Search

Shao-Hui Lin,1 Wei Cui,2 Gui-Ling Wang,1 Shuai Meng,1 Ying-Chun Liu,3 Hong-Wei Jin,4 Liang-Ren Zhang,4 Ying Xie1,4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, 2School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 3Soft Matter Research Center, Department of Chemistry, Zhejiang University, Hangzhou, 4State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China Abstract: Albumin-based nanoparticles (NPs) are a promising technology for developing drug-carrier systems, with improved deposition and retention profiles in lungs. Improved understanding of these drug–carrier interactions could lead to better drug-delivery systems. The present study combines computational and experimental methods to gain insights into the mechanism of binding of albuterol sulfate (AS) to bovine serum albumin (BSA) on the molecular level. Molecular dynamics simulation and surface plasmon resonance spectroscopy were used to determine that there are two binding sites on BSA for AS: the first of which is a high-affinity site corresponding to AS1 and the second of which appears to represent the integrated functions of several low-affinity sites corresponding to AS2, AS3, and AS8. AS1 was the strongest binding site, established via electrostatic interaction with Glu243 and Asp255 residues in a hydrophobic pocket. Hydrogen bonds and salt bridges played a main role in the critical binding of AS1 to BSA, and water bridges served a supporting role. Based upon the interaction mechanism, BSA NPs loaded with AS were prepared, and their drug-loading efficiency, morphology, and -release profiles were evaluated. Successful clinical development of AS-BSA-NPs may improve therapy and prevention of bronchospasm in patients with reversible obstructive airway disease, and thus provide a solid basis for expanding the role of NPs in the design of new drug-delivery systems. Keywords: molecular dynamics, surface plasmon resonance, interaction mechanism, BSA nanoparticles, drug delivery systems

Abstract In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer.

Abstract Histone lysine methylation is pivotal in shaping the epigenetic landscape and is linked to cell physiology. Coordination of the activities of multiple histone lysine methylation modifiers, namely, methyltransferases and demethylases, modulates chromatin structure and dynamically alters the epigenetic landscape, orchestrating almost all DNA-templated processes, such as transcription, DNA replication, and DNA repair. The stability of modifier proteins, which is regulated by protein degradation, is crucial for their activity. Here, we review the current knowledge of modifier-protein degradation via specific pathways and its subsequent impact on cell physiology through epigenetic changes. By summarizing the functional links between the aberrant stability of modifier proteins and human diseases and highlighting efforts to target protein stability for therapeutic purposes, we aim to promote interest in defining novel pathways that regulate the degradation of modifiers and ultimately increase the potential for the development of novel therapeutic strategies.

Abstract Despite its widespread use, the close proximity (CPX) test for tire-pavement noise is limited to existing pavements, posing challenges for timely and effective corrections of noisy pavements. Additionally, the CPX test entails significant procurement and operation costs. Addressing these issues, this study introduces the rubber plate impact (RPI) method as a simple experimental technique for assessing tire-pavement noise in both laboratory and field settings. The RPI test utilizes the folding motion of the treaded rubber plate on the road surface to simulate air pumping and tread impact noise as two main contributors to tire-pavement noise. Indoor RPI tests on asphalt concrete samples of dense graded asphalt and porous asphalt mixes revealed dominant effects of air void content and associated surface texture on the level of noise. The RPI testing procedure was verified at 17 highway test sections, where both CPX and RPI tests were conducted for comparison. Multiple linear regressions between RPI and CPX data were analyzed to propose CPX prediction models at different speeds (80, 100, 120 km/h), and the performance of these prediction models was validated with independent noise datasets collected from four different highway routes. The findings suggest promising prospects for the RPI test as a cost-effective and versatile alternative to CPX for tire-pavement noise characterization on asphalt-surfaced roads, with implications for road materials design and noise mitigation strategies.

Objectives: Intradiscal steroid injection (ISI) use has been proven as a low-risk and rapid treatment for disc degeneration disease (DDD). However, the histological effects of steroids on human discs remain poorly understood. The purpose of this study is to investigate whether ISI induces histologic degeneration of the disc. Methods: In this study, a histological analysis was carried out on the nucleus pulposus obtained from 150 patients who underwent posterior lumbar interbody fusion. Among these individuals, 59 received ISI before the surgery, while 91 did not. After staining with hematoxylin and eosin, the histological classification was performed based on chondrocyte proliferation (C1, C2, and C3) and granular matrix change (M1 and M2). Logistic regression analysis was used to identify the main factors influencing chondrocyte proliferation and granular matrix change. Additionally, histological differences between the ISI group and the non-ISI group were analyzed. Results: Chondrocyte proliferation and granular matrix changes were not significantly different between the ISI and non-ISI groups. The logistic regression analysis indicated that age is the most significant risk factor for both chondrocyte proliferation (P = 0.02) and granular matrix changes (P

Abstract The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83–0.94; p

Abstract Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)−1-(3-pyridyl)−1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.

Mucormycosis encompasses a range of fungal infections that can impact various organs. Although pulmonary mucormycosis is relatively rare, it poses a significant threat, particularly to individuals with compromised immune systems. Pulmonary mucormycosis presents with various radiological manifestations. Notably, the involvement of the angioinvasive pulmonary artery in pulmonary mucormycosis cases has seldom been documented. In this report, we showcase the radiological characteristics of angioinvasive mucormycosis, which can mimic pulmonary thromboembolism or a pulmonary artery tumor, in a patient diagnosed with myelodysplastic syndrome.

Abstract Lemnoideae, commonly referred to as the duckweed, are aquatic plants found worldwide. Wolffia species are known for their extreme reduction in size and complexity, lacking both roots and leaves, and they hold the distinction of being the smallest plants among angiosperms. Interestingly, it belongs to the Araceae family, despite its apparent morphological differences from land plants in the same family. Traditional morphological methods have limitations in classifying these plants, making molecular-level information essential. The chloroplast genome of Wolffia arrhiza is revealed that a total length of 169,602 bp and a total GC content of 35.78%. It follows the typical quadripartite structure, which includes a large single copy (LSC, 92,172 bp) region, a small single copy (SSC, 13,686 bp) region, and a pair of inverted repeat (IR, 31,872 bp each) regions. There are 131 genes characterized, comprising 86 Protein-Coding Genes, 37 Transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Moreover, 48 simple sequence repeats and 32 long repeat sequences were detected. Comparative analysis between W. arrhiza and six other Lemnoideae species identified 12 hotspots of high nucleotide diversity. In addition, a phylogenetic analysis was performed using 14 species belonging to the Araceae family and one external species as an outgroup. This analysis unveiled W. arrhiza and Wolffia globosa as closely related sister species. Therefore, this research has revealed the complete chloroplast genome data of W. arrhiza, offering a more detailed understanding of its evolutionary position and phylogenetic categorization within the Lemnoideae subfamily.

IntroductionBruton’s tyrosine kinase (BTK) and interleukin (IL)-2 Inducible T-cell Kinase (ITK) inhibitors have anti-inflammatory properties. We investigated the therapeutic effect of ibrutinib, an orally bioavailable BTK/ITK inhibitor, in a mouse model of Graves’ orbitopathy (GO).MethodsGenetic immunization was performed through intramuscular administration of the recombinant plasmid, pCMV6-hTSHR cDNA, to 8-week-old female BALB/c mice. Serum levels of T3, T4, and thyroid-stimulating hormone receptor (TSHR) antibodies (TRAbs) were quantified using enzyme-linked immunosorbent assay. Histopathological changes in orbital tissues were examined using immunohistochemistry (IHC) staining for TSHR and various inflammatory markers. Following successful genetic immunization, ibrutinib was orally administered daily for 2 weeks in the GO model mice. After treatment, the mRNA and protein expression levels of BTK, ITK, IL-1β, and IL-6 in orbital tissues were evaluated using real-time PCR and Western blotting.ResultsIn total, 20 mice were sacrificed to confirm successful genetic immunization. The GO mouse group exhibited significantly increased serum T3, T4, and TRAb levels. IHC revealed increased expression of TSHR, IL-1β, IL-6, transforming growth factor-β1, interferon-γ, CD40, CD4, BTK, and ITK in the GO mouse model. The orbital inflammation was significantly attenuated in ibrutinib-treated mice. The mRNA and protein expression levels of BTK, ITK, IL-1β, and IL-6 in orbital tissue were lower in ibrutinib-treated GO mouse group compared to the phosphate-buffered saline-treated GO mouse group.ConclusionThe GO mouse model demonstrated enhanced BTK and ITK expression. Ibrutinib, a BTK/ITK inhibitor, suppressed the inflammatory cytokine production. These findings highlight the potential involvement of BTK/ITK in the inflammatory pathogenesis of GO, suggesting its role as a novel therapeutic target.

This study was the first to document the fluctuations of nutritional constituents, antioxidant capacities, and physicochemical characteristics during the aging processes of red ginseng sprouts (RGS) and black ginseng sprouts (BGS) from dried ginseng sprouts (DGS). Total ginsenoside levels differed with 54.72 (DGS) → 57.15 (RGS) and 6.98 (BGS) mg/g, specifically, ginsenoside F2 and Rd2 in RGS remarkably increased with 1.97 → 5.88 and 2.41 → 5.49 mg/g, respectively. Phenolics increased dramatically as 297.02 → 1770.01 (6.0-fold); 1834.94 (6.2-fold) μg/g in DGS → RGS; BGS with abundance contents of benzoic acid (>15.3-fold), chlorogenic acid (>9.5-fold), and catechin (>4.2-fold), whereas amino acids markedly decreased (3686.81 → 1505.00; 364.64 mg/100 g), with arginine showing a significant decrease. Moreover, beneficial factors (total phenolic content: TPC; total flavonoid content: TFC; maillard reaction products: MRP) displayed increase tendencies (approximately 2.0-fold) with BGS > RGS > DGS, and antioxidant patterns significantly increased with potential capacities as follows: ABTS (48.3: DGS → 65.8: RGS; 70.2 %: BGS) > DPPH (18.5 → 44.6; 59.2 %) > hydroxyl (23.2 → 35.4; 39.9 %) > FRAP (0.6 → 1.8; 1.8 %) at 500 μg/mL. In particular, DNA protection exhibited excellent rates of 100 %, in the order of BGS (25 μg/mL) > RGS (50 μg/mL) > DGS (500 μg/mL). These findings suggest that processed ginseng sprouts can be excellent agents for natural antioxidants.

Background Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P

The purpose of this study was to investigate the effect of parental autonomy support on adolescents’ exercise adherence and the combined mediating effects of psychological resilience and coping style. A total of 478 male adolescents were evaluated using the Parental Autonomy Support Scale (PASS), the Connor-Davidson Resilience Scale (CD-RISC), the Coping Inventory for Competitive Sport (CICS), and the Scale of Exercise Adherence (SEA). The combined mediating effects of resilience and coping style were validated through hierarchical regression and bootstrap analysis. The results showed that: (1) parental autonomy support had a significant positive effect on exercise adherence in adolescents; (2) resilience and coping style mediated the relationship between parental autonomy support and exercise adherence. Parental autonomy support can not only directly promote exercise adherence in adolescents, but also indirectly promote it through the combined mediating effects of resilience and coping style. The mediating effect model constructed in this study demonstrates the internal mechanism through which parental autonomous support can have a positive influence on exercise adherence. It provides valuable information that can be used to promote exercise adherence among male Korean adolescents.

Objectives. This study aimed to compare the oncological outcomes of partial versus superficial or total parotidectomy for superficial T1 or T2 primary parotid cancers and investigate their prognostic factors and recurrence patterns. Methods. The medical records of 77 patients with T1–2 primary parotid malignancies between May 2003 and March 2022 were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the prognostic factors associated with overall survival, disease-free survival, and local and distant recurrence. Results. The average follow-up duration was 70.2 months (range, 12–202 months). The 5-year overall and disease-free survival rates were 88.7% and 77.1%, respectively. Twenty-two patients underwent partial parotidectomy, and 55 underwent superficial or total parotidectomy. There were no significant differences in the disease recurrence (P=0.320) and mortality rates (P=0.884) of the partial and superficial or total parotidectomy groups. The mean duration of surgery was shorter and the overall complication rates were significantly lower in the partial group than in the superficial or total parotidectomy group (P=0.049). Sixteen cases of recurrence occurred during the study period (20.8%). Univariate analyses showed that high-grade tumors (P=0.006), lymphovascular invasion (P=0.046), and regional lymph node metastasis (P=0.010) were significant risk factors for disease recurrence. Multivariate analysis identified regional lymph node metastasis as an independent prognostic factor for disease recurrence (P=0.027), and lymphovascular invasion as an independent prognostic factor for overall survival (P=0.033). Conclusion. The conservative surgical approach of partial parotidectomy can yield oncological outcomes comparable to those of superficial or total parotidectomy with careful patient selection in T1-2 parotid cancers.

Abstract Background Viral infection is a risk factor for asthma exacerbation (AE). However, bacterial infections related to AE in adults are poorly known. On the other hand, obese patients with asthma have their own clinical and biological characteristics compared with non-obese patients. Methods We investigated the differences in isolated pathogens for AE between obese and non-obese patients with asthma. We included 407 patients with AE from 24 medical centers in Korea. Microorganisms isolated from culture, RT-PCR or serologic tests using lower respiratory tract specimens were retrospectively investigated. Results A total of 171 obese and 236 non-obese patients with asthma were included for analysis. Compared to non-obese patients, obese patients were associated with women (77.2% vs. 63.6%), never smoker (82.5% vs. 73.9%), shorter duration of asthma (7.9 ± 8.4 vs. 10.5 ± 10.1 years), less history of pulmonary tuberculosis (8.8% vs. 17.4%), and more comorbidity of allergic rhinitis (48.5% vs. 0.8%). Viral and/or bacterial infections were detected in 205 patients (50.4%) with AE. The numbers of patients with viral only, bacterial only, or both infections were 119, 49, and 37, respectively. The most commonly isolated bacterium was Streptococcus pneumoniae, followed by Pseudomonas aeruginosa and Chlamydia pneumoniae. Obese patients showed a lower incidence of Chlamydia pneumoniae infection. In the non-obese group, bacterial infection, especially Chlamydia pneumoniae infection, was significantly associated with the duration of systemic corticosteroid use (13.6 ± 19.8 vs. 9.7 ± 6.7 days, p = 0.049). Conclusion Bacterial infection was associated with a longer period of corticosteroid use in the non-obese group. Acute Chlamydia pneumoniae infection was less associated with obese patients with AE. Further well-designed studies are needed to evaluate microorganisms and the efficacy of antibiotics in patients with AE.

This systematic review summarizes existing evidence and outlines the benefits of artificial intelligence-assisted spine surgery. The popularity of artificial intelligence has grown significantly, demonstrating its benefits in computer-assisted surgery and advancements in spinal treatment. This study adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), a set of reporting guidelines specifically designed for systematic reviews and meta-analyses. The search strategy used Medical Subject Headings (MeSH) terms, including “MeSH (Artificial intelligence),” “Spine” AND “Spinal” filters, in the last 10 years, and English—from January 1, 2013, to October 31, 2023. In total, 442 articles fulfilled the first screening criteria. A detailed analysis of those articles identified 220 that matched the criteria, of which 11 were considered appropriate for this analysis after applying the complete inclusion and exclusion criteria. In total, 11 studies met the eligibility criteria. Analysis of these studies revealed the types of artificial intelligence-assisted spine surgery. No evidence suggests the superiority of assisted spine surgery with or without artificial intelligence in terms of outcomes. In terms of feasibility, accuracy, safety, and facilitating lower patient radiation exposure compared with standard fluoroscopic guidance, artificial intelligence-assisted spine surgery produced satisfactory and superior outcomes. The incorporation of artificial intelligence with augmented and virtual reality appears promising, with the potential to enhance surgeon proficiency and overall surgical safety.

Abstract Background The increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the 18F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury. Methods Ten-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, 18F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5). Results 18F-ASEM PET/MRI showed significantly increased 18F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant 18F-ASEM uptake in the denervated side when compared to the control (P = 0.0796). Conclusions Our results suggest that nAChR imaging with 18F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders.

In this study, a previously developed fully passive hydrokinetic turbine with two flapping foils was used to directly drive a reciprocating pump, and the performance of this system was investigated at an offshore site in Republic of Korea. The fully passive operation of the turbine worked effectively due to its coupling mechanism, and pumping was successfully carried out during flood tides when the pumping height was consistently maintained using a water level gauge and winch system. Pumping occurred at a height of approximately 9 m when the flow velocity reached 1.8 m/s, at which point the corresponding Reynolds number exceeded one million. In one case where a high pumping flow rate was achieved during offshore trials conducted over a period of time, the pumping efficiency reached up to 34% when the reduced frequency of the turbine was 0.126, falling within the known optimum range. The pump driven by the flapping-foil hydrokinetic turbine, which can be positioned near the shore or in shallow water, could provide a viable solution for off-grid communities needing to pump seawater or generate hydroelectric power.

In this study, the nutrients, phytochemicals (including isoflavone and ginsenoside derivatives), and antioxidant activities of cheonggukjang with different ratios (0%, 2.5%, 5%, and 10%) of mountain-cultivated ginseng (MCG) were compared and analyzed using microorganisms isolated from traditional cheonggukjang. The IDCK 30 and IDCK 40 strains were confirmed as Bacillus licheniformis and Bacillus subtilis, respectively, based on morphological, biological, biochemical, and molecular genetic identification, as well as cell wall fatty acid composition. The contents of amino acids and fatty acids showed no significant difference in relation to the ratio of MCG. After fermentation, isoflavone glycoside (such as daidzin, glycitin, and genistin) contents decreased, while aglycone (daidzein, glycitein, and genistein) contents increased. However, total ginsenoside contents were higher according to the ratio of MCG. After fermentation, ginsenoside Rg2, F2, and protopanaxadiol contents of cheonggukjang decreased. Conversely, ginsenoside Rg3 (2.5%: 56.51 → 89.43 μg/g, 5.0%: 65.56 → 94.71 μg/g, and 10%: 96.05 → 166.90 μg/g) and compound K (2.5%: 28.54 → 69.43 μg/g, 5.0%: 41.63 → 150.72 μg/g, and 10%: 96.23 → 231.33 μg/g) increased. The total phenolic and total flavonoid contents were higher with increasing ratios of MCG and fermentation (fermented cheonggukjang with 10% MCG: 13.60 GAE and 1.87 RE mg/g). Additionally, radical scavenging activities and ferric reducing/antioxidant power were significantly increased in fermented cheonggukjang. This study demonstrates that the quality of cheonggukjang improved, and cheonggukjang with MCG as natural antioxidants may be useful in food and pharmaceutical applications.

Regular exercise as part of one’s lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2α (p-eIF2α) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota α-diversity and BiP (r = 0.464~0.677, p < 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome.

Oxidative stress is a primary contributor to human skin aging, while antioxidants are known to mitigate skin damage related to aging processes. In this study, we investigated the possible action of trifluoromethyl phenethyl mesalazine (TFM), an antioxidizing agent, on skin aging processes, including skin wrinkles and pigmentation. Our data revealed that TFM exerted a strong free radical scavenging capability and notably inhibited melanin production. Moreover, TFM downregulated the UV-induced production of matrix metalloproteinase-1 and interleukin-6 in cultured human skin fibroblasts. Furthermore, in a clinical study with 24 women, TFM significantly reduced skin wrinkles and improved skin brightness compared to a placebo. These findings highlight the previously unrecognized effects of TFM on skin health by mitigating skin aging processes associated with oxidative damage.

The effectiveness of radiation therapy in the treatment of cerebral cavernous malformations (CCM) remains debatable. However, numerous studies have shown a reduction in hemorrhage risk following radiotherapy for CCM. Therefore, herein, we share our experiences utilizing linear accelerator (LINAC)-based radiation for treating CCMs, with the aim of identifying the key factors influencing the therapeutic outcomes. We conducted a retrospective review of all patients with non-brainstem CCMs who underwent radiation treatment, as recorded in the NOVALIS registry at our institution. T2-weighted MR images were used for volumetric assessments using the iPlan radiotherapy planning software. To determine the independent predictors of nidus volume reduction and perilesional brain edema (PBE), we performed multivariate Cox regression analysis to calculate hazard ratios. Twenty patients with 31 non-brainstem CCMs were enrolled in this study. Analysis revealed age as an independent predictive factor for both nidus volume reduction and PBE after radiation treatment for CCM. Furthermore, a single fraction dose of 17 Gy or more was identified as an independent predictor of nidus volume decrease, while a single fraction dose of 18 Gy or more was found to be an independent risk factor for PBE in patients with CCM following LINAC-based radiation therapy. LINAC-based radiation therapy for non-brainstem CCMs with a single fraction radiation dose between 16.5 and 17.5 Gy, or a biologically equivalent dose of approximately 120 Gy, may be the most effective at reducing nidus volume and limiting side effects, particularly in patients under the age of 55 years. We further observed that the risk of PBE increased as the maximum radiation dose delivered to a 1 cc volume of the surrounding normal brain exceeded approximately 17.3 Gy. Therefore, we believe that calculating the D1cc of the normal brain may help to predict the occurrence of PBE when radiotherapy is administered to non-brainstem CCMs.

Recurrence after stroke is common, and associated with a high mortality rate. Degradation of the elastic tissue in the arterial wall has been shown to aggravate atherosclerosis in blood vessels. Considering that type 1 collagen is present in both bone and vascular smooth muscle cells, we explored whether osteoporotic conditions affect the likelihood of stroke recurrence in postmenopausal women following atherosclerotic ischemic stroke. To determine actual bone mineral density (BMD), the Hounsfield unit values in the frontal skull were evaluated using brain computed tomography (CT) scans taken at admission. A multivariate Cox regression analysis was also performed to examine if osteoporosis could independently predict stroke recurrence in postmenopausal patients with large artery atherosclerosis (LAA) or small vessel occlusion (SVO) stroke. This study included 2130 consecutive patients (both males and females aged 50 and older) with acute LAA or SVO strokes. After adjusting for all covariates, hypothetical osteoporosis was identified as an independent predictor of stroke recurrence in female patients ≥50 years with acute LAA or SVO stroke (hazard ratio, 1.84; 95 % confidence interval, 1.05 to 3.24; p = 0.034). Our findings showed that osteoporosis could potentially affect the recurrence of ischemic stroke in postmenopausal patients with LAA or SVO stroke.

In this study, the microbial diversity, free amino acid (FAA), and biological activities of household doenjang (HDJ) from four different regions and commercial doenjang (CDJ) four manufacturers were analyzed. And volatile flavor compound (VFC) and isoflavone profiles were analyzed using gas chromatograph-mass spectrometer (GC-MS) and high performance liquid chromatography (HPLC), respectively. The major bacterial genus in 1HDJ and 2HDJ was Bacillus (97.5%), while in 3HDJ and 4HDJ, it was Enterobacter (47.5%) and Pseudomonas (80%), respectively. Tetragenococcus was the main bacterial genus of CDJ. The Zygosaccharomyces genus among yeast was comparatively high in all samples. In all samples, glutamic acid predominated among the FAAs, and the 3-methyl butanal, benzeneacetaldehyde, and diallyl disulphide were major VFCs. CDJ contained higher levels of isoflavone-glycoside and total phenolics. Except for 3HDJ and 4CDJ, the isoflavone-aglycone and total flavonoid contents were higher in HDJ. The correlation between bacterial genus and metabolited of doenjang showed that Tetragenococcus was closely related to glutamic acid, Bacillus was related to aglycones and ammonia, and Pseudomonas was highly related to isovaleric acid. While, correlation between yeast genus and metabolited of doenjang confirmed that Candida, Hanseniaspora, and Saccharomyces were related with furfural, benzeneacetaldehyde, and 3-methyl butanal, respectively. The results of this study can be utilized as basic data for the industrialization and development of doenjang.

Primary masses rarely originate from the heart and great vessels, and a malignant peripheral nerve sheath tumor (MPNST) is extremely rare. A 76-year-old male with pleural effusion underwent contrast- enhanced computed tomography, which revealed a hypoattenuating mass involving the right pulmonary vein and left atrium. Ultrasonography showed that the mass originated from the right pulmonary vein. Surgical resection confirmed an MPNST that originated from the pulmonary vein. We report the first Korean case of a primary MPNST originating from the pulmonary vein. We have also described the radiologic findings suggestive of a pulmonary vein mass.

Abstract The CRISPR–Cas9 system is a widely used gene-editing tool, offering unprecedented opportunities for treating various diseases. Controlling Cas9/dCas9 activity at specific location and time to avoid undesirable effects is very important. Here, we report a conditionally active CRISPR–Cas9 system that regulates target gene expression upon sensing cellular environmental change. We conjugated the oxygen-sensing transcription activation domain (TAD) of hypoxia-inducing factor (HIF-1α) with the Cas9/dCas9 protein. The Cas9-TAD conjugate significantly increased endogenous target gene cleavage under hypoxic conditions compared with that under normoxic conditions, whereas the dCas9-TAD conjugate upregulated endogenous gene transcription. Furthermore, the conjugate system effectively downregulated the expression of SNAIL, an essential gene in cancer metastasis, and upregulated the expression of the tumour-related genes HNF4 and NEUROD1 under hypoxic conditions. Since hypoxia is closely associated with cancer, the hypoxia-dependent Cas9/dCas9 system is a novel addition to the molecular tool kit that functions in response to cellular signals and has potential application for gene therapeutics.

Abscess formation due to Candida albicans infection is extremely rare. Radiological diagnosis of an atypical abscess at an uncommon site is challenging. In this study, we present a case of insidious onset multifocal chest wall and spinal abscess after candidemia in a young woman in the intensive care unit due to postpartum bleeding.

Abstract Background Hand hygiene (HH) is a fundamental component of infection prevention and control in healthcare settings. This study aimed to identify knowledge, attitude, and barriers to HH according to occupational groups and strategies to increase the rate of HH compliance among healthcare workers (HCWs). Methods This cross-sectional survey was conducted in July 2018 at four university-affiliated hospitals. The survey comprised seven parts with 49 items, including self-reported HH compliance, knowledge, attitudes, behaviours, barriers to HH, and improvement strategies. Results A total of 1046 HCWs participated in the survey. The nursing group’s self-reported HH compliance rate was the highest, followed by other HCWs and physicians. The scores regarding knowledge, attitudes, and behaviours regarding HH were the highest in the nursing group. The nursing group also had higher internal and emotional motivation scores. Physicians and nurses found HH the most challenging in emergencies, while other HCWs considered skin problems caused by HH products the most significant barrier. Among 12 improvement measures, approximately 20% of the respondents ranked “diversify types of hand sanitisers,“ “install soap and paper towels in each hospital room,“ and “change perception through various HH campaigns” as the top three priorities. The physician group deemed the timely reminder of HH compliance as the second most critical improvement measure. Conclusion Differences in knowledge, attitude and barriers hindering HH compliance and improvement plans were identified for each group. The findings suggest that targeted interventions tailored to the specific needs of different occupational groups may effectively improve HH compliance in healthcare settings.

Chromophoric dissolved organic matter (CDOM) is a mixture of various types of organic matter and a useful parameter for monitoring complex inland surface waters. Remote sensing has been widely utilized to detect CDOM in various studies; however, in many cases, the dataset is relatively imbalanced in a single region. To address these concerns, data were acquired from hyperspectral images, field reflection spectra, and field monitoring data, and the imbalance problem was solved using a synthetic minority oversampling technique (SMOTE). Using the on-site reflectance ratio of the hyperspectral images, the input variables Rrs (452/497), Rrs (497/580), Rrs (497/618), and Rrs (684/618), which had the highest correlation with the CDOM absorption coefficient aCDOM (355), were extracted. Random forest and light gradient boosting machine algorithms were applied to create a CDOM prediction algorithm via machine learning, and to apply SMOTE, low-concentration and high-concentration datasets of CDOM were distinguished by 5 m−1. The training and testing datasets were distinguished at a 75%:25% ratio at low and high concentrations, and SMOTE was applied to generate synthetic data based on the training dataset, which is a sub-dataset of the original dataset. Datasets using SMOTE resulted in an overall improvement in the algorithmic accuracy of the training and test step. The random forest model was selected as the optimal model for CDOM prediction. In the best-case scenario of the random forest model, the SMOTE algorithm showed superior performance, with testing R2, absolute error (MAE), and root mean square error (RMSE) values of 0.838, 0.566, and 0.777 m−1, respectively, compared to the original algorithm’s test values of 0.722, 0.493, and 0.802 m−1. This study is anticipated to resolve imbalance problems using SMOTE when predicting remote sensing-based CDOM. It is expected to produce and implement a machine learning model with improved reliable performance.

Abstract In this study, a parametric analysis was conducted for the design of a suggested dual flapping hydrofoil turbine. A Navier–Stokes‐based computational fluid dynamics code was utilized for the analysis while varying the pitch angle, reduced frequency, separation distance, and phase difference. The smallest pitch angle of 60° and the reduced frequency of 0.1 among the given ranges of the parameters were fixed for the first parametric analysis. After an assessment, the 90° front‐lead with the longest distance of 6c and the 90° rear‐lead with the shortest distance of 2c were chosen for further parametric analysis based on a suggested performance indicator and a margin for improvement. It was derived from a subsequent parametric analysis that a 70° pitch angle, 0.12 reduced frequency, and a 4c distance for the 90° front‐lead was the final optimum with 59.48% efficiency and 55.44% fluctuation according to the performance indicator as well as the system length and power balance of dual hydrofoils.

Abstract Background Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus, real-world evidence regarding their benefits to diabetic patients with acute myocardial infarction (AMI) is insufficient. This study evaluated cardiovascular outcomes by comparing SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4i) in combination with metformin in diabetic patients with AMI. Methods This study involved 779 diabetic participants with AMI from a Korean nationwide multicenter observational cohort, who were divided into two groups: (1) metformin plus SGLT2i group (SGLT2i group, n = 186) and (2) metformin plus DPP-4i (DPP-4i group, n = 593). The primary endpoint was one year of major adverse composite events (MACEs), a composite outcome of all-cause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. To balance the baseline differences, inverse probability of treatment weighting (IPTW) was performed. Results After IPTW, the rate of MACEs in the SGLT2i group was not significantly lower than that in the DPP-4i group (hazard ratio [HR], 0.99; 95% confidence interval [Cl], 0.46 to 2.14, p = 0.983). In the unadjusted and adjusted analyses, all items for clinical outcomes were comparable between the two groups. In our exploratory analysis, the left ventricular ejection fraction showed a significant improvement in the SGLT2i group than in the DPP-4i group before achieving statistical balancing (6.10 ± 8.30 versus 2.95 ± 10.34, p = 0.007) and after IPTW adjustment (6.91 ± 8.91 versus 3.13 ± 10.41, p = 0.027). Conclusions Our findings demonstrated that SGLT2i did not influence the rate of MACEs compared with DPP-4i in combination with metformin in diabetic patients with AMI but did improve left ventricular ejection fraction. Trial registration Not applicable (retrospectively registered).

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea. Methods A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis. Results More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis. Conclusion Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.

Objective This retrospective cohort study has been aimed at evaluating the incidence of complications after vertebral body sliding osteotomy (VBSO) and analyzing some cases. Furthermore, the complications of VBSO were compared with those of anterior cervical corpectomy and fusion (ACCF). Methods This study included 154 patients who underwent VBSO (n = 109) or ACCF (n = 45) for cervical myelopathy and were followed up for > 2 years. Surgical complications, clinical and radiological outcomes were analyzed. Results The most common surgical complications after VBSO were dysphagia (n = 8, 7.3%) and significant subsidence (n = 6, 5.5%). There were 5 cases of C5 palsy (4.6%), followed by dysphonia (n = 4, 3.7%), implant failure (n = 3, 2.8%), pseudoarthrosis (n = 3, 2.8%), dural tears (n = 2, 1.8%), and reoperation (n = 2, 1.8%). C5 palsy and dysphagia did not require additional treatment and spontaneously resolved. The rates of reoperation (VBSO, 1.8%; ACCF, 11.1%; p = 0.02) and subsidence (VBSO, 5.5%; ACCF, 40%; p < 0.01) were significantly lower in VBSO than in ACCF. VBSO restored more C2–7 lordosis (VBSO, 13.9°±7.5°; ACCF, 10.1°±8.0°; p = 0.02) and segmental lordosis (VBSO, 15.7°±7.1°; ACCF, 6.6°±10.2°; p < 0.01) than ACCF. The clinical outcomes did not significantly differ between both groups. Conclusion VBSO has advantages over ACCF in terms of low rate of surgical complications related to reoperation and significant subsidence. However, dural tears may still occur despite the lessened need for ossified posterior longitudinal ligament lesion manipulation in VBSO; hence, caution is warranted.

Purpose: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. Methods and materials: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. Results: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5–19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. Conclusion: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Donepezil (DPZ), a piperidine-based reversible cholinesterase inhibitor, finds extensive use in treating Alzheimer's disease (AD). Originally designed as an oral formulation, DPZ encounters drawbacks such as a brief duration of action and reduced treatment effectiveness in elderly patients with memory impairment or difficulty swallowing medications. To address these issues and improve patient compliance, researchers are actively exploring alternative DPZ formulations. Consequently, reliable methods are necessary to quantitate DPZ in biological samples for in vivo assessment. Therefore, we propose an efficient, sensitive, wide-dynamic, and cost-effective method for quantitating DPZ in rat plasma. Our method employs liquid-liquid extraction (LLE) followed by liquid chromatography and tandem mass spectrometry, enabling in vivo evaluation of novel DPZ formulations. Notably, our method requires only 20 μL of rat plasma and employs icopezil as the internal standard-a cost-effective compound with chemical similarity to DPZ. We meticulously optimized LLE conditions, taking into account factor interactions through design of experiments (DOE). Our rapid and straightforward extraction and purification involved using 500 μL of pure methyl tert-butyl ether to extract DPZ from the sample within five minutes. The dynamic range of the method extends from 0.5 ng/mL to 1,000 ng/mL, demonstrating excellent sensitivity and suitability for pharmacokinetic studies across diverse DPZ formulations. Following the FDA guidelines, we rigorously validated the developed method, evaluating selectivity, linearity (with a coefficient of determination ≥0.9999), accuracy (ranging from 96.0% to 109.6%), precision (≤13.9%), matrix effect (92.2% to 103.8%), recovery (98.5% to 106.8%), the lower limit of quantitation (0.5 ng/mL), and stability. Finally, we effectively employed the validated method for the long-term pharmacokinetic assessment of a DPZ formulation. We expect that this approach will make a substantial contribution to the advancement of new DPZ formulations, ultimately benefiting individuals afflicted by AD.

BackgroundRobust and accurate prediction of severity for patients with COVID-19 is crucial for patient triaging decisions. Many proposed models were prone to either high bias risk or low-to-moderate discrimination. Some also suffered from a lack of clinical interpretability and were developed based on early pandemic period data. Hence, there has been a compelling need for advancements in prediction models for better clinical applicability. ObjectiveThe primary objective of this study was to develop and validate a machine learning–based Robust and Interpretable Early Triaging Support (RIETS) system that predicts severity progression (involving any of the following events: intensive care unit admission, in-hospital death, mechanical ventilation required, or extracorporeal membrane oxygenation required) within 15 days upon hospitalization based on routinely available clinical and laboratory biomarkers. MethodsWe included data from 5945 hospitalized patients with COVID-19 from 19 hospitals in South Korea collected between January 2020 and August 2022. For model development and external validation, the whole data set was partitioned into 2 independent cohorts by stratified random cluster sampling according to hospital type (general and tertiary care) and geographical location (metropolitan and nonmetropolitan). Machine learning models were trained and internally validated through a cross-validation technique on the development cohort. They were externally validated using a bootstrapped sampling technique on the external validation cohort. The best-performing model was selected primarily based on the area under the receiver operating characteristic curve (AUROC), and its robustness was evaluated using bias risk assessment. For model interpretability, we used Shapley and patient clustering methods. ResultsOur final model, RIETS, was developed based on a deep neural network of 11 clinical and laboratory biomarkers that are readily available within the first day of hospitalization. The features predictive of severity included lactate dehydrogenase, age, absolute lymphocyte count, dyspnea, respiratory rate, diabetes mellitus, c-reactive protein, absolute neutrophil count, platelet count, white blood cell count, and saturation of peripheral oxygen. RIETS demonstrated excellent discrimination (AUROC=0.937; 95% CI 0.935-0.938) with high calibration (integrated calibration index=0.041), satisfied all the criteria of low bias risk in a risk assessment tool, and provided detailed interpretations of model parameters and patient clusters. In addition, RIETS showed potential for transportability across variant periods with its sustainable prediction on Omicron cases (AUROC=0.903, 95% CI 0.897-0.910). ConclusionsRIETS was developed and validated to assist early triaging by promptly predicting the severity of hospitalized patients with COVID-19. Its high performance with low bias risk ensures considerably reliable prediction. The use of a nationwide multicenter cohort in the model development and validation implicates generalizability. The use of routinely collected features may enable wide adaptability. Interpretations of model parameters and patients can promote clinical applicability. Together, we anticipate that RIETS will facilitate the patient triaging workflow and efficient resource allocation when incorporated into a routine clinical practice.

Abstract Extracellular vesicle‐derived microRNAs (EV‐miRNAs) are promising biomarkers for early cancer diagnosis. However, existing EV‐miRNA extraction technologies have a complex two‐step process that results in low extraction efficiency and inconsistent results. This study aimed to develop and evaluate a new single‐step extraction method, called miRQuick, for efficient and high‐recovery extraction of EV‐miRNAs from samples. The miRQuick method involves adding positively charged substances to the sample, causing negatively charged EVs to quickly aggregate and precipitate. A membrane lysate is then added to extract only miRNA. The entire process can be completed within an hour using standard laboratory equipment. We validated the miRQuick method using various analytical techniques and compared its performance to other methods for plasma, urine and saliva samples. The miRQuick method demonstrated significantly higher performance than other methods, not only for blood plasma but also for urine and saliva samples. Furthermore, we successfully extracted and detected nine biomarker candidate miRNAs in the plasma of breast cancer patients using miRQuick. Our results demonstrate that miRQuick is a rapid and efficient method for EV‐miRNA extraction with excellent repeatability, making it suitable for various applications including cancer diagnosis.

Purpose To investigate the incidence, outcomes, and imaging characteristics of clustered microcysts detected on breast US in asymptomatic women, and suggest appropriate management guidelines. Materials and Methods We identified and reviewed the lesions recorded as “clustered microcysts” on breast US performed in asymptomatic women between August 2014 and December 2019. The final diagnosis was based on pathology and imaging follow-up results for at least 12 months. Results The incidence was 1.5% and 100 patients with 117 lesions were included. Among 117 lesions, 3 (2.6%), 2 (1.7%), and 112 (95.7%) were malignant, high-risk benign, and benign lesions, respectively. The malignant lesions included two cases of ductal carcinoma in situ and one invasive ductal carcinoma. Two of them were assessed as category 4, showing mammographic suspicious microcalcifications and internal vascularity on Doppler US. The remainder was a false negative case and showed echo pattern change on the 12-month follow-up US. Conclusion The incidence of clustered microcysts on breast US in asymptomatic women was 1.5% and malignancy rate was 2.6% (3 of 117). Knowledge of outcomes and imaging features of benign and malignant clustered microcysts may be helpful for radiologists, thereby aiding categorization and management recommendations.

Abstract Purpose We previously reported that expression of dickkopf-3 (DKK3), which is involved in the Wnt/β-catenin pathway, is significantly associated with prognosis in patients with glioblastoma multiforme (GBM). The aim of this study was to compare the association of DKK3 with other Wnt/β-catenin pathway-related genes and immune responses between lower grade glioma (LGG) and GBM. Methods We obtained the clinicopathological data of 515 patients with LGG (World Health Organization [WHO] grade II and III glioma) and 525 patients with GBM from the Cancer Genome Atlas (TCGA) database. We performed Pearson’s correlation analysis to investigate the relationships between Wnt/β-catenin-related gene expression in LGG and GBM. Linear regression analysis was performed to identify the association between DKK3 expression and immune cell fractions in all grade II to IV gliomas. Results A total of 1,040 patients with WHO grade II to IV gliomas were included in the study. As the grade of glioma increased, DKK3 showed a tendency to be more strongly positively correlated with the expression of other Wnt/β-catenin pathway-related genes. DKK3 was not associated with immunosuppression in LGG but was associated with downregulation of immune responses in GBM. We hypothesized that the role of DKK3 in the Wnt/β-catenin pathway might be different between LGG and GBM. Conclusion According to our findings, DKK3 expression had a weak effect on LGG but a significant effect on immunosuppression and poor prognosis in GBM. Therefore, DKK3 expression seems to play different roles, through the Wnt/β-catenin pathway, between LGG and GBM.

Study Design Retrospective case-control study. Purpose This study aimed to analyze the etiology of low-grade lytic spondylolisthesis based on the radiologic features of the vertebra. Overview of Literature According to the Marchetti-Bartolozzi classification scheme, high-grade lytic spondylolisthesis (Meyerding grade 3–5) is classified as dysplastic. However, determination of the etiology for low-grade lytic spondylolisthesis as developmental or traumatic remains controversial. Methods Patients admitted and treated for one-level (L4/5 or L5/S1) low-grade spondylolisthesis were included in the study. A total of 135 patients were divided into the degenerative or lytic spondylolisthesis groups according to their condition (81 patients [degenerative group] vs. 54 patients [lytic group]). To assess the level of similarity in the radiological findings between low-grade lytic spondylolisthesis and dysplastic spondylolisthesis, the pedicle diameters and vertebral heights of the L4 and L5 vertebrae were measured on computed tomography images. Measurements were then converted to each vertebra’s ratio to reduce confounding factors among individuals. Results The affected vertebra had a smaller sagittal pedicle diameter/transverse pedicle diameter ratio in the low-grade lytic spondylolisthesis group compared to the degenerative group, and the posterior vertebral height/anterior vertebral height ratio of L5 was smaller in the L5/S1 lytic spondylolisthesis group compared to the degenerative spondylolisthesis group. Conclusions Low-grade lytic spondylolisthesis and dysplastic spondylolisthesis demonstrated similar radiological findings. Hence, surgeons should be attentive to the morphology of the vertebral body and posterior column during preoperative planning for the treatment of low-grade lytic spondylolisthesis.

The current research was the first to prove the existence of fluctuations in the metabolite constituents and antioxidant properties in different organs (leaves, stems, and roots) of the mountain-cultivated ginseng (MCG) plant during a two-month maturation period. Four metabolites, including fatty acids, amino acids, ginsenosides, and phenolic phytochemicals, exhibited considerable differences in organs and maturation times with the following order: leaves > stems > roots. The predominant metabolite contents were found in leaves, with fatty acid (1057.9 mg/100 g) on 31 May, amino acid (1989.2 mg/100 g) on 13 July, ginsenosides (88.7 mg/g) on 31 May, and phenolic phytochemical (638.3 μg/g) on 31 May. Interestingly, ginsenoside content in leaves were highest, with 84.8 → 88.7 → 82.2 → 78.3 mg/g. Specifically, ginsenosides Re, Rd, and F2 showed abundant content ranging from 19.1 to 16.9 mg/g, 8.5 to 14.8 mg/g, and 9.5 to 13.1 mg/g, respectively. Phenolic phytochemicals exhibited remarkable differences in organs compared to maturation periods, with the highest total phenolic content and total flavonoid content recorded at 9.48 GAE and 1.30 RE mg/g in leaves on 31 May. The antioxidant capacities on radical, FRAP, and DNA protection differed significantly, with leaves on 31 May exhibiting the highest values: 88.4% (DPPH), 89.5% (ABTS), 0.84 OD593 nm (FRAP) at 500 μg/mL, and 100% DNA protection at 50 μg/mL. Furthermore, principal cluster analysis revealed metabolite variability as follows: ginsenoside (83.3%) > amino acid (71.8%) > phenolic phytochemical (61.1%) > fatty acid (58.8%). A clustering heatmap highlighted significant changes in metabolite components under the maturation times for each organ. Our findings suggest that MCG leaves on 31 May may be a potential source for developing nutraceuticals, offering highly beneficial components and strong antioxidants.

Effective management of water quality in watersheds is crucial because it is directly linked to the sustainability of aquatic ecosystems. In conventional watershed management, best management practices (BMPs) have been instrumental in addressing deteriorating water quality issues caused by non-point source pollution. Greenhouse gas (GHG) emissions have emerged as a global concern, necessitating immediate and diverse environmental actions to mitigate their impacts. This study aims to explore BMPs that maximize total phosphorus (TP) load removal efficiencies, while minimizing costs and GHG emissions within watersheds, using the Soil and Water Assessment Tool (SWAT) and non-dominated sorting genetic algorithm III (NSGA-III). The Yeongsan River Watershed between 2012 and 2021 was selected as the study area. Hydrological and BMP data were analyzed. Applying identical BMPs to the watershed showed that the BMPs with high TP removal efficiency may not be effective in terms of cost and GHG emissions. Therefore, the optimal combination of BMPs for the Yeongsan River Watershed was determined using NSGA-III considering TP removal efficiency, cost, and GHG emissions. This study is the first to consider GHG emissions at the watershed level when applying BMPs and is expected to contribute to the development of BMP implementation incorporating GHG emissions.

Background: The Wnt/β-catenin pathway plays a critical role in the tumorigenesis and maintenance of glioma stem cells. This study aimed to evaluate significant genes associated with the Wnt/β-catenin pathway involved in mortality and disease progression in patients with grade II and III glioma, using the Cancer Genome Atlas (TCGA) database. Methods: We obtained clinicopathological information and mRNA expression data from 515 patients with grade II and III gliomas from the TCGA database. We performed a multivariate Cox regression analysis to identify genes independently associated with glioma prognosis. Results: The analysis of 34 genes involved in Wnt/β-catenin signaling demonstrated that four genes (CER1, FRAT1, FSTL1, and RPSA) related to the Wnt/β-catenin pathway were significantly associated with mortality and disease progression in patients with grade II and III glioma. We also identified additional genes related to the four significant genes of the Wnt/β-catenin pathway mentioned above. The higher expression of BMP2, RPL18A, RPL19, and RPS12 is associated with better outcomes in patients with glioma. Conclusions: Using a large-scale open database, we identified significant genes related to the Wnt/β-catenin signaling pathway associated with mortality and disease progression in patients with grade II and III gliomas.

The growth of the Urban Air Mobility (UAM) industry emphasizes the need for considerable study into assembly procedures and dependability to guarantee its effective integration into air transport networks. In this context, this study seeks to evaluate the mechanical characteristics of bolted joint Carbon Fiber Reinforced Plastic (CFRP), with a particular emphasis on bearing strength. By altering the w/D (specimen width to hole diameter) and e/D (distance between hole center and specimen end to hole diameter) ratios, the study investigates how edge and end distances affect material performance. The study discovered a shift from tension to bearing failure at w/D ratios of 4.0, with maximum bearing strength decreases of 90.50% and 69.96% compared to full bearing failure. Similarly, for e/D ratios of 1.5, 2.0, and 3.0, transitioning from shear to bearing failure at 2.0 resulted in maximum bearing strength losses of 94.90% and 75.96%, respectively. Maintaining a w/D ratio of at least 6.0 and an e/D ratio of at least 3.0 is critical for maintaining maximum performance and stability in CFRP structure design.

Abstract The clinical usefulness of repeat colonoscopic polypectomy in patients with numerous polyps has not been sufficiently determined. We aimed to analyze the clinical outcomes of colonoscopic polypectomy with surveillance colonoscopies in patients with ≥ 10 polyps. We reviewed the medical records of 152 patients who underwent polypectomy of ≥ 10 polyps at the baseline colonoscopy. We investigated polyp number, polyp size, polypectomy method, procedure time, and adverse events of the baseline colonoscopy. We also investigated the frequency and interval of surveillance colonoscopies and their findings. The mean number of polyps detected at the baseline colonoscopy was 20.0, of which 16.0 polyps were endoscopically resected. The mean size of the largest polyp was 13.4 mm. The mean procedure time was 54.9 min. Post-polypectomy bleeding occurred in 6 (3.9%) patients, all of whom were treated conservatively. No patients developed perforation. With an increasing number of surveillance colonoscopies, the number of detected polyps and the procedure time decreased. Surveillance colonoscopies identified colorectal cancer only in three patients (2.0%), all of which were mucosal cancers that could be curatively treated by polypectomy. Colonoscopic polypectomy with repeat surveillance colonoscopies is a clinically effective, efficient, and safe management option in patients with ≥ 10 polyps.

This paper presents a novel variable flux memory motor (VFMM) with a series–parallel configuration that employs a constant-magnetization permanent magnet (CPM) with high coercivity and a variable-magnetization permanent magnet (VPM) with low coercivity. The CPMs in the proposed VFMM are arranged in parallel. Therefore, they share an air gap. Meanwhile, the VPMs are arranged in series with respect to the CPMs, as well as each other. The CPM-induced magnetic field not only reduces the re-magnetizing current for the VPMs but also enhances the torque density. Additionally, it can assist VPMs in resisting demagnetization under loaded conditions. For verification, we compared the performance of the proposed model with that of a series-type model widely applied in VFMMs. The magnetization characteristics were investigated using nonlinear finite element analysis by deriving the VPM load line. Furthermore, the electromagnetic performance under re-magnetization and demagnetization conditions was analyzed.