Search Results (175)

Avian influenza A viruses (IAVs) pose a persistent threat to the poultry industry, causing substantial economic losses. Although traditional vaccines have helped reduce the disease burden, they typically rely on multivalent antigens, emphasize humoral immunity, and require intensive production. This study aimed to establish a genetically matched host–cell system to evaluate antigen-specific immune responses and identify conserved CD8+ T cell epitopes in avian influenza viruses. To this end, we developed an MHC class I genotype (B21)-matched host (Lohmann VALO SPF chicken) and cell vector (DF-1 cell line) model. DF-1 cells were engineered to express the hemagglutinin (HA) gene of clade 2.3.4.4b H5N1 either transiently or stably, and to stably express the matrix 1 (M1) and nucleoprotein (NP) genes of A/chicken/South Korea/SL20/2020 (H9N2, Y280-lineage). Following prime-boost immunization with HA-expressing DF-1 cells, only live cells induced strong hemagglutination inhibition (HI) and virus-neutralizing (VN) antibody titers in haplotype-matched chickens. Importantly, immunization with DF-1 cells transiently expressing NP induced stronger IFN-γ production than those expressing M1, demonstrating the platform’s potential for differentiating antigen-specific cellular responses. CD8+ T cell epitope mapping by mass spectrometry identified one distinct MHC class I-bound peptide from each of the HA-, M1-, and NP-expressing DF-1 cell lines. Notably, the identified HA epitope was conserved in 97.6% of H5-subtype IAVs, and the NP epitope in 98.5% of pan-subtype IAVs. These findings highlight the platform’s utility for antigen dissection and rational vaccine design. While limited by MHC compatibility, this approach enables identification of naturally presented epitopes and provides insight into conserved, functionally constrained viral targets. Full article

Medical education often emphasizes theoretical knowledge, limiting students’ opportunities to practice history taking, a structured interview that elicits relevant patient information before clinical decision making. Large language models (LLMs) offer novel solutions by generating simulated patient interviews. This study evaluated the educational potential of LLM-generated history-taking dialogues, focusing on clinical validity and diagnostic diversity. Chest pain was chosen as a representative case given its frequent presentation and importance for differential diagnosis. A fine-tuned Gemma-3-27B, specialized for medical interviews, was compared with GPT-4o-mini, a freely accessible LLM, in generating multi-branching history-taking dialogues, with Claude-3.5 Sonnet inferring diagnoses from these dialogues. The dialogues were assessed using a Chest Pain Checklist (CPC) and entropy-based metrics. Gemma-3-27B outperformed GPT-4o-mini, generating significantly more high-quality dialogues (90.7% vs. 76.5%). Gemma-3-27B produced diverse and focused diagnoses, whereas GPT-4o-mini generated broader but less specific patterns. For demographic information, such as age and sex, Gemma-3-27B showed significant shifts in dialogue patterns and diagnoses aligned with real-world epidemiological trends. These findings suggest that LLMs, particularly those fine-tuned for medical tasks, are promising educational tools for generating diverse, clinically valid interview scenarios that enhance clinical reasoning in history taking. Full article

Due to the structural aspects of the wind turbine, such as wind shear and tower shadow effects, the output power of the wind turbine has periodic fluctuations, known as 3P fluctuations. These fluctuations can reduce overall power generation and deteriorate power quality. In this context, this paper proposes a power smoothing control method that utilizes rotor inertia and a DC-link capacitor as small-scale energy storage devices. First, the typical energy storage capacities of the rotor’s rotational kinetic energy and the DC-link capacitor’s electrostatic energy are analyzed to assess their smoothing potential. Secondly, a control method is presented to apply the rotor and the DC-link capacitor as small-scale energy storage, with the smoothing frequency range allocated according to their respective storage capacities. Finally, the proposed method is compared with the conventional maximum power point tracking (MPPT) method and the 3P-notch filter method. The effectiveness of the proposed algorithm is verified through MATLAB/Simulink simulations, demonstrating its capability to mitigate periodic power fluctuations. The results showed that the proposed control method is applicable, reliable, and effective in mitigating periodic power fluctuations. Full article

Background/Objectives: Lung cancer screening with low-dose computed tomography (LDCT) has reduced lung cancer mortality in high-risk smokers. However, the evidence on LDCT screening in the elderly is limited, with there being few older participants in major trials and ongoing debate about the benefits, risks, and appropriate age limits of LDCT. This study aimed to investigate the prevalence of pulmonary nodules and lung cancer detection rates in men aged 70 and above who underwent a single round of LDCT screening. Methods: We retrospectively analyzed data from elderly male participants aged 70 years or older who underwent a single low-dose CT lung cancer screening at the Veterans Health Service Medical Center between 2010 and 2023. The participants included those who requested screening or were asymptomatic but recommended by physicians. Individuals with prior lung cancer, symptoms suggestive of lung cancer, or suspicious findings on previous imaging were excluded. The nodule prevalence, lung cancer diagnoses, pathological subtypes, and clinical stages were reviewed. Results: A total of 1409 individuals with a mean age of 74.2 years were included. The median follow-up duration was 3.6 years. Among the included individuals, 1304 (92.6%) had a history of smoking. Positive nodules were detected in 179 patients (12.7%, 95% CI: 11.0–14.5%), and lung cancer was diagnosed in 31 patients (2.2%, 95% CI: 1.5–3.1%). Of the diagnosed cases, 14 (45.2%) were adenocarcinomas and 12 (38.7%) were squamous cell carcinomas. Nineteen patients (51.3%) were diagnosed with stage I or II cancer, while seven (22.6%) were diagnosed at stage IV. Conclusions: A single round of LDCT screening in elderly men resulted in a relatively high lung cancer detection rate, with over half of the diagnosed cases being identified at an early stage. This highlights the potential clinical benefit of even one-time screening in enabling timely treatment, which may still be feasible in older adults. However, potential harms such as overdiagnosis should also be considered. Full article

Background/Objectives: Most previous studies using artificial intelligence (AI) to detect left ventricular systolic dysfunction (LVSD) from electrocardiograms (ECGs) relied on data obtained near the time of echocardiography or included patients with known cardiac disease, limiting their specificity for screening. We aimed to evaluate whether AI models could predict future LVSD from ECGs interpreted as normal and recorded one to two years before echocardiography. Methods: We retrospectively analyzed 24,203 sinus rhythm ECGs from 11,131 patients. Two convolutional neural network models (DenseNet-121 and ResNet-101) were trained (70%), validated (10%), and tested (20%) to predict LVSD (defined as ejection fraction ≤50%). Survival analysis was performed using Kaplan–Meier curves and the log-rank test. Results: Of the total population, 2734 patients had LVSD and 8397 had preserved EF. DenseNet-121 and ResNet-101 demonstrated excellent discrimination for LVSD with AUROCs of 0.930 and 0.925, accuracies of 0.887 and 0.860, sensitivities of 0.821 and 0.856, and specificities of 0.908 and 0.861, respectively. In the test set, patients predicted to have LVSD showed a significantly higher risk of echocardiographic LVSD (hazard ratio 9.89, 95% CI 8.20–11.92, p = 0.005) and lower 24-month survival (log-rank p < 0.001). Conclusions: AI-enabled ECG models predicted future LVSD from clinically normal ECGs recorded up to two years prior to imaging. These findings suggest a potential role for AI-ECG in the early detection of subclinical LVSD and improved risk stratification in asymptomatic individuals. Full article

During the 2009 H1N1 pandemic (pdm09), the poor replication of PR8-derived vaccine strains in embryonated chicken eggs (ECEs) delayed vaccine production, necessitating costly adjuvants. To improve egg-based yield, we generated PB2-substituted H1N1 strains via reverse genetics, replacing PR8 PB2 with a PB2 lacking mammalian-adaptive mutations (dtxPB2), cognate pdm09 PB2 (19PB2), or avian PB2. All PB2-substituted strains achieved over tenfold higher titers than the conventional PR8 PB2-containing strain (rGD19), with rGD19/dtxPB2 and rGD19/19PB2 exhibiting significantly higher titers and reduced murine virulence. Among these, rGD19/19PB2 produced the highest hemagglutinin (HA) yield and, when administered intranasally as a binary ethyleneimine (BEI)-inactivated whole-virion vaccine, elicited a significantly stronger broncho-alveolar IgA response than rGD19. Both rGD19 and rGD19/19PB2 provided comparable protection against a homologous H1N1 challenge, yet only rGD19/19PB2 conferred full survival protection after a lethal heterologous H3N2 challenge. These findings show that incorporation of cognate PB2 enhances H1N1 replication in ECEs and antigen yield, reduces murine virulence, and confers robust homo- and heterosubtypic protection via intranasal immunization, underscoring the promise of PB2-modified H1N1 strains as inactivated mucosal whole-virion vaccines for future vaccine development. Full article

Background/Objectives: Tranexamic acid (TXA) reduces mortality in patients with massive hemorrhage by inhibiting fibrinolysis. However, it is associated with an increased risk of thrombosis. The activation of neutrophil extracellular traps (NETs) has been implicated in the formation of thrombosis. This study investigated the effects of tranexamic acid on circulating and localized NETs, neutrophils, platelets, and the vascular endothelium in a mouse model of thrombosis. Methods: A ferric chloride-induced thrombosis mouse model was used and divided into five groups: a Control group that received intraperitoneal phosphate-buffered saline (PBS), and four experimental groups that received intraperitoneal tranexamic acid at doses of 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg, respectively. To evaluate the expression of circulating and localized NETs, neutrophils, platelets, vascular endothelial cells, fibrinogen, and D-dimer, the following markers were analyzed: myeloperoxidase (MPO), neutrophil marker, cluster of differentiation (CD)31, CD34, fibrinogen α-chain, and D-dimer. These markers were assessed using flow cytometry, immunohistofluorescence staining, and Western blot analysis. The primary endpoint was the differential expression of anti-MPO antibody among the groups. Results: In total, data from 20 thrombosis mouse models were analyzed. For each group, four samples were assessed by flow cytometry, and three samples by immunohistofluorescence staining and Western blot analysis, respectively. In the flow cytometric analysis, circulating anti-MPO antibody expression was significantly higher in the TXA 20 and TXA 30 groups compared to the Control group (p = 0.001 and p = 0.001, respectively). Immunohistofluorescence staining revealed that D-dimer expression in the thrombotic femoral artery was significantly lower in the TXA 5, TXA 10, and TXA 20 groups compared to the Control group (p = 0.005; p = 0.018; p = 0.004, respectively), but significantly higher in the TXA 30 group than in the Control group (p = 0.044). Similarly, the expression of anti-fibrinogen antibody was significantly lower in the TXA 5, TXA 10, and TXA 20 groups compared to the Control group (p = 0.038; p = 0.003; p = 0.041, respectively). Western blot analysis showed no significant differences in the expression of anti-Ly6B.2, anti-fibrinogen, and anti-CD31 antibodies among the groups. Conclusions: The present study suggests that high-dose tranexamic acid (30 mg/kg) administration may increase circulating NETs and localized D-dimer levels, indicating a higher potential for thrombosis in a thrombosis mouse model. These findings imply that the prothrombotic effects of tranexamic acid may be dose-dependent and could vary based on underlying disease conditions. Therefore, the careful dosage adjustment of tranexamic acid may be necessary, particularly in patients at risk of thrombosis. Full article

Background/Objectives: This study is a pilot evaluation of the applicability of wearable digital healthcare devices for Korean male seafarers. Seafarers are exposed to health risks due to unstable and confined living conditions, and their access to healthcare services becomes significantly challenging, especially with the substantial decrease in physical activity onboard. This study aimed to monitor the physical activity of these seafarers through wearable devices and evaluate the potential of managing their health using these technologies. Methods: During the 12-week study, which included 11 participants, it was confirmed that monitoring physical activity using wearable devices and smartphone applications was effective. Results: Over the 12-week period, the average systolic blood pressure decreased from 137.09 ± 13.05 mmHg to 124.36 ± 5.66 mmHg, and the average diastolic blood pressure decreased from 86.45 ± 10.24 mmHg to 77.45 ± 5.26 mmHg, showing a statistically significant reduction (p = 0.011). Additionally, participants experienced an average weight reduction of 1.19 kg. Satisfaction with the use of wearable devices was reported to be moderate. Conclusions: Such digital healthcare can encourage the maintenance of healthy habits by continuously monitoring physical activity and providing feedback. Considering the difficulties seafarers face in accessing medical services, the adoption of digital healthcare through wearable devices is essential, contributing to the prevention of chronic diseases and overall health improvement of seafarers. Future research should explore the long-term benefits and potential challenges of these digital healthcare solutions on a larger scale. Full article

Shinorine is a mycosporine-like amino acid isolated from laver (Porphyra dentata), and interest in its functionality has increased recently due to increased production using yeast. There have been few reports on the pharmacological activity of shinorine, and we sought to find the pharmacological significance of shinorine. In the present study, we investigated the pharmacological effects of shinorine purified from Porphyra dentata on ARPE-19 cells. First, when ARPE-19 cells were treated with bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) and blue light (BL), cytotoxicity increased, and apoptosis was observed. We investigated the effects of shinorine on A2E- and BL-induced cytotoxicity and changes in apoptotic factors, inflammation, and carbonyl stress. A2E and BL exposure increased ARPE-19 cell apoptosis, but this increase was attenuated by shinorine in a concentration-dependent manner. Treatment with A2E and BL induced ARPE-19 cell apoptosis, but treatment with shinorine decreased the apoptotic factors, such as MAPKs. Shinorine reduced p-JNK and p-P38, which were increased by A2E and BL. In addition, shinorine was found to regulate inflammatory proteins and proteins associated with carbonyl stress. In conclusion, shinorine may suppress cell damage caused by A2E treatment and BL exposure at the cellular level by regulating various cell death and inflammatory response pathways. Full article

Background: Probiotics have been shown to enhance cognitive function in individuals with mild cognitive impairment (MCI), but their efficacy varies, depending on the strain and dosage. Objectives: Clinical investigations are crucial to confirm their safety, efficacy, and mechanism of action. This study was designed to assess the effective dosage, safety, and efficacy of MH-Pro, a test product containing Lacticaseibacillus rhamnosus CBT-LR5 (LR5) and skim milk (non-fat dry milk), in improving cognitive function and related physiological changes in older adults suspected of MCI over 12 weeks. Methods: In total, 20 participants (mean age: 68.9 years) were randomly assigned in a 1:1 ratio to either a low-dose group (1 × 10¹⁰ CFU LR5 with 1622 mg) or a high-dose group (1 × 10¹⁰ CFU LR5 with 4055 mg skim milk) in a double-blind, parallel-group clinical trial. Results: After 12 weeks, the low-dose group showed significant improvements in the MOCA-K subdomains, specifically in naming (p = 0.01) and delayed recall (p = 0.003). Additionally, levels of amyloid-β1 40/42 in the blood significantly decreased (p = 0.03) following supplementation in the low-dose group. The high-dose group exhibited significant improvement in orientation (p = 0.05). Moreover, overall cognitive enhancement was observed in the low-dose group (p = 0.003), while the high-dose group showed a trend toward improvement (p = 0.06). Fecal analysis revealed significant changes in bacterial composition, with an increase in Lacticaseibacillus after 12 weeks of MH-Pro consumption. Together, these findings provide foundational evidence suggesting that MH-Pro supplementation may serve as a potential intervention for enhancing cognitive function through gut–brain axis pathways in the elderly population. However, given the small sample size and the predominance of female participants, the impact of the outcome may be limited. Further large-scale studies are necessary to validate these preliminary results. Conclusions: This study provides foundational evidence to recognize the use of LR5 and skim milk to prepare a probiotic supplement that enhances cognitive function in the aging population. Full article

Introduction: This study assessed the therapeutic effectiveness of a single-pill combination (SPC) of olmesartan/amlodipine plus rosuvastatin for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in patients with hypertension and dyslipidemia. Methods: Adult patients with hypertension and dyslipidemia who were decided to be treated with the study drug were eligible. The primary endpoint was the proportion of patients who achieved BP, LDL-C and both BP and LDL-C treatment goals at weeks 24–48. Secondary endpoints were assessed at weeks 24–48 and included changes in BP and LDL-C levels from baseline; the proportion of patients who achieved treatment goals who were initially classified as uncontrolled at baseline; changes and percent changes in lipid parameters; changes in both BP and LDL-C levels among patients who reached treatment goals who were followed for more than 24 weeks; and the overall safety profile. Results: A total of 5476 patients were enrolled, and 4411 patients comprised the effectiveness evaluation set. The proportions of patients who reached the treatment goals for BP, LDL-C levels, and both BP and LDL-C levels were 67.93% [95% confidence interval (CI) 66.52–69.32], 80.19% [95% CI 78.85–81.49], and 58.07% [95% CI 56.43–59.7], respectively. Secondary endpoints showed statistically significant changes. Overall, the treatment was well tolerated. Conclusions: The treatment of patients with hypertension and dyslipidemia with the olmesartan/amlodipine plus rosuvastatin SPC was associated with significant decreases in SBP/DBP and LDL-C levels, and a high proportion of patients achieved the BP and LDL-C treatment goals. The finding of this study is worthwhile in that this study evaluated the effectiveness and safety in a broad patient population representative of those seen in everyday clinical practice. Full article

A novel monomer, 9-bis[4-(2-hydroxyethoxy)phenyl]fluorene di(mercaptopropionate), with a highly refractive index, purity, and excellent UV-curable properties, is synthesized through an optimized Fischer esterification process, reacting 9,9-bis[4-(2-hydroxyethoxy)phenyl]fluorene with 3-mercaptopropionic acid. The structural characterization of this monomer is performed using Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, and liquid chromatography-mass spectrometry. The synthesis conditions are optimized using a design-of-experiments approach. UV-curable resins are obtained by incorporating the synthesized monomer as the thiol component. The effects of thiol content on the UV-curing behavior, refractive index, shrinkage, adhesion to the polyethylene terephthalate (PET) foil, and viscoelastic recovery are examined. The thermal properties are assessed using differential scanning calorimetry and thermogravimetric analysis. Field-emission scanning electron microscopy confirms the successful replication of the prism film. In edge-lit light-emitting diode (LED) backlight units, the prism film showed increased luminance with higher thiol monomer content in the UV-curable resin while maintaining stable color coordinates. This novel highly refractive index monomer can be utilized in luminance-enhancing prism films, thereby contributing to future innovations in the display film industry. Full article

Background/Objective: Highly pathogenic (HP) H5Nx and low-pathogenicity (LP) H9N2 avian influenza viruses (AIVs) pose global threats to the poultry industry and public health, highlighting the critical need for a dual-protective vaccine. Methods: In this study, we generated a model PR8-derived recombinant H5N2 vaccine strain with hemagglutinin (HA) and neuraminidase (NA) genes from clade 2.3.2.1c H5N1 and Y439-like H9N2 viruses, respectively. To enhance the immunogenicity of the recombinant H5N2 vaccine strain, N-glycans of the HA2 subunit, NA, and M2e were modified. Additionally, we replaced M2e with avian M2e to enhance the antigenic homogeneity of AIVs for better protection. We also replaced PR8 PB2 with 01310 PB2, which is the PB2 gene derived from an LP H9N2 avian influenza virus, to eliminate pathogenicity in mammals. The productivity of the model vaccine strain (rvH5N2-aM2e-vPB2) in embryonated chicken eggs (ECEs), its potential risk of mammalian infection, and the immunogenicity associated with different inactivation methods (formaldehyde (F/A) vs. binary ethyleneimine (BEI)) were evaluated. Results: The rvH5N2-aM2e-vPB2 strain demonstrated high productivity in ECEs and exhibited complete inhibition of replication in mammalian cells. Furthermore, compared with using F/A inactivation, inactivation using BEI significantly enhanced the immune response, particularly against NA. This enhancement resulted in increased virus neutralization titers, supporting its efficacy for dual protection against H5Nx and H9N2 avian influenza viruses. Furthermore, we demonstrated that M2e-specific immune responses, difficult to induce with inactivated vaccines, can be effectively elicited with live vaccines, suggesting a strategy to enhance M2e immunogenicity in whole influenza virus vaccines. Conclusions: Finally, the successful development of the model rH5N2 vaccine strain is described; this strain provides dual protection, has potential applicability in regions where avian influenza is endemic, and can be used to promote the development of versatile H5N2 recombinant vaccines for effective avian influenza control. Full article

White organic light-emitting diodes (OLEDs) represent a significant technology in the display industry for the achievement of full color. However, sophisticated technologies are required for white light emission. In this paper, we developed a simple white light-emitting display device using a quantum-dot (QD) film and a greenish-blue OLED. The resulting QD-OLED produced a high-purity white color with a color temperature of 6000 K (CIE_x,y = 0.32, 0.34) and achieved a maximum brightness of 14,638 cd/m² at 7 V. This paper reports the fabrication of a white light-emitting QD-OLED with a straightforward structure and technology suitable for flexible displays. Full article

Introduction: The immune system’s defense against pathogens involves innate and adaptive responses, crucial in maintaining overall health. Immunosuppressed states render individuals more susceptible to potential diseases, indicating the need for effective strategies to bolster immune functions. Objectives: Although the immunostimulatory effects of various probiotics have been studied, the specific effects and molecular mechanisms of Lactococcus lactis OTG1204 (OTG1204) remain unknown. In this study, the aim was to investigate the molecular mechanisms of OTG1204 in RAW 264.7 macrophages, the key effector cells of the innate immune system involved in host defense and inflammatory responses. Additionally, in this study, the effects of OTG1204 on cyclophosphamide (CTX)-induced immunosuppression states were investigated, thereby demonstrating its potential as an immune stimulant. Methods: To assess the macrophage activation ability and underlying mechanisms of OTG1204, RAW 264.7 cells were utilized with transfection, enzyme-linked immunosorbent assay, and quantitative real-time PCR analyses. Furthermore, to evaluate the immunostimulatory effects under immunosuppressed conditions, CTX-induced immunosuppression mice model was employed, and analyses were performed using hematoxylin and eosin staining, flow cytometry, and microbiota examination. Results: OTG1204 activated RAW 264.7 macrophages, leading to increased production of nitric oxide, prostaglandin E2, and cytokines. This immune activation was mediated through the upregulation of toll-like receptor 2, which subsequently activated the nuclear factor-κB (NF-kB) and mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) pathways, thereby stimulating the immune response. In CTX-treated mice, OTG1204 recovered body weight, spleen, and mesenteric lymph node indices, and natural killer cell activity. It re-established populations of innate and adaptive immune cells and activated T cells to secrete cytokines. We also examined the gut barrier integrity and microbiota composition to assess OTG1204’s impact on intestinal health, as these factors play a significant role in immune enhancement. OTG1204 enhanced gut barrier integrity by upregulating mucin 2 and tight junction proteins and modulated the gut microbiota by restoring the Firmicutes/Bacteroidetes balance and reducing the abundance of Actinobacteria and Tenericutes. Conclusion: These results suggest that OTG1204 may serve as an effective probiotic for immune enhancement and gut health management by targeting the NF-κB and MAPK/AP-1 pathways, with minimal side effects. Full article