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Exosome-mediated delivery of super-repressor IκBα alleviates infammation and joint damages in rheumatoid arthritis
No full textBackground
This study aims to investigate the potential anti-infammatory efects of exosomes engineered to carry super-repressor IκB (Exo-srIκB), an exosome-based NF-κB inhibitor, in the context of RA.
Methods
Peripheral blood mononuclear cells (PBMCs) and synovial fuid mononuclear cells (SFMCs) were collected from patients diagnosed with RA and treated with Exo-srIκB to test the therapeutic potential. Flow cytometry analysis was performed to assess the production of infammatory cytokines (IL-17A and GM-CSF) by the cells. ELISA was utilized to measure the levels of TNF-α, IL-17A, IL-6, and GM-CSF. Arthritis was induced in SKG mice by intraperitoneal injection of curdlan. DBA/1 J mice were used in collagen-induced arthritis (CIA) experiments. After the development of arthritis, mice were injected with either Exo-Naïve (control exosome) or Exo-srIκB. Arthritis scores were recorded biweekly, and histological observations of the ankle joint were conducted using H&E and safranin-O staining. Additionally, bone erosion was evaluated using micro-CT imaging.
Results
In the ex vivo study involving human PBMCs and SFMCs, treatment with Exo-srIκB demonstrated a notable reduction in infammatory cytokines. Furthermore, in both the SKG and CIA models, Exo-srIκB treatment exhibited signifcant reductions in infammation, cartilage destruction, and bone erosion within the joint tissues when compared to the Exo-Naive control group. Additionally, the radiographic score assessed through microCT showed a signifcant decrease compared to the Exo-Naive control group.
Conclusion
Overall, these fndings suggest that Exo-srIκB possesses anti-infammatory properties in human RA cells and animal models, making it a promising therapeutic candidate for the treatment of RA
CT Colonography Reporting and Data System (C-RADS): Version 2023 Update
No full textThe CT Colonography Reporting and Data System (C-RADS) has withstood the test of time and proven to be a robust classification scheme for CT colonography (CTC) findings. C-RADS version 2023 represents an update on the scheme used for colorectal and extracolonic findings at CTC. The update provides useful insights gained since the implementation of the original system in 2005. Increased experience has demonstrated confusion on how to classify the mass-like appearance of the colon consisting of soft tissue attenuation that occurs in segments with acute or chronic diverticulitis. Therefore, the update introduces a new subcategory, C2b, specifically for mass-like diverticular strictures, which are likely benign. Additionally, the update simplifies extracolonic classification by combining E1 and E2 categories into an updated extracolonic category of E1/E2 since, irrespective of whether a finding is considered a normal variant (category E1) or an otherwise clinically unimportant finding (category E2), no additional follow-up is required. This simplifies and streamlines the classification into one category, which results in the same management recommendation
오류 정정 코드 변환기를 위한 향상된 신드롬 기반 신뢰성 디코딩
No full textIn this work, dynamically adaptive refinement masking (DARM) and mirror- sharing variational U-shaped architecture are proposed in order to improve the performance of error correction code transformer (ECCT). Instead of fixed binary masking, DARM module is designed to create unique masking for each attention head that reinforces the self-attention mechanism by further enhanc-ement of the contrast in the attention map with dynamic magnitudes taking the distribution of the attention weight as reference. Furthermore, under the use of sequential neural architecture, DARM modules are designed to be sequentially connected, creating an iterative refinement effect. For moderate coding lengths, the mirror-sharing variational U-shaped architecture is introduced to enhance the overall efficiency of the transformer-based decoder. The U-shaped architecture with variational-autoencoder-like skip-connection provides a segmentation like behavior that operates well with moderate length codes, especially at low coding rates. As the U-shaped model requires a certain level of depth to achieve desirable performance, an architectural-level parameter-sharing scheme called mirror-sharing is introduced to effectively scale the U-shaped model to achieve better efficiency and performance. Experimental results show considerable improvements in bit error rates compared to the baseline ECCT, while also significantly increasing the training convergence speed.Maste
Hydrothermally Grown Halogen-Doped ZnO Nanorods for Photoelectrochemical Water Oxidation: Experimental and DFT Insights
No full textThis study demonstrates the photoelectrochemical (PEC) aspects of hydrothermally grown halogen-doped ZnO nanorods, analyzing their structural, morphological, optical, and electrical properties under visible light illumination. We find that halogen doping in the ZnO matrix significantly enhances the PEC water splitting performance. Among the four halogen atoms (Cl, Br, F, and I), Cl yields the highest photocurrent density of 0.75 mA/cm2 at 1.5 V vs Ag/AgCl, nearly 5 times that of pristine ZnO nanorods (0.16 mA/cm2). This improvement in PEC activity is attributed to the increased light absorption, higher charge carrier density, and efficient separation of the photoexcited electron-hole pairs. Cl doping in ZnO increases the free electron concentration and tends to substitute oxygen vacancies, thereby reducing the recombination of photogenerated electron-hole pairs. In addition, the density functional theory calculations provide theoretical insights into the effect of halogen doping on the photocatalytic activity of ZnO. These findings pave the way for the design of efficient and cost-effective photoanode materials for PEC applications
Prediction Model for Contributing Factors to Fall Risk among Elderly in Korea Using Decision Tree Analysis
No full text본 연구는 코로나 전후 시기인 2017년(10235명)과 2020년(10097명)에 실시된 노인실태조사 결과를 바탕으로 낙상에 영향을미치는 요인을 검토하고 의사결정나무분석을 통해 낙상위험요인들 간의 구조적 관계를 분석하였다. 교차분석을 통해 낙상 유무에 따른그룹의 특성을 검토하였고, 낙상 유무 결정요인을 분석하기 위해 의사결정나무 분석을 실시하였다. 낙상 발생은 2017년에 15.9%, 2020년에 6.4%로 나타났다. 코로나로 인한 낙상 경험의 감소는 제한적인 외부 활동과 외출 제한으로 넘어짐에 직면하는 상황이 상대적으로적게 발생한 것이 그 원인으로 파악된다. 2020년과 2017년의 의사결정나무분석 결과를 정리하면, 입원 경험이 있거나 건강만족도가낮고 독립적인 일상생활동작이 어려울 경우 낙상 위험이 높아지며, 신체활동량 감소로 이어질 수 있는 우울감(배우자요인포함)도 낙상위험을 높일 수 있는 잠재요인으로 작용할 수 있음을 확인할 수 있었다. 이러한 주요 요인을 제대로 인지하고 낙상고위험군을 조기에발견하고 집중적으로 낙상을 예방할 수 있는 중재가 가해진다면 보다 효과적으로 낙상을 예방할 수 있을 것이다.
This study reviewed the factors affecting falls based on the results of National survey of Older Koreans in 2017(n=10,235) and2020(n=10,097) before and after COVID-19, and analyzed the structural relationships of risk factors for falls through decision tree analysis. The incidence of falls was 15.9% in 2017 and 6.4% in 2020. The decrease in reported incidents of falls during the COVID-19 pandemicis attributed to the reduced outdoor activities and restrictions on mobility, which naturally result in fewer opportunities for falls to occur. In summarizing the decision tree analysis findings from 2020 and 2017, it is evident that hospitalization, low health satisfaction, and challengesin performing independent activities of daily living are factors associated with an increased risk of falling. Additionally, depression, includingspousal factors, which may contribute to decreased physical activity, is also linked to falls. Recognizing these significant factors allowsfor the early identification of high-risk groups for falls and enables the implementation of interventions aimed at preventing falls more effectively
The Effect of Executive Safety Leadership on Workplace Hazard Levels: Focusing on the Mediating Effect of the Supervisor Role
No full textExecutive safety leadership is essential to prevent accidents in the workplace. However, will safety be secured by emphasizing only executive safety leadership to workers? In this study, the impact of executive safety leadership on the workplace hazard level was analyzed by adding the supervisor's safety role as a mediating variable.
This paper shows that executive safety leadership has no direct effect on workplace hazard levels. However, executive safety leadership was found to have a significant impact on the supervisor safety role, and the supervisor safety role was found to lower the hazard levels in the workplace. In summary, executive safety leadership was found to reduce the hazard levels in the workplace through the full mediating effect of the supervisor safety role.
Based on these research results, this study seeks to present the following recommendations to the government and management: The government should ensure that a workplace safety and health system is established by strengthening the effects of other mediating factors, such as strengthening the role of supervisors who are actually responsible for workplace safety and health. Executives must grant supervisors actual authority and responsibility to properly perform their safety roles and establish personnel and performance evaluation systems
Effect of pre-transplantation use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in kidney transplant recipients-propensity score-matched analysis
No full textBackground: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARBs) can cause acute kidney injury under dehydratation or in hemodynamically unstable conditions. Regarding kidney transplantation (KT), the risk of using ACEi/ARBs before surgery is not well established. Therefore, we evaluated the clinical outcomes to determine the effect of preoperative use of ACEi/ARBs on KT.
Methods: We retrospectively collected 1187 patients who received living-donor KT between January 2017 and December 2021. We conducted a propensity score-matched analysis between the ACEi/ARB(+) and ACEi/ARB(-) groups and evaluated the effects of ACEi/ARBs on delayed graft function, post-KT renal function, hyperkalemia events, rejection, and graft survival.
Results: The ACEi/ARB(+) group showed a similar incidence of delayed graft function as the ACEi/ARB(-) group (1.8% vs. 1.0%, P = 0.362). The risk of delayed graft function was not upregulated in the ACEi/ARB(+) group after propensity score-matching (odds ratio: 0.50, 95% confidence interval (CI) 0.13-2.00). Postoperative creatinine levels and the slope of creatinine levels after KT also were not significantly different between the two groups (creatinine slope from POD#0 to POD#7: - 0.73 ± 0.35 vs. - 0.75 ± 0.32 mg/dL/day, P = 0.464). Hyperkalemia did not occur more often in the ACEi/ARB(+) group than in the ACEi/ARB(-) group during perioperative days. Rejection-free survival (P = 0.920) and graft survival (P = 0.621) were not significantly different between the two groups.
Conclusions: In KT, the preoperative use of ACEi/ARBs did not significantly affect clinical outcomes including delayed graft function, postoperative renal function, hyperkalemia events, incidence of rejection, and graft survival rates compared to the patients who did not receive ACEi/ARBs
A randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679/ECHO-302)
No full textBackground: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC.
Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1.
Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2-14.3) and 10.3 months (2.7-13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2-44.1] and sunitinib/pazopanib (29.2% [18.6-41.8]). Grade 3-5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects.
Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab
Factors of Healthy Lifestyle by Life Cycle According to the Characteristics of Single-Person Households
No full text1인가구 증가는 전 세계적 현상으로 한국 또한 1인가구 비중의 증가가 급속히 진행 중이다. 1인가구는 그 형성 계기, 성별, 생애주기 등에 따라 매우 다양한 스펙트럼을 갖고 있으며, 각각의 특성을 반영한 지원이 가능하도록 1인가구 집단을 세분화하여 연구할 필요가 있다. 이 연구는 생애주기에 따라 청년기, 중장년기, 노년기 1인가구 등 세 개의 집단으로 분류하고, 1인가구 건강성 수준에 있어 집단 간 유의한 차이가 있는지, 나아가 건강성에 영향을 미치는 인구사회학적 특성 및 1인가구 삶의 특성에는 어떠한 것들이 있는지 살펴보았다. 분석을 위해 2022년도 김포시 거주 1인가구 237명을 대상으로 설문조사를 통해 수집된 자료를 이용하였고, 기술통계, 평균차이 검증(t-test, ANOVA), 중다회귀분석 등을 실시하였다. 1인가구의 전반적 건강성 수준을 살펴보면 생애주기별로 차이가 있었는데, 청년기 1인가구가 노년기 1인가구에 비해 건강성 수준이 유의하게 높았다. 중다회귀분석 결과, 1인가구 건강성에는 성별, 교육수준, 자발성, 차별경험 여부가 유의한 영향을 미치는 것으로 나타났으며, 건강성을 구성하는 하위영역별로 영향을 미치는 변수에는 차이가 있었다. 생애주기에 따른 1인가구의 건강성 수준에 대한 결과를 토대로 하여 1인가구 정책의 방향성을 논의하고 실천적 함의를 제공하였다.
The rate of single-person households has been increasing all over the world, and there has been a particularly rapid increase in them in Korea. Single-person households show unique and various characteristics related to the reasons for becoming a single-person household, gender, life cycle, and so on. Thus, research needs to focus on the specific groups of single-person households in order to provide tailored policies and programs. This study segmented single-person households in three groups based on life cycle: young, middle-aged, and older adults. Differences in the level of healthy lifestyle, as well as factors affecting that, were investigated according to the groups. The data were collected in 2022, with 237 respondents from single-person households in Kimpo. Descriptive statistics, t-test, ANOVA, and multiple regression analysis were conducted. The overall level of healthy lifestyle was found to be significantly higher for young adults compared to older adults. Results from multiple regression show that significant factors related to the healthy lifestyle of single-person households were gender, educational attainment, whether becoming a single-person household was voluntary, and whether the respondents had experienced discrimination as a single-person household. Significant factors differed by the sub-categories of the healthy lifestyle scale. This study has implications related to discovering differences in the level of healthy lifestyles of single-person households through examining the factors affecting it according to life cycle