Search

Abstract This post hoc analysis of the randomized, placebo‐controlled N‐MOmentum study (NCT02200770) of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD) evaluated relationships between circulating B‐cell subsets and aquaporin‐4 immunoglobulin G (AQP4‐lgG) titers and attacks. Among participants receiving placebo, CD20+ and CD27+ B‐cell counts were modestly increased from the pre‐attack visit to attack; plasmablast/plasma cell gene signature was increased from baseline to the pre‐attack visit (p = 0.016) and from baseline to attack (p = 0.009). With inebilizumab treatment, B‐cell subset counts decreased and did not increase with attacks. No difference in change of AQP4‐IgG titers from baseline to time of attack was observed.

Abstract Alternative cleavage and polyadenylation within introns (intronic APA) generate shorter mRNA isoforms; however, their physiological significance remains elusive. In this study, we developed a comprehensive workflow to analyze intronic APA profiles using the mammalian target of rapamycin (mTOR)-regulated transcriptome as a model system. Our investigation revealed two contrasting effects within the transcriptome in response to fluctuations in cellular mTOR activity: an increase in intronic APA for a subset of genes and a decrease for another subset of genes. The application of this workflow to RNA-seq data from The Cancer Genome Atlas demonstrated that this dichotomous intronic APA pattern is a consistent feature in transcriptomes across both normal tissues and various cancer types. Notably, our analyses of protein length changes resulting from intronic APA events revealed two distinct phenomena in proteome programming: a loss of functional domains due to significant changes in protein length or minimal alterations in C-terminal protein sequences within unstructured regions. Focusing on conserved intronic APA events across 10 different cancer types highlighted the prevalence of the latter cases in cancer transcriptomes, whereas the former cases were relatively enriched in normal tissue transcriptomes. These observations suggest potential, yet distinct, roles for intronic APA events during pathogenic processes and emphasize the abundance of protein isoforms with similar lengths in the cancer proteome. Furthermore, our investigation into the isoform-specific functions of JMJD6 intronic APA events supported the hypothesis that alterations in unstructured C-terminal protein regions lead to functional differences. Collectively, our findings underscore intronic APA events as a discrete molecular signature present in both normal tissues and cancer transcriptomes, highlighting the contribution of APA to the multifaceted functionality of the cancer proteome.

In this study, a skewness estimation method (SEM) and kurtosis estimation method (KEM) are introduced to determine the number of inactive cycles in Monte Carlo eigenvalue calculations. The SEM and KEM can determine the number of inactive cycles on the basis that fully converged fission source distributions may follow normal distributions without asymmetry or outliers. Two convergence criteria values and a minimum cycle length for the SEM and KEM were determined from skewness and kurtosis analyses of the AGN-201K benchmark and 1D slab problems. The SEM and KEM were then applied to two OECD/NEA slow convergence benchmark problems to evaluate the performance and reliability of the developed methods. Results confirmed that the SEM and KEM provide appropriate and effective convergence cycles when compared to other methods and fission source density fraction trends. Also, the determined criterion value of 0.5 for both ε1 and ε2 was concluded to be reasonable. The SEM and KEM can be utilized as a new approach for determining the number of inactive cycles and judging whether Monte Carlo tally values are fully converged. In the near future, the methods will be applied to various practical problems to further examine their performance and reliability, and optimization will be performed for the convergence criteria and other parameters as well as for improvement of the methodology for practical usage.

Objectives In cases of nonvariceal upper gastrointestinal bleeding (NVUGIB), endoscopic intervention within the first 24 hours is widely recommended. However, data on the efficacy of urgent endoscopy are limited. Here, we used the Glasgow–Blatchford score to assess bleeding outcomes based on time-to-endoscopy. Methods Prospectively collected multicenter data, which included 1554 patients with NVUGIB, were retrospectively reviewed between February 2011 and December 2013. Based on time-to-endoscopy, patients were grouped into the early (

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models. We evaluated the effects the activity of EDC metabolites generated through mLOs based on human cell-based reporter gene assays in addition to existing models. This study emphasizes the importance of hepatic ex-vivo and suggests the need a new metabolic model through a 3D mLOs platform. These results indicate that mLOs provides a novel biological method to screen for potential endocrine-disrupting activities of EDC metabolites.

This study evaluates the effectiveness of hot isostatic pressing (HIP) in mitigating porosity in TZM-NbZr1 bimetallic structures fabricated via wire-arc directed energy deposition (DED). Two distinct HIP conditions and a combined HIP and heat treatment (HT) were investigated. The pore area fraction decreased from 4 ± 0.05% in the as-built condition to 3.05 ± 0.02% and 1 ± 0.01% after treatment at 1200°C and 1500°C, respectively. Porosity was further reduced to 0.01 ± 0.005% with HIP at 1800°C followed by HT. Plastic deformation strongly influenced pore size and shape at elevated temperatures, particularly above the recrystallisation temperatures of both alloys. At lower treatment temperature, disparity in material flow around the pores resulted in interconnected micro-cracks or micro-void formation. However, the combined HIP and HT process effectively eliminated both cracks and porosities from the interface altering the pore recovery mechanism from micro-void formation to dynamic recrystallisation. Additionally, enhanced Mo diffusion from TZM to NbZr1 was observed at higher temperature.

Abstract This study investigates the effects of different types of physical activity (PA) on the physical fitness (PF) of young children in Japan, with a particular focus on how substituting sedentary behavior (SB) with active behaviors influences PF. We conducted a cross-sectional analysis of 1843 participants aged 3–6 years from northeastern Japan. Using triaxial accelerometers, we quantified PA, and PF was assessed via standardized tests. The innovative application of isotemporal substitution modeling (ISM) allowed us to analyze the impact of reallocating time from SB to more active states, specifically moderate-to-vigorous physical activity (MVPA) and light physical activity (LPA). Our findings reveal a robust association between increased MVPA and enhanced PF outcomes, underscoring the health benefits of reducing SB. Notably, replacing SB with LPA also showed beneficial effects on certain PF metrics, indicating LPA's potential role in early childhood fitness. These results highlight the critical importance of promoting MVPA and minimizing sedentary periods to bolster PF in young children. The study offers vital insights for shaping public health policies and emphasizes the need to cultivate an active lifestyle from an early age to secure long-term health advantages.

Abstract Background The operative outcomes of thoracoabdominal aortic aneurysms (TAAAs) are challenged by high operative mortality and disabling complications. This study aimed to explore the baseline clinical, anatomical, and procedural risk factors that impact early and late outcomes following open repair of TAAAs. Methods We reviewed the medical records of 290 patients who underwent open repair of TAAAs between 1992 and 2020 at a tertiary referral center. Determinants of early mortality (within 30 days or in hospital) were analyzed using multivariable logistic regression models, while those of overall follow-up mortality were explored using multivariable Cox proportional hazards models and landmark analyses. Results The rates of early mortality and spinal cord deficits were 13.1% and 11.0%, respectively, with Crawford extent II showing the highest rates. In the logistic regression models, older age (P 0.05). Conclusion There were differential temporal impacts of perioperative risk variables on mortality in open repair of TAAAs, with older age and low hemoglobin level having significant impacts throughout the postoperative period, and low surgical volume, high CPB time, and Crawford extent II having impacts in the early postoperative phase.

The two commonest kelp-encrusting bryozoans, Membranipora villosa and M. membranacea, are difficult to distinguish morphologically. Molecular studies of M. villosa should thus be helpful for the identification of both species because the mitogenome of M. membranacea was already sequenced. The complete mitogenome of M. villosa collected from Sinjido was determined in this study through Illumina NovaSeq sequencing. Maximum-likelihood (ML) analysis was based on concatenated 13 protein-coding genes dataset from nine bryozoan species. The mitogenome length was 15,407 bp, and its gene arrangement was similar to those of the mitogenome of other membraniporids, having 13 PCGs, two ribosomal RNAs, and 22 tRNAs. It had an overall A + T content of 63.7% (29.7% A, 16.7% C, 19.6% G, and 34.0% T). M. villosa and M. membranacea showed sequence differences of 20% for the total length of mitogenome and 16.1.% for 13 PCGs. Molecular data definitely consider them to be separate species. Phylogenetic analyses based on the amino acids of 13 PCGs indicated that M. villosa has the closest relationship with another kelp-encrusting bryozoan, M. membranacea of membraniporids. The phylogenetic position of genera and families within the suborder Membraniporina coincides with the Bayesian phylogenetic analysis of the mixed concatenated alignment consisting of three partitions.

Objective To evaluate C2 muscle preservation effect and the radiological and clinical outcomes after C2 recapping laminoplasty. Methods Fourteen consecutive patients who underwent C2 recapping laminoplasty around C1–2 level were enrolled. To evaluate muscle preservation effect, the authors conducted a morphological measurement of extensor muscles between the operated and nonoperated side. Two surgeons measured the cross-sectional area (CSA) of obliquus capitis inferior (OCI) and semispinalis cervicis (SSC) muscle before and after surgery to determine atrophy rates (ARs). Additionally, we examined range of motion (ROM), sagittal vertical axis (SVA), neck visual analogue scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) score to assess potential changes in alignment and consequent clinical outcomes following posterior cervical surgery. Results We measured the CSA of OCI and SSC before surgery, and at 6 and 12 months postoperatively. Based on these measurements, the AR of the nonoperated SSC was 0.1% ± 8.5%, the AR of the operated OCI was 2.0% ± 7.2%, and the AR of the nonoperated OCI was -0.7% ± 5.1% at the 12 months after surgery. However, the AR of the operated side’s SSC was 11.2% ± 12.5%, which is a relatively higher value than other measurements. Despite the atrophic change of SSC on the operated side, there were no prominent changes observed in SVA, C0–2 ROM, and C2–7 ROM between preoperative and 12 months postoperative measurements, which were 11.8 ± 10.9 mm, 16.3° ± 5.9°, and 48.7° ± 7.7° preoperatively, and 14.1 ± 11.6 mm, 16.1° ± 7.2°, and 44.0° ± 10.3° at 12 months postoperative, respectively. Improvement was also noted in VAS, NDI, and JOA scores after surgery with JOA recovery rate of 77.3% ± 29.6%. Conclusion C2 recapping laminoplasty could be a useful tool for addressing pathologies around the upper cervical spine, potentially mitigating muscle atrophy and reducing postoperative neck pain, while maintaining sagittal alignment and ROM.

Exposure to environmental heavy metals such as lead (Pb) and cadmium (Cd) is a global concern due to their widespread presence. However, the specific pulmonary effects of inhaled exposure, especially related to long-term effects, remain poorly understood. In this study, we developed a novel mouse model of Pb and Cd inhalation to mimic real-world conditions and investigate pulmonary effects. Mice were exposed to Pb and Cd inhalation for 6 months using a whole-body exposure system, resulting in decreased lung compliance and progression from emphysematous changes to fibrosis. In addition, the blood Pb/Cd levels of mice exposed to Pb/Cd for 6 months are like those of humans occupationally exposed to heavy metals. Histology revealed inflammation and collagen deposition. Transcriptomic analysis highlighted immune responses and macrophage activity in developing fibrosis. These results confirm an association between Pb/Cd exposure and emphysema and fibrosis, reflecting clinical findings. The study highlights the importance of long-term exposure assessment and time-course analysis for understanding Pb/Cd-induced lung disease. The relevance of the mouse model in replicating human exposure scenarios underscores its value in studying fibrosis and emphysema simultaneously. These findings provide a basis for targeted therapeutic interventions against heavy metal-induced lung injury.

A search coil magnetometer (SCM) is a common equipment to observe energy transmission and vibrations in space physics, enabling measurements across a wide frequency range of up to tens of kilohertz. This study proposes the designs of a magnetic core that allows a low-mass sensor and improves its performance: a rod core, sheet-stacked core, and rolling-sheet core. Subsequently, the performance of each sensor was investigated. The sheet-stacked core using the cobalt-based alloy exhibited the highest sensitivity, although it exhibited instability beyond 20 kHz. In contrast, the rod and rolling-sheet core sensors demonstrated stability in the magnetic field measurements (10 Hz–40 kHz). Moreover, the noise equivalent magnetic induction (NEMI) of the rod- and rolling-sheet core sensors were 0.014 pT Hz–1/2 and 0.012 pT Hz–1/2 at 1 kHz, respectively. The rolling-sheet core with high relative permeability achieved a mass reduction of over three times that of the rod core while exhibiting sufficient sensitivity.

Background: This study compared the outcomes of surgical aortic valve replacement (AVR) in patients aged 50 to 70 years based on the type of prosthetic valve used. Methods: We compared patients who underwent mechanical AVR to those who underwent bioprosthetic AVR at our institution between January 2000 and March 2019. Competing risk analysis and the inverse probability of treatment weighting (IPTW) method based on propensity score were employed for comparisons. Results: A total of 1,580 patients (984 patients with mechanical AVR; 596 patients with bioprosthetic AVR) were enrolled. There was no significant difference in early mortality between the mechanical AVR and bioprosthetic AVR groups (0.9% vs. 1.7%, p=0.177). After IPTW adjustment, the risk of all-cause mortality was significantly higher in the bioprosthetic AVR group than in the mechanical AVR group (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.07–1.80; p=0.014). Competing risk analysis revealed lower risks of stroke (sub-distributional hazard ratio [sHR], 0.44; 95% CI, 0.28–0.67; p

Gender disparities in intensive care unit (ICU) treatment approaches and outcomes are evident. However, clinicians often pay little attention to the importance of biological sex and sociocultural gender in their treatment courses. Previous studies have reported that differences between sexes or genders can significantly affect the manifestation of diseases, diagnosis, clinicians' treatment decisions, scope of treatment, and treatment outcomes in the intensive care field. In addition, numerous reports have suggested that immunomodulatory effects of sex hormones and differences in gene expression from X chromosomes between genders might play a significant role in treatment outcomes of various diseases. However, results from clinical studies are conflicting. Recently, the need for customized treatment based on physical, physiological, and genetic differences between females and males and sociocultural characteristics of society have been increasingly emphasized. However, interest in and research into this field are remarkably lacking in Asian countries, including South Korea. Through this review, we hope to enhance our awareness of the importance of sex and gender in intensive care treatment and research by briefly summarizing several principal issues, mainly focusing on sex and sex hormone-based outcomes in patients admitted to the ICU with sepsis and septic shock.

Abstract Background Red pepper paste is a common ingredient used in food in Korea. The discrimination of the geographical origin of agricultural products is important to protect the agricultural industry and customers from the misinformation regarding the product origin. Several studies have attempted to identify the geographical origin of red pepper based on its characteristic features using diverse methods, such as inorganic elemental analysis. However, similar studies on red pepper pastes have not been conducted thus far. Results In, this study, we established methods based on inductively coupled plasma optical emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) for determining inorganic elements in red pepper pastes. The limit of detection (LOD) of ICP-AES was in the range of 0.006–0.531 mg∙kg−1 and the limit of quantification (LOQ) was 0.017–1.593 mg∙kg−1. In addition, LOD and LOQ ranges for ICP-MS were 0.001–1.553, and 0.002–5.176 μg∙kg−1, respectively. The concentrations of Ca, K, Mg, Na, P, S, Cr, Mn, Co, Ni, Cu, Ga, As, Sr, Zr, Mo, Pd, Cd, Sn, Sb, Ce, Pt, Pb, and U were high in the Korean red pepper paste. All the employed discrimination models could clearly distinguish between Korean and Chinese red pepper pastes. In particular, among the four different models, CDA showed the most accurate ability to discriminate the geological origin of Korean and Chinese red pepper paste compared to that achieved using the other models with 100% accuracy. Conclusions Based on, the findings of this study, the use of ICP-AES and ICP-MS analyses for discriminating the inorganic elements in food products in combination with the aforementioned statistical analysis models could help the mitigation of issues associated with the misinformation of the geographical origin of agricultural products, aiding customer protection. Graphical Abstract

Abstract Background Breast cancer, the most prevalent cancer in women worldwide, faces treatment challenges due to drug resistance, posing a serious threat to patient survival. The present study aimed to identify the key molecules that drive drug resistance and aggressiveness in breast cancer cells and validate them as therapeutic targets. Methods Transcriptome microarray and analysis using PANTHER pathway and StemChecker were performed to identify the most significantly expressed genes in tamoxifen-resistant and adriamycin-resistant MCF-7 breast cancer cells. Clinical relevance of the key genes was determined using Kaplan-Meier survival analyses on The Cancer Genome Atlas dataset of breast cancer patients. Gene overexpression/knockdown, spheroid formation, flow cytometric analysis, chromatin immunoprecipitation, immunocytochemistry, wound healing/transwell migration assays, and cancer stem cell transcription factor activation profiling array were used to elucidate the regulatory mechanism of integrin α11 expression. Tumour-bearing xenograft models were used to demonstrate integrin α11 is a potential therapeutic target. Results Integrin α11 was consistently upregulated in drug-resistant breast cancer cells, and its silencing inhibited cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) while restoring sensitivity to anticancer drugs. HIF1α, GLI-1, and EZH2 contributed the most to the regulation of integrin α11 and EZH2 expression, with EZH2 being more necessary for EZH2 autoinduction than HIF1α and GLI-1. Additionally, unlike HIF1α or EZH2, GLI-1 was the sole transcription factor activated by integrin-linked focal adhesion kinase, indicating GLI-1 as a key driver of the EZH2-integrin α11 axis operating for cancer stem cell survival and EMT. Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset also revealed both EZH2 and integrin α11 could be strong prognostic factors of relapse-free and overall survival in breast cancer patients. However, the superior efficacy of integrin α11 siRNA therapy over EZH2 siRNA treatment was demonstrated by enhanced inhibition of tumour growth and prolonged survival in murine models bearing tumours. Conclusion Our findings elucidate that integrin α11 is upregulated by EZH2, forming a positive feedback circuit involving FAK-GLI-1 and contributing to drug resistance, cancer stem cell survival and EMT. Taken together, the results suggest integrin α11 as a promising prognostic marker and a powerful therapeutic target for drug-resistant breast cancer.

Abstract Background White standard Dendranthema grandiflorum (D. grandiflorum) is widely used for ornamental purposes. The volatile organic components (VOCs) of D. grandiflorum vary depending on the geographical origin and cultivar, which influence the market value. Here, we applied headspace extraction coupled with gas chromatography–mass spectrometry (HS–GC–MS) for the first time to determine the different origins (Korea, China, Vietnam) of D. grandiflorum in three genotypes (Baekgang, Jinba, Iwa-no-hakusen) based on volatile fingerprints and to assess the correlation among the metabolites identified in Korean and non-Korean D. grandiflorum. Results A total of 41 VOCs, mainly monoterpenoids, sesquiterpenoids, alcohols, and fatty acids, were identified. Principal component analysis showed that instead of geographical origin, genotype influences D. grandiflorum fingerprints. Cultivar discrimination was mainly affected by the metabolites associated with the alpha-terpinyl cation pathway. The orthogonal partial least squares discriminant analysis model achieved 100% and 93.3% accuracies in the calibration and validation sets, respectively. The results of volcano plots and clustering analysis, sesquiterpenoids were significantly more abundant in non-Korean than in Korean, whereas monoterpenoids were abundant in Korean samples. Conclusions 41 makers confirmed robustness maintenance over two years. These findings can be useful for reliably identifying the geographical origin of D. grandiflorum and providing a comprehensive understanding of VOCs in D. grandiflorum cultivars grown in different countries of origins. Graphical Abstract

Abstract In the semiconductor manufacturing process, when conducting inductively coupled plasma-reactive ion etching in challenging environments, both wafers and the ceramic components comprising the chamber’s interior can be influenced by plasma attack. When ceramic components are exposed to long-term plasma environments, the eroded components must be replaced. Furthermore, non-volatile reactants can form and settle on semiconductor chips, acting as contaminants and reducing semiconductor production yield. Therefore, for semiconductor processing equipment parts to be utilized, it is necessary that they exhibit minimized generation of contaminant particles and not deviate significantly from the composition of conventionally used Al2O3 and Y2O3; part must also last long in various physicochemical etching environment. Herein, we investigate the plasma etching behavior of Y2O3–Y4Al2O9 (YAM) composites with a variety of mixing ratios under different gas fraction conditions. The investigation revealed that the etching rates and changes in surface roughness for these materials were significantly less than those of Y2O3 materials subjected to both chemical and physical etching. Microstructure analysis was conducted to demonstrate the minimization of crater formation. Mechanical properties of the composite were also analyzed. The results show that the composite can be commercialized as next-generation ceramic component in semiconductor processing equipment applications.

Abstract Obesity, a prevalent disease associated with numerous chronic conditions, including hyperlipidemia, hyperglycemia, diabetes, and metabolic syndrome, remains a major global health challenge. This study investigated the potential of green tea (GT), fermented tea (FT), and γ-aminobutyric acid (GABA) tea (GBT), which are rich in phytonutrients and polyphenols, for the management of obesity. Using a high-fat diet-induced obese mouse model (C57BL/6N), we explored the effect of these teas on various obesity-related parameters. The mice were categorized into five groups: normal diet with water, high-fat diet with water, and high-fat diet supplemented with GT, FT, or GBT. Over 13 weeks, we monitored body weight, perirenal and liver fat, adipocyte lipid accumulation, and key metabolic indicators, such as serum cholesterol, leptin, insulin, and fasting blood glucose. These teas contain beneficial phytochemicals such as GABA, theanine, and caffeine, and have demonstrated an enhanced antioxidant capacity, which increases the scavenging of free radicals and may reduce oxidative stress. The animal study indicated a decrease in feeding efficiency and significant reductions in body weight liver fat, epididymal fat, and perirenal fat, as well as in adipocyte lipid accumulation. Additionally, notable improvements were observed in metabolic health indicators, including reductions in serum cholesterol, leptin, insulin, and fasting blood glucose levels. Our findings revealed that GT, FT, or GBT significantly counteracted the negative effects of a high-fat diet, suggesting their potential in combating obesity and related metabolic disorders.

High-entropy ceramics exhibit novel intrinsic properties. Hence, they have been explored for a wide range of applications ranging from thermal insulation and energy storage to advanced optical components. Recently, the semiconductor industry has faced a demand for higher-performance chips, necessitating higher aspect ratios in wafer fabrication and further miniaturization of linewidths. Therefore, novel materials with high plasma etching resistance and minimal contaminant generation are needed. The plasma-etching resistance displayed by high-entropy ceramics can be an innovative solution to this emerging challenge. In this study, we successfully fabricated single-phase high-entropy sesquioxide ceramics with high optical transparency, dense microstructure, and minimal residual pores. A structural analysis of the fabricated samples revealed a single-phase structure with excellent phase homogeneity. An evaluation of the plasma-etching resistance of high-entropy ceramics revealed for the first time a low etching rate of 8 nm/h compared with that of conventional plasma-resistant materials. These comprehensive characterizations of high-entropy ceramics indicate that they are promising candidates for significantly improving the production yield of semiconductors and for a wide range of potential applications, such as next-generation active optical ceramics.

This research evaluated the protective role of a combined extract of Dioscorea bulbifera and Zingiber officinale (DBZO) against respiratory dysfunction caused by particulate matter (PM2.5) exposure in BALB/c mice. The bioactive compounds identified in the DBZO are catechin, astragalin, 6-gingerol, 8-gingerol, and 6-shogaol. DBZO ameliorated cell viability and reactive oxygen species (ROS) production in PM2.5-stimulated A549 and RPMI 2650 cells. In addition, it significantly alleviated respiratory dysfunction in BALB/c mice exposed to PM2.5. DBZO improved the antioxidant systems in lung tissues by modulating malondialdehyde (MDA) content, as well as levels of reduced glutathione (GSH) and superoxide dismutase (SOD). Likewise, DBZO restored mitochondrial dysfunction by improving ROS levels, mitochondrial membrane potential, and ATP production. Moreover, DBZO modulated the levels of neutrophils, eosinophils, monocytes, and lymphocytes (specifically CD4+, CD8+, and CD4+IL-4+ T cells) in blood and IgE levels in serum. DBZO was shown to regulate the c-Jun N-terminal kinase (JNK) pathway, nuclear factor kappa B (NF-κB) pathway, and transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) pathway. Histopathological observation indicated that DBZO mitigates the increase in alveolar septal thickness. These findings indicate that DBZO is a promising natural agent for improving respiratory health.

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

BackgroundThis study aimed to investigate the association between continuous polypharmacy and hospitalization, emergency department (ED) visits, and death.MethodsThis retrospective study utilized 6,443,896 patients aged between 65 and 84 years of National Health Insurance claims data from 2016 to 2018. Polypharmacy and excessive polypharmacy were defined as the concurrent use of 5 or more and 10 or more medications, respectively, for durations of both 90 days or more and 180 days or more within a 1-year observation period. The primary outcome measures included all-cause hospitalization, ED visits, and mortality. Multiple logistic regression models were used adjusting for patients’ general characteristics, comorbidities, and history of hospitalization or ED visits.ResultsAmong 2,693,897 patients aged 65–84 years who had used medicines for 180 days or more (2,955,755 patients taking medicines for 90 days or more), the adverse outcomes were as follows: 20.5% (20.3%) experienced hospitalization, 10.9% (10.8%) visited the ED, and 1% (1%) died, respectively. In patients who exhibited polypharmacy for more than 180 days, the adjusted odds ratio of adverse outcomes was 1.32 (95% confidence interval [CI], 1.31–1.33) for hospitalization, 1.32 (95% CI, 1.31–1.33) for ED visits, 1.63 (95% CI, 1.59–1.67) for death, and that in excessive polypharmacy patients for more than 180 days was 1.85 for hospitalization, 1.92 for ED visits, and 2.57 for death, compared to non-polypharmacy patients.ConclusionOur results suggest that polypharmacy in older adults might lead to negative health consequences. Thus, interventions to optimize polypharmacy may need to be implemented.

Background/Aims: Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failure and high short-term mortality. On the other hand, few studies reflecting the various etiologies of cirrhosis are available. This study examined the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods: Between January 2005 and December 2018, 109 HCV-related cirrhosis patients hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and bacterial infection) were enrolled for ACLF defined by the European Association for the Study of the Liver (EASL). Results: ACLF developed in 35 patients (32.1%) on admission. Eight, eight, and 19 patients had ACLF grades 1, 2, and 3, respectively. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%). Compared with all other prognostic scores, the Chronic liver failure Consortium Organ Failure score predicted the 90-day mortality most accurately, with an area under the receiver operator characteristic of 0.921. Conclusions: HCV-related ACLF has unique clinical characteristics distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful for predicting the short-term mortality in HCV-related cirrhosis.

Abstract Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B‐cells, is approved to treat aquaporin 4 (AQP4) IgG‐seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III‐A (FCGR3A) receptors on natural killer cells to maximize antibody‐dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG‐binding affinity and reduce rituximab (anti‐CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab‐treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

Objective Achieving successful fusion during spine surgery is dependent on rigid pedicle screw fixation. To assess fixation strength, the insertional torque can be measured during intraoperative screw fixation. This study aimed to explore the technical feasibility of measuring the insertional torque of a pedicle screw, while investigating its relationship with bone density. Methods Thoraco-lumbar screw fixation fusion surgery was performed on 53 patients (mean age, 65.5 ± 9.8 years). The insertional torque of 284 screws was measured at the point passing through the pedicle using a calibrated torque wrench, with a specially designed connector to the spine screw system. The Hounsfield units (HU) value was determined by assessing the trabecular portion of the index vertebral body on sagittal computed tomography images. We analyzed the relationship between the measured insertional torque and the following bone strength parameters: bone mineral density (BMD) and HU of the vertebral body. Results The mean insertion torque was 105.55 ± 58.08 N∙cm and T-score value (BMD) was -1.14 ± 1.49. Mean HU value was 136.37 ± 57.59. Screw insertion torque was positively correlated with BMD and HU in whole patients. However, in cases of osteopenia, all variables showed very weak correlations with insertional torque. In patients with osteoporosis, there was no statistically significant correlation between BMD and torque strength; HU showed a significant correlation. Conclusion The insertional torque of screw fixation significantly correlated with bone density (BMD and HU). HU measurements showed greater clinical significance than did BMD values in patients with osteoporosis.

Background: Active compounds from plants and herbs are increasingly incorporated into modern medical systems to address cardiovascular diseases (CVDs). Foeniculum vulgare Mill., commonly known as fennel, is an aromatic medicinal plant and culinary herb that is popular worldwide. Methods: Protective effects against cellular damage were assessed in the H9C2 cardiomyocyte hypoxia/reoxygenation (H/R) experimental model. The identities of phytochemicals in FVSE were determined by GC-MS analysis. The phytochemical’s potential for nutrients and pharmacokinetic properties was assessed by ADMET analysis. Results: GC-MS analysis of the ethanol extracts of F. vulgare identified 41 bioactive compounds, with four prominent ones: anethole, 1-(4-methoxyphenyl)-2-propanone, ethoxydimethylphenylsilane, and para-anisaldehyde diethyl acetal. Among these, anethole stands out due to its potential for nutrients and pharmacokinetic properties assessed by ADMET analysis, such as bioavailability, lipophilicity, flexibility, and compliance with Lipinski’s Rule of Five. In the H/R injury model of H9C2 heart myoblast cells, FVSE and anethole suppressed H/R-induced reactive oxygen species (ROS) generation, DNA double-strand break damage, nuclear condensation, and the dissipation of mitochondrial membrane potential (ΔΨm). Conclusions: These findings highlight the therapeutic potential of FVSE and its prominent component, anethole, in the treatment of CVDs, particularly those associated with hypoxia-induced damage.

Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P

This study investigates that the subsurface pathways, travel time, and its interannual variability of Fukushima-derived tracers subducted with the North Pacific subtropical mode water (NPSTMW) using 22-year-long (1994–2015) eddy-resolving (1/12°) and eddy-permitting (1/4°) ocean reanalysis. The NPSTMW is a thick subsurface layer with low potential vorticity and relatively uniform potential density, making it a key indicator of the North Pacific oceanic conditions. A series of Lagrangian particle tracking simulations quantitatively revealed that the Fukushima-derived particles moved along the Kuroshio Extension (KE) and spread over the majority of the subtropical region in the northwestern Pacific within 4–5 years. Approximately 36% of the particles flowed eastward in the Kuroshio-Oyashio transition zone (KO) and thereafter re-emerged to the sea surface at the remote area (near dateline), and 30% of particles moved along the KE. The remaining 34% subducted into NPSTMW layer and then widely spread out to the subtropical region along the re-circulation gyre (RG), exhibiting a subsurface pathway during entire particle tracking. When the particles were released, their pathway was immediately determined, whether it flowed along the KO (>36°N), KE (30°–36°N), or RG (

BackgroundMyelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases.MethodsThe sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9).ResultsIn attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p

Background: The surgical threshold for bicuspid aortic valve (BAV)-related aortopathy is a matter of debate due to its uncertain etiology and prognosis. This study investigated the prognosis of unrepaired BAV aortopathy in patients undergoing surgical aortic valve replacement (SAVR). Methods: We retrospectively analyzed data from 720 patients (age, 60.8±11.5 years; 246 women) who underwent SAVR for BAV disease without aortic repair between 2005 and 2020 at Asan Medical Center. The clinical endpoints were defined as occurrences of sudden death, aortic dissection or rupture, and elective aortic repair. To estimate postoperative changes in the dimensions of the unrepaired aorta, the individual annual aortic expansion rate was calculated. Multiple linear regression models were used to evaluate the risk of aortic expansion. Results: The mean ascending aortic diameter was 39.5±4.6 mm, and 299 patients (41.5%) had a baseline ascending aorta diameter >40 mm. During 70.0±68.3 months of follow-up, the mean annual aortic expansion rate was 0.39±1.96 mm/yr, no aortic dissection or rupture was observed, and sudden deaths were reported in 12 patients (0.34% per person-year). Linear regression analysis revealed no significant correlation between the baseline ascending aortic diameter and postoperative aortic expansion (R2=0.004, β=-0.84, p=0.082). Conclusion: In selected patients undergoing SAVR for a BAV (45 mm, the study results need further validation by studies involving larger populations or randomized controlled trials.

This study investigated the neuroprotective effect of 70% ethanol extract of Ecklonia cava (EE) in amyloid beta (Aβ)-induced cognitive deficit mice. As a result of analyzing the bioactive compounds in EE, nine compounds were identified using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In particular, the diekcol content was quantified by high-performance liquid chromatography with diode-array detection (DAD-HPLC). Biochemical analysis was performed on brain tissue to determine the mechanism of the cognitive function improvement effect of EE. The result showed that EE ameliorated learning and memory decline in behavioral tests on Aβ-induced mice. EE also attenuated oxidative stress by regulating malondialdehyde (MDA) content, reduced glutathione (GSH), and superoxide dismutase (SOD) levels. Similarly, EE also improved mitochondrial dysfunction as mitochondrial membrane potential, ATP production, and reactive oxygen species (ROS) levels. In addition, EE enhanced synapse function by modulating acetylcholine-related enzymes and synaptic structural proteins in the whole brain, hippocampus, and cerebral cortex tissues. Also, EE regulated Aβ-induced apoptosis and inflammation through the c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, EE protected neurotoxicity by increasing brain-derived neurotrophic factor (BDNF) production. These results suggest that EE may be used as a dietary supplement for the prevention and treatment of Alzheimer’s disease (AD).

BackgroundBone marrow (BM) involvement is an indicator of a poor prognosis in diffuse large B-cell lymphoma (DLBCL); however, few studies have evaluated the role of immunoglobulin gene rearrangement (IgR) in detecting BM involvement.MethodsWe evaluated the clinical characteristics and treatment outcomes of patients with DLBCL based on histological BM involvement or positive BM IgR using polymerase chain reaction or next-generation sequencing. We also investigated the role of consolidative upfront autologous hematopoietic stem cell transplantation (ASCT) in patients with DLBCL and BM involvement.ResultsAmong 624 patients, 123 (19.7%) with histological BM involvement and 88 (17.5%) with positive IgR in histologically negative BM had more advanced disease characteristics. Overall (OS) and progression-free (PFS) survival was better for patients with negative BM histology and negative IgR than that in patients with histological BM involvement (P = 0.050 and P < 0.001, respectively) and positive IgR with negative BM histology (P = 0.001 and P = 0.005, respectively). Survival rates did not differ among 82 (13.1%) patients who were treated with upfront ASCT and had histological BM involvement or positive IgR with negative BM histology. The survival outcomes were worse for patients who were not treated with upfront ASCT and for those with histological BM involvement or positive IgR, than for those with negative BM histology and negative IgR.ConclusionPatients diagnosed with DLBCL and BM involvement based on histology or IgR had aggressive clinical features and poor survival. Upfront ASCT mitigated poor prognosis due to BM involvement.

ObjectiveTo assess the pharmacokinetics and pharmacodynamics of the long-acting terminal complement 5 (C5) inhibitor ravulizumab in adults with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the phase 3, open-label CHAMPION-NMOSD trial (NCT04201262).MethodsPatients aged 18 years or older received a weight-based intravenous loading dose of ravulizumab (2,400–3,000 mg) on day 1, followed by weight-based maintenance doses (3,000–3,600 mg) on day 15 and once every 8 weeks thereafter. Pharmacokinetic assessments were maximum observed concentration (Cmax, assessed at the end of the infusion) and concentration at the end of the dosing interval (Ctrough, assessed before dosing) for ravulizumab. Pharmacodynamic assessment was time-matched observed free C5 concentration in serum up to 50 weeks.ResultsThe pharmacokinetic/pharmacodynamic analysis included 58 patients treated with ravulizumab. Serum ravulizumab concentrations at or above the therapeutic threshold (175 μg/mL) were achieved in all patients after administration of the first dose and maintained for 50 weeks. At week 50, the mean (standard deviation) Cmax (n = 51) and Ctrough (n = 52) were 1,887.6 (411.38) and 764.4 (217.68) μg/mL, respectively. Immediate and complete terminal complement inhibition (free C5 serum concentrations < 0.5 μg/mL) was achieved by the end of the first ravulizumab infusion and sustained throughout the treatment period. No treatment-emergent antibodies to ravulizumab were observed. No impact on ravulizumab pharmacokinetics was seen for age, sex, race, hematocrit, hemoglobin, markers of renal and liver impairment, or medications commonly used by patients with NMOSD. Body weight and BMI were significant covariates of ravulizumab pharmacokinetics.ConclusionsSerum ravulizumab concentrations were maintained above the therapeutic threshold in all patients through 50 weeks of treatment. Ravulizumab achieved immediate and complete terminal complement inhibition that was sustained throughout the treatment period in adults with AQP4+ NMOSD.

In this study, a DeCART/MIG uncertainty quantification (UQ) analysis code system with a multi-correlated cross section stochastic sampling (S.S.) module was established and verified through the UAM (Uncertainty Analysis in Modeling) and the BEAVRS (Benchmark for Evaluation And Validation of Reactor Simulations) benchmark calculations. For the S.S. calculations, a sample of 500 DeCART multi-group cross section sets for two major actinides, i.e., 235U and 238U, were generated by the MIG code and covariance data from the ENDF/B-VII.1 evaluated nuclear data library. In the three pin problems (i.e. TMI-1, PB2, and Koz-6) from the UAM benchmark, the uncertainties in kinf by the DeCART/MIG S.S. calculations agreed very well with the sensitivity and uncertainty (S/U) perturbation results by DeCART/MUSAD and the S/U direct subtraction (S/U-DS) results by the DeCART/MIG. From these results, it was concluded that the multi-group cross section sampling module of the MIG code works correctly and accurately. In the BEAVRS whole benchmark problems, the uncertainties in the control rod bank worth, isothermal temperature coefficient, power distribution, and critical boron concentration due to cross section uncertainties were calculated by the DeCART/MIG code system. Overall, the uncertainties in these design parameters were less than the general design review criteria of a typical pressurized water reactor start-up case. This newly-developed DeCART/MIG UQ analysis code system by the S.S. method can be widely utilized as uncertainty analysis and margin estimation tools for developing and designing new advanced nuclear reactors.

Background/Aims Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Methods Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Results Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression-free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Conclusions Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Abstract Polypharmacy may cause adverse health outcomes in the elderly. This study examined the prevalence of continuous polypharmacy and hyper‐polypharmacy, factors associated with polypharmacy, and the most frequently prescribed medications among older adults in South Korea. This was a retrospective observational study using National Health Insurance claims data. In total, 7,358,953 Korean elderly patients aged 65 years and older were included. Continuous polypharmacy and hyper‐polypharmacy were defined as the use of ≥5 and ≥10 medications, respectively, for both ≥90 days and ≥180 days within 1 year. A multivariate logistic regression analysis was conducted with adjustment for general characteristics (sex, age, insurance type), comorbidities (12 diseases, number of comorbidities, and Elixhauser Comorbidity Index [ECI] classification), and healthcare service utilization. Among 7.36 million elderly patients, 47.8% and 36.9% had polypharmacy for ≥90 and ≥180 days, and 11.9% and 7.1% of patients exhibited hyper‐polypharmacy for ≥90 and ≥180 days, respectively. Male sex, older age, insurance, comorbidities (cardio‐cerebrovascular disease, diabetes mellitus, depressive disorder, dementia, an ECI score of ≥3), and healthcare service utilization were associated with an increased probability of polypharmacy. The therapeutic class with the most prescriptions was drugs for acid‐related disorders (ATC A02). The number of outpatient visit days more strongly influenced polypharmacy than hospitalizations and ED visits. This study provides health policymakers with important evidence about the critical need to reduce polypharmacy among older adults.

Various decontamination technologies have been developed for removing contaminated areas in industries. Although it is important to consider parameters such as safety, cost, and time when selecting the decontamination technology, till date their comparative study is missing. Furthermore, different decontamination technologies influence the decontamination effects in different ways. Therefore, this study compares different decontamination techniques for the steam generator using a multicriteria decision-making method. A steam generator is a large device comprising both low- and very low-level waste (LLW, VLLW) and reflects the difference in weights of the standards according to the classification of the waste. For LLW and VLLW decontaminations, chemical oxidizing reduction decontamination (CORD) and decontamination grit blasting were used as the preferred techniques, respectively, considering the purpose of decontamination differs based on the initial state of waste. An expert survey revealed that safety in LLW and waste minimization in VLLW exhibited high preference. This evaluation method can be applied not only to the comparison between each process, but also to the creation of process scenarios. Therefore, determining the decontamination approach using logical decision-making methods may improve the safety and economic feasibility of each step in the decommissioning process and ensure a public acceptance.

Despite extensive efforts over 40 years, few effective KRAS inhibitors have been developed to date, mainly due to the undruggable features of KRAS proteins. In addition to the direct approach to KRAS via covalent inhibition, modulation of the prenyl-binding protein PDEδ that binds with farnesylated KRAS has emerged as an alternative strategy to abrogate KRAS activity. For the verification of new therapeutic strategies, chemical probes with the dual functions of visualisation and pharmacological inhibition against oncogenic proteins are enormously valuable to understand cellular events related to cancer. Here, we report indolizino[3,2-c]quinoline (IQ)-based fluorescent probes (PD3 and PD3-B) for PDEδ inhibition. By using the unique fluorescent characteristics of the IQ scaffold, a fluorescence polarisation (FP)-based binding assay identified PD3 as the most effective PDEδ probe among the tested PD analogues, with a low Kd value of 0.491 µM and long retention time in the binding site of PDEδ. In particular, a FP-based competition assay using deltarasin verified that PD3 occupies the farnesylation binding site of PDEδ, excluding the possibility that the FP signals resulted from non-specific hydrophobic interactions between the ligand and protein in the assay. We also designed and synthesised PD3-B (5), an affinity-based probe (ABP) from the PD3 structure, which enabled us to pull down PDEδ from bacterial lysates containing a large number of intrinsic bacterial proteins. Finally, KRAS relocalization was verified in PANC-1 cells by treatment with PD3, suggesting its potential as an effective probe to target PDEδ.

Objective This multicenter study compared radiological parameters and clinical outcomes between surgical and nonsurgical management and investigated treatment characteristics associated with the successful management of unstable atlas fractures. Methods We retrospectively evaluated 53 consecutive patients with unstable atlas fracture who underwent halo-vest immobilization (HVI) or surgical fixation. Clinical outcomes were assessed using neck visual analogue scale and disability index. The radiological assessment included total lateral mass displacement (LMD) and the anterior atlantodental interval (AADI). Results Thirty-two patients underwent surgical fixation and 21 received HVI (mean follow-up, 24.9 months). In the surgical fixation, but not in the HVI, LMD, and AADI showed statistically significant improvements at the last follow-up. The osseous healing rate and time-to-healing were 100% and 14.3 weeks with surgical fixation, compared with 71.43% and 20.0 weeks with HVI, respectively. Patients treated with HVI showed poorer neck pain and neck disability outcomes than those who received surgical treatment. LMD showed an association with osseous healing outcomes in nonoperative management. Clinical outcomes and osseous healing showed no significant differences according to Dickman’s classification of transverse atlantal ligament injuries. Conclusion Surgical internal fixation had a higher fusion rate, shorter fracture healing time, more favorable clinical outcomes, and a more significant reduction in LMD and AADI compared to nonoperative management. The pitfalls of external immobilization are inadequate maintenance and a lower probability of reducing fractured lateral masses. Stabilization by surgical reduction with interconnected fixation proved to be a more practical management strategy than nonoperative treatment for unstable atlas fractures.

In this study, a cross section stochastic sampling (S.S.) capability is implemented into both the McCARD continuous energy Monte Carlo code and MIG multiple-correlated data sampling code. The ENDF/B-VII.1 covariance data based 30 group cross section sets and the SCALE6 covariance data based 44 group cross section sets are sampled by the MIG code. Through various uncertainty quantification (UQ) benchmark calculations, the McCARD/MIG results are verified to be consistent with the McCARD stand-alone sensitivity/uncertainty (S/U) results and the XSUSA S.S. results. UQ analyses for Three Mile Island Unit 1, Peach Bottom Unit 2, and Kozloduy-6 fuel pin problems are conducted to provide the uncertainties of keff and microscopic and macroscopic cross sections by the McCARD/MIG code system. Moreover, the SNU S/U formulations for uncertainty propagation in a MC depletion analysis are validated through a comparison with the McCARD/MIG S.S. results for the UAM Exercise I-1b burnup benchmark. It is therefore concluded that the SNU formulation based on the S/U method has the capability to accurately estimate the uncertainty propagation in a MC depletion analysis.

Abstract Although myelitis is the second most common presentation in adults with myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD), studies on MOG‐IgG seroprevalence in patients with myelitis episodes are sparse. Herein, we investigated MOG‐IgG seroprevalence in Korean adults who exhibited myelitis since 2017. Among 151 adults with acute myelitis, 11 (7.3%) tested positive for MOG‐IgG by the initial screening and 10 (6.6%) patients were finally diagnosed with MOGAD during the study period. This study is the first to provide data on MOG‐IgG seroprevalence in adults with myelitis and supports the clinical utility and importance of MOG‐IgG testing in myelitis episodes.

ABSTRACT: Objectives: Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea. Methods: The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated. Results: The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699). Conclusion: This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

Abstract The cell signaling factors EGFR, EphA2, and Ephexin1 are associated with lung and colorectal cancer and play an important role in tumorigenesis. Although the respective functional roles of EGFR and EphA2 are well known, interactions between these proteins and a functional role for the complex is not understood. Here, we showed that Ephexin1, EphA2, and EGFR are each expressed at higher levels in lung and colorectal cancer patient tissues, and binding of EGFR to EphA2 was associated with both increased tumor grade and metastatic cases in both cancer types. Treatment with Epidermal Growth Factor (EGF) induced binding of the RR domain of EGFR to the kinase domain of EphA2, and this binding was promoted by Ephexin1. Additionally, the AKT-mediated phosphorylation of EphA2 (at Ser897) promoted interactions with EGFR, pointing to the importance of this pathway. Two mutations in EGFR, L858R and T790M, that are frequently observed in lung cancer patients, promoted binding to EphA2, and this binding was dependent on Ephexin1. Our results indicate that the formation of a complex between EGFR, EphA2, and Ephexin1 plays an important role in lung and colorectal cancers, and that inhibition of this complex may be an effective target for cancer therapy.

Abstract Single nucleotide variations in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with many neurodegenerative diseases, including Nasu-Hakola disease (NHD), frontotemporal dementia (FTD), and late-onset Alzheimer's disease because they disrupt ligand binding to the extracellular domain of TREM2. However, the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) in TREM2 on disease progression remain unknown. In this study, we identified several high-risk nsSNPs in the TREM2 gene using various deleterious SNP predicting algorithms and analyzed their destabilizing effects on the ligand recognizing region of the TREM2 immunoglobulin (Ig) domain by molecular dynamics (MD) simulation. Cumulative prediction by all tools employed suggested the three most deleterious nsSNPs involved in loss of TREM2 function are rs549402254 (W50S), rs749358844 (R52C), and rs1409131974 (D104G). MD simulation showed that these three variants cause substantial structural alterations and conformational remodeling of the apical loops of the TREM2 Ig domain, which is responsible for ligand recognition. Detailed analysis revealed that these variants substantially increased distances between apical loops and induced conformation remodeling by changing inter-loop nonbonded contacts. Moreover, all nsSNPs changed the electrostatic potentials near the putative ligand-interacting region (PLIR), which suggested they might reduce specificity or loss of binding affinity for TREM2 ligands. Overall, this study identifies three potential high-risk nsSNPs in the TREM2 gene. We propose further studies on the molecular mechanisms responsible for loss of TREM2 function and the associations between TREM2 nsSNPs and neurodegenerative diseases.

In this study, a similarity coefficient generation code system was established using the Monte Carlo Code for Advanced Reactor Design (McCARD) transport code and the MIG multi-correlated input sampling code. We considered the adjoint-based sensitivity and uncertainty (S/U) and stochastic sampling (S.S.) approaches to the generation of the ck similarity coefficient. To examine the code system, the ck similarity coefficients of 23 relevant critical experiments and the System-Integrated Modular Advanced Reactor (SMART) small modular reactor (SMR) target system were generated using ENDF/B-VII.1 covariance data with the Los Alamos National Laboratory (LANL) 30-group energy group structure. Our results show that the similarity coefficients between the 16 LEU thermal-spectrum-based critical experiments and SMART are more than 0.90, which is the recommended criterion of the U.S. Nuclear Regulatory Commission (NRC). These results are very helpful for licensees and can be used to justify the determination of critical experiment benchmarks for computational bias estimations of the SMART target system. To examine the discrepancy in the similarity coefficient, ck, due to the covariance data, similarity analyses for a 24 × 24 benchmark matrix were performed using ENDF-VIII.0, JENDL-5.0, and JEFF-3.3 covariance data. The results show that the selection of the covariance data used for ck generation significantly impacts the similarity coefficient. Moreover, it was observed that the current results for the SCALE 6.1 covariance data show a consistent trend with the results reported in earlier studies.