls were 4.08 and 1.30, respectively. After adjusting for confounders, SLE patients had a higher risk of MACE compared to the general population (adjusted IRR of 2.40 [95% confidence interval [CI] 1.88–3.05]), with no gender differences observed. The increased risk of MACE in SLE patients was highest in the 18–39 age group (IRR 11.70, 95% CI 5.95–23.01) and gradually decreased with age. The increased risk of ischemic stroke (IRR 2.41, 95% CI 1.84–3.15) and myocardial infarction (IRR 2.19, 95% CI 1.30–3.68) in SLE patients was comparable. The risk of MACE in SLE patients is 2.40 times higher than that of the general population, with a higher relative risk observed in younger individuals.

Small bowel variceal bleeding is a rare cause of gastrointestinal hemorrhage, with clinical manifestations ranging from asymptomatic incidental findings to life-threatening conditions. The diagnosis and management of small bowel bleeding are challenging because of the localization of the lesion and the difficulty of the procedure. Trans-arterial embolization (TAE) is a secure and straightforward method for treating ectopic varices. On the other hand, there have been limited local studies on the outcomes of TAE for patients with small bowel variceal hemorrhage. This paper reports patients diagnosed with small bowel variceal bleeding and treated with TAE.

Abstract Hyposalivation is a common complaint among the elderly, but no established treatment prevents age-induced hyposalivation. Platelet derivatives such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and plasma rich in growth factor (PRGF), are used widely in different areas of regenerative medicine to enhance the wound healing processes. This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction. The platelets were separated from the blood of male SD rats (220 ± 20 g). saPRP was manufactured by removing the fibrin clot after activating platelet with calcium ionophore 10 μM (A23187). The total protein and TGF-β1 levels were significantly higher in saPRP than in PRP. Human salivary gland epithelial cell(hSGEC) was treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation significantly reduced in saPRP group. The SG function and structural tissue remodeling by the saPRP were investigated with naturally aged mice. The mice were divided into three groups: 3 months old (3 M), 22 months old (22 M), and 22 months old treated with saPRP (22 M + saPRP). Salivary flow rate and lag time were significantly improved in 22 M + saPRP group compared to 22 M group. The histologic examinations showed the significant proliferation of acinar cell in 22 M + saPRP group. The decrease of senescence, apoptosis, and inflammation observed by western blot in 22 M + saPRP group. The saPRP induced the proliferation of hSGECs, leading to a significant decrease in cellular senescence via decrease inflammation and apoptosis, in vitro. Moreover, the acini cells of the salivary gland were regenerated, and the salivary function increased in aged mice. These results showed that saPRP could be a treatment agent against aging-induced SG dysfunction.

Abstract The molecular changes that occur with the progression of Alzheimer’s disease (AD) are well known, but an understanding of the spatiotemporal heterogeneity of changes in the brain is lacking. Here, we investigated the spatially resolved transcriptome in a 5XFAD AD model at different ages to understand regional changes at the molecular level. Spatially resolved transcriptomic data were obtained from 5XFAD AD models and age-matched control mice. Differentially expressed genes were identified using spots clustered by anatomical structures. Gene signatures of activation of microglia and astrocytes were calculated and mapped on the spatially resolved transcriptomic data. We identified early alterations in the white matter (WM) of the AD model before the definite accumulation of amyloid plaques in the gray matter (GM). Changes in the early stage of the disease involved primarily glial cell activation in the WM, whereas the changes in the later stage of pathology were prominent in the GM. We confirmed that disease-associated microglia (DAM) and astrocyte (DAA) signatures also showed initial changes in WM and that activation spreads to GM. Trajectory inference using microglial gene sets revealed the subdivision of DAMs with different spatial patterns. Taken together, these results help to understand the spatiotemporal changes associated with reactive glial cells as a major pathophysiological characteristic of AD. The heterogeneous spatial molecular changes apply to identifying diagnostic and therapeutic targets caused by amyloid accumulation in AD.

Abstract NA4/NA6, an intermediate degradation product of β-agarase, is a high value-added product with anticancer, anti-obesity, and anti-diabetic effects. Therefore, a method that enables the efficient production of NA4/NA6 would be useful from economic and medical perspectives. In this study, we aimed to generate a Streptomyces coelicolor A3(2) mutant M22-2C43 that produces NA4/NA6 as a final product; this method serves as a more efficient alternative to the enzymatic conversion of β-agarase for the generation of these products. The M22-2C43 strain was generated through two rounds of mutagenesis and screening for increased β-agarase activity and effective production of NA4/NA6. We assembled the complete genomes of two mutants, M22 and M22-2C43, which were identified following a two-round screening. Large and small genetic changes were found in these two mutants, including the loss of two plasmids present in wild-type S. coelicolor A3(2) and chromosome circularization of mutant M22-2C43. These findings suggest that mutant M22-2C43 can produce NA4/NA6 as a degradation product due to functional inactivation of the dagB gene through a point mutation (G474A), ultimately preventing further degradation of NA4/NA6 to NA2. To our knowledge, this is the first report of a microbial strain that can effectively produce NA4/NA6 as the main degradation product of β-agarase, opening the door for the use of this species for the large-scale production of this valuable product.

Abstract Exposure to heavy metals such as lead, cadmium, and mercury poses serious health risks to pregnant women because of their high toxicity. In this study, we investigated the associations of heavy metal exposure with birth outcomes of Korean infants. Data of 5,215 women between 2015 and 2019 were analyzed. This study was part of the Korean Children’s Environmental Health (Ko-CHENS) study. Linear regression and logistic regression analyses were used to examine effects of concentrations of lead, cadmium, and mercury on birth weight, small for gestational age, and large for gestational age after adjusting for maternal age groups, parity, infant sex, education, income, smoking, drinking, body mass index, stillbirth, premature birth, diabetes, hypertension, and gestational diabetes. Besides adjusting for these covariates, each metal was mutually adjusted to estimate birth weight and large for gestational age status. Maternal cadmium concentrations during early pregnancy (β = − 39.96; 95% confidence interval (CI): − 63.76, − 16.17) and late pregnancy (β = − 37.24; 95% CI − 61.63, − 12.84) were significantly associated with birth weight. Cadmium levels during early pregnancy (adjusted OR = 0.637; 95% CI 0.444, 0.912) were also associated with large for gestational age status. Our findings suggest that prenatal cadmium exposure, even at a low level of exposure, is significantly associated with low birth weight.

Abstract Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III.

Abstract Although reports vary, the prevalence of true resistant hypertension and apparent treatment-resistant hypertension (aTRH) has been reported to be 10.3% and 14.7%, respectively. As there is a rapid increase in the prevalence of obesity, chronic kidney disease, and diabetes mellitus, factors that are associated with resistant hypertension, the prevalence of resistant hypertension is expected to rise as well. Frequently, patients with aTRH have pseudoresistant hypertension [aTRH due to white-coat uncontrolled hypertension (WUCH), drug underdosing, poor adherence, and inaccurate office blood pressure (BP) measurements]. As the prevalence of WUCH is high among patients with aTRH, the use of out-of-office BP measurements, both ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM), is essential to exclude WUCH. Non-adherence is especially problematic, and methods to assess adherence remain limited and often not clinically feasible. Therefore, the use of HBPM and higher utilization of single-pill fixed-dose combination treatments should be emphasized to improve drug adherence. In addition, primary aldosteronism and symptomatic obstructive sleep apnea are quite common in patients with hypertension and more so in patients with resistant hypertension. Screening for these diseases is essential, as the treatment of these secondary causes may help control BP in patients who are otherwise difficult to treat. Finally, a proper drug regimen combined with lifestyle modifications is essential to control BP in these patients. Graphical Abstract

Background/Aims There are limited studies on the management of hepatic hemangiomas (HHs). We investigated the proportion and predictors of surgical resection and analyzed HH growth rates in addition to associated factors. Methods A retrospective case-control study of patients treated in 2 centers was conducted. Thirty-six patients who underwent surgical resection were assigned to the case group. Patients who did not undergo surgical treatment were randomly selected at a 1:10 ratio and assigned to the control group (n = 360). Baseline characteristics, clinical course and surgical outcomes were analyzed. Results The proportion of surgically treated HH patients was 0.3% (36 per 11,049). The longest diameter at diagnosis (mean ± standard deviation) was 7.7 ± 5.2 cm in the case group and 2.4 ± 1.8 cm in the control group (p < 0.001). In the multivariate analysis, the presence of more than 2 HHs (odds ratio [OR] 7.64, 95% confidence interval [CI] 1.40–41.72) and a growth rate of more than 4.8%/year (OR 30.73, 95% CI 4.86–194.51) were independently associated with surgical treatment. Symptom development during follow-up was related to HH size > 10 cm (OR 10.50, 95% CI 1.06–103.77, p = 0.04). The subgroup analysis showed substantial growth in 41.3% with an overall mean annual growth rate of 0.14 cm. Conclusions Approximately one in 300 patients with an HH underwent surgical treatment. Multiple HHs and a growth rate of more than 4.8%/year were indications for surgical treatment. Nearly half of the HHs showed growing pattern in our study.

Background Traditionally, the patient's head is placed in a neutral position with a chin-lift to facilitate light wand guided endotracheal intubation. However, our study found that the sniffing position was more effective. In this study, we aimed to compare the two positions of light wand guided endotracheal intubation. Methods Sixty adult patients were included in the study, after obtaining informed consent, and were randomly assigned to one of two groups: a control group in a neutral position with a chin-lift (group C, n = 30) and a sniffing position group (group S, n = 30). In group C, the anesthesiologist inserted a light wand after lifting the patient's mandible using the thumb of their non-dominant hand inside the patient's mouth. In group S, a light wand was inserted after the patient's head was flexed with the neck extended. We assessed variables such as light-search time, number of intubation attempts, time to achieve intubation, and side effects including blood tinge on the endotracheal tube, hoarseness, sore throat, and anesthesiologist satisfaction. Results The light-search and intubation times were shorter in group S than in group C. The incidence of blood tinge on the endotracheal tube was higher in group C than in group S. Anesthesiologist satisfaction was higher in group S than in group C. Conclusions The sniffing position was more effective in facilitating light wand guided endotracheal intubation than the neutral position with a chin-lift.

Abstract In this study, to develop soft pressure sensor applicable to wearable robots using stretchable polymers and conductive fillers, 3.25 wt% carbon nanotubes/thermoplastic polyurethane filament with shore 94 A were manufactured. Three infill densities (20%, 50%, and 80%) and patterns (zigzag (ZG), triangle (TR), honeycomb (HN)) were applied to print cubes via fused filament fabrication 3D printing. Most suitable infill conditions were confirmed based on the slicing images, morphologies, compressive properties, electrical properties, and electrical heating properties. For each infill pattern, ZG and TR divided the layers into lines and figures, and the layers were stacked by rotation. For HN, the same layers were stacked in a hexagonal pattern. Consequently, TR divided layer in various directions, showed the strongest compressive properties with toughness 1.99 J for of infill density 80%. Especially, the HN became tougher with increased infill density. Also, the HN laminated with the same layer showed excellent electrical properties, with results greater than 14.7 mA. The electrical heating properties confirmed that ZG and HN had the high layer density, which exhibited excellent heating characteristics. Therefore, it was confirmed that performance varies depending on the 3D printing direction, and it was confirmed that HN is suitable for manufacturing soft sensors.

With an aging population, the number of patients with difficulty in swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. However, the long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach that is aided endoscopically and may be an alternative to a nasogastric tube when enteral nutritional is required for four weeks or more. This paper is the first Korean clinical guideline for PEG developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tubes removal for PEG based on the currently available clinical evidence.

Abstract To evaluate the differential associations of high-risk plaque characteristics (HRPC) with resting or hyperemic physiologic indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve [FFR]), a total of 214 vessels from 127 patients with stable angina or acute coronary syndrome who underwent coronary computed tomography angiography (CCTA) and invasive physiologic assessment were investigated. HPRC were classified into quantitative (minimal luminal area 0.80 or iFR > 0.89, respectively. FFR was independently associated with both quantitative and qualitative HRPC, but iFR was only associated with quantitative HRPC. Both FFR and iFR were significantly associated with the presence of ≥ 3 HRPC, and FFR demonstrated higher discrimination ability than iFR (AUC 0.703 vs. 0.648, P = 0.045), which was predominantly driven by greater discriminating ability of FFR for quantitative HRPC (AUC 0.832 vs. 0.744, P = 0.005). In conclusion, both FFR and iFR were significantly associated with CCTA-derived HRPC. Compared with iFR, however, FFR was independently associated with the presence of qualitative HRPC and showed a higher predictive ability for the presence of ≥ 3 HRPC.