Objective: To investigate the feasibility and effects of a mobile app-based home cycling exercise program compared to home cycling exercise without additional monitoring system. Compared with fitness facilities or outdoor exercise, home-based exercise programs effectively improve physical performance in an indwelling community. However, a flexible, informal environment may decrease motivation and impair adherence to physical exercise. Mobile devices for aerobic exercise and mobile applications provide real-time monitoring, immediate feedback, and encouragement to increase motivation and promote physical performance. We investigated the feasibility and effects of a mobile app-based home exercise program on body composition, muscular strength, and cardiopulmonary function. Methods: Between February and May 2023, 20 participants were randomly allocated to the intervention (mobile application with a tablet) and control groups, and they performed aerobic exercise using a stationary bicycle for ≥150 minutes per week for 6 weeks (≤30-minute exercise session, with 3-minute warm-up and 3-minute cool-down). Karvonen formula-based heartrate defined the weekly increase in exercise intensity. Outcome measures included body-composition parameters, isokinetic knee flexor and extensor strength tests, cardiopulmonary exercise test results, and rate of target heart rate (HR) achievement. Participants were assessed at baseline and after the intervention. Results: Unrelated personal events led two participants to drop out. The intervention and control groups had similar baseline characteristics. Compared with the control group, in the post-intervention isokinetic strength test, bilateral knee flexor and extensor power, and time to target HR achievement significantly increased each week in the intervention group. Conclusion Home-based exercise to achieve long-term cardiovascular fitness with portable electronic/mobile devices facilitates individualized exercise using real-time feedback to improve motivation and adherence.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Objectives: . Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. Methods: . This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. Results: . Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). Conclusion . We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Regdanvimab is the only monoclonal antibody available in Korea that targets severe acute respiratory syndrome coronavirus 2. We retrospectively evaluated the clinical characteristics of 374 adults hospitalized with coronavirus disease 2019 (COVID-19) who were treated with regdanvimab from September through December 2021. In total, 322 (86.1%) patients exhibited risk factors for disease progression. Most patients (91.4%) improved without additional treatment. No patient died or was transferred to intensive care. This study shows that regdanvimab prevented disease progression in high-risk patients with mild to moderate COVID-19 infections during Delta variant predominance.

Purpose: Although protein-induced vitamin K absence or antagonist II (PIVKA-II) has been used as a diagnostic tool for hepatocellular carcinoma (HCC), its prognostic value remains unclear. Methods: This was a nationwide multicenter study using the database of the Korean Liver Cancer Association. Patients with hepatitis B-related HCC who underwent liver resection as the first treatment after initial diagnosis (2008–2014) were selected randomly. Propensity score matching (1:1) was performed for comparative analysis between those with low and high preoperative PIVKA-II. Univariable and multivariable Cox proportional-hazards regression were used to identify prognostic factors for HCC-specific survival. Results: Among 6,770 patients, 956 patients were included in this study. After propensity score matching, the 2 groups (n = 245, each) were well balanced. The HCC-specific 5-year survival rate was 80.9% in the low PIVKA-II group and 78.7% in the high PIVKA-II group (P = 0.605). In univariable analysis, high PIVKA-II (>106.0 mAU/mL) was not a significant predictor for worse HCC-specific survival (hazard ratio [HR], 1.183; 95% confidence interval [CI], 0.76–1.85; P = 0.461). In multivariable analysis, hyponatremia of <135 mEq/L (HR, 4.855; 95% CI, 1.67–14.12; P = 0.004), preoperative ascites (HR, 4.072; 95% CI, 1.59–10.43; P = 0.003), microvascular invasion (HR, 3.112; 95% CI, 1.69–5.74; P < 0.001), and largest tumor size of ≥5.0 cm (HR, 2.665; 95% CI, 1.65–4.31; P < 0.001), but not preoperative high PIVKA-II, were independent predictors for worse HCCspecific survival. Conclusion Preoperative PIVKA-II is not an independent prognostic factor for HCC-specific survival after liver resection for hepatitis B-related HCC.

Background: The aryl hydrocarbon receptor (AHR) and autophagy are both important to maintain skin homeostasis.However, they are also involved in skin disorders. So far, their roles in psoriasis pathogenesis are unknown. Objective: We studied the immunohistochemical and gene expression of AHR, CYP1A1, and microtubule-associated protein light chain 3 (LC3) in lesional skin of psoriasis patients to determine correlations among them. Methods: We included 24psoriasis patients and ten healthy volunteers. Skin biopsies were collected. AHR, CYP1A1, and LC3 protein expression was examined by immunohistochemistry, immunofluorescence, and western blotting. AHR, CYP1A1, LC3, ATG5, BECN1 and Nrf2 mRNA levels were measured by quantitative polymerase chain reaction. Results: AHR and CYP1A1 protein expression were higher in psoriasis lesional skin than in normal skin. LC3 protein expression was lower in psoriasis lesions than in normal controls. AHR and CYP1A1 protein expression in psoriasis lesions showed significant positive correlations with mean epidermal thickness and inflammatory cell density. Significant negative correlations were noted between LC3 protein expression in psoriasis lesions and the mean epidermal thickness or inflammatory cell density. A significant negative correlation was found between AHR and LC3 expression in psoriatic skin. AHR, CYP1A1 and Nrf2 mRNA expression were upregulated while LC3, ATG5, and BECN1 mRNA were down-regulated, in psoriatic lesional skin compared with normal controls. Conclusion AHR and autophagy could play a role in psoriasis pathogenesis by modifying epidermal hyperproliferation and inflammation. AHR and autophagy regulation are potential therapeutic targets in chronic inflammatory skin diseases.

Purpose: This study is a pseudo-experimental study of design before and after the non-equivalent control group, which was attempted to verify that the application of the ukulele to the elderly has the effects of reducing depression, improving self-efficacy, strengthening social bonding, and improving cognitive function. Methods: 46 (23 in the experimental group and 23 in the control group) participants were selected. The experimental group was provided with three sessions of a music program using eight Ukuleles for the elderly, while the control group was provided with three sessions for the elderly. IBM SPSS 25.0 was used for data analysis, and the independent t-test, x2 -test, and Fisher's exact probability test were performed to verify the homogeneity of the subject's general characteristics.The effect verification after the experimental treatment was analyzed by Fisher's exact probability test, Friedman test, and Mann-Whitney U test. Results: Depression showed a statistically significant difference between the two groups (F=39.88, p<.001), self-efficacy showed a statistically significant difference between the two groups (z=-4.96, p<.001), social bonding showed a statistically significant difference between the two groups (z=-5.19, p<.001), and cognitive function showed a statistically significant difference between the two groups (z=-3.98, p<.001). Conclusion It was found that the ‘Music Program using the Ukulele’ was effective in reducing depression of the elderly, improving self-efficacy, reinforcing social bonding, and improving cognitive function. We hope that the Music Program using the Ukulele can be used in the elderly nursing curriculum in the future, and we suggest it should be applied as a nursing intervention to those who are experiencing cognitive decline.

Objective: In 2001, the Korean College of Neuropsychopharmacology and the Korean Society for Schizophrenia Research developed the Korean Medication Algorithm Project for Schizophrenia (KMAP-SPR 2001, revised 2006) through a consensus of expert opinion. The present study was carried out to support the second revision of the KMAP-SPR. Methods: Based on clinical guidelines and studies on the treatment of psychotic symptoms in schizophrenia, the Executive committee completed a draft of KMAP-SPR 2019. To obtain an expert consensus, a Review committee of 100 Korean psychiatrists was formed and 69 responded to a 30-item questionnaire. Based on their responses, the KMAP-SPR 2019 was finalized. Results: The revised schizophrenia algorithm now consists of 5 stages. At Stage 1, monotherapy with atypical antipsychotics was recommended by expert reviewers as the first-line strategy. At Stage 2, most reviewers recommended the use of typical or atypical antipsychotic drugs not used at Stage 1. At Stage 3, many reviewers agreed with the administration of clozapine. At Stage 4, a combination of clozapine and other agents such as antipsychotics, mood stabilizers, antidepressants, or electroconvulsive therapy was recommended. At Stage 5, most reviewers recommended combined treatment with an antipsychotic other than clozapine; and a mood stabilizer, antidepressant, or electroconvulsive therapy. At any stage, prescribing long-acting injectable antipsychotics at the discretion of the clinician was recommended. Conclusion Compared with previous versions, the KMAP-SPR 2019 now recommends using clozapine earlier in treatment-refractory schizophrenia. In addition, the use of long-acting injectable antipsychotics is now considered to be available at any stage.