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.

The process of cancer metastasis is dependent on the cancer cells’ capacity to detach from the primary tumor, endure in a suspended state, and establish colonies in other locations.Anchorage dependence, which refers to the cells’ reliance on attachment to the extracellular matrix (ECM), is a critical determinant of cellular shape, dynamics, behavior, and, ultimately, cell fate in nonmalignant and cancer cells. Anchorage-independent growth is a characteristic feature of cells resistant to anoikis, a programmed cell death process triggered by detachment from the ECM. This ability to grow and survive without attachment to a substrate is a crucial stage in the progression of metastasis. The recently discovered phenomenon named “adherent-to-suspension transition (AST)” alters the requirement for anchoring and enhances survival in a suspended state. AST is controlled by four transcription factors (IKAROS family zinc finger 1, nuclear factor erythroid 2, BTG anti-proliferation factor 2, and interferon regulatory factor 8) and can detach cells without undergoing the typical epithelialmesenchymal transition. Notably, AST factors are highly expressed in circulating tumor cells compared to their attached counterparts, indicating their crucial role in the spread of cancer.Crucially, the suppression of AST substantially reduces metastasis while sparing primary tumors. These findings open up possibilities for developing targeted therapies that inhibit metastasis and emphasize the importance of AST, leading to a fundamental change in our comprehension of how cancer spreads.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

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.

Purpose: Neutralizing antibodies (NAbs) have been considered effective in preventing and treating viral infections. However, until now, the duration and clinical implications of antibody-mediated nature immunity in Koreans have remained unknown.Therefore, we examined NAbs levels and clinical characteristics in recovered coronavirus disease 2019 (COVID-19) patients. Materials and Methods: Blood samples were collected from 143 adult patients who had been diagnosed with and had recovered from COVID-19 from February to March in 2020 at a tertiary-care university-affiliated hospital in Daegu, Korea. A plaque reduction neutralization test was conducted to analyze NAb titers. Individualized questionnaires were used to identify patient clinical information. Results: The median number of days from symptom onset to the blood collection date was 109.0 (104.0; 115.0). The NAb titers ranged from 10 to 2560. The median NAb titer value was 40. Of the 143 patients, 68 (47.6%) patients had NAb titers ≥80, and 31 (21.7%) patients had NAb titers ≥160. The higher the age or disease severity, the higher the NAb titer. In univariate logistic regression, statistically significant predictors of high NAb titers (≥80) were age, myalgia, nausea or vomiting, dyspnea, and disease severity (p<0.05). Multivariable logistic regression showed that age ≥50 years (p=0.013) and moderate or higher disease severity (p<0.001) were factors associated with high NAb titers (≥80). None of the patients had reinfection of COVID-19. Conclusion All recovered patients were found to have NAbs regardless of the NAb titers maintained by natural immunity. Age and disease severity during COVID-19 infection were associated with high NAb titers.

Purpose: Neutralizing antibodies (NAbs) have been considered effective in preventing and treating viral infections. However, until now, the duration and clinical implications of antibody-mediated nature immunity in Koreans have remained unknown.Therefore, we examined NAbs levels and clinical characteristics in recovered coronavirus disease 2019 (COVID-19) patients. Materials and Methods: Blood samples were collected from 143 adult patients who had been diagnosed with and had recovered from COVID-19 from February to March in 2020 at a tertiary-care university-affiliated hospital in Daegu, Korea. A plaque reduction neutralization test was conducted to analyze NAb titers. Individualized questionnaires were used to identify patient clinical information. Results: The median number of days from symptom onset to the blood collection date was 109.0 (104.0; 115.0). The NAb titers ranged from 10 to 2560. The median NAb titer value was 40. Of the 143 patients, 68 (47.6%) patients had NAb titers ≥80, and 31 (21.7%) patients had NAb titers ≥160. The higher the age or disease severity, the higher the NAb titer. In univariate logistic regression, statistically significant predictors of high NAb titers (≥80) were age, myalgia, nausea or vomiting, dyspnea, and disease severity (p<0.05). Multivariable logistic regression showed that age ≥50 years (p=0.013) and moderate or higher disease severity (p<0.001) were factors associated with high NAb titers (≥80). None of the patients had reinfection of COVID-19. Conclusion All recovered patients were found to have NAbs regardless of the NAb titers maintained by natural immunity. Age and disease severity during COVID-19 infection were associated with high NAb titers.

OBJECTIVE: To investigate the effects of combination functional electrical stimulation (FES) and standing frame training on standing balance in stroke patients. METHODS: Patients who had hemiparesis and postural instability after stroke were randomly assigned to one of the two groups; study group underwent FES on the quadriceps and tibialis anterior muscle simultaneously with standing balance training. The control group received standing frame training and FES separately. Both the groups received their respective therapies for 3 weeks. Stability index in Biodex Balance master system, Berg Balance Scale (BBS), manual muscle test, the Korean version of Modified Barthel Index, and Korean version of Mini-Mental State Examination were used to evaluate the effects of the treatment. RESULTS: In total, 30 patients were recruited to the study group and 30 to the control group. Three weeks after treatment, both the groups showed improvement in postural stability scores and physical and cognitive functions. When changes in postural stability were compared between the groups, the study group showed more significant improvement than the control group with regards to the scores of BBS and the stability indices. CONCLUSION: In this study, we found the therapeutic effectiveness of combined therapy of FES and standing frame in subacute stroke patients. The presented protocol is proposed as time-saving and can be applied easily in the clinical setting. Thus, the proposed combined therapy could be a useful method for improving standing balance in subacute stroke patients.
Cognition ; Electric Stimulation ; Humans ; Methods ; Paresis ; Rehabilitation ; Stroke

OBJECTIVE: To investigate the effect of decreased Skeletal Muscle Index (SMI) and hand grip strength on functional recovery in subacute ambulatory stroke patients. METHODS: Subacute stroke patients who were referred to the rehabilitation center were recruited. Decreased SMI and hand grip strength were diagnosed according to the Asian Working Group on Sarcopenia. Diagnostic criteria were decreased SMI and decreased unaffected hand grip strength. SMI was measured by bioelectrical impedance analysis. Unaffected hand grip strength was measured with a hand dynamometer. Patients were divided into two groups, decreased group (DG) and not-decreased group (NDG), according to the presence of decreased SMI and hand grip strength. Both groups received conventional stroke rehabilitation for 3 weeks. All patients were evaluated at the baseline and at 3 weeks after treatment. Functional status was evaluated with 4-meter walk test (4MWT), 6-minute walk test (6MWT), Timed Up and Go test (TUG), and Modified Barthel Index (MBI). RESULTS: Both groups showed improvement in 4MWT, TUG, and MBI. NDG showed improvement in 6MWT. Comparing improvements between the two groups, NDG showed more improvement in 6MWT and TUG than DG. CONCLUSION: The presence of decreased SMI and hand grip strength had negative effects on functional recovery in subacute ambulatory stroke patients.
Asian Continental Ancestry Group ; Electric Impedance ; Hand Strength ; Hand ; Humans ; Muscle, Skeletal ; Rehabilitation ; Rehabilitation Centers ; Sarcopenia ; Stroke

Hypoxia-inducible factor 1 (HIF1) is a master transcription factor that induces the transcription of genes involved in the metabolism and behavior of stem cells. HIF1-mediated adaptation to hypoxia is required to maintain the pluripotency and survival of stem cells under hypoxic conditions. HIF1 activity is well known to be tightly controlled by the alpha subunit of HIF1 (HIF1α). Understanding the regulatory mechanisms that control HIF1 activity in stem cells will provide novel insights into stem cell biology under hypoxia. Recent research has unraveled the mechanistic details of HIF1α regulating processes, suggesting new strategies for regulating stem cells. This review summarizes recent experimental studies on the role of several regulatory factors (including calcium, 2-oxoglutarate-dependent dioxygenase, microtubule network, importin, and coactivators) in regulating HIF1α activity in stem cells.
Anoxia ; Biology ; Calcium ; Hypoxia-Inducible Factor 1 ; Karyopherins ; Metabolism ; Microtubules ; Stem Cells ; Transcription Factors

PURPOSE: Bone single-photon emission computed tomography/computed tomography (SPECT/CT) has been widely used for evaluation of femoral head viability in patients with femoral neck fracture. The current study aimed to investigate utility of standardized uptake value (SUV) from quantitative bone SPECT/CT for assessment of femoral head viability.METHODS: From March 2015 to November 2018, quantitative bone SPECT/CT was performed in 9 patients with non-viable femoral head post femoral neck fracture and in 31 controls. Maximum (SUV(max)), mean (SUVmean), and minimum standardized uptake values (SUVmin) were measured over femoral head and neck. Mann-Whitney U test with Bonferroni correction was used to compare SUVs of ipsilateral and contralateral femurs from femoral neck fracture patients with those of control femurs.RESULTS: As for femoral head viability, SUV(max) and SUVmean were not significantly decreased in non-viable femoral heads compared to those in controls. Only the SUVmin was significantly reduced in non-viable femoral heads (mean ± standard deviation, 0.57 ± 0.38) than in controls (0.95 ± 0.26, p = 0.006) and contralateral femoral heads (1.36 ± 0.59, p = 0.008). The cutoff SUVmin of 0.61 (g/mL) yielded a sensitivity of 77.8% and specificity of 87.1% for detection of non-viable femoral heads (p = 0.006). Contralateral femoral necks of the femoral neck fracture patients showed significantly higher SUVmean and SUVmin (3.17 ± 1.20 and 1.64 ± 0.63) than those of controls (2.32 ± 0.53 and 1.04 ± 0.27; p = 0.021 and p = 0.002, respectively), which seemed to reflect weight bearing effect or metabolic derangement.CONCLUSIONS: The non-viable femoral heads from the femoral neck fracture showed significantly reduced SUVmin. Quantitative bone SPECT/CT holds promise for objective evaluation of femoral head viability.
Femoral Neck Fractures ; Femur ; Femur Neck ; Head ; Humans ; Neck ; Sensitivity and Specificity ; Weight-Bearing