The first report of single nucleotide polymorphisms in the open reading frame of the prion-like protein gene in rabbits.

Background: Natural cases of prion disease have not been reported in rabbits, and prior attempts to identify a prion conversion agent have been unsuccessful. However, recent applications of prion seed amplifying experimental techniques have sparked renewed interest in the potential susceptibility of rabbits to prion disease infections. Among several factors related to prion disease, polymorphisms within the prion-like protein gene (PRND), a member of the prion protein family, have been reported as significantly associated with disease susceptibility in various species. Therefore, our study aimed to investigate polymorphisms in the PRND gene of rabbits and analyze their genetic characteristics. Methods: Genomic DNA was extracted from 207 rabbit samples to investigate leporine PRND polymorphisms. Subsequently, amplicon sequencing targeting the coding region of the leporine PRND gene was conducted. Additionally, linkage disequilibrium (LD) analysis was employed to assess the connection within and between loci. The impact of non-synonymous single nucleotide polymorphisms (SNPs) on the Doppel protein was evaluated using PolyPhen-2. Results: We found nine novel SNPs in the leporine PRND gene: c.18A > G, c.76G > C, c.128C > T, c.146C > T, c.315A > G, c.488G > A, c.525G > C, c.544G > A, and c.579A > G. Notably, seven of these PRND SNPs, excluding c.525G > C and c.579A > G, exhibited strong LD values exceeding 0.3. In addition, LD analysis confirmed a robust link between PRNP SNP c.234C > T and PRND SNPs at c.525G > C and c.579A > G. Furthermore, according to PolyPhen-2 and SIFT analyses, the four non-synonymous SNPs were predicted to have deleterious effects on the function or structure of the Doppel protein. However, PANTHER and Missense3D did not indicate such effects. Conclusion: In this paper, we have identified novel SNPs in the rabbit PRND gene and predicted their potential detrimental effects on protein function or structure through four non-synonymous SNPs. Additionally, we observed a genetic linkage between SNPs in the PRND and PRNP genes. These findings may provide insights into understanding the characteristics of rabbits as partially resistant species. To the best of our knowledge, this study is the first to genetically characterize PRND SNPs in rabbits.

Usefulness of the MFIS-K, FSS, and FACIT-F Fatigue Scales in Korean Patients With MS, NMOSD, and MOGAD.

BACKGROUND AND PURPOSE: Fatigue is common in demyelinating disorders of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aimed to validate the usefulness of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Fatigue Severity Scale (FSS) relative to the Korean version of the Modified Fatigue Impact Scale (MFIS-K) in Korean patients with MS, NMOSD, and MOGAD. METHODS: There were 294 patients with MS (n=120), NMOSD (n=103), or MOGAD (n=71) enrolled in a prospective demyelinating CNS registry. Fatigue was measured using the FACIT-F, MFIS-K, and FSS. Sleep quality, quality of life, depression, and pain were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 36-item Short-Form Survey (SF-36), and Beck Depression Inventory-II (BDI-II). RESULTS: The MFIS-K, FACIT-F, and FSS scores showed high internal consistencies and strong correlations with each other in the MS, NMOSD, and MOGAD groups. The scores on all three fatigue scales were correlated with PSQI, SF-36, and BDI-II results in the three groups. The areas under the receiver operating characteristic curves for the FSS and FACIT-F were 0.834 and 0.835, respectively, for MS, 0.877 and 0.833 for NMOSD, and 0.925 and 0.883 for MOGAD. CONCLUSIONS: These results suggest that the MFIS-K, FSS, and FACIT-F are useful and valuable assessment instruments for evaluating fatigue in Korean patients with MS, NMOSD, and MOGAD.

Systematic analysis of the Candida albicans kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation in vitro and in vivo.

Protein kinases are critical regulatory proteins in both prokaryotes and eukaryotes. Accordingly, protein kinases represent a common drug target for a wide range of human diseases. Therefore, understanding protein kinase function in human pathogens such as the fungus Candida albicans is likely to extend our knowledge of its pathobiology and identify new potential therapies. To facilitate the study of C. albicans protein kinases, we constructed a library of 99 non-essential protein kinase homozygous deletion mutants marked with barcodes in the widely used SN genetic background. Here, we describe the construction of this library and the characterization of the competitive fitness of the protein kinase mutants under 11 different growth and stress conditions. We also screened the library for protein kinase mutants with altered filamentation and biofilm formation, two critical virulence traits of C. albicans. An extensive network of protein kinases governs these virulence traits in a manner highly dependent on the specific environmental conditions. Studies on specific protein kinases revealed that (i) the cell wall integrity MAPK pathway plays a condition-dependent role in filament initiation and elongation; (ii) the hyper-osmolar glycerol MAPK pathway is required for both filamentation and biofilm formation, particularly in the setting of in vivo catheter infection; and (iii) Sok1 is dispensable for filamentation in hypoxic environments at the basal level of a biofilm but is required for filamentation in normoxia. In addition to providing a new genetic resource for the community, these observations emphasize the environmentally contingent function of C. albicans protein kinases.IMPORTANCECandida albicans is one of the most common causes of fungal disease in humans for which new therapies are needed. Protein kinases are key regulatory proteins and are increasingly targeted by drugs for the treatment of a wide range of diseases. Understanding protein kinase function in C. albicans pathogenesis may facilitate the development of new antifungal drugs. Here, we describe a new library of 99 protein kinase deletion mutants to facilitate the study of protein kinases. Furthermore, we show that the function of protein kinases in two virulence-related processes, filamentation and biofilm formation, is dependent on the specific environmental conditions.

Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma.

Introduction: We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients. Methods: Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models. Results: Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps<0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39-1.59]) and non-curative (1.22 [1.17-1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74-0.92]) and best supportive care (0.85 [0.79-0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48-2.00]) and ablation (1.44 [1.08-1.92]). Conclusion: Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.

Lead exposure estimation through a physiologically based toxicokinetic model using human biomonitoring data and comparison with scenario-based exposure assessment: A case study in Korean adults.

Pb toxicity is linked to cardiovascular and nephrotoxicity issues. Exposure to this heavy metal can occur through food and drinking water. Therefore, this study aimed to evaluate Pb exposure and assess health risks in Korean adults using a physiologically based toxicokinetic (PBTK) model. Human blood Pb concentrations were monitored using the Korean National Environmental Health Survey (KoNEHS) Cycle 4. The average Pb exposure in Korean adults was 0.520 µg/kg bw/day. The PBTK results were compared with scenario-based results from the 2021 risk assessment report of five heavy metals, including Pb, conducted by the MFDS. Exposure determined through reverse dosimetry was approximately two times higher than scenario-based exposure (0.264 µg/kg bw/day). The higher exposure levels obtained during PBTK analysis may be attributed to sustained exposure within historically more contaminated living environments and the long half-life of Pb. These findings suggest that the PBTK-based method can quantify aggregated exposure levels in the body over time, potentially serving as a complementary tool to address the constraints of scenario-based assessment methods for integrated risk assessment. Moreover, this model is convenient and cost-effective compared with scenario-based exposure estimation. These findings can facilitate the application of model for tracking continuous national changes in hazardous substance levels.

Comparison of the impact of longitudinal body mass index changes on cardiac arrest risk between normal and overweight populations.

BACKGROUND: Being overweight is a key modifiable risk factor for cardiovascular disease. However, the impact of longitudinal changes in body mass index (BMI) on the risk of out-of-hospital cardiac arrests (OHCA) remains unclear, especially among overweight populations. METHODS: This nested case-control study utilized data from the Korean National Health Information Database between 2009 and 2018. A total of 23 453 OHCA patients, who underwent national health check-ups within 1 and 2-4 years before OHCA occurrence, and 31 686 controls, who underwent similar national health check-ups, were included. The study population was matched for sex, age and survival status. Conditional logistic regression was employed to analyse the odds ratios (ORs) and 95% confidence intervals (CIs) of each BMI per cent change in assessing the risk of OHCA occurrence within 1 year. RESULTS: A reverse J-shaped association between BMI per cent change and OHCA risk was observed, even among overweight populations. Among the overweight populations, weight loss significantly increased OHCA risk, with ORs (95% CI) of 4.10 (3.23-5.20) for severe weight loss (BMI decrease > 15%), 2.72 (2.33-3.17) for moderate weight loss (BMI decrease 10-15%) and 1.46 (1.35-1.59) for mild weight loss (BMI decrease 5-10%). Conversely, mild weight gain (BMI increase 5-10%) did not significantly increase OHCA risk. The impact of weight changes on the occurrence of OHCA differed by sex, being more prominent in males. CONCLUSIONS: Significant weight changes within a 4-year period increase the risk of OHCA with a reverse J-shaped association, even among overweight and obese individuals. Maintaining a stable weight could be a reliable public health strategy irrespective of the weight status, particularly for males.

Severity of hyperechoic pancreas on preoperative ultrasonography: high potential as a clinically useful predictor of a postoperative pancreatic fistula.

PURPOSE: This study aimed to evaluate the effectiveness of using the severity of hyperechoic pancreas (HP) observed on preoperative ultrasonography (US) as a predictor of clinically relevant postoperative pancreatic fistula (CR-POPF). METHODS: A retrospective study was conducted with 94 patients who underwent pancreatectomy between April 2006 and March 2021. The severity of HP on US was classified into two categories (normal to mild vs. moderate to severe [obvious HP]). Multiple preoperative and intraoperative parameters were analyzed to predict CR-POPF. RESULTS: Out of the 94 patients, CR-POPF occurred in 21 (22%) patients, and obvious HP was observed in 30 (32%). Univariate analysis revealed that moderate to severe HP (obvious HP) was significantly associated with an increased incidence of CR-POPF (P<0.001). Factors such as the absence of pancreatitis, a small main pancreatic duct (<3 mm), intraoperative soft pancreas, increased body mass index, and lower pancreatic attenuation and attenuation index were also associated with CR-POPF (all P<0.05). Multivariate analysis showed that obvious HP and soft pancreatic texture were independent predictors of CR-POPF, with odds ratios of 11.53 (P=0.001) and 14.12 (P=0.003), respectively. The combination of obvious HP and soft pancreatic texture provided the most accurate prediction for CR-POPF. CONCLUSION: The severity of HP, as observed on preoperative US, was significantly associated with CR-POPF. Severe HP may serve as a clinically useful predictor of POPF, especially when evaluated alongside the intraoperative pancreatic texture.

Antidepressant Effect of Enzymatic Porcine Placenta Hydrolysate in Repeated Immobilization Stress-Induced Ovariectomized Female Mice.

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1ß) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic the symptoms of women with menopause-related depression, a stressed ovariectomized (OVX) female mouse model was used to evaluate the antidepressant effects of EPPH. The female mice were randomly divided into five groups: (1) the sham-operated (Sham) group, (2) the OVX + repeated stress + saline-treated (OVX + ST) group, (3) the OVX + repeated stress + estradiol (0.2 mg/kg)-treated (positive control) group, (4) the OVX + repeated stress + EPPH (300 mg/kg)-treated (300) group, and (5) the OVX + repeated stress + EPPH (1500 mg/kg)-treated (1500) group. Female mice were OVX and repeatedly immobilization-stressed for 2 weeks (2 h/day). A tail suspension test was conducted on the 13th day, followed by the forced swimming test on the 14th day to assess the antidepressant effects of EPPH. After the behavioral tests, the levels of CORT, PGE2, and IL-1ß were evaluated. In addition, c-Fos expression in the paraventricular nucleus (PVN) was evaluated using immunohistochemistry. The concentrations of NO, PGE2, and IL-1ß stimulated by LPS were significantly reduced via the addition of EPPH to RAW 264.7 cells. EPPH significantly promoted neurite outgrowth in PC12 cells compared to that of the controls. In the tail suspension test, the duration of immobility was reduced in mice treated with EPPH 1500 compared to the OVX + ST group. The EPPH 1500 group had significantly decreased levels of c-Fos-positive neurons in the PVN and reduced levels of CORT and IL-1ß in the serum of the Sham group. These results suggested that the high dose of EPPH administration induced the antidepressant-like effect in the ovariectomized mice with repeated stress via downregulating the levels of CORT, IL-1ß, and PGE2 in the serum through reducing the expression of c-Fos in the PVN regions.

Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin.

Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.

Natural killer cells associate with epithelial cells in the pancreatic ductal adenocarcinoma tumor microenvironment.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. PDAC's poor prognosis and resistance to immunotherapy are attributed in part to its dense, fibrotic tumor microenvironment (TME), which is known to inhibit immune cell infiltration. We recently demonstrated that PDAC patients with higher natural killer (NK) cell content and activation have better survival rates. However, NK cell interactions in the PDAC TME have yet to be deeply studied. We show here that NK cells are present and active in the human PDAC TME. Methods: We used imaging mass cytometry (IMC) to assess NK cell content, function, and spatial localization in human PDAC samples. Then, we used CellChat, a tool to infer ligand-receptor interactions, on a human PDAC scRNAseq dataset to further define NK cell interactions in PDAC. Results: Spatial analyses showed for the first time that active NK cells are present in the PDAC TME, and both associate and interact with malignant epithelial cell ducts. We also found that fibroblast-rich, desmoplastic regions limit NK cell infiltration in the PDAC TME. CellChat analysis identified that the CD44 receptor on NK cells interacts with PDAC extracellular matrix (ECM) components such as collagen, fibronectin and laminin expressed by fibroblasts and malignant epithelial cells. This led us to hypothesize that these interactions play roles in regulating NK cell motility in desmoplastic PDAC TMEs. Using 2D and 3D in vitro assays, we found that CD44 neutralization significantly increased NK cell invasion through matrix. Conclusions: Targeting ECM-immune cell interactions may increase NK cell invasion into the PDAC TME.

Deep learning-assisted inverse design of nanoparticle-embedded radiative coolers.

Radiative cooling is an energy-efficient technology without consuming power. Depending on their use, radiative coolers (RCs) can be designed to be either solar-transparent or solar-opaque, which requires complex spectral characteristics. Our research introduces a novel deep learning-based inverse design methodology for creating thin-film type RCs. Our deep learning algorithm determines the optimal optical constants, material volume ratios, and particle size distributions for oxide/nitride nanoparticle-embedded polyethylene films. It achieves the desired optical properties for both types of RCs through Mie Scattering and effective medium theory. We also assess the optical and thermal performance of each RCs.

Migraine Risk in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Nationwide Cohort Study in South Korea.

INTRODUCTION: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. METHODS: This study analyzed claims data from 1,492 patients with MS and 1,551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. RESULTS: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95% CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction = 0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. CONCLUSION: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.

Virus-like particles expressing microneme-associated antigen of Plasmodium berghei confer better protection than those expressing apical membrane antigen 1.

Malaria is a global disease affecting a large portion of the world's population. Although vaccines have recently become available, their efficacies are suboptimal. We generated virus-like particles (VLPs) that expressed either apical membrane antigen 1 (AMA1) or microneme-associated antigen (MIC) of Plasmodium berghei and compared their efficacy in BALB/c mice. We found that immune sera acquired from AMA1 VLP- or MIC VLP-immunized mice specifically interacted with the antigen of choice and the whole P. berghei lysate antigen, indicating that the antibodies were highly parasite-specific. Both VLP vaccines significantly enhanced germinal center B cell frequencies in the inguinal lymph nodes of mice compared with the control, but only the mice that received MIC VLPs showed significantly enhanced CD4+ T cell responses in the blood following P. berghei challenge infection. AMA1 and MIC VLPs significantly suppressed TNF-α and interleukin-10 production but had a negligible effect on interferon-γ. Both VLPs prevented excessive parasitemia buildup in immunized mice, although parasite burden reduction induced by MIC VLPs was slightly more effective than that induced by AMA1. Both VLPs were equally effective at preventing body weight loss. Our findings demonstrated that the MIC VLP was an effective inducer of protection against murine experimental malaria and should be the focus of further development.

Development and validation of a prediction model for postoperative urinary retention after prolapse surgery: A retrospective cohort study.

BACKGROUND: Postoperative urinary retention (POUR), a common condition after prolapse surgery with potential serious sequelae if left untreated, lacks a clearly established optimal timing for catheter removal. This study aimed to develop and validate a predictive model for postoperative urinary retention lasting > 2 and > 4 days after prolapse surgery. METHODS: We conducted a retrospective review of 1,122 patients undergoing prolapse surgery. The dataset was divided into training and testing cohorts. POUR was defined as the need for continuous intermittent catheterization resulting from a failed spontaneous voiding trial, with passing defined as two consecutive voids ≥ 150 mL and a postvoid residual urine volume ≤ 150 mL. We performed logistic regression and the predicted model was validated using both training and testing cohorts. RESULTS: Among patients, 31% and 12% experienced POUR lasting > 2 and > 4 days, respectively. Multivariable logistic model identified 6 predictors. For predicting POUR, internal validation using cross-validation approach showed good performance, with accuracy lasting > 2 (area under the curve [AUC] 0.73) and > 4 days (AUC 0.75). Split validation using pre-separated dataset also showed good performance, with accuracy lasting > 2 (AUC 0.73) and > 4 days (AUC 0.74). Calibration curves demonstrated that the model accurately predicted POUR lasting > 2 and > 4 days (from 0 to 80%). CONCLUSIONS: The proposed prediction model can assist clinicians in personalizing postoperative bladder care for patients undergoing prolapse surgery by providing accurate individual risk estimates.

Ventral Anterior Cingulate Atrophy as a Predisposing Factor for Transient Global Amnesia.

Background and Purpose: This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. Methods: We evaluated the brain MRI data from 87 TGA patients and 20 age- and sex-matched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. Results: TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). Conclusions: TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

Pyrogallol intermediates elicit beta-amyloid secretion via radical formation and alterations in intracellular trafficking, distinct from pyrogallol-generated superoxide.

This study unveils a novel role of pyrogallol (PG), a recognized superoxide generator, in inducing beta-amyloid (Aß) secretion in an Alzheimer's disease (AD) cellular model. Contrary to expectations, the analysis of dihydroethidium fluorescence and UV-VIS spectrum scanning reveals that Aß secretion arises from PG reaction intermediates rather than superoxide or other by-products. Investigation into Aß secretion mechanisms identifies dynasore-dependent endocytosis and BFA-dependent exocytosis as independent pathways, regulated by tiron, tempol, and superoxide dismutase. Cell-type specificity is observed, with 293sw cells showing both pathways, while H4sw cells and primary astrocytes from an AD animal model exclusively exhibit the Aß exocytosis pathway. This exploration contributes to understanding PG's chemical reactions and provides insights into the interplay between environmental factors, free radicals, and AD, linking occupational PG exposure to AD risk as reported in the literature.

Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Psychometrics of the Korean Version of the screen for adult anxiety related disorders (SCAARED).

BACKGROUND: For enhanced management of anxiety disorders, early screening and accurate diagnostic differentiation are essential. The Screen for Adult Anxiety Related Disorders (SCAARED) has been developed to identify and categorize anxiety disorders, thereby facilitating timely and appropriate interventions. In line with this, we aimed to translate and validate the Korean version of the SCAARED questionnaire for the Korean population. METHODS: The original SCAARED was translated into Korean and administered to community adult population (N = 119) ages 18-45 years old in South Korea. The internal consistency and test-retest reliability of the SCAARED were evaluated. In addition, its factor structure was examined using confirmatory and exploratory factor analysis. Concurrent validity was evaluated by comparing SCAARED with the Depression, Anxiety and Stress Scale-21 (DASS), the Beck's Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI). Test-retest reliability was evaluated one week after the first assessment. RESULTS: The SCAARED showed good internal consistency (Cronbach's α = 0.945) and test-retest reliability (γ = 0.883). The SCAARED had significant correlation with DASS-21 subscales (γ = 0.655-0.701), BAI (γ = 0.788) and STAI subscales (γ = 0.548-0.736), confirming good concurrent validity. The results of the Exploratory Factor Analysis showed four factors comparable to the original SCAARED (Generalized anxiety, Somatic/Panic/Agoraphobia, Social anxiety, and Separation anxiety). The area under the curve of the receiver operating characteristic of total and each of the factor scores ranged from 0.724 to 0.942. CONCLUSIONS: The Korean version of the SCAARED is a reliable and valid instrument to screen for anxiety disorders in the Korean adult populations.

Ultrasound-triggered three dimensional hyaluronic acid hydrogel promotes in vitro and in vivo reprogramming into induced pluripotent stem cells.

Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells (iPSCs). Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming. Here, we present a new reprogramming strategy using low-intensity ultrasound (LIUS) to improve cellular reprogramming of iPSCs in vitro and in vivo. Under 3D microenvironment conditions, increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs. The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification. LIUS stimulation transiently modulates the cytoskeletal rearrangement, along with increased membrane fluidity and mobility to increase HA/CD44 interactions. Furthermore, LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment, for enhanced reprogrammed cells into iPSCs. Thus, LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments, which can be applied in various biomedical fields.

Characterization of Yeast Protein Hydrolysate for Potential Application as a Feed Additive.

Yeast protein can be a nutritionally suitable auxiliary protein source in livestock food. The breakdown of proteins and thereby generating high-quality peptide, typically provides nutritional benefits. Enzyme hydrolysis has been effectively uesed to generate peptides; however, studies on the potential applications of different types of enzymes to produce yeast protein hydrolysates remain limited. This study investigated the effects of endo- (alcalase and neutrase) and exotype (flavourzyme and prozyme 2000P) enzyme treatments on yeast protein. Endotype enzymes facilitate a higher hydrolysis efficiency in yeast proteins than exotype enzymes. The highest degree of hydrolysis was observed for the protein treated with neutrase, which was followed by alcalase, prozyme 2000P, and flavourzyme. Furthermore, endotype enzyme treated proteins exhibited higher solubility than their exotype counterparts. Notably, the more uniform particle size distribution was observed in endotype treated yeast protein. Moreover, compared with the original yeast protein, the enzymatic protein hydrolysates possessed a higher content of ß-sheets structures, indicating their higher structural stability. Regardless of enzyme type, enzyme treated protein possessed a higher total free amino acid content including essential amino acids. Therefore, this study provides significant insights into the production of protein hydrolysates as an alternative protein material.