Purpose: Adjuvant chemotherapy (AC) is recommended for muscle-invasive or lymph node-positive upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). However, disease recurrences are frequently observed in pT1 disease, and AC may increase the risk of overtreatment in pT2 UTUC patients. This study aimed to validate a risk-adapted scoring model for selecting UTUC patients with ≤pT2 disease who would benefit from AC. Materials and Methods: We retrospectively analyzed 443 ≤pT2 UTUC patients who underwent RNU. A risk-adapted scoring model was applied, categorizing patients into low- or high-risk groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were analyzed according to risk group. Results: Overall, 355 patients (80.1%) and 88 patients (19.9%) were categorized into the low- and high-risk groups, respectively, with the latter having higher pathological stages, concurrent carcinoma in situ, and synchronous bladder tumors. Disease recurrence occurred in 45 patients (10.2%), among whom 19 (5.4%) and 26 (29.5%) belonged to the low- and high-risk groups, respectively (p<0.001). High-risk patients had significantly shorter RFS (64.3% vs. 93.6% at 60 months; hazard ratio [HR] 13.66; p<0.001) and worse CSS (80.7% vs. 91.5% at 60 months; HR 4.25; p=0.002). Multivariate analysis confirmed that pT2 stage and the high-risk group were independent predictors of recurrence and cancer-specific death (p<0.001). Decision curve analysis for RFS showed larger net benefits with our model than with the T stage model. Conclusions The risk-adapted scoring model effectively predicts recurrence and identifies optimal candidates for AC post RNU in non-metastatic UTUC.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

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.

Objective: This study aimed to evaluate the potential of PDRN and explore its combined effect with adipose tissue-derived MSCs (AdMSCs) in treating canine OA. Methods: To study the impact of PDRN, canine chondrocytes, synoviocytes, and AdMSCs were exposed to various PDRN concentrations, and viability was assessed using cell counting kit-8. The OA model was created by treating chondrocytes and synoviocytes with lipopolysaccharide, followed by treatment under three different conditions: PDRN alone, AdMSCs alone, and a combination of PDRN and AdMSCs. Using real-time quantitative polymerase chain reaction, the anti-inflammatory effects and mechanisms were investigated by quantitatively assessing pro-inflammatory cytokines, collagen degradation markers, adenosine A2a receptor (ADORA2A), and nuclear factor-kappa B. Results: PDRN alone and combined with AdMSCs significantly reduced the expression of pro-inflammatory cytokines and collagen degradation markers in an OA model. PDRN promoted AdMSC proliferation and upregulated ADORA2A expression. AdMSCs exhibited comprehensive anti-inflammatory effects through paracrine effects, and both substances reduced inflammatory gene expression through different mechanisms, potentially enhancing therapeutic effects. Conclusions and Relevance: The results indicate that PDRN is a safe and effective antiinflammatory material that can be used independently or as an adjuvant for AdMSCs.Although additional research is necessary, this study is significant because it provides a foundation for future research at the cellular level.

Background: Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC. Methods: We analyzed the medical records of patients diagnosed with stage I or II NSCLC who underwent curative resection at a tertiary university hospital between January 2010 and December 2017. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS) according to anesthesia type. Results: We included 1,508 patients with stage I/II NSCLC. The patients were divided into the TIVA (n = 980) and Inhalation (n = 528) groups. The two groups were well-balanced in terms of baseline clinical characteristics. The TIVA group demonstrated significantly improved RFS (7.7 years, 95% CI [7.37, 8.02]) compared with the Inhalation group (6.8 years, 95% CI [6.30, 7.22], P = 0.003). Similarly, TIVA was superior to inhalation agents with respect to OS (median OS; 8.4 years, 95% CI [8.08, 8.69] vs. 7.3 years, 95% CI [6.81, 7.71]; P < 0.001). Multivariable Cox regression analysis revealed that TIVA was an independent prognostic factor related to recurrence (hazard ratio [HR]: 1.24, 95% CI [1.04, 1.47], P = 0.014) and OS (HR: 1.39, 95% CI [1.12, 1.72], P = 0.002). Conclusions Propofol-based TIVA was associated with better RFS and OS than inhalation anesthesia in patients with stage I/II NSCLC who underwent curative resection.

Purpose: The purpose of this study was to investigate the effectiveness of the elastic compression stockings and Kinesio taping on muscle activity and mechanical properties in healthy women during the heel raise exercise that causes muscle fatigue. Methods: Participants were divided into the elastic compression stockings group (ESG, n= 8), Kinesio taping group (KTG, n= 8), and control group (CG, n= 8). All participants performed the heel raise exercise to cause muscle fatigue. Muscle activity, stiffness, and the muscle tone of the gastrocnemius and tibialis anterior were measured before and after the heel raise exercise. Results: In the gastrocnemius, muscle activity was significantly increased after the heel raise exercise in both the ESG and KTG (p< 0.05).There was a significant difference in the change in the gastrocnemius muscle activity between the groups (p< 0.05). Post hoc analysis showed that the ESG exhibited a significantly greater change in gastrocnemius muscle activity than the CG (p< 0.05). The muscle stiffness of the gastrocnemius was significantly decreased after the heel raise exercise in the ESG (p< 0.05). The muscle tone of the gastrocnemius was significantly increased after the heel raise exercise in the control group (p< 0.05). There were no significant differences in the change in the gastrocnemius stiffness and muscle tone between the groups (p> 0.05). In the tibialis anterior, there were no significant differences in muscle activity, stiffness, and muscle tone between and within the groups (p> 0.05). Conclusion Our findings suggest that the use of elastic compression stockings and Kinesio taping during the heel raise exercise are beneficial and delay muscle fatigue in the gastrocnemius.

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.