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Background: Recently, cough reflex hypersensitivity has been proposed as a common underlying feature of chronic cough in adults. However, symptoms and clinical characteristics of cough hypersensitivity have not been studied amongst phenotypes of chronic cough. This study aimed to compare symptom features, such as cough triggers and associated throat sensations, of cough hypersensitivity in patients with asthmatic chronic cough and those with refractory chronic cough (RCC)., Methods: Patients with chronic cough from the Korean Chronic Cough Registry were prospectively evaluated over 6 months. Physicians determined the aetiological diagnosis based on clinical evaluations and responses to treatment at the 6-month follow-up visit. Symptoms of cough hypersensitivity and cough-specific quality of life were assessed using the Cough Hypersensitivity Questionnaire (CHQ) and the Leicester Cough Questionnaire (LCQ), respectively., Results: The analysis included 280 patients who completed the follow-up: 79 with asthmatic cough (cough variant asthma or eosinophilic bronchitis) and 201 with RCC. Baseline CHQ scores were similar between the groups (8.3±3.7 in asthmatic cough versus 8.9±3.9 in RCC; p=0.215, adjusted for age, sex and LCQ score). There were no significant between-group differences in the LCQ and cough severity Visual Analog Scale scores. Both groups showed a similar negative correlation with LCQ scores (asthmatic cough: r=-0.427, p<0.001; RCC: r=-0.306, p<0.001)., Conclusions: The symptoms of cough hypersensitivity may not distinguish between asthmatic cough and RCC. This suggests that chronic cough is the primary diagnosis in both phenotypes. It indicates a shared mechanism in their cough pathogenesis, despite having potentially different treatable traits., Competing Interests: Conflict of interest: S.S. Birring declares grants from Merck Sharp & Dohme Corp. and consulting fees from Merck, Shionogi, Bayer, Nerre, Genentech/Roche and Bellus. Conflict of interest: W-J. Song declares grants from Merck Sharp & Dohme Corp. and AstraZeneca; consulting fees from Merck, Bellus, AstraZeneca, Shionogi and GSK; and lecture fees from Merck, AstraZeneca, GSK, Sanofi and Novartis; and is deputy chief editor of this journal. Conflict of interest: The other authors declare that they have no competing interests., (Copyright ©The authors 2024.)

Objective: To analyze the factors influencing the increase in the cesarean delivery (CD) rate in South Korea and test the hypothesis on advanced maternal age driving the trend., Method: The present study is a population-based retrospective observational study utilizing administrative data from the Korean National Health Insurance Service. We analyzed a total 3 416 517 births from 2013 to 2022 covered by the national health insurance. The CD rate and contribution of demographic variables to changes in CD rates were calculated using Das Gupta's decomposition method., Results: The CD rate increased from 37.8% in 2013 to 61.6% in 2022. The decomposition analysis revealed that changes in maternal age structure contributed only 8.7% to the increase in the CD rate. When parity was added to maternal age, the explained proportion increased to 17.8%. When other factors were added to the model, such as multiple births, residential area, and income level, it did not contribute significantly to the increase in the CD rates, accounting for 19.0%, 18.6%, and 18.0%, respectively., Conclusions: According to our analysis, less than one-fifth of the increase in CD rate was explained by the change in maternal age. The rising CD rate in Korea should not be considered an unavoidable consequence of demographic change. Much more diverse factors, including increased risk of medical lawsuits, changes in childbirth culture, and other health system determinants, may be driving the trend., (© 2024 International Federation of Gynecology and Obstetrics.)

Research on keloid is limited by the lack of proper in vitro and animal model reflecting in vivo status. Based on heterogeneity of keloid and important role of endothelial cells in its pathogenesis, a novel 3D in vitro keloid spheroid prepared with keloid fibroblasts and endothelial cells was evaluated in this study. Commercial cell lines of keloid fibroblasts and endothelial cells were used at various cellular ratios to generate keloid spheroids to determine the optimal condition. Keloid spheroids from three keloid patients were also made and their usefulness as in vitro models, including their responses to drugs, were assessed. Spheroids with higher endothelial cell proportions exhibited increased viability and propagation ability. Patient-derived keloid spheroids showed heterogeneity which might reflect individual clinical conditions. The optimal ratio of fibroblasts to endothelial cells was determined to be 4:1 for keloid spheroids based on gene expression and viability analyses. Patient-derived keloid spheroid showed better keloidal changes in genetic expressions than 2D monolayer culture. Spheroids exhibited varied responses and resistance to each drug used for keloids, depending on the cell type used. 3D keloid spheroids might provide an effective in vitro model for investigating disease pathogenesis and appropriate treatment modalities for future precision medicine., (© 2024. The Author(s).)

Glioblastoma multiforme (GBM) is among the most aggressive brain cancers, and it contains glioma stem cells (GSCs) that drive tumor initiation, progression, and recurrence. These cells resist conventional therapies, contributing to high recurrence rates in GBM patients. Developing in vitro models that mimic the tumor microenvironment (TME), particularly the GSC niche, is crucial for understanding GBM growth and therapeutic resistance. Three-dimensional (3D) spheroid models provide a more physiologically relevant approach than traditional two-dimensional (2D) cultures, recapitulating key tumor features like hypoxia, cell heterogeneity, and drug resistance. This review examines scaffold-free and scaffold-based methods for generating 3D GBM spheroids, focusing on their applications in studying the cancer stem cell niche. The discussion encompasses methods such as the hanging drop, low-adhesion plates, and magnetic levitation, alongside advancements in embedding spheroids within extracellular matrix-based hydrogels and employing 3D bioprinting to fabricate more intricate tumor models. These 3D culture systems offer substantial potential for enhancing our understanding of GBM biology and devising more effective targeted therapies.

Despite the use of conventional dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), the risk of adverse events remains high among patients with increased thrombotic risk. Until recently, the optimal antiplatelet strategy to balance the ischaemic and bleeding risks in patients who are undergoing complex high-risk PCI has been unclear. The TAILored Versus COnventional AntithRombotic StratEgy IntenDed for Complex HIgh-Risk PCI (TAILORED-CHIP) trial is an investigator-initiated, multicentre, prospective randomised trial to evaluate the efficacy and safety of a time-dependent tailored antiplatelet therapy with an early (<6 months post-PCI) escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin) and a late (>6 months post-PCI) de-escalation (clopidogrel monotherapy) in patients undergoing complex high-risk PCI as compared with standard DAPT (clopidogrel plus aspirin for 12 months). Eligible patients had to have at least one high-risk anatomical or procedural feature or clinical characteristic associated with an increased risk of ischaemic or thrombotic events. The primary endpoint was the net clinical outcome, a composite of death from any cause, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, or clinically relevant bleeding (Bleeding Academic Research Consortium type 2, 3, or 5) at 12 months after randomisation. (ClinicalTrials.gov: NCT03465644).

Conductive 2D nanosheets have evoked tremendous scientific efforts because of their high efficiency as hybridization matrices for improving diverse functionalities of nanostructured materials. To address the problems posed by previously reported conductive nanosheets like poorly-interacting graphene and cost-ineffective RuO 2 nanosheets, economically feasible noble-metal-free conductive [Mn x Co 1-2x Ni x ]O 2 oxide nanosheets are synthesized with outstanding interfacial interaction capability. The surface-optimized [Mn 1/4 Co 1/2 Ni 1/4 ]O 2 nanosheets outperformed RuO 2 /graphene nanosheets as hybridization matrices in exploring high-performance visible-light-active (λ >420 nm) photocatalysts. The most efficient g-C 3 N 4 -[Mn 1/4 Co 1/2 Ni 1/4 ]O 2 nanohybrid exhibited unusually high photocatalytic activity (NH 4 + formation rate: 1.2 mmol g -1 h -1 ), i.e., one of the highest N 2 reduction efficiencies. The outstanding hybridization effect of the defective [Mn 1/4 Co 1/2 Ni 1/4 ]O 2 nanosheets is attributed to the optimization of surface bonding character and electronic structure, allowing for improved interfacial coordination bonding with g-C 3 N 4 at the defect sites. Results from spectroscopic measurements and theoretical calculations reveal that hybridization helps optimize the bandgap energy, and improves charge separation, N 2 adsorptivity, and surface reactivity. The universality of the [Mn 1/4 Co 1/2 Ni 1/4 ]O 2 nanosheet as versatile hybridization matrices is corroborated by the improvement in the electrocatalytic activity of hybridized Co-Fe-LDH as well as the photocatalytic hydrogen production ability of hybridized CdS., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Job stress was found to directly increase the likelihood of accidents and indirectly increase the likelihood of accidents by lowering the safety atmosphere. Job stress has a significant impact on the safety environment, and job satisfaction is effective in reducing accident rates. Accordingly, we sought to investigate the correlation between safety level, job stress, and job satisfaction in small businesses with a high risk of industrial accidents. Additionally, we aim to investigate factors that may affect job stress, job satisfaction, and safety levels., Methods: This study was conducted on 230 workers in small businesses in Korea. First, hierarchical regression analysis was conducted using SPSS software, and anova analysis was used to investigate significant variables. Finally, the relationships between variables were investigated using structural equation modeling (SEM)., Results: The analysis results showed that safety level and job stress had a negative correlation with a coefficient of -0.8. Safety level and job satisfaction had a correlation with a coefficient of 0.2. Job satisfaction and job stress had a negative correlation with a coefficient of -0.7. This shows that when job stress is high, there is a negative correlation between job satisfaction and safety level. In addition, 4 general characteristics items and 3 job characteristics items showed a correlation with job stress. 2 general characteristics items and 8 job characteristics items showed a correlation with job satisfaction. 4 general characteristics items and 11 job characteristics items showed a correlation with safety level., Conclusion: Small businesses' job stress, safety level, and job satisfaction showed a significant correlation. In addition, the relationship between the variables affecting them was significant. In order to reduce the occurrence of accidents among workers in small businesses, control of factors and efforts to reduce job stress are necessary., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study presents findings that demonstrate the possibility of simplifying neural networks by inducing multifunctionality through separate manipulation within a single material. Herein, two-terminal memristor W/ZnTe/W devices implemented a multifunctional memristor comprising a selector, synapse, and a neuron using an ovonic threshold switching material. By setting the low-current level (µA) in the forming process, a stable memory-switching operation is achieved, and the capacity to implement a synapse is demonstrated based on paired-pulse facilitation/depression, potentiation/depression, spike-amplitude-dependent plasticity, and spike-number-dependent plasticity outcomes. Based on synaptic behavior, the Modified National Institute of Standards and Technology database image classification accuracy is up to 90%. Conversely, by setting the high-current level (mA) in the forming process, the stable bipolar threshold switching operation and good selector characteristics (300 ns switching speed, free-drift, recovery properties) are demonstrated. In addition, a stochastic neuron is implemented using the stochastic switching response in the positive voltage region. Utilizing stochastic neurons, it is possible to create a generative restricted Boltzmann machine model., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Evidence has suggested an increased risk of psychiatric manifestations following viral infections including coronavirus disease-2019 (COVID-19). However, psychiatric adverse events (AEs) after COVID-19 vaccination, which were documented in case reports and case series, remain unclear. This study is aimed to investigate the psychiatric AEs after COVID-19 vaccination from a large population-based cohort in Seoul, South Korea. We recruited 50% of the Seoul-resident population randomly selected from the Korean National Health Insurance Service (KNHIS) claims database on 1, January, 2021. The included participants (n = 2,027,353) from the Korean National Health Insurance Service claims database were divided into two groups according to COVID-19 vaccination. The cumulative incidences per 10,000 of psychiatric AEs were assessed on one week, two weeks, one month, and three months after COVID-19 vaccination. Hazard ratios (HRs) and 95% Confidence interval (CIs) of psychiatric AEs were measured for the vaccinated population. The cumulative incidence of depression, anxiety, dissociative, stress-related, and somatoform disorders, sleep disorders, and sexual disorders at three months following COVID-19 vaccination were higher in the vaccination group than no vaccination group. However, schizophrenia and bipolar disorders showed lower cumulative incidence in the vaccination group than in the non-vaccinated group. Depression (HR [95% CI] = 1.683 [1.520-1.863]), anxiety, dissociative, stress-related, and somatoform disorders (HR [95% CI] = 1.439 [1.322-1.568]), and sleep disorders (HR [95% CI] = 1.934 [1.738-2.152]) showed increased risks after COVID-19 vaccination, whereas the risks of schizophrenia (HR [95% CI] = 0.231 [0.164-0.326]) and bipolar disorder (HR [95% CI] = 0.672 [0.470-0.962]). COVID-19 vaccination increased the risks of depression, anxiety, dissociative, stress-related, and somatoform disorders, and sleep disorders while reducing the risk of schizophrenia and bipolar disorder. Therefore, special cautions are necessary for administering additional COVID-19 vaccinations to populations vulnerable to psychiatric AEs., (© 2024. The Author(s).)

Although iatrogenic pseudoaneurysm is an infrequent complication, it can be life threatening if ruptured. There are several treatment methods for managing this complication. This case report demonstrates a technique using ultrasonography-guided suture-mediated vascular closure devices without angiography to successfully treat iatrogenic superficial femoral pseudoaneurysm following an unintended hemodialysis catheter insertion. In particular, when it is difficult to use a contrast due to a patient's condition as in this case, suture-mediated vascular closure device with ultrasonography guidance can be used as a therapeutic method., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Programmed cell death 6 (PDCD6) is known to be involved in apoptosis and tumorigenesis. Given the reported association with urinary cancer susceptibility through SNP analysis, we further analyzed the entire genomic structure of PDCD6., Methods: Three VNTR regions (MS1-MS3) were identified through the analysis of the genomic structure of PDCD6. To investigate the association between these VNTR regions and urinary cancer susceptibility, genomic DNA was extracted from 413 cancer-free male controls, 267 bladder cancer patients, and 331 prostate cancer patients. Polymerase chain reaction (PCR) was performed to analyze the PDCD6-MS regions. Statistical analysis was performed to determine the association between specific genotypes and cancer risk. In addition, the effect of specific VNTRs on PDCD6 expression was also confirmed using a reporter vector., Results: Among the three VNTR regions, MS1 and MS2 exhibited monomorphism, while the MS3 region represented polymorphism, with its transmission to subsequent generations through meiosis substantiating its utility as a DNA typing marker. In a case-control study, the presence of rare alleles within PDCD6-MS3 exhibited significant associations with both bladder cancer (OR = 2.37, 95% CI: 1.33-4.95, P = 0.019) and prostate cancer (OR = 2.11, 95% CI: 1.03-4.36, P = 0.038). Furthermore, through luciferase assays, we validated the impact of the MS3 region on modulating PDCD6 expression., Conclusions: This study suggests that the PDCD6-MS3 region could serve as a prognostic marker for urinary cancers, specifically bladder cancer and prostate cancer. Moreover, the subdued influence exerted by PDCD6-MS3 on the expression of PDCD6 offers another insight concerning the progression of urinary cancer., Competing Interests: Declarations. Ethical approval: Cases with bladder cancer and controls were recruited from two different hospitals in the same city. The bioethics committees of Dong-A University Hospital, Pusan National University Hospital approved research plan and procedure: [Dong-A University Hospital (#IRB-06–10-02, #IRB-07–10-7; Busan, Korea), Pusan National University Hospital (#IRB-H-1706–002-007; #IRB-H-1804–002-065; Busan, Korea)]. Informed consent was obtained from all subjects and/or their legal guardians. Conflict of interest: All of authors declare that they have no competing interests., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Backgruound: We investigated the association between body composition changes and new-onset diabetes mellitus (DM) development according to the body mass index (BMI) in a longitudinal setting in the general Korean population., Methods: From 2010 to 2011 (1st) and 2012 to 2013 (2nd), we included 1,607,508 stratified random sample participants without DM from the National Health Insurance Service-Health Screening dataset of Korean. The predicted appendicular skeletal muscle mass index (pASMMI), body fat mass index (pBFMI), and lean body mass index (pLBMI) were calculated using pre-validated anthropometric prediction equations. A prediction equation was constructed by combining age, weight, height, waist circumference, serum creatinine levels, alcohol consumption status, physical activity, and smoking history as variables affecting body composition., Results: Decreased pASMMI (men: hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.830 to 0.903; P<0.001; women: HR, 0.748; 95% CI, 0.635 to 0.881; P<0.001), decreased pLBMI (men: HR, 0.931; 95% CI, 0.912 to 0.952; P<0.001; women: HR, 0.906; 95% CI, 0.856 to 0.959; P=0.007), and increased pBFMI (men: HR, 1.073; 95% CI, 1.050 to 1.096; P<0.001; women: HR, 1.114; 95% CI, 1.047 to 1.186; P=0.007) correlated with the development of new-onset DM. Notably, only in the overweight and obese BMI categories, decreases in pASMMI and pLBMI and increases in pBFMI associated with new-onset DM, regardless of gender., Conclusion: Decreased pASMMI and pLBMI, and increased pBFMI with excess fat accumulation may enhance the risk of newonset DM. Therefore, appropriate changes in body composition can help prevent new-onset DM.

The phenylpropanoid pathway is vital for plant growth and development, producing lignin and flavonoids. This study investigates PtrMYB203, a homolog of MYB repressors of proanthocyanidin (PA) biosynthesis in Populus trichocarpa, as a transcriptional repressor in the phenylpropanoid pathway of hybrid poplar (Populus alba x P. glandulosa). Overexpression of PtrMYB203 (35S::PtrMYB203) in hybrid poplar detrimentally impacted plant growth and development. Histological analysis revealed irregular xylem vessel formation and decreased lignin content, corroborated by Klason lignin assays. Moreover, 35S::PtrMYB203 transgenic poplars exhibited significant decreases in anthocyanin and PA accumulations in callus tissues, even under high light conditions. Quantitative RT-PCR analysis and protoplast-based transcriptional activation assay confirmed the downregulation of lignin and flavonoid biosynthesis genes. This genetic modification also alters the expression of several MYB transcription factors, essential for phenylpropanoid pathway regulation. Remarkably, saccharification efficiency in the 35S::PtrMYB203 poplar was improved by over 34% following hot water treatment alone. These findings suggest PtrMYB203 as a potential genetic target for enhancing wood properties for bioenergy production, providing valuable insights into the manipulation of metabolite pathways in woody perennials to advance wood biotechnology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: Despite the emerging biologics, biomarkers and treatment options for asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) are still limited, requiring further research., Methods: We enrolled 378 ACO patients from a multicenter real-world asthma cohort in Korea and compared the clinical characteristics, lung function, and exacerbation between type 2 (T2)-high and T2-low groups. We used the following comparisons: 1) low vs. high immunoglobulin E (IgE) group (≥ 100 IU/mL), 2) non-atopy vs. atopy group (sensitized to aeroallergen), 3) low vs. high blood eosinophil group (≥ 150/µL), and 4) low vs. high sputum eosinophil group (≥ 2%)., Results: The high sputum eosinophil ACO group (n = 37) showed significantly lower pre- and post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) (45.7% ± 15.8% vs . 55.9% ± 16.2%, P = 0.016; 1.3 ± 0.6 L vs . 1.6 ± 0.5 L, P = 0.013 for pre-BD FEV1; 0.53 ± 0.1 vs . 0.59 ± 0.1, P = 0.018 for post-BD FEV1/FVC) than the low sputum eosinophil ACO group (n = 25). When examining changes in lung function at the 3-month follow-up, there were significant decreases in FEV1 in the high IgE ACO group (n = 104; -11.4% ± 16.7% vs . -4.4% ± 9.2%, P = 0.023) and ΔFEV1/FVC in the high sputum eosinophil ACO group (-0.049 ± 0.063 vs . -0.004 ± 0.064, P = 0.049) than in the low IgE ACO group (n = 44) and in the low sputum eosinophil ACO group, respectively. The risk of asthma exacerbation was significantly higher in the atopic ACO group (odds ratio, 4.2; 95% confidence interval, 1.0-17.4; P = 0.049) in the adjusted model., Conclusions: Since ACOs with T2-high profiles may have lower lung function and more frequent exacerbations, T2-high specific therapies, such as biologics, should be actively considered in T2-high ACO patients., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications., Methods: Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI])., Result: In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712])., Conclusion: Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

It would be clinically valuable if the efficacy of antiarrhythmic drugs could be simulated in advance. We developed a digital twin to predict amiodarone efficacy in high-risk atrial fibrillation (AF) patients post-ablation. Virtual left atrium models were created from computed tomography and electroanatomical maps to simulate AF and evaluate its response to varying amiodarone concentrations. As the amiodarone concentration increased in the virtual setting, action potential duration lengthened, peak upstroke velocities decreased, and virtual AF termination became more frequent. Patients were classified into effective (those with virtually terminated AF at therapeutic doses) and ineffective groups. The one-year clinical outcomes after AF ablation showed significantly better results in the effective group compared to the ineffective group, with AF recurrence rates of 20.8% vs. 45.1% (log-rank p = 0.031, adjusted hazard ratio, 0.37 [0.14-0.98]; p = 0.046). This study highlights the potential of a digital twin-guided approach in predicting amiodarone's effectiveness and improving personalized AF management. Clinical Trial Registration Name: The Evaluation for Prognostic Factors After Catheter Ablation of Atrial Fibrillation: Cohort Study, Registration number: NCT02138695. The date of registration: 2014-05. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695., (© 2024. The Author(s).)

Background: Molecular screening using next-generation sequencing (NGS) in the pathologic evaluation of lung cancer is considered the standard in clinical practice; hence, we evaluated the diagnostic yields of various sampling methods for NGS., Methods: NGS data from patients with lung cancer at the Pusan National University Hospital (Busan, South Korea), admitted October, 2020-April, 2023, was obtained. The sampling methods by which NGS data was obtained were divided into surgical and nonsurgical. Surgical methods included thoracoscopic surgery, surgical biopsy from the metastatic site, and lymph node excisional biopsy, whereas nonsurgical methods included bronchoscopy procedures and medical thoracoscopic biopsy., Results: In total, we obtained 319 patients' NGS data:150 (47.0%) and 169 (53.0%) was obtained using surgical and nonsurgical methods, respectively. The overall diagnostic yield of NGS analysis was 97.5% for all samples. There were no significant differences in the success rates of deoxyribonucleic acid sequencing between surgical and nonsurgical sampling methods (98.0% vs. 96.4%, p = 0.313). On the other hand, the success rate of ribonucleic acid (RNA) sequencing was significantly lower in the surgical method group (78.0% vs. 92.3%; p < 0.001). Multivariate analysis showed that surgical sampling significantly correlated with RNA sequencing failure (Odd Ratio 4.128, 95% Confidence Interval 1.681-10.133, p = 0.002)., Conclusions: Small samples obtained using nonsurgical procedures are suitable for NGS analysis in clinical practice. However, surgical sampling showed a relatively lower success rate for RNA sequencing than nonsurgical sampling. This information may help in the development of protocols to reduce RNA degradation during the surgical process., Competing Interests: Author JS was employed by GC Genome Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eom, Kim, Kim, Kim, Ahn, Mok, Cho, Lee, Song and Kim.)

Context: Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions., Objective: This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD., Methods: This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7719 ultrasonography images from 351 patients with GD and 2980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0&#95;2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image preprocessing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform., Results: The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0&#95;2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99., Conclusion: Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Although socioeconomic status (SES) is considered a risk factor for cardio-cerebrovascular diseases (CCVDs), few studies have examined this association. In this cross-sectional study, we aimed to assess the prevalence and trends of CCVDs across different SES groups over a 12-year period in a representative Korean population., Methods: We analysed 47 745 economically active adults aged ≥30 and <65 years from 97 622 patients in the Korean National Health and Nutrition Examination Survey (2007-18), where a new independent sample of the population was examined each year. We categorised the participants into four groups based on education level and income. The prevalence of hypertension, diabetes mellitus, dyslipidaemia, and CCVD, including angina, myocardial infarction, and stroke, was analysed at four-year intervals., Results: Average age, urban residence, white-collar occupation, and body mass index >30 increased, whereas CCVD prevalence did not change significantly (P = 0.410) over the study period. Low education (odds ratio (OR) = 1.24; 95% confidence interval (CI) = 1.04-1.47, P < 0.001) and low income (OR = 1.14; 95% CI = 1.02-1.28, P = 0.017) were significant determinants of CCVD in addition to existing traditional risk factors. CCVD prevalence was significantly higher in both the low-education and low-income groups compared to the high-education and high-income groups every four years, with no significant change in this gap over the study period (P = 0.239)., Conclusions: Despite the increase in the elderly population and the prevalence of obesity, the incidence of CCVDs in Korea has remained unchanged. Individuals with low education or low income had a significantly higher prevalence of CCVD, with the lowest SES group, defined by both low education and low income, consistently having the highest prevalence of CCVDs., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interest., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: The burden of nonalcoholic fatty liver disease is increasing, and limited therapeutic drugs are available for its treatment. Serotonin binds to approximately 14 serotonin receptors (HTR) and plays diverse roles in obesity and metabolic complications. In this study, we focused on the function of HTR4 on nonalcoholic fatty liver disease using GR113808, a selective HTR4 antagonist., Methods: Male C57BL/6J mice were fed high-fat diet for 12 weeks with intraperitoneal GR113808 injection, and HTR expression, weight changes, glucose and lipid metabolism, hepatic fat accumulation, changes in adipose tissue, the changes in transcriptional factors of signaling pathways, and inflammations were assessed. Hep3B cells and 3T3-L1 cells were treated with siRNA targeting HTR4 to downregulate its expression and then cultured with palmitate to mimic a high-fat diet. The changes in transcriptional factors of signaling pathways, and inflammations were assessed in those cells., Results: After feeding a high-fat diet to male C57BL/6J mice, HTR4 expression in the liver and adipose tissues decreased. GR113808 suppressed body weight gain and improved glucose intolerance. Furthermore, GR113808 not only decreased fatty liver formation but also reduced adipose tissue size. Additionally, GR113808 reduced inflammatory cytokine serum levels and inflammasome complex formation in both tissues. Palmitate treatment in HTR4-downregulated Hep3B cells, also reduced peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein-1 pathway induction as well as inflammasome complex formation, thus decreasing inflammatory cytokine levels. HTR4 downregulation in 3T3-L1 cells also reduced palmitate-induced inflammasome complex formation and inflammatory cytokine production. Palmitate-induced insulin resistance in Hep3B cells, but not in 3T3-L1 cells, was improved by HTR4 downregulation., Conclusions: In summary, GR113808 protected against fatty liver formation and improved inflammation in the liver and adipose tissue. Downregulation of HTR4 ameliorated insulin resistance in the liver. These results suggest that HTR4 could serve as a promising therapeutic target for metabolic diseases., (© 2024. The Author(s).)

Despite widespread application during the coronavirus disease-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection using patient-performed rapid antigen tests (RATs) is limited, especially regarding the Delta and Omicron variants. Therefore, in this study, we evaluated the performance of RATs in identifying Delta and Omicron infections in self-test settings. In this multicenter clinical performance study conducted in Korea between November 2021 and February 2022, we included participants without prior diagnostic device experience. Using 2 RAT types, we compared the results with real-time reverse transcriptase-polymerase chain reaction testing, focusing on clinical sensitivity and specificity. Reverse transcriptase-polymerase chain reaction helped confirm 77 SARS-CoV-2 infections among 280 participants. RATs exhibited high positive agreement for Omicron detection but lower rates for Delta, especially among partially vaccinated individuals. This study provides direct evidence that RATs, originally developed for ancestral strains of SARS-CoV-2, effectively detect major variants such as Delta and Omicron in real patient/clinical settings. By confirming variant presence through sequencing, our research offers significant and novel insights into the performance of RATs, particularly in the context of breakthrough infections postvaccination, with precise data on vaccination status and timing obtained from government records., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cancer vaccines have been developed as a promising way to boost cancer immunity. However, their clinical potency is often limited due to the imprecise delivery of tumor antigens. To overcome this problem, we conjugated an endogenous Toll-like receptor (TLR)2/6 ligand, UNE-C1, to human papilloma virus type 16 (HPV-16)-derived peptide antigen, E7, and found that the UNE-C1-conjugated cancer vaccine (UCV) showed significantly enhanced antitumor activity in vivo compared with the noncovalent combination of UNE-C1 and E7. The combination of UCV with PD-1 blockades further augmented its therapeutic efficacy. Specifically, the conjugation of UNE-C1 to E7 enhanced its retention in inguinal draining lymph nodes, the specific delivery to dendritic cells and E7 antigen-specific T cell responses, and antitumor efficacy in vivo compared with the noncovalent combination of the two peptides. These findings suggest the potential of UNE-C1 derived from human cysteinyl-tRNA synthetase 1 as a unique vehicle for the specific delivery of cancer antigens to antigen-presenting cells via TLR2/6 for the improvement of cancer vaccines., Competing Interests: Declaration of interests S.K. is an inventor on patents 10-2022-0070287 related to this paper and is a founder of Zymedi., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Backgruound: Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression., Methods: OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia., Results: TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia., Conclusion: Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.

Background and Purpose: Choline alfoscerate (CA) is an acetylcholine precursor known for its beneficial effect on cognition in patient with Alzheimer's disease dementia (ADD). However, there is little evidence of its effects in patients with mild cognitive impairment (MCI). We assessed the influence of CA on the progression from MCI to all-cause dementia or ADD in three observational Korean databases using a Common Data Model (CDM)., Methods: Patients who were diagnosed with MCI and were aged over 60 years were included. After propensity score matching, 3,062 matched pairs patients using CA use and those not using CA were included. The Cox regression model was used to analyze the hazard ratio (HR) of CA use for conversion from MCI to all-cause dementia or ADD. Subgroup analyses were performed based on sex, acetylcholine esterase inhibitor (AchEI) use, and donepezil use., Results: A meta-analysis across three hospitals revealed that CA use was not associated with the progression from MCI to all-cause dementia (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.59-1.26) or ADD (HR, 1.05; 95% CI, 0.51-1.59). Subgroup analyses revealed that CA use was not related to progression to all-cause dementia or ADD when stratified by sex, AchEI use, and donepezil use., Conclusions: In this multicenter cohort study based on the Observational Medical Outcomes Partnership CDM real-world data, no association was noted between CA use and disease progression from MCI to all-cause dementia or ADD., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (© 2024 Korean Dementia Association.)

The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits (KIF3A, and KIF3B) and a non-motor subunit, kinesin-associated protein 3 (KAP3). The cargo-binding domain (CBD) at the carboxyl (C)-terminus of KIF3s plays an important role in the interaction with several different binding proteins. To identify the binding proteins for heterotrimeric kinesin-2, we performed a yeast two-hybrid screen and found a new interaction with Disables-1 (Dab1), the intracellular adaptor protein of reelin receptors. Dab1 bound to the CBD of KIF3A, but did not interact with the C-terminal domain of KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding (PTB) domain-containing region of Dab1 is essential for the interaction with KIF3A. KIF3A interacted with GST-Dab1, and GST-CaMKIIα, but did not interact with GST-apolipoprotein E receptor 2 (ApoER2)-C or with GST alone. When co-expressed in HEK-293T cells, Dab1 co-precipitated with KIF3A, but not with KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2 in KIF3A dominant-negative cells. These results suggest that the KIF3A plays a role in the intracellular trafficking of ApoER2 to the cell surface. [BMB Reports 2024; 57(10): 447-452].

Background: The age-standardised incidence ratio of gastrointestinal cancers in type 1 diabetes (T1D) patients has been reported to be higher than that in the general population. After adjusting for shared risk factors, we aimed to explore the association between T1D and gastrointestinal cancer and examine how this relationship varies by age and sex., Materials and Methods: This retrospective cohort study included 268,179 participants from the Korean National Health Insurance Service-National Sample Cohort. The primary outcome is the incident of gastrointestinal cancers, based on diagnostic codes. Multivariate Cox regression analyses were performed to assess the association between T1D and gastrointestinal cancers., Results: Of the 268,179 participants, 2681 had T1D at baseline and were followed for 12.98 (± 2.92) years. Compared with non-T1D, T1D patients had a significantly increased risk of all gastrointestinal cancer (adjusted hazard ratio [aHR]: 1.403, 95% confidence interval [CI]: 1.253-1.573). T1D patients increased risks of oesophageal cancer (aHR: 1.864, 95% CI: 1.038-3.349), gastric cancer (aHR: 1.313, 95% CI: 1.066-1.616), colon cancer (aHR: 1.365, 95% CI: 1.110-1.678), liver cancer (aHR: 1.388, 95% CI: 1.115-1.727), and pancreatic cancer (aHR: 1.716, 95% CI: 1.182-2.492). The consistency of this association persisted among both male and female, with its strength increasing with older age., Conclusions: The risk of gastrointestinal cancer was significantly increased in T1D patients. Older male T1D patients exhibit a higher risk, suggesting the need for targeted attention in their care., (© 2024 John Wiley & Sons Ltd.)

Gauze or bandages are commonly used to effectively control bleeding during trauma and surgery. However, conventional treatment methods can sometimes lead to secondary damages. In recent years, there has been increased interest in developing adhesive hemostatic hydrogels as a safer alternative for achieving hemostasis. Methylcellulose (MC) is a well-known thermo-sensitive polymer with excellent biocompatibility that is capable of forming a hydrogel through physical crosslinking owing to its inherent thermo-reversible properties. However, the poor mechanical properties of the MC hydrogel comprising a single crosslinked network (SN) limit its application as a hemostatic material. To address this issue, we incorporated a chitosan-gallol (CS-GA) conjugate, which has the ability to form chemical crosslinks through self-crosslinking reactions under specific pH conditions, into the MC hydrogel to reinforce the MC hydrogel network. The resulting MC/CS-GA hydrogel with a dual-crosslinked network (DN), involving both physical and chemical crosslinks, exhibited synergistic effects of the two types of crosslinks. Thus, compared with those of the SN hydrogel, the composite DN hydrogel exhibited significantly enhanced mechanical strength and tissue adhesive properties. Moreover, the DN hydrogel presented excellent biological activity in vitro. Additionally, in rat hepatic hemorrhage models, the DN hydrogel exhibited high hemostatic efficiency, showcasing its multifunctional capabilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim: Durvalumab consolidation is less effective in patients with epidermal growth factor receptor mutant (EGFR M+) NSCLC. Studies of durvalumab on EGFR M+ NSCLC as an expression of programmed death-ligand 1 (PD-L1) expression are limited. The purpose of this study was to determine the effect of durvalumab on PD-L1 expression in EGFR M+ patients., Patients and Methods: This study included 249 unresectable stage III NSCLC patients treated with durvalumab. The primary outcome was progression-free survival (PFS). Cox multivariate analysis was performed based on EGFR and PD-L1 statuses: EGFR M-, PD-L1 ≥50% (cohort A); EGFR M-, PD-L1 <50% (cohort B); EGFR M+, PD-L1 ≥50% (cohort C); and EGFR M+, PD-L1 <50% (cohort D)., Results: Overall, 31 of 249 (12.4%) and 218 of the 249 (87.6%) patients had EGFR M+ and EGFR M- NSCLC, respectively. Median PFSs and OSs did not differ (PFS: 16.6 vs. 18.7 months, p=0.591; OS: 37.4 vs. 35.7 months, p=0.271). Median PFS of cohort A did not significantly differ from the median PFSs of cohorts B and C, but it was significantly longer than the median PFS of cohort D (23.7 vs. 15.2 months, p=0.045). Cox multivariate analysis revealed that cohort D exhibited a worse PFS (adjusted hazard ratio=2.27, 95% confidence interval=1.11-4.66, p=0.025) compared with cohort A. Median OSs were not different between the four cohorts., Conclusion: Durvalumab consolidation provided similar benefit in EGFR M+ patients with PD-L1 ≥50% compared with EGFR M- patients. A therapeutic role of durvalumab in patients with EGFR M+, high PD-L1 unresectable stage III NSCLC should be considered., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Since the introduction of powered circular staplers in colorectal surgery, there has been growing interest in their impact on reducing complications, particularly anastomotic leakage. This study compared short-term postoperative outcomes between powered and manual circular staplers., Methods: This retrospective study included colorectal cancer patients at the tertiary referral center from April to October 2023 who underwent anterior or low anterior resection (LAR) using a circular stapler. According to energy source, patients were divided into powered and manual groups, which used two powered and four types of manual staplers, respectively. All open, laparoscopic, and robotic approaches were included. Propensity score matching (PSM) analysis was used to reduce selection bias. Postoperative complications within 30 days, especially for anastomosis-related complications, were compared between the groups., Results: Among 511 patients, the powered group was 161 (32%). After PSM, 143 pairs of 286 patients were analyzed. The proportions of LAR were 53.8% and 51.0%, and initial diverting stoma rates were 23.1% and 22.4% for the Powered and Manual groups, respectively. Comprehensive complication rates were similar between the Powered group and the Manual group, without statistical significance (13.3% vs. 21.0%, P = 0.063). Anastomotic leakage was not different between the Powered and Manual groups (4.2% vs. 4.9%, P = 0.782). There was no significant difference in other complications, including anastomotic bleeding, ileus, surgical site infection, and intra-abdominal hematoma., Conclusions: The study implies that powered circular staplers may not significantly reduce postoperative complications, including anastomotic leakages, compared to manual staplers in colorectal surgery of high-volume centers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The challenges of the COVID-19 pandemic extend to concerns about vaccine side effects, particularly potential links to neurodegenerative diseases such as Alzheimer's disease (AD)., Aim: This study investigates the association between COVID-19 vaccination and the onset of AD and its prodromal state, mild cognitive impairment (MCI)., Design: A nationwide, retrospective cohort study leveraging data from the Korean National Health Insurance Service was conducted., Methods: The study, conducted in Seoul, South Korea, analyzed data from a random 50% sample of city residents aged 65 and above, totaling 558 017 individuals. Participants were divided into vaccinated and unvaccinated groups, with vaccinations including mRNA and cDNA vaccines. The study focused on AD and MCI incidences post-vaccination, identified via ICD-10 codes, using multivariable logistic and Cox regression analyses. Patients with vascular dementia or Parkinson's disease served as controls., Results: Findings showed an increased incidence of MCI and AD in vaccinated individuals, particularly those receiving mRNA vaccines, within three months post-vaccination. The mRNA vaccine group exhibited a significantly higher incidence of AD (odds ratio [OR]: 1.225; 95% confidence interval [CI]: 1.025-1.464; P = 0.026) and MCI (OR: 2.377; CI: 1.845-3.064; P < 0.001) compared to the unvaccinated group. No significant relationship was found with vascular dementia or Parkinson's disease., Conclusions: Preliminary evidence suggests a potential link between COVID-19 vaccination, particularly mRNA vaccines, and increased incidences of AD and MCI. This warrants the need for further research to elucidate the relationship between vaccine-induced immune responses and neurodegenerative processes, advocating for continuous monitoring and investigation into the vaccines' long-term neurological impacts., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Alzheimer's disease, a prevalent neurodegenerative condition primarily affecting older adults, remains incurable. Its principle pathological hallmark is the accelerated accumulation of amyloid β (Aβ) protein. This study investigates the potential of photobiomodulation using near infrared light to counteract Aβ 1-42 -induced synaptic degeneration and neurotoxicity. We focused on the effect of 808 nm near-infrared laser diode (LD) on Aβ 1-42 cytotoxicity in primary cultured cortical neurons. We assessed cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, observing substantial benefits from LD irradiation with a power of 10 mW and a dose of 30 J. Cells exposed to Aβ 1-42 exhibited morphological changes indicative of synaptic damage and a significant decrease in the number of postsynaptic density protein-95 (PSD-95) contacts, which were significantly improved with near-infrared LD therapy. Furthermore, this therapy reduced Aβ and phosphorylated tau (P-tau) protein accumulation. Additionally, near-infrared LD irradiation substantially lessened the Aβ 1-42 -induced rise in glial fibrillary acid protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) in astrocytes and microglia. Remarkably, near-infrared LD irradiation effectively inhibited phosphorylation of key proteins involved in Aβ 1-42 -induced necroptosis, namely Receptor-interacting protein kinase-3 (RIP3) and Mixed Lineage Kinase domain-Like protein (MLKL). Our findings suggest that near-infrared LD treatment significantly reduces neurodegeneration by reducing glial overactivation and neuronal necroptosis triggered by Aβ 1-42 . Thus, near-infrared LD treatment emerges as a promising approach for slowing or treating Alzheimer's disease, offering new avenues in its management., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Suicide is a significant public health issue, with South Korea having the highest suicide rate among Organisation for Economic Cooperation and Development countries. This study aimed to develop clinical guidelines for suicide prevention in psychiatric patients in Korea using the ADAPTE methodology., Methods: The development process involved a comprehensive review of literature, expert consultations, and consensus-building using the Nominal Group Technique and Delphi method. The guidelines focus on evidence-based psychiatric treatments, including both pharmacological and non-pharmacological approaches, tailored to the Korean context. Key findings underscoring the need for standardized treatment protocols for patients with major psychiatric disorders, including bipolar disorder, major depressive disorder, and schizophrenia., Results: The guidelines incorporate treatments like lithium, clozapine, atypical antipsychotics, electroconvulsive therapy, and cognitive behavioral therapy, which have shown effectiveness in suicide prevention. Applicability and acceptability within Korea's healthcare system were addressed, ensuring feasibility given the country's medical insurance coverage and accessibility. The guidelines were validated through expert reviews and Delphi rounds, achieving consensus on the final recommendations., Conclusion: The developed guidelines provide a structured, evidence-based approach to reducing suicide rates among psychiatric patients in Korea. Future research will focus on expanding these guidelines to include screening protocols for high-risk groups.

Background: Acute lung injury (ALI) is a devastating condition caused by sepsis, pneumonia, trauma, and more recently, COVID-19. SH003, an herbal formula consisted of Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii, is known for its effects on cancer and immunoregulation., Hypothesis/purpose: Previous studies show SH003 exerts a promising anti-inflammatory effect. This study investigates the effect of modified SH003 on ALI using in silico, in vivo, and in vitro models., Study Design and Methods: We performed in silico-based analysis of SH003 on ALI-related pathways. C57BL/6 mice were intraperitoneally subjected to lipopolysaccharide (LPS) to induce septic ALI, followed by oral administration of SH003 for 2 weeks. Dexamethasone was used as the positive control. Human peripheral blood-derived polymorphonuclear neutrophils (PMN) were used to investigate the effect and mechanisms of SH003 on neutrophil extracellular trap (NET) formation., Results: Network pharmacology analysis suggested SH003 regulates lung inflammation by modulating NET formation. SH003 significantly reduced mortality in sepsis in vivo by inhibiting local and systemic inflammation, likely via nuclear factor kappa B and mitogen-activated protein kinase pathways-mediated inflammasome suppression. SH003 also decreased NET-related markers in lung tissues and inhibited LPS- and phorbol myristate acetate-induced NET formation in PMN. Cytometry time-of-flight analysis confirmed regulation of NETosis-related pathways by SH003., Conclusion: SH003 effectively inhibits excessive immune responses in the lung by suppressing inflammasome activation and NET formation. These findings suggest SH003 as a potential therapeutic agent for septic ALI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Disease control in chronic diseases is an overarching concept that reflects the degree to which the goals of therapy are met. However, to date, there is no consensus on the definition of disease control in chronic cough. This study aimed to provide a conceptual exploration of patient-reported cough control in chronic cough., Methods: This research is comprised of two subanalyses. First, patients with chronic cough receiving care at referral clinics were evaluated. Correlation analyses were performed between patient-reported cough control (a 5-point Likert scale), cough-specific patient-reported outcomes (PROs) and generic health PRO scores. Second, a survey was conducted among patients with refractory chronic cough and physicians to identify factors pertinent to cough control., Results: The analysis of 341 patients (mean age: 55.5±15.1 years; female: 66.6%) revealed that cough control rating was moderately correlated with cough severity visual analogue scale and Leicester Cough Questionnaire scores, while demonstrating weaker correlations with cough-associated throat symptoms, cough-related complications or general health-related quality of life (QoL). In the survey of patients and physicians, both groups considered certain factors, such as cough frequency, severity and impact on QoL, to be relevant to the concept of cough control. However, patients rated "need for cough rescue drug" notably higher than physicians., Conclusion: Patient-reported cough control was associated with cough severity or impact on QoL; however, cough control may not be fully captured by conventional cough PRO measurement tools. Further studies are warranted to define the consensus and tools to measure disease control in chronic cough., Competing Interests: Conflict of interest: S.S. Birring declares grants from Merck Sharp & Dohme Corp., and consulting fees from Merck, Shionogi, Bayer, Nerre, Genentech/Roche and Bellus. Conflict of interest: W-J. Song declares grants from Merck Sharp & Dohme Corp. and AstraZeneca, consulting fees from Merck, Bellus, AstraZeneca, Shionogi and GSK, and lecture fees from Merck, AstraZeneca, GSK, Sanofi and Novartis; and is chief editor of this journal. Conflict of interest: Other authors declare that they have no competing interests., (Copyright ©The authors 2024.)

Purpose: To assess the effects of testosterone replacement therapy (TRT) compared to placebo or other medical treatments in men with sexual dysfunction., Materials and Methods: We performed a comprehensive search with no restrictions on publication language or status up to 29 August 2023. We only included randomized controlled trials (RCTs)., Results: We identified 43 studies with 11,419 randomized participants. We found that TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference [MD]: 2.37, 95% confidence interval [CI]: 1.67 to 3.08; I²=0%; 6 RCTs, 2016 participants; moderate-certainty evidence) compared to placebo. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD: -2.31, 95% CI: -3.63 to -1.00; I²=0%; 5 RCTs, 1,030 participants; moderate-certainty evidence) compared to placebo. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio: 0.83, 95% CI: 0.21 to 3.26; I²=0%; 10 RCTs, 3,525 participants; moderate-certainty evidence) compared to placebo. TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or lower urinary tract symptoms., Conclusions: TRT for men with sexual dysfunction showed no difference in erectile function, sexual quality of life, or cardiovascular mortality compared to placebo. Furthermore, it also appears to no difference in treatment withdrawals due to adverse events, prostate-related events, or lower urinary tract symptoms., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Competing Interests: None declared.

Background: We aimed to investigate the radiation dose to the eye lens (lens dose) during cerebral angiography and to evaluate the effectiveness of the lens dose reduction protocol for 3-dimensional rotational angiography (3D-RA) in reducing overall lens dose exposure., Methods: We conducted a randomized, controlled clinical trial at a tertiary hospital with patients undergoing cerebral angiography. The lens dose reduction protocol in 3D-RA involved raising the table to position the patient's eye lens away from the rotation axis. The lens dose was estimated by measuring the entrance surface air kerma using a photoluminescent glass dosimeter. The lens doses of 3D-RA, overall examination, and image quality were analyzed and compared between the two groups., Results: A total of 20 participants (mean age, 58±9.4 years; including 12 men [60%]) were enrolled and randomly assigned to either the conventional group or the dose reduction group. The median lens dose in 3D-RA was significantly lower in the dose reduction group compared with the conventional group (1.1 mGy vs 4.5 mGy, p<0.001). The total dose was significantly lower in the dose reduction group (median of 7.5 mGy vs 10.2 mGy, p=0.003). In the conventional group, 3D-RA accounted for 46% of the total lens dose, while in the dose reduction group, its proportion decreased to 16%. No significant differences were observed in the image quality between the groups., Conclusion: The lens dose reduction protocol resulted in a significant reduction in the lens dose of the 3D-RA as well as entire cerebral angiography, while maintaining the image quality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Numerous studies have investigated methods of predicting postoperative pulmonary complications (PPCs) in lung cancer surgery, with chronic obstructive pulmonary disease (COPD) and low forced expiratory volume in 1 second (FEV 1 ) being recognized as risk factors. However, predicting complications in COPD patients with preserved FEV 1 poses challenges. This study considered various diffusing capacity of the lung for carbon monoxide (DL CO ) parameters as predictors of pulmonary complication risks in mild COPD patients undergoing lung resection., Methods: From January 2011 to December 2019, 2,798 patients undergoing segmentectomy or lobectomy for non-small cell lung cancer (NSCLC) were evaluated. Focusing on 709 mild COPD patients, excluding no COPD and moderate/severe cases, 3 models incorporating DL CO , predicted postoperative DL CO (ppoDL CO ), and DL CO divided by the alveolar volume (DL CO /VA) were created for logistic regression. The Akaike information criterion and Bayes information criterion were analyzed to assess model fit, with lower values considered more consistent with actual data., Results: Significantly higher proportions of men, current smokers, and patients who underwent an open approach were observed in the PPC group. In multivariable regression, male sex, an open approach, DL CO <80%, ppoDL CO <60%, and DL CO /VA <80% significantly influenced PPC occurrence. The model using DL CO /VA had the best fit., Conclusion: Different DL CO parameters can predict PPCs in mild COPD patients after lung resection for NSCLC. The assessment of these factors using a multivariable logistic regression model suggested DL CO /VA as the most valuable predictor.

Purpose: Invasive mucinous adenocarcinoma (IMA) of the lungs is a rare subtype of lung adenocarcinoma with a limited understanding of its prognosis, particularly in advanced stages. This study aimed to assess the prognosis of patients with advanced IMA by focusing on treatment modalities., Methods: This single-center retrospective study evaluated 33 patients with IMAs diagnosed with advanced-stage disease or disease progression after curative treatment between 2011 and 2021. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). OS and PFS were calculated from the date of the diagnosis of advanced IMA., Results: The study cohort included 13 patients at the initial advanced stage and 20 patients who progressed after curative treatment. Treatment modalities included conventional chemotherapy in 24 patients (72.7%), targeted therapy in seven (21.2%), immunotherapy in 13 (39.4%), and local ablative therapy (LAT) in 13 (39.4%). The median OS was 32 months (95% confidence interval [CI], 2.9-61.0), with LAT significantly associated with improved OS compared to non-LAT treatment (not reached vs. 11.3 months, p = 0.001). However, there was no significant difference in OS based on conventional chemotherapy (p = 0.396), targeted therapy (p = 0.655), or immunotherapy (p = 0.992). In multivariate analysis, LAT remained an independent prognostic factor for OS (hazard ratio, 0.125; 95% CI, 0.026-0.608; p = 0.01). PFS was 8.6 months (95% CI, 3.6-13.7), with no significant differences observed among the treatment modalities., Conclusion: Our findings suggest that LAT may provide favorable survival outcomes in patients with advanced IMA., (© 2024. The Author(s).)

Background: Increased left atrial pressure (LAP) contributes to dyspnea and heart failure with preserved ejection fraction in patients with atrial fibrillation (AF). The purpose of this study was to investigate the differences in baseline LAP and LAP response to rapid pacing between paroxysmal and persistent AF., Methods and Results: This observational study prospectively enrolled 1369 participants who underwent AF catheter ablation, excluding those with reduced left ventricular ejection fraction. H 2 FPEF score was calculated by echocardiography and baseline characteristics. Patients underwent LAP measurements during AF, sinus rhythm, and heart rates of 90, 100, 110, and 120 beats per minute (bpm), induced by right atrial pacing and isoproterenol. The baseline LAP-peak in the persistent AF group consistently exceeded that in the paroxysmal AF (PAF) group across each H 2 FPEF score subgroup (all P <0.05). LAP-peak increased with pacing (19.5 to 22.5 mm Hg) but decreased with isoproterenol (20.4 to 18.4 mm Hg). Under pacing, patients with PAF exhibited a significantly lower LAP-peak (90 bpm) than those with persistent AF (17.7±8.2 versus 21.1±9.3 mm Hg, P <0.001). However, there was no difference in LAP-peak (120 bpm) between the 2 groups (22.1±8.1 versus 22.9±8.4 mm Hg, P =0.056) because the LAP-peak significantly increased with heart rate in the group with PAF., Conclusions: Patients with PAF exhibited lower baseline LAP with greater increases during rapid pacing compared with individuals with persistent AF, indicating a need to revise the H 2 FPEF score for distinguishing PAF from persistent AF and emphasizing the importance of rate and rhythm control in PAF for symptom control., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02138695.

Actionable mutations of RET kinase have been identified as oncogenic drivers of solid tumors, including thyroid cancer, metastatic colorectal cancer, and nonsmall cell lung cancer. Although multikinase inhibitors and RET selective inhibitors are used to treat patients with RET alterations, there is insufficient research addressing certain issues: which actionable mutations arise from these therapies, how to improve the clinical response rate to RET inhibitors, and how to design new inhibitors to overcome drug resistance. Therefore, the development of sophisticated tool compounds is required to investigate the molecular mechanisms of actionable mutations and to develop breakthrough therapeutics for different RET alterations. Herein, we present our investigation into the side chains of imidazopyridazine hinge binders that are capable of inducing protein-ligand interaction patterns from the gatekeeper to the waterfront regions. Extending the substituents at the second and sixth positions enhanced the IC 50 up to < 0.5 nM for diverse RET alterations., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Background: Androgenetic alopecia (AGA) is a prevalent hair loss disorder with psychological repercussions. Traditional treatments have limitations, leading to the exploration of regenerative therapies such as exosomes derived from adipose tissue stem cells (ASC-Exosomes)., Methods: First, using human hair follicle (HF) dermal papilla cells (hDPCs) treated with ASC-Exosomes, ALP, VCAN, β-catenin, and LEF-1 levels with RT-PCR and p-GSK3β, GSK3β, β-catenin, ALP, and β-actin levels with western blot analysis were assessed. Hair shaft elongation test and assay for ALP, Ki-67, and β-catenin were done using human HF organ culture. Patients with AGA had ASC-Exosomes treatment and were evaluated for hair counts, photographic assessments, subjective satisfaction, and safety profiles., Results: ASC-Exosomes impact hDPCs, increasing proliferation and the upregulation of hair growth-related genes, including ALP, VCAN, β-catenin, and LEF-1. The Wnt/β-catenin pathway was activated, indicating their role in promoting hair growth. ASC-Exosomes also promoted hair shaft elongation and ALP activity, suggesting a potential for hair regeneration. Thirty participants with AGA enrolled and treated over 24 weeks. The subjects experienced a significant increase in total hair density, improved global photographic assessments, and reported higher subjective satisfaction without severe adverse reactions., Conclusion: This research contributes to the growing body of evidence supporting the use of exosomes in hair loss treatment, offering a safe and effective alternative for individuals with AGA., (© 2024 the International Society of Dermatology.)

In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly induced c-Fos expression in both the dorsal and ventral hippocampi. The suppression of GABAergic transmission in the dHP-induced molecular changes similar to those induced by ketamine administration, including eukaryotic elongation factor 2 (eEF2) dephosphorylation, brain-derived neurotrophic factor (BDNF) elevation, and extracellular signal-regulated kinase (ERK) phosphorylation. These synaptic and molecular changes in the dHP induced a reduction in the immobility time of the mice in the tail-suspension and forced swim tests without affecting anxiety-related behavior. Conversely, pharmacological and chemogenetic potentiation of inhibitory neurotransmission in the dHP CA1 region induced passive coping behaviors during the tests. Transneuronal tracing and electrophysiology revealed monosynaptic excitatory connections between dHP CA1 neurons and mPFC neurons. Optogenetic stimulation of dHP CA1 neurons in freely behaving mice produced c-Fos induction and spike firing in the mPFC neurons. Chemogenetic activation of the dHP-recipient mPFC neurons reversed the passive coping behaviors induced by suppression of dHP CA1 neuronal activity. Collectively, these results indicate that neuronal activity in the dHP modulates stress-coping strategies to inescapable stress and contributes to the antidepressant effects of ketamine via the dHP-mPFC circuit., (© 2024. The Author(s).)

Purpose: By utilizing both protein and mRNA expression patterns, we can identify more detailed and diverse immune cells, providing insights into understanding the complex immune landscape in cancer ecosystems., Materials and Methods: This study was performed by obtaining publicly available Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus database. A total of 94674 total cells were analyzed, of which 32412 were T cells. There were 228 protein features and 16262 mRNA features in the data. The Seurat package was used for quality control and preprocessing, principal component analysis was performed, and Uniform Manifold Approximation and Projection was used to visualize the clusters. Protein and mRNA levels in the CITE-seq were analyzed., Results: We observed that a subset of T cells in the clusters generated at the protein level divided better. By identifying mRNA markers that were highly correlated with the CD4 and CD8 proteins and cross-validating CD26 and CD99 markers using flow cytometry, we found that CD4 + and CD8 + T cells were better discriminated in PBMCs. Weighted Nearest Neighbor clustering results identified a previously unobserved T cell subset., Conclusion: In this study, we used CITE-seq data to confirm that protein expression patterns could be used to identify cells more precisely. These findings will improve our understanding of the heterogeneity of immune cells in the future and provide valuable insights into the complexity of the immune response in health and disease., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Combination products (CPs) combine two or more product types such as drugs, devices, and/or biological products for increased safety and clinical effectiveness. The emergence of innovative CPs poses new challenges for regulatory agencies in assigning jurisdiction for premarket review and oversight. In US, the 1990 Safe Medical Devices Act defines and provides classification criteria for CPs, and the US government has developed a regulatory process through multiple acts, including the 21st Century Cures Act of 2016. Meanwhile, regulators in the European Union (EU) and the Republic of Korea have recently recognized the importance of premarket pathways for CPs. The European Medicines Agency (EMA) has issued guidelines and explanations on compliance issues related to drug-device CPs under MDR. EMA doesn't have the definitions of CPs, but uses the term drug-device combination products (drug-device CPs). CPs are categorized as drugs or medical devices, which follow their relevant regulatory framework. The Ministry of Food and Drug Safety (MFDS) in Korea has legal definitions of CPs under the Notice of the MFDS. CPs are designated as drugs or medical devices according to their primary mode of actions (PMOA) and follow regulatory processes through the framework of drugs or medical devices. This study aims to comprehensively summarize the regulatory oversight of CPs by analyzing the regulatory policies and legal frameworks in the US, the EU, and Korea. The regulatory challenges encountered when developing CPs are also discussed. With specific emphasis on the combination of drugs and devices, this study provides in-depth insights into the regulatory landscape, shedding light on the unique challenges associated with the development of CPs for this particular intersection of drugs and devices., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

In this study, it is analyzed how sample geometry (spheres, nanofibers, or films) influences the graphitization behavior of polyacrylonitrile (PAN) molecules. The chemical bonding and changes in the composition of these three geometries are studied at the oxidation, carbonization, and graphitization stages via scanning electron microscopy (SEM), in situ thermogravimetric-infrared (TGA-IR) analysis, elemental analysis, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The influence of molecular alignment on the graphitization of the three sample geometries is investigated using synchrotron wide-angle X-ray diffraction (WAXD) and transmission electron microscopy (TEM). The effects of molecular alignment at different draw rates during spinning are explored in detail., (© 2024 Wiley‐VCH GmbH.)

Introduction: Housing insecurity is rising among older adults; health researchers know little about how this may impact their cognitive health. We investigated links between foreclosure and older adults' memory and probability of dementia., Methods: Using the Health and Retirement Study (2008 to 2018), we fit mixed models comparing the memory and dementia probability scores of 249 older adults who experienced foreclosure (treated) with 15,645 who did not. Baseline covariates included sociodemographics and health. Models were stratified by age group., Results: Foreclosure was associated with faster memory decline among middle-aged (50 to 64) older adults (-0.007 standard deviations/year, 95% confidence interval: -0.13, -0.001). Compared to average memory decline among middle-aged older adults who were stably housed, foreclosure equated to 3.7 additional years of aging over 10 years. Among those 65+, differences between those who were and were not foreclosed upon were short-lived and less clear, potentially driven by depletion-of-susceptibles bias., Discussion: Foreclosure may endanger older adults' memory., Highlights: Housing instability is a key determinant of cognitive aging. We examined foreclosure and levels and changes in memory and dementia probability scores in the US older adult population. Foreclosure was associated with faster memory decline among middle-aged (50 to 64) older adults, equivalent to 3.7 additional years of cognitive aging over 10 years. Foreclosure yielded sharp memory declines and increases in dementia probability among older adults 65 and above. Foreclosure imposes a greater risk for older adults' cognitive decline., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)