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: 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: To report a case of secondary Descemet membrane endothelial keratoplasty (DMEK) for graft failure after primary DMEK.Case summary: A 47-year-old female underwent primary DMEK in her left eye with a diagnosis of Fuchs’ endothelial dystrophy. At 6 weeks later, corneal stromal edema with epithelial and subepithelial bullae was first observed. From that point on, the condition of the cornea and the visual acuity continued to degrade. After 7 months, a second DMEK procedure (i.e., a repeat DMEK) for graft failure was performed successfully without any complications. Since the second procedure, the cornea has been clear, and the best-corrected visual acuity has remained at 0.6 for 8 months. Conclusions To manage graft failure after primary DMEK, we performed a second DMEK procedure. The removal of the previous graft was easy, and there were no complications. Thus, repeat DMEK may be a feasible procedure.

Purpose: Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer. Materials and Methods: Tissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration. Results: EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4, p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells. Conclusion Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.

Purpose: To report a case of secondary Descemet membrane endothelial keratoplasty (DMEK) for graft failure after primary DMEK.Case summary: A 47-year-old female underwent primary DMEK in her left eye with a diagnosis of Fuchs’ endothelial dystrophy. At 6 weeks later, corneal stromal edema with epithelial and subepithelial bullae was first observed. From that point on, the condition of the cornea and the visual acuity continued to degrade. After 7 months, a second DMEK procedure (i.e., a repeat DMEK) for graft failure was performed successfully without any complications. Since the second procedure, the cornea has been clear, and the best-corrected visual acuity has remained at 0.6 for 8 months. Conclusions To manage graft failure after primary DMEK, we performed a second DMEK procedure. The removal of the previous graft was easy, and there were no complications. Thus, repeat DMEK may be a feasible procedure.

Purpose: Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer. Materials and Methods: Tissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration. Results: EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4, p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells. Conclusion Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.

Objective: External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. Methods: In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study. Results: The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p<0.001). Brachytherapy utilization rates varied by region, ranging from 72% to 100% except for in Jeju Island, where the rate was 56%. The brachytherapy utilization rate was lower in patients older than 80 years; patients with localized disease, non-squamous cell carcinoma, or Charlson comorbidity index 3 or more; patients diagnosed after 2010; patients from certain regions; patients receiving medical aid; and patients who underwent gynecologic procedures. Multivariable Cox regression analysis showed that brachytherapy when added to curative EBRT was independently associated with better cancer-specific survival (CSS) and overall survival (OS) than curative EBRT only. Conclusion The brachytherapy utilization rate decreased from 2005 to 2013 and varied by region in Korea. Brachytherapy use is independently associated with significantly higher CSS and OS in cervical cancer.

Background: Regeneration of soft tissue defects is essential for adipose tissue pathologies and disease, trauma, or injury-induced damage. Here, we show that umbilical cord blood-derived mesenchymal stem cells could potentially be tailored and used for the reconstruction of specific damaged sites. Adipogenesis can be exploited in soft tissue reconstruction. Also, primary cilia play a role in the control of adipogenesis. Methods: The adipogenic differentiation capacity of mesenchymal stem cells (MSCs) was shown to influence ciliogenesis. MSCs transfected with intraflagellar transport 88 (IFT88) small interfering RNA (siRNA), which blocks the assembly and maintenance of cilia, were examined to confirm the relationship between adipogenesis and ciliogenesis. Also, 1,2-Bis(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), calcium chelator, inhibited the ciliogenesis of MSCs in adipogenic differentiation. Results: IFT88-knockdown led to decreased cilia formation and limitation of cilia elongation in adipogenesis. Additionally, intracellular calcium triggered cilia formation in MSCs adipogenesis. Interestingly, intracellular calcium cannot overcome the inhibition of adipogenesis caused by low numbers of cilia in MSCs. Conclusion Our data suggested that ciliogenesis was negatively regulated by Wnt5a/β-catenin signaling during adipogenesis. Thus, we suggest that calcium induction triggers adipogenesis and ciliogenesis.

PURPOSE: Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers.METHODS: Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method.RESULTS: The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PETand a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen's kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively.CONCLUSION: We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers.
Alzheimer Disease ; Amyloid ; Cognition Disorders ; Humans ; Learning ; Magnetic Resonance Imaging ; Methods ; Neuroimaging ; Positron-Emission Tomography

PURPOSE: This study aimed to compare lung perfusion scan with single photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of lung function and to elucidate the most appropriate modality for the prediction of postoperative lung function in patients with lung cancer.METHODS: A total of 181 patients underwent Tc-99m macroaggregated albumin lung perfusion scan and SPECT/CT to examine the ratio of diseased lung and diseased lobe. Forty-one patients with lung cancer underwent both preoperative and postoperative pulmonary function tests within 1 month to predict postoperative pulmonary function. Predicted postoperative forced expiratory volume in 1 s (ppoFEV₁) was calculated by the % radioactivity of lung perfusion scan and SPECT, and the % volume of the residual lung, assessed on CT.RESULTS: The ratios of diseased lung as seen on lung perfusion scan and SPECT showed significant correlation, but neither modality correlated with CT. The ratios of the diseased lung and diseased lobe based on CT were higher than the ratios based on either perfusion scan or SPECT, because CT overestimated the function of the diseased area. The lobar ratio of both upper lobes was lower based on the perfusion scan than on SPECT but was higher for both lower lobes. Actual postoperative FEV₁ showed significant correlation with ppoFEV₁ based on lung perfusion SPECT and perfusion scan.CONCLUSIONS: We suggest SPECT/CT as the primary modality of choice for the assessment of the ratio of diseased lung area. Both perfusion scan and SPECT/CT can be used for the prediction of postoperative lung function.
Forced Expiratory Volume ; Humans ; Lung Neoplasms ; Lung Volume Measurements ; Lung ; Perfusion ; Radioactivity ; Respiratory Function Tests ; Tomography, Emission-Computed, Single-Photon