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Protonic ceramic fuel or electrolysis cells (PCFC/PCEC) have shown promising performance at intermediate temperatures. However, these technologies have not yet been demonstrated in a stack, hence the oxidation behavior of the metallic interconnect under relevant operating environments is unknown. In this work, ferritic stainless steels 430 SS, 441 SS, and Crofer 22 APU were investigated for their use as interconnect materials in the PCFC/PCEC stack. The bare metal sheets were exposed to a humidified air environment in the temperature range from 450 °C to 650 °C, to simulate their application in a PCFC cathode or PCEC anode. Breakaway oxidation with rapid weight gain and Fe outward diffusion/oxidation was observed on all the selected stainless steel materials. A protective coating is deemed necessary to prevent the metallic interconnect from oxidizing. To mitigate the observed breakaway oxidation, state-of-the-art protective coatings, Y2O3, Ce0.02Mn1.49Co1.49O4, CuMn1.8O4 and Ce/Co, were applied to the stainless steel sheets and their oxidation resistance was investigated. Dual atmosphere testing further validated the effectiveness of the protective coatings in realistic PCFC/PCEC environments, with a hydrogen gradient across the interconnect. Several combinations of metal and coating material were found to be viable for use as the interconnect for PCFC/PCEC stacks.

Thermomechanical processing (TMP) of ferritic-martensitic (FM) steels, such as HT9 (Fe-12Cr-1MoWV) steels, involves normalizing, quenching, and tempering to create a microstructure of fine ferritic/martensitic laths with carbide precipitates. HT9 steels are used in fast reactor core components due to their high-temperature strength and resistance to irradiation damage. However, traditional TMP methods for these steels often result in performance limitations under irradiation, including embrittlement at low temperatures (<~430 °C), insufficient strength and toughness at higher temperatures (>500 °C), and void swelling after high-dose irradiation (>200 dpa). This research aimed to enhance both fracture toughness and strength at high temperatures by creating a quenched and tempered martensitic structure with ultrafine laths and precipitates through rapid quenching and unconventional tempering. Mechanical testing revealed significant variations in strength and fracture toughness depending on the processing route, particularly the tempering conditions. Tailored TMP approaches, combining rapid quenching with limited tempering, elevated strength to levels comparable to nano-oxide strengthened ferritic alloys while preserving fracture toughness. For optimal properties in high-Cr steels for future reactor applications, this study recommends a modified tempering treatment, i.e., post-quench annealing at 500 °C or 600 °C for 1 h, possibly followed by a brief tempering at a slightly higher temperature.

A three-dimensional (3D) numerical model was developed to explore the intricate aerodynamic mechanisms associated with aerosol jet printing (AJP). The proposed approach integrates computational fluid dynamics and discrete phase modeling, offering a comprehensive understanding of the deposition mechanisms of the AJP process. Initially, numerical solutions of the governing equations were obtained under the assumptions of compressible and laminar flows, facilitating an analysis of certain key flow variables, in this case, the sheath gas flow rate and carrier gas flow rate across the fluid domain. Subsequently, incorporating a Lagrangian discrete phase model allowed a detailed examination of the droplet behavior after nozzle ejection, considering the influence of the Saffman lift force. Finally, experiments were performed to elucidate the influence of key flow variables on the printed width. Generally, the measured printed line morphology and corresponding line electrical performance exhibited close conformity with the numerical model, demonstrating that the proposed numerical model is important for making well-informed decisions during process optimization.

We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues ( 3 Asp, 25 Lys, and 34 Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3 Glu, 25 Arg, and 34 Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts.

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the β -Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization., 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.)

Objective: Employing three cycles of Design Science Research (DSR) to develop a mobile app 'ESSC (Excellent Self Supervised HIV Care)' to improve self-management among people living with HIV (PLWH)., Methods: This study is based on the DSR framework comprising three iterative cycles. In the Relevance cycle, PLWH participated in a survey of mobile health (mHealth) experiences and needs. In the Rigor cycle, the information-motivation-behavioural skills (IMB) model was applied to foundations of the app, and HIV specialists verified the contents. Experts evaluated the heuristic system and the app quality with the Mobile Application Rating Scale (MARS). In the Design cycle, ESSC was built on the findings of the other two cycles, and end-users tested the usability using uMARS., Results: The contents of the app were developed based on user requirements. The IMB model led ESSC to supplement motivational components for self-management, which built five functions: information contents; health life records including mental and sexual health; interactive counselling with healthcare providers; setting health goals after watching videos; and my page for self-reflection. To reduce social stigma and promote acceptance of the information-driven app, we created animated characters with neutral and bright features. The HIV specialists evaluated content validity as highly appropriate. The MARS score by the overall raters was between 3- acceptable and 4- good : functionality, 4.38; information, 4.12; aesthetics, 3.96; engagement, 3.37; and subjective quality, 3.25., Conclusions: The DSR approach is effective for implementing usable and useful mHealth. The ESSC app would be feasible and contribute PLWH to retention in care., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Competing Interests: The authors have no potential conflicts of interest to disclose.

To develop a universal coronavirus (CoV) vaccine, long-term immunity against multiple CoVs, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, Middle East respiratory syndrome (MERS)-CoV, and future CoV strains, is crucial. Following the 2015 Korean MERS outbreak, we conducted a long-term follow-up study and found that although neutralizing antibodies and memory T cells against MERS-CoV declined over 5 years, some recovered patients exhibited increased antibody levels during the COVID-19 pandemic. This likely resulted from cross-reactive immunity induced by SARS-CoV-2 vaccines or infections. A significant correlation in antibody responses across various CoVs indicates shared immunogenic epitopes. Two epitopes-the spike protein's stem helix and intracellular domain-were highly immunogenic after MERS-CoV infection and after SARS-CoV-2 vaccination or infection. In addition, memory T cell responses, especially polyfunctional CD4 + T cells, were enhanced during the pandemic, correlating significantly with MERS-CoV spike-specific antibodies and neutralizing activity. Therefore, incorporating these cross-reactive and immunogenic epitopes into pan-CoV vaccine formulations may facilitate effective vaccine development.

In the laser powder bed fusion process, the melting-solidification characteristics of 316L stainless steel have a great effect on the workpiece quality. In this paper, a multi-physics model was constructed using the finite volume method (FVM) to simulate the melting-solidification process of a 316L powder bed via laser powder bed fusion. In this physical model, the phase change process, the influence of temperature gradient on surface tension of molten pool, and the influence of recoil pressure caused by the metal vapor on molten pool surface were considered. Using this model, the effects of laser scanning speed, hatch space, and laser power on temperature distribution, keyhole depth, and workpiece quality were studied. This study can be used to guide the optimization of process parameters, which is beneficial to the improvement of workpiece quality.

Background: Mpox is a viral illness with a characteristic skin rash caused by the monkeypox virus. In 2022, Mpox spread throughout the world, and an epidemic through domestic transmission started in South Korea in early 2023. This study aimed to summarize the clinical features of Mpox patients in South Korea., Methods: This is a multicenter retrospective study conducted at four hospitals in South Korea. All adult patients diagnosed with Mpox who were admitted to the study hospitals between June 1, 2022 and May 26, 2023 and were discharged by June 30, 2023 were reviewed., Results: Sixty patients were included, accounting for 65.9% of Mpox cases reported in South Korea during the study period. Median age was 32 years and 97% (58/60) of patients were male. In total, 85% (51/60) of patients reported their sexual orientation as homosexual or bisexual. The most common route of transmission was sexual or close contact (55/60). Every patient had a skin rash and 88% (53/60) had constitutional symptoms. In total, 42% (25/60) of patients had human immunodeficiency virus and 25% (15/60) had concomitant sexually transmitted infections. Severe manifestations of Mpox were identified in only two patients., Conclusion: Mpox patients in South Korea were mainly young adult males and were infected through sexual contact. The clinical outcomes were favorable., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Backgrounds: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary., Methods: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed., Results: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups., Conclusion: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity., (© 2023. The Author(s).)

Invariant natural-killer T ( i NKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this in i NKT cells is very limited. It is also not clear whether such metabolic regulation of i NKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediated de novo fatty-acid synthesis is required for the survival of i NKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lung i NKT cells from WT mice that were developing asthma. Cd4 -Cre:: Acc1 fl/fl mice failed to develop OVA-induced and HDM-induced asthma. Moreover, i NKT cell-deficient mice that were reconstituted with ACC1-deficient i NKT cells failed to develop asthma, unlike when WT i NKT cells were transferred. ACC1 deficiency in i NKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR)γ, but increased glycolytic capacity that promoted i NKT-cell death. Furthermore, circulating i NKT cells from allergic-asthma patients expressed higher ACC1 and PPARG levels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus, de novo fatty-acid synthesis prevents i NKT-cell death via an ACC1-FABP-PPARγ axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma., Competing Interests: JK, YW, HY, JC, SK, YC, KJ, JK, YJ, HK, DC No competing interests declared, (© 2023, Koh, Woo et al.)

Allergic diseases are a major public health problem with increasing prevalence. These immune-mediated diseases are characterized by defective epithelial barriers, which are explained by the epithelial barrier theory and continuously emerging evidence. Environmental exposures (exposome) including global warming, changes and loss of biodiversity, pollution, pathogens, allergens and mites, laundry and dishwasher detergents, surfactants, shampoos, body cleaners and household cleaners, microplastics, nanoparticles, toothpaste, enzymes and emulsifiers in processed foods, and dietary habits are responsible for the mucosal and skin barrier disruption. Exposure to barrier-damaging agents causes epithelial cell injury and barrier damage, colonization of opportunistic pathogens, loss of commensal bacteria, decreased microbiota diversity, bacterial translocation, allergic sensitization, and inflammation in the periepithelial area. Here, we review scientific evidence on the environmental components that impact epithelial barriers and microbiome composition and their influence on asthma and allergic diseases. We also discuss the historical overview of allergic diseases and the evolution of the hygiene hypothesis with theoretical evidence., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Objectives: Adolescents who engage in unhealthy behaviors are particularly vulnerable to anxiety. We hypothesized that participation in physical activity could influence the relationship between anxiety and unhealthy behaviors in adolescents. These behaviors include smoking, alcohol consumption, and unsafe sexual activity., Methods: This study included 50 301 students from the first year of middle school to the third year of high school, all from Korea. The unhealthy adolescent behaviors examined included current alcohol consumption, current smoking, and unsafe sexual behavior. Anxiety levels were assessed using the Generalized Anxiety Disorder-7 questionnaire (GAD-7)., Results: The participants had a mean age of 15.19 years and an average GAD-7 score of 4.23. No significant differences were observed in GAD-7 score among exercising participants when categorized by smoking status (p=0.835) or unsafe sexual behavior (p=0.489). In contrast, participants in the non-exercise group who engaged in these behaviors demonstrated significantly higher GAD-7 scores (p<0.001 and 0.016, respectively). The only significant interaction was found between unsafe sexual behavior and exercise (p=0.009). Based on logistic regression analysis, within the non-exercise group, significant positive associations were observed between current smoking and anxiety (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.18 to 1.57), as well as between unsafe sexual behavior and anxiety (OR, 1.33; 95% CI, 1.02 to 1.73). However, within the exercise group, no significant association was found between anxiety and either smoking or unsafe sexual behavior. Furthermore, no significant interaction was observed between unhealthy behaviors and exercise., Conclusions: These findings are insufficient to conclude that physical activity influences the relationship between unhealthy behaviors and anxiety.

The electronic tongue (E-tongue) system has emerged as a significant innovation, aiming to replicate the complexity of human taste perception. In spite of the advancements in E-tongue technologies, two primary challenges remain to be addressed. First, evaluating the actual taste is complex due to interactions between taste and substances, such as synergistic and suppressive effects. Second, ensuring reliable outcomes in dynamic conditions, particularly when faced with high deviation error data, presents a significant challenge. The present study introduces a bioinspired artificial E-tongue system that mimics the gustatory system by integrating multiple arrays of taste sensors to emulate taste buds in the human tongue and incorporating a customized deep-learning algorithm for taste interpretation. The developed E-tongue system is capable of detecting four distinct tastes in a single drop of dietary compounds, such as saltiness, sourness, astringency, and sweetness, demonstrating notable reversibility and selectivity. The taste profiles of six different wines are obtained by the E-tongue system and demonstrated similarities in taste trends between the E-tongue system and user reviews from online, although some disparities still exist. To mitigate these disparities, a prototype-based classifier with soft voting is devised and implemented for the artificial E-tongue system. The artificial E-tongue system achieved a high classification accuracy of ∼95% in distinguishing among six different wines and ∼90% accuracy even in an environment where more than 1/3 of the data contained errors. Moreover, by harnessing the capabilities of deep learning technology, a recommendation system was demonstrated to enhance the user experience.

Background: Nirmatrelvir-ritonavir is highly effective in preventing severe coronavirus disease 2019 (COVID-19) in high-risk patients with mild-to-moderate severity. However, real-world performance data are limited, and the drug is not so acceptable to the COVID-19 patients at high risk who need it in Korea., Methods: To evaluate the effectiveness of nirmatrelvir-ritonavir, we conducted a propensity score-matched retrospective cohort study on patients with mild-to-moderate COVID-19 at high risk for a severe disease who were hospitalized at four hospitals in South Korea from February 2022 to April 2022. A total of 236 patients in the treatment group (administered nirmatrelvir-ritonavir) and 236 in the matched control group (supportive care only) were analyzed for the primary outcome, i.e., the time to oxygen support-free survival. The secondary outcome was a composite result of disease progression. The reason for not prescribing nirmatrelvir-ritonavir to the indicated patients was also investigated., Results: The treatment group showed significantly longer oxygen support-free survival than the matched control group (adjusted hazard ratio [aHR], 0.07; 95% confidence interval [CI], 0.01-0.31; P < 0.001). Multivariate Cox regression analysis showed that age (aHR, 1.03; 95% CI, 1.00-1.07), National Early Warning Score-2 at admission (aHR, 1.36; 95% CI, 1.08-1.71), nirmatrelvir-ritonavir treatment, female sex (aHR, 0.37; 95% CI, 0.15-0.88), and time from symptom onset to admission (aHR, 0.67; 95% CI, 0.48-0.95) were significantly associated with oxygen therapy. However, none of the factors were related to the composite outcome. In the unmatched control group, 19.9% of 376 patients had documented explanations for nirmatrelvir-ritonavir non-prescription, and 44.0% of these were due to contraindication criteria. In the treatment group, 10.9% of patients discontinued the medication primarily because of adverse events (71.4%), with gastrointestinal symptoms being the most common (50.0%)., Conclusion: Nirmatrelvir-ritonavir treatment significantly reduced oxygen therapy requirements in high-risk patients with COVID-19 during the omicron variant surge in South Korea. Physicians are encouraged to consider the active use of nirmatrelvir-ritonavir and to be watchful for gastrointestinal symptoms during medication., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Glycopeptide antibiotics (vancomycin and teicoplanin) are usually used for the treatment of Staphylococcus epidermidis infections owing to their increased oxacillin resistance. However, S. epidermidis strains with decreased susceptibility to teicoplanin have become increasingly incident in recent years. We aimed to identify the characteristics of teicoplanin-non-susceptible (Teico-NS) S. epidermidis isolated at our hospital and analyze its relationship with teicoplanin usage. We retrospectively evaluated 328 S. epidermidis strains isolated from clinical isolates between January 2016 and December 2021. All strains were susceptible to vancomycin (minimal inhibitory concentration (MIC) ≤ 4 mg/L). The annual incidence for S. epidermidis strains with an elevated teicoplanin MIC of 8 mg/L ranged from 22.2 to 28.9%. In addition, in 2021, the number of S. epidermidis strains with teicoplanin MIC ≥ 16 mg/L rapidly increased (n = 13, 32.5%). Furthermore, teicoplanin use increased annually until 2019; however, in 2020, it decreased abruptly due to the COVID 19 pandemic. Thus, we could not confirm the existence of a clear correlation between teicoplanin usage and increased incidence of S. epidermidis with reduced teicoplanin-susceptibility. We showed the increased incidence of Teico-NS S. epidermidis in recent years. Further studies are needed to identify the mechanisms and risk factors for teicoplanin-resistance in S. epidermidis., (© 2023. Springer Nature Limited.)

Rana coreana is a brown frog species native to the Korean Peninsula. We characterized the complete mitochondrial genome of the species. The mitochondrial genome sequence of R. coreana is 22,262 bp and comprises 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and two control regions (CRs). The CR duplication and gene organization were identical to those observed in Rana kunyuensis and Rana amurensis . A total of 13 protein-coding genes were used to examine the phylogenetic relationships between this species and the genus Rana. R. coreana living on the Korean Peninsula, formed a cluster with R. kunyuensis and R. amurensis , with R. coreana showing the closest phylogenetic affinity for R. kunyuensis., Competing Interests: J. B. is the CEO of Clinomics, Inc. The authors declare that they have no competing financial interests or personal relationships that could influence the work reported in this study., (© 2023 National Institute of Biological Resources. Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Accumulating evidence suggests that the gut microbiome is associated with asthma. However, altered gut microbiome in adult asthma is not yet well established. We aimed to investigate the gut microbiome profiles of adult asthmatic patients with symptomatic eosinophilic inflammation., Methods: The 16 s rRNA gene metagenomic analysis of feces in the symptomatic eosinophilic asthma group (EA, n = 28) was compared with the healthy control (HC, n = 18) and the chronic cough control (CC, n = 13). A correlation analysis between individual taxa and clinical markers was performed within the EA group. Changes in the gut microbiome were examined in patients with significant symptom improvement in the EA group., Results: The relative abundances of Lachnospiraceae and Oscillospiraceae significantly decreased and Bacteroidetes increased in the EA group. Within EA group, Lachnospiraceae was negatively correlated with indicators of type 2 inflammation and lung function decline. Enterobacteriaceae and Prevotella was positively associated with type 2 inflammation and lung function decline, respectively. The abundance of predicted genes associated with amino acid metabolism and secondary bile acid biosynthesis was diminished in the EA group. These functional gene family alterations could be related to gut permeability, and the serum lipopolysaccharide concentration was actually high in the EA group. EA patients with symptom improvement after 1 month did not show a significant change in the gut microbiome., Conclusions: Symptomatic eosinophilic adult asthma patients showed altered the gut microbiome composition. Specifically, a decrease in commensal clostridia was observed, and a decrease in Lachnospiraceae was correlated with blood eosinophilia and lung function decline., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background/aims: Flagellin, which is abundant in gram-negative bacteria, including Pseudomonas , is reported to influence on inflammatory responses in various lung diseases. However, its effect on airway epithelial cells in contribution to asthma pathogenesis is not elucidated yet. We aimed to investigate the effect of TLR5 ligand flagellin on the transcriptomic profile of primary human epithelial cells and to determine the markers of airway inflammation., Methods: Normal human bronchial epithelial (NHBE) cells were grown and differentiated in air-liquid interface (ALI) culture for 14-16 days. The cells were treated with flagellin in vitro at 10 and 100 ng/ml for 3 and 24 h. The conditioned media and cells were harvested to validate inflammatory markers involved in airway inflammation using ELISA, Western blot, and quantitative PCR methods. RNA-sequencing was performed to investigate the transcriptional response to flagellin in ALI-NHBE cells., Results: Altered transcriptional responses to flagellin in differentiated bronchial epithelial cells were determined, including genes encoding chemokines, matrix metalloproteinases, and antimicrobial biomolecules. Pathway analysis of the transcriptionally responsive genes revealed enrichment of signaling pathways. Flagellin induced the mRNA expressions of proinflammatory cytokines and chemokines, and secretion of GM-CSF, CXCL5, CCL5 and CXCL10. Flagellin enhanced the protein expression of MMP-13 in TGF-β1 and TGF-β2 pretreated cell lysates and Wnt/β-catenin signaling., Conclusions: These findings suggest that flagellin could be a potent inducer of inflammatory markers that may contribute to airway inflammation and remodeling., (© 2023 The Author(s).)

This prospective observational study examined whether Staphylococcus aureus (SA) nasal colonization and staphylococcal enterotoxin (SE)-specific IgE sensitization synergistically affect clinical outcomes of adults with late-onset asthma (onset age ≥ 40 years). Nasal swabs were taken to evaluate SA colonization. Serum SE-IgE level was measured. Subjects were classified into 4 groups according to SA colonization and SE-IgE sensitization positivity. Among 181 patients with late-onset asthma recruited, the proportions of SA/SE (‒/‒), SA/SE (+ /‒), SA/SE (‒/ +), and SA/SE (+ / +) were 33.7%, 15.5%, 28.2%, and 22.6%, respectively. Severe asthma was more frequent in the SA/SE (+ / +) group than in the SA/SE (‒/‒) group (41.5% vs. 13.1%). The relationship of SA/SE (+ / +) with severe asthma was significant in multivariate logistic regression (vs. SA/SE (‒/‒); adjusted odds ratio: 4.36; 95% confidence intervals: 1.50‒12.73; p = 0.007), whereas SA/SE (+ /‒) or SA/SE (‒/ +) was not. In conclusion, SA nasal colonization and SE-IgE sensitization may synergistically affect disease severity in late-onset asthmatics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In 2005, the Korea Disease Control and Prevention Agency (KDCA) launched "Health Care Facility Counseling Project on People Living with human immunodeficiency virus (HIV)" funded by the private-subsidy project for the prevention of acquired immune deficiency syndrome (AIDS) and sexually transmitted diseases to provide people living with HIV (PLWH) psychological support and counsel them about the disease and antiretroviral therapy (ART). Currently, 38 counseling nurse specialists work at 28 healthcare facilities for patient care. Of all PLWH in Korea, 71.9% received benefits from the Counseling Project. Adherence to ART medication (>95.0%), level of depression or anxiety, counseling coverage, and viral load status were monitored as common project indicators. Various specialized programs have been implemented in diverse facilities. This project has played a pivotal role in HIV care continuum and viral suppression policies, resulting in 95.9% of PLWH maintaining undetectable status (<40 copies/ml) in 2021. In this review, we present the chronology and fulfillment of this project, which will be an essential step for future planning in the context of aging and the chronic comorbid nature of HIV/AIDS., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: Information on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated., Methods: Mild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days., Results: A total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization ( P = 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group ( P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively., Conclusions: Nirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

It has been reported that some exercise could enhance the anti-viral antibody titers after vaccination including influenza and coronavirus disease 2019 vaccines. We developed SAT-008, a novel digital device, consists of physical activities and activities related to the autonomic nervous system. We assessed the feasibility of SAT-008 to boost host immunity after an influenza vaccination by a randomized, open-label, and controlled study on adults administered influenza vaccines in the previous year. Among 32 participants, the SAT-008 showed a significant increase in the anti-influenza antibody titers assessed by hemagglutination-inhibition test against antigen subtype B Yamagata lineage after 4 wk of vaccination and subtype B Victoria lineage after 12 wk (p<0.05). There was no difference in the antibody titers against subtype "A." The SAT-008 also showed significant increase in the plasma cytokine levels of IL-10, IL-1β, and IL-6 at weeks 4 and 12 after the vaccination (p<0.05). A new approach using the digital device may boost host immunity against virus via vaccine adjuvant-like effects., Trial Registration: ClinicalTrials.gov Identifier: NCT04916145., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2023. The Korean Association of Immunologists.)

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P  = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P  = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P  = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Objectives: To assess the risk of lymphadenopathy following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination., Methods: A self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1-day to 42-day risk interval after coronavirus disease 2019 (COVID-19) vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval., Results: The risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% confidence interval [CI], 1.17 to 1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44 to 1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson's comorbidity index <5, and those who received mRNA vaccines (mRNA-1273>BNT162b2). Within the 1-day to 42-day post-dose risk period, the relative risk was highest during the 1-day to 7-day post-dose period (1.59; 95% CI, 1.57 to 1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI., Conclusions: SARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.

Multinational enterprises (MNEs) have incentive to reduce tax payment through transfer pricing. The incentive is stronger when MNEs own intangibles, because it is easy to transfer them across countries. To mitigate such strategic tax planning, the OECD proposes the arm's length principle (ALP). This paper deals with technology patents as an example of intangibles and investigates how the ALP affects MNEs' licensing strategies and welfare in a model with a tax haven. The ALP may distort MNEs' licensing decisions, because providing a license to unrelated firms restricts MNEs' profit-shifting opportunities due to the emergence of comparable transaction. Interestingly, the termination of licensing in the presence of the ALP may worsen domestic welfare if the (potential) licensee and the MNE's subsidiary do not compete in the domestic market but may improve welfare if they compete. The results under ad valorem royalty are in distinct contrast with those under per-unit royalty., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Allergen-specific immunotherapy (AIT) is considered the only curative treatment for allergic diseases mediated by immunoglobulin E (IgE). Currently, the route of administration depends both on the different types of causal allergens and on its effectiveness and safety profile. Several studies have reported the mechanisms and changes in humoral and cellular response underlying AIT; however, the full picture remains unknown. Knowledge of who can benefit from this type of treatment is urgently needed due to the patient safety risks and costs of AIT. In vivo or in vitro biomarkers have become a strategy to predict clinical outcomes in precision medicine. There are currently no standardized biomarkers that allow determining successful responses to AIT, however, some studies have found differences between responders and nonresponders. In addition, different candidates have been postulated that may have the potential to become biomarkers. In this review, we aim to summarize the findings to date related to biomarkers in different IgE-mediated allergic diseases (respiratory, food, and venom allergy) with the potential to define who will benefit from AIT., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Background: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19., Methods: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021., Results: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2., Conclusion: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis., Competing Interests: The authors have no potential conflicts of interest to disclosure., (© 2022 The Korean Academy of Medical Sciences.)

Pharmacogenomics (PGx) provides information about routine precision medicine, based on the patient's genotype. However, many of the available information about human allele frequencies, and about clinical drug-gene interactions, is based on American and European populations. PharmaKoVariome database was constructed to support genetic testing for safe prescription and drug development. It consolidated and stored 2507 diseases, 11 459 drugs and 61 627 drug-target or druggable genes from public databases. PharmaKoVariome precomputed ethnic-specific abundant variants for approximately 120 M single-nucleotide variants of drug-target or druggable genes. A user can search by gene symbol, drug name, disease and reference SNP ID number (rsID) to statistically analyse the frequency of ethnical variations, such as odds ratio and P-values for related genes. In an example study, we observed five Korean-enriched variants in the CYP2B6 and CYP2D6 genes, one of which (rs1065852) is known to be incapable of metabolizing drug. It is also shown that 4-6% of North and East Asians have risk factors for drugs metabolized by the CYP2D6 gene. Therefore, PharmaKoVariome is a useful database for pharmaceutical or diagnostic companies for developing diagnostic technologies that can be applied in the Asian PGx industry. Database URL: http://www.pharmakovariome.com/., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a zoonotic betacoronavirus. The development of effective vaccines and control measures requires a thorough understanding of the immune response to this viral infection., Methods: We investigated cellular immune responses up to 5 years after infection in a cohort of 59 MERS survivors by performing enzyme-linked immunospot assay and intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with synthetic viral peptides., Results: Memory T-cell responses were detected in 82%, 75%, 69%, 64%, and 64% of MERS survivors from 1-5 years post-infection, respectively. Although the frequency of virus-specific interferon gamma (IFN-γ)-secreting T cells tended to be higher in moderately/severely ill patients than in mildly ill patients during the early period of follow-up, there was no significant difference among the different clinical severity groups across all time points. While both CD4+ and CD8+ T cells were involved in memory T-cell responses, CD4+ T cells persisted slightly longer than CD8+ T cells. Both memory CD4+ and CD8+ T cells recognized the E/M/N proteins better than the S protein and maintained their polyfunctionality throughout the period examined. Memory T-cell responses correlated positively with antibody responses during the initial 3-4 years but not with maximum viral loads at any time point., Conclusions: These findings advance our understanding of the dynamics of virus-specific memory T-cell immunity after MERS-coronavirus infection, which is relevant to the development of effective T cell-based vaccines., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Stony corals often harbor intracellular photosynthetic dinoflagellate algae that receive dissolved inorganic nutrients. However, Dendrophyllia cribrosa is a nonsymbiotic stony coral distributed in the western Pacific. We assembled a chromosome-level D. cribrosa genome using PacBio and Hi-C technologies. The final assembly was 625 Mb, distributed on 14 chromosomes, and contained 30,493 protein-coding genes. The Benchmarking Universal Single-Copy Orthologs analysis revealed a percentage of 96.8 of the metazoan genome. A comparative phylogenetic analysis revealed that D. cribrosa, which lacks symbionts, evolved to acquire cellular energy by expanding genes related to acyl-CoA metabolism and carbohydrate transporters. This species also has expanded immune-related genes involved in the receptor protein tyrosine kinase signaling pathway. In addition, we observed a specific expansion of calcification genes, such as coral acid-rich proteins and carbonic anhydrase, in D. cribrosa. This high-quality reference genome and comparative analysis provides insights into the ecology and evolution of nonsymbiotic stony corals., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Purpose: To evaluate the efficacy of intervention policies on coronavirus disease-19 (COVID-19) dissemination., Materials and Methods: An age-structured compartmental model for the COVID-19 outbreak was proposed to predict the impact of control measures in the Seoul/Gyeonggi region. The model was calibrated based on actual data and realistic situations, including daily vaccine doses, proportion of delta variant cases, and confirmed cases by age. We simulated different scenarios for non-pharmaceutical interventions by varying social distancing and school attendance strategies., Results: Two-step mitigation of social distancing without in-person classes would result in a rapid increase in confirmed cases up to 10000 but would keep severe cases within the manageable range of the health care system. The overall impact of taking down the distancing level by one step with twice the increase in contacts at school was comparable to the above scenario. Implementation of two-step mitigation of social distancing along with a two-fold increase in contacts among the school-age group would dramatically increase confirmed and severe cases by over 80000 and 100, respectively, as early as the beginning of December. This policy would cause the situation to spiral out of control, considering the scale of the response and time to prepare. On the other hand, the burden on the current healthcare system caused by two-step mitigation of social distancing and 40% increased contacts in the school-age group was manageable if prepared., Conclusion: A compromise between social distancing and school attendance policy and timely preparations for the spread of COVID-19 are required., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Herein, we provide the first whole-genome sequence of the purple butter clam (Saxidomus purpuratus), an economically important bivalve shellfish. Specifically, we sequenced and de novo assembled the genome of Sa. purpuratus based on PromethION long reads and Hi-C data. The 978-Mb genome of Sa. purpuratus comprises 19 chromosomes with 36,591 predicted protein-coding genes. The N50 length of Sa. purpuratus genome is 52 Mb, showing the highest continuous assembly among bivalve genomes. The Benchmarking by Universal Single-Copy Orthologs assessment indicated that 95.07% of complete metazoan universal single-copy orthologs (n = 954) were present in the assembly. Approximately 51% of Sa. purpuratus genome comprises repetitive sequences. Based on the high-quality Sa. purpuratus genome, we resolved half of the immune-associated genes, namely, scavenger receptor (SR) proteins, which are collinear to those in the closely related Cyclina sinensis genome. This finding suggested a high degree of conservation among immune-associated genes. Twenty-two (19%) SR proteins are tandemly duplicated in Sa. purpuratus genome, suggesting putative convergence evolution. Overall, Sa. purpuratus genome provides a new resource for the discovery of economically important traits and immune-response genes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Foreign molecules, including viruses and bacteria-derived toxins, can also induce airway inflammation. However, to the best of our knowledge, the roles of these molecules in the development of airway inflammation have not been fully elucidated. Herein, we investigated the precise role and synergistic effect of virus-mimicking double-stranded RNA (dsRNA) and staphylococcal enterotoxin B (SEB) in macrophages and epithelial cells. To identify cytokine expression profiles, both the THP-1-derived macrophages and BEAS-2B epithelial cells were stimulated with dsRNA or SEB. A total of 21 cytokines were evaluated in the culture supernatants. We observed that stimulation with dsRNA induced cytokine production in both cell types. However, cytokine production was not induced in SEB-stimulated epithelial cells, compared to the macrophages. The synergistic effect of dsRNA and SEB was evaluated observing cytokine level and intracellular phospho-signaling. Fifteen different types were detected in high-dose dsRNA-stimulated epithelial cells, and 12 distinct types were detected in macrophages; those found in macrophages lacked interferon production compared to the epithelial cells. Notably, a synergistic effect of cytokine induction by co-stimulation of dsRNA and SEB was observed mainly in epithelial cells, via activation of most intracellular phosphor-signaling. However, macrophages only showed an accumulative effect. This study showed that the type and severity of cytokine productions from the epithelium or macrophages could be affected by different intensities and a combination of dsRNA and SEB. Further studies with this approach may improve our understanding of the development and exacerbation of airway inflammation and asthma., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2022. The Korean Association of Immunologists.)

Cymbidium goeringii, commonly known as the spring orchid, has long been favoured for horticultural purposes in Asian countries. It is a popular orchid with much demand for improvement and development for its valuable varieties. Until now, its reference genome has not been published despite its popularity and conservation efforts. Here, we report the de novo assembly of the C. goeringii genome, which is the largest among the orchids published to date, using a strategy that combines short- and long-read sequencing and chromosome conformation capture (Hi-C) information. The total length of all scaffolds is 3.99 Gb, with an N50 scaffold size of 178.2 Mb. A total of 29,556 protein-coding genes were annotated and 3.55 Gb (88.87% of genome) repetitive sequences were identified. We constructed pseudomolecular chromosomes using Hi-C, incorporating 89.4% of the scaffolds in 20 chromosomes. We identified 220 expanded and 106 contracted genes families in C. goeringii after divergence from its close relative. We also identified new gene families, resistance gene analogues and changes within the MADS-box genes, which control a diverse set of developmental processes during orchid evolution. Our high quality chromosomal-level assembly of C. goeringii can provide a platform for elucidating the genomic evolution of orchids, mining functional genes for agronomic traits and for developing molecular markers for accelerated breeding as well as accelerating conservation efforts., (© 2021 John Wiley & Sons Ltd.)

Objectives: We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients., Methods: We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens., Results: The seropositivity rate persisted for up to 4 years (50.7-56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT 50 , and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection., Discussion: The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune responses compared to the brain. Though physiologically, structural components of the BSCB and BBB share many similarities, the clinical landscape significantly differs. Thus, it is crucial to understand the composition of BSCB and also to establish the cause-effect relationship with aberrations and spinal cord dysfunctions. Here, we provide a descriptive analysis of the anatomy, current techniques to assess the impairment of BSCB, associated risk factors and impact of spinal disorders such as spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), peripheral nerve injury (PNI), ischemia reperfusion injury (IRI), degenerative cervical myelopathy (DCM), multiple sclerosis (MS), spinal cavernous malformations (SCM) and cancer on BSCB dysfunction. Along with diagnostic and mechanistic analyses, we also provide an up-to-date account of available therapeutic options for BSCB repair. We emphasize the need to address BSCB as an individual entity and direct future research towards it., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2021 by the authors.)