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Background: Targeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown., Methods: In this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified., Results: IDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial-mesenchymal transition., Conclusions: Our findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research., (© 2024. The Author(s).)

Background: Despite advancements in emergency medical systems, inter-hospital transfer (IHT) remains a critical component. Several studies have analyzed the impact of IHT on patient outcomes. Some studies have reported positive effects, indicating that transfers can improve patient prognosis. However, other studies have suggested that transfers may worsen outcomes. We investigated whether IHT is associated with in-hospital mortality. Methods: This retrospective observational study utilized data on patient outcomes from the National Emergency Department Information System (NEDIS) from 2016 to 2018, focusing on patients admitted to hospitals after visiting the emergency department (ED). The primary outcome was the in-hospital mortality rate. Results: This study included 2,955,476 adult patients admitted to emergency medical centers, with 832,598 (28.2%) undergoing IHT. The in-hospital mortality rate was significantly higher in the transfer group (6.9%) than in the non-transfer group (4.8%). Multiple logistic regression analysis revealed that IHT was an independent predictor of in-hospital mortality (adjusted odds ratio [aOR] 1.114, 95% confidence interval [CI] 1.101-1.128) after adjusting for variables. Sub-analysis indicated that higher severity scores, shorter symptom onset-to-arrival duration, and diagnoses of infectious or respiratory diseases were significantly associated with increased in-hospital mortality among transferred patients. Conclusions: This study identifies IHT as a significant factor associated with increased in-hospital mortality. Additionally, it suggested the need for policies to mitigate the risks associated with IHT, particularly in critically ill patients, those with the acute phase response, and those with infectious, genitourinary, and respiratory diseases.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and amyloid beta oligomers (AβO), which are pathological markers of AD, are known to be highly toxic. AβO increase mitochondrial dysfunction, which is accompanied by a decrease in mitochondrial fusion. Although mitofusin (Mfn) 1 and Mfn2 are mitochondrial fusion proteins, Mfn2 is known to regulate endoplasmic reticulum (ER) function, as it is located in the ER. Several studies have shown that AβO exacerbates ER stress, however, the exact mechanism requires further elucidation. In this study, we used mouse neuroblastoma cells stably overexpressing the amyloid precursor protein (APP) with the Swedish mutation (N2a APPswe cells) to investigate the role of Mfn in ER stress. Our results revealed that  amyloid beta (Aβ) caused cellular toxicity in N2a APPswe cells, upregulated ER stress-related proteins, and promoted ER expansion. The AβO-mediated ER stress was reduced when Mfn1 and Mfn2 were overexpressed. Moreover, Mfn1 and Mfn2 overexpressed resulted in reduced apoptosis of N2a APPswe cells. In conclusion, our results indicate that both Mfn1 and Mfn2 reduce ER stress and apoptosis. Our data provide a foundation for future studies on the roles of Mfn1 and Mfn2 in the molecular mechanisms underlying AβO-mediated ER stress and the pathogenesis of AD.

Background: This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity., Methods: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity., Results: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21-1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78-2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09-1.99; p = 0.01) but not among those with low disease severity., Conclusion: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Background: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD., Methods: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents., Results: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents., Conclusion: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy., (© 2024. The Author(s).)

The differentiation of naive CD8 + T cells into effector cells is important for establishing immunity. However, the effect of heterogeneous naive CD8 + T cell populations is not fully understood. Here, we demonstrate that steady-state naive CD8 + T cells are composed of functionally heterogeneous subpopulations that differ in their ability to differentiate into type 17 cytotoxic effector cells (Tc17) in a context of murine inflammatory disease models, such as inflammatory bowel disease and graft-versus-host disease. The differential ability of Tc17 differentiation is not related to T-cell receptor (TCR) diversity and antigen specificity but is inversely correlated with self-reactivity acquired during development. Mechanistically, this phenomenon is linked to differential levels of intrinsic TCR sensitivity and basal Suppressor of Mothers Against Decapentaplegic 3 (SMAD3) expression, generating a wide spectrum of Tc17 differentiation potential within naive CD8 + T cell populations. These findings suggest that developmental self-reactivity can determine the fate of naive CD8 + T cells to generate functionally distinct effector populations and achieve immense diversity and complexity in antigen-specific T-cell immune responses., (© 2024. The Author(s).)

This study develops machine learning-based algorithms that facilitate accurate prediction of cerebral oxygen saturation using waveform data in the near-infrared range from a multi-modal oxygen saturation sensor. Data were obtained from 150,000 observations of a popular cerebral oximeter, Masimo O3™ regional oximetry (Co., United States) and a multi-modal cerebral oximeter, Votem (Inc., Korea). Among these observations, 112,500 (75%) and 37,500 (25%) were used for training and test sets, respectively. The dependent variable was the cerebral oxygen saturation value from the Masimo O3™ (0-100%). The independent variables were the time of measurement (0-300,000 ms) and the 16-bit decimal amplitudes values (infrared and red) from Votem (0-65,535). For the right part of the forehead, the root mean square error of the random forest (0.06) was much smaller than those of linear regression (1.22) and the artificial neural network with one, two or three hidden layers (2.58). The result was similar for the left part of forehead, that is, random forest (0.05) vs logistic regression (1.22) and the artificial neural network with one, two or three hidden layers (2.97). Machine learning aids in accurately predicting of cerebral oxygen saturation, employing the data from a multi-modal cerebral oximeter., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: The study aimed to assess the clinical outcomes of arthroscopic debridement and partial excision in patients with traumatic central tears of the triangular fibrocartilage complex (TFCC), and to identify prognostic factors associated with unfavourable clinical outcomes., Methods: A retrospective analysis was conducted on patients arthroscopically diagnosed with Palmer 1 A lesions who underwent arthroscopic debridement and partial excision from March 2009 to February 2021, with a minimum follow-up of 24 months. Patients were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Mayo Wrist Score (MWS), and visual analogue scale (VAS) for pain. The poor outcome group was defined as patients whose preoperative and last follow-up clinical score difference was less than the minimal clinically important difference of the DASH score (10.83). Baseline characteristics, arthroscopic findings, and radiological factors (ulnar variance, MRI, or arthrography) were evaluated to predict poor clinical outcomes., Results: A total of 114 patients were enrolled in this study, with a mean follow-up period of 29.8 months (SD 14.4). The mean DASH score improved from 36.5 (SD 21.5) to 16.7 (SD 14.3), the mean MWS from 59.7 (SD 17.9) to 79.3 (SD 14.3), and the mean VAS pain score improved from 5.9 (SD 1.8) to 2.2 (SD 2.0) at the last follow-up (all p < 0.001). Among the 114 patients, 16 (14%) experienced poor clinical outcomes and ten (8.8%) required secondary ulnar shortening osteotomy. Positive ulnar variance was the only factor significantly associated with poor clinical outcomes (p < 0.001). Positive ulnar variance was present in 38 patients (33%); among them, eight patients (21%) required additional operations., Conclusion: Arthroscopic debridement alone appears to be an effective and safe initial treatment for patients with traumatic central TFCC tears. The presence of positive ulnar variance was associated with poor clinical outcomes, but close observation after arthroscopic debridement is more likely to be recommended than ulnar shortening osteotomy as a primary treatment., Competing Interests: The authors were supported by a faculty research grant from the Yonsei University College of Medicine (6-2019-0183)., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Although the cardiovascular benefits of an increased urinary potassium excretion have been suggested, little is known about the potential cardiac association of urinary potassium excretion in patients with chronic kidney disease. In addition, whether the cardiac association of urinary potassium excretion was mediated by serum potassium levels has not been studied yet. We reviewed the data of 1633 patients from a large-scale multicentre prospective Korean study (2011-2016). Spot urinary potassium to creatinine ratio was used as a surrogate for urinary potassium excretion. Cardiac injury was defined as a high-sensitivity troponin T ≥ 14 ng/l. OR and 95 % (CI for cardiac injury were calculated using logistic regression analyses. Of 1633 patients, the mean spot urinary potassium to creatinine ratio was 49·5 (sd 22·6) mmol/g Cr and the overall prevalence of cardiac injury was 33·9 %. Although serum potassium levels were not associated with cardiac injury, per 10 mmol/g Cr increase in the spot urinary potassium to creatinine ratio was associated with decreased odds of cardiac injury: OR 0·917 (95 % CI 0·841, 0·998), P = 0·047) in multivariate logistic regression analysis. In mediation analysis, approximately 6·4 % of the relationship between spot urinary potassium to creatinine ratio and cardiac injury was mediated by serum potassium levels, which was not statistically significant ( P = 0·368). Higher urinary potassium excretion was associated with lower odds of cardiac injury, which was not mediated by serum potassium levels.

Xerostomia may be accompanied by changes in salivary flow rate and the incidence increases in elderly. We aimed to use machine learning algorithms, to identify significant predictors for the presence of xerostomia. This study is the first to predict xerostomia with salivary flow rate in elderly based on artificial intelligence. In a cross-sectional study, 829 patients with oral discomfort were enrolled, and six features (sex, age, unstimulated and stimulated salivary flow rates (UFR and SFR, respectively), number of systemic diseases, and medication usage) were used in four machine learning algorithms to predict the presence of xerostomia. The incidence of xerostomia increased with age. The SFR was significantly higher than the UFR, and the UFR and SFR were significantly correlated. The UFR, but not SFR, decreased with age significantly. In patients more than 60 years of age, the UFR had a significantly higher predictive accuracy for xerostomia than the SFR. Using machine learning algorithms with tenfold cross-validation, the prediction accuracy increased significantly. In particular, the prediction accuracy of the multilayer perceptron (MLP) algorithm that combined UFR and SFR data was significantly better than either UFR or SFR individually. Moreover, when sex, age, number of systemic diseases, and number of medications were added to the MLP model, the prediction accuracy increased from 56 to 68%., (© 2024. The Author(s).)

Introduction: The evaluation of acute poisoning is challenging due to varied toxic substances and clinical presentations. The new-Poisoning Mortality Score was recently developed to assess patients with acute poisoning and showed good performance in predicting in-hospital mortality. The objective of this study is to externally validate the performance of the new-Poisoning Mortality Score and to compare it with the Modified Early Warning Score., Methods: This retrospective analysis used data from the 2019-2020 Injury Surveillance Cohort, established by the Korea Center for Disease Control and Prevention, to perform external validation of the new-Poisoning Mortality Score. The statistical performances of the new-Poisoning Mortality and Modified Early Warning Scores were assessed and compared in terms of discrimination and calibration. Discrimination analysis involved metrics such as sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve. For calibration analysis, the Hosmer-Lemeshow goodness-of-fit test was utilized and calibration curves for each score were generated to elucidate the relationship between observed and predicted mortalities., Results: This study analysed 16,570 patients with acute poisoning. Significant differences were observed between survivors and those who died in-hospital, including age, sex, and vital signs. The new-Poisoning Mortality Score showed better performance over the Modified Early Warning Score in predicting in-hospital mortality, in terms of the area under the receiver operating characteristic curve (0.947 versus 0.800), sensitivity (0.863 versus 0.667), specificity (0.912 versus 0.817), and accuracy (0.911 versus 0.814). When evaluated through calibration curves, the new-Poisoning Mortality Score showed better concordance between predicted and observed mortalities. In subgroup analyses, the score system consistently showed strong performance, excelling particularly in substances with high mortality indices and remaining superior in all substances as a group., Conclusions: Our study has helped to validate the new-Poisoning Mortality Score as an effective tool for predicting in-hospital mortality in patients with acute poisoning in the emergency department. The score system demonstrated superior performance over the Modified Early Warning Score in various metrics. Our findings suggest that the new-Poisoning Mortality Score can contribute to the enhancement of clinical decision-making and patient management.

Introduction: C-reactive protein-to-albumin ratio (CAR) is a prognostic marker in various diseases that represents patients' inflammation and nutritional status. Here, we aimed to investigate the prognostic value of CAR in critically ill patients with severe acute kidney injury requiring continuous renal replacement therapy (CRRT)., Methods: We retrospectively collected data from eight tertiary hospitals in Korea from 2006-2021. The patients were divided into quartiles according to CAR levels at the time of CRRT initiation. Cox regression analyses were performed to investigate the effect of CAR on in-hospital mortality. The mortality prediction performance of CAR was evaluated using the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI)., Results: In total, 3,995 patients who underwent CRRT were included, and the in-hospital mortality rate was 67.3% during the follow-up period. The 7-day, 30-day, and in-hospital mortality rates increased toward higher CAR quartiles (all p &lt; 0.001). After adjusting for confounding variables, the higher quartile groups had an increased risk of in-hospital mortality (quartile 3: adjusted hazard ratio [aHR], 1.26, 95% confidence interval [CI], 1.10-1.43, p &lt; 0.001; quartile 4: aHR, 1.22, 95% CI, 1.07-1.40, p = 0.003). CAR combined with Acute Physiology and Chronic Health Evaluation II or Sequential Organ Failure Assessment scores significantly increased the predictive power compared to each severity score alone for AUC, NRI, and IDI (all p &lt; 0.05)., Conclusions: A high CAR is associated with increased in-hospital mortality in critically ill patients requiring CRRT. The combined use of CAR and severity scores provides better predictive performance for mortality than the severity score alone., (© 2023 S. Karger AG, Basel.)

Crosslinked hydrophilic polymers with high water absorption rates are known as superabsorbent polymers (SAPs). Most commercial superabsorbent polymers are made with acrylic acid, which is difficult to biodegrade. So, in this investigation, carboxymethyl cellulose (CMC) was utilized as a significant component in the synthesis of polysaccharide-based SAPs. Citric acid (CA) and starch were chosen as crosslinking agents because they are more eco-friendly, non-toxic, and biodegradable than traditional crosslinking agents. FTIR analysis revealed that the superabsorbent polymer product contains a crosslinked structure of CMC and starch with side chains that carry carboxylate functional groups. Superabsorbent weight loss and grafting data were satisfactorily studied using the TGA approach. Under optimum circumstances, the SAP2 water absorbency capacity in distilled water was 287.37 g.g -1 and SAP1 absorbency capacity in a solution containing 0.9 wt% NaCl was 52.18 g.g -1 . Moreover, Schott's pseudo-second-order model was used to determine the kinetic swelling of the superabsorbent. The initial swelling rate of SAPs can be calculated using the Q ∞ data acquired in the following order: SAP2 > SAP1 > SAP3 > SAP4 in distilled water and SAP1 > SAP2 > SAP3 > SAP4 in 0.9 wt% NaCl solution, respectively. The findings suggested that a small amount of citric acid introduced into the SAPs matrix could enhance the swelling rate of SAPs. The results of the cytotoxicity tests show that the extraction liquid of composite hydrogel fibers is less cytotoxic than the positive control. As well, SAP underwent in silico docking investigations on the DNA Gyrase enzyme. As the ligand is a monomer of SAP, it was a long chain of carbohydrate molecules with alcoholic groups, esters groups, and keto groups forms a strong binding interaction with DNA gyrase., Competing Interests: Declaration of competing interest The submission of this work has no potential conflicts of interest. The study was original research that had not yet been published and was not being considered for full or partial publication elsewhere. International ethical standards served as the guide for the study presented in the publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: Contouring of organs at risk is important for studying health effects following breast radiotherapy. However, manual contouring is time-consuming and subject to variability. The purpose of this study was to develop a deep learning-based method to automatically segment multiple structures on breast radiotherapy planning computed tomography (CT) images., Materials and Methods: We used data from 118 patients, including 90 diagnostic CT scans with expert structure delineations for training and 28 breast radiotherapy planning CT images for testing. The radiotherapy CT images also had expert delineations for evaluating performance. We targeted a total of eleven organs at risk including five heart substructures. Segmentation performance was evaluated using the metrics of Dice similarity coefficient (DSC), overlap fraction, volume similarity, Hausdorff distance, mean surface distance, and dose., Results: The average DSC achieved on the radiotherapy planning images was 0.94 ± 0.02 for the whole heart, 0.96 ± 0.02 and 0.97 ± 0.01 for the left and right lung, 0.61 ± 0.10 for the esophagus, 0.81 ± 0.04 and 0.86 ± 0.04 for left and right atrium, 0.91 ± 0.02 and 0.84 ± 0.04 for left and right ventricle, and 0.21 ± 0.11 for the left anterior descending artery (LAD), respectively. Except for the LAD, the median difference in mean dose to these structures was small with absolute (relative) differences < 0.1 Gy (6 %)., Conclusions: Except for the LAD, our method demonstrated excellent performance and can be generalized to segment additional structures of interest., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8 + T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8 + T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8 + T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8 + T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8 + T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8 + T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2023. The Korean Association of Immunologists.)

In this study, we examined the mechanisms of cadmium exposure-induced endoplasmic reticulum (ER) stress response and apoptosis in spermatocytes. Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The massive generation of synthetic textile waste has drawn considerable attention. Landfilling/incineration of textile waste has been widely made. To abate the environmental burdensome from the conventional management processes, a thermo-catalytic conversion was used for rapid volume reduction of textile waste and simultaneous valorization by recovering textile monomer in this study. Stockings were chosen as a model feedstock. Because stockings consisted of nylon with other contents, different products (caprolactam (nylon monomer), imines, cyclic dimers, and azepines) were recovered. The yield of caprolactam from the thermal conversion at 500 °C was 53.6 wt%. To selectively enhance the caprolactam yield, catalytic pyrolysis was done using γ-Al 2 O 3 supported metal catalysts (Ni, Cu, Fe, or Co). γ-Al 2 O 3 itself increased the caprolactam yield up to 69.0 wt% via a based-catalyzed reaction of nylon depolymerization and intramolecular cyclization. Under the presence of metal catalysts, the caprolactam yield increased up to 73.3 wt%. To offer desired feature of green chemistry, CO 2 was adopted as reactive gas. Under the CO 2 -mediated catalytic pyrolysis, caprolactam yield was enhanced up to 77.1 wt% over Cu/Al 2 O 3 (basis: stocking mass). Based on the net content of nylon in the stockings, the yield of caprolactam was deemed 95.3 wt%. This study proves that textile waste (stocking) and CO 2 are useful resources for recovery of nylon monomer, which can reduce the waste generation with simultaneous recovery of value-added product., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Overcrowding of emergency department (ED) has put a strain on national healthcare systems and adversely affected the clinical outcomes of critically ill patients. Early identification of critically ill patients prior to ED visits can help induce optimal patient flow and allocate medical resources effectively. This study aims to develop ML-based models for predicting critical illness in the community, paramedic, and hospital stages using Korean National Emergency Department Information System (NEDIS) data. Random forest and light gradient boosting machine (LightGBM) were applied to develop predictive models. The predictive model performance based on AUROC in community stage, paramedic stage, and hospital stage was estimated to be 0.870 (95% CI: 0.869-0.871), 0.897 (95% CI: 0.896-0.898), and 0.950 (95% CI: 0.949-0.950) in random forest and 0.877 (95% CI: 0.876-0.878), 0.899 (95% CI: 0.898-0.900), and 0.950 (95% CI: 0.950-0.951) in LightGBM, respectively. The ML models showed high performance in predicting critical illness using variables available at each stage, which can be helpful in guiding patients to appropriate hospitals according to their severity of illness. Furthermore, a simulation model can be developed for proper allocation of limited medical resources., Competing Interests: The authors declare that they have no conflicts of interest. Chulung Lee and Su Jin Kim received funding from Korea University., (Copyright © 2023 Sijin Lee et al.)

Obesity is caused by the accumulation of excess lipids due to an energy imbalance. Differentiation of pre-adipocytes induces abnormal lipid accumulation, and reactive oxygen species (ROS) generated in this process promote the differentiation of pre-adipocytes through mitogen-activated protein kinase (MAPK) signaling. Peroxiredoxin (Prx) is a potent antioxidant enzyme, and peroxiredoxin 5 (Prx5), which is mainly expressed in cytosol and mitochondria, inhibits adipogenesis by regulating ROS levels. Based on previous findings, the present study was performed to investigate whether cytosolic Prx5 (CytPrx5) or mitochondrial Prx5 (MtPrx5) has a greater effect on the inhibition of adipogenesis. In this study, MtPrx5 decreased insulin-mediated ROS levels to reduce adipogenic gene expression and lipid accumulation more effectively than CytPrx5. In addition, we found that p38 MAPK mainly participates in adipogenesis. Furthermore, we verified that MtPrx5 overexpression suppressed the phosphorylation of p38 during adipogenesis. Thus, we suggest that MtPrx5 inhibits insulin-induced adipogenesis more effectively than CytPrx5., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Municipal solid waste (MSW) management is an essential municipal service. Proper waste treatment is an important part of the waste management. Thermocatalytic waste upcycling has recently gained great interest and attention as a method to extract value from waste, which potentially substitutes traditional waste treatment methods. This study aims at demonstrating the potential for thermocatalytic waste upcycling using spent disposable wipes as an MSW surrogate. Two different Ni/Al 2 O 3 catalysts were prepared, treated under two different atmospheres (N 2 and CO 2 ). The catalyst treated in N 2 (Ni/Al 2 O 3 -N 2 ) exhibited a higher surface metallic Ni site than the catalyst treated in CO 2 (Ni/Al 2 O 3 -CO 2 ). The use of the Ni/Al 2 O 3 -N 2 increased the yield of gas pyrolysate and decreased the yield of byproduct (e.g., wax), compared with no catalyst and the Ni/Al 2 O 3 -CO 2 . In particular, the Ni/Al 2 O 3 -N 2 catalyst affected the generation of gaseous hydrogen (H 2 ) by increasing the H 2 yield by up to 102% in comparison with the other thermocatalytic systems. The highest H 2 yield obtained with the Ni/Al 2 O 3 -N 2 was attributed to the most surface metallic Ni sites. However, the Ni/Al 2 O 3 -N 2 catalyst led to char having a lower higher heating value than the other catalysts due to its lowest carbon content. The results indicated that the reduction treatment environment for Ni/Al 2 O 3 catalyst influences thermocatalytic conversion product yields of spent disposable wipes, including enhanced H 2 production., Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11814-023-1461-8., (© The Korean Institute of Chemical Engineers 2023.)

This study examined the effects of muscle mass on mortality in patients with acute kidney injury requiring continuous renal replacement therapy. It was conducted in eight medical centers between 2006 and 2021. The data of 2200 patients over the age of 18 years with acute kidney injury who required continuous renal replacement therapy were retrospectively collected. Skeletal muscle areas, categorized into normal and low attenuation muscle areas, were obtained from computed tomography images at the level of the third lumbar vertebra. Cox proportional hazards models were used to investigate the association between mortality within 1, 3, and 30 days and skeletal muscle index. Sixty percent of patients were male, and the 30-day mortality rate was 52%. Increased skeletal muscle areas/body mass index was associated with decreased mortality risk. We also identified a 26% decreased risk of low attenuation muscle area/body mass index on mortality. We established that muscle mass had protective effects on the mortality of patients with acute kidney injury requiring continuous renal replacement therapy. This study showed that muscle mass is a significant determinant of mortality, even if the density is low., (© 2023. The Author(s).)

In mid-2022, as the wave of pediatric coronavirus disease 2019 (COVID-19) cases escalated in South Korea, a public-private partnership was made to establish a Pediatric COVID-19 Module Clinic (PMC). We describe the utilization of the first prototype children's modular clinic in Korea University Anam Hospital functioning as the COVID-19 PMC. Between August 1 and September 30, 2022, a total of 766 children visited COVID-19 PMC. Daily number of patient visits to the COVID-19 PMC ranged between 10 and 47 in August; and less than 13 patients per day in September 2022. Not only the model provided timely care for the COVID-19 pediatric patients, but it also enabled safe and efficacious care for the non-COVID-19 patients in the main hospital building while minimizing exposure risk to severe acute respiratory syndrome coronavirus 2 transmission. Current description highlights the importance of spatial measures for mitigating in-hospital transmission of COVID-19, in specifically on pediatric care., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: The relationship between self-rated health (SRH) and the development of incident chronic kidney disease (CKD) has not been explored in the general population., Methods: We reviewed the data of 7027 participants in the Ansung-Ansan cohort study. SRH was categorized as poor, fair, or good, and the outcome was the development of CKD, defined as the first event of an estimated glomerular filtration rate < 60 mL/min/1.73 m 2 , at least twice during the follow-up period. Hazard ratios (HRs) and confidence intervals (CIs) were calculated using Cox proportional hazards regression analysis., Results: Over a mean follow-up duration of 11.9 years, 951 participants (13.5%) developed CKD. Compared with poor self-rated health, the HR (95% CI) of fair self-rated health for incident CKD development was 0.771 (0.657-0.905; P = 0.001), whereas that of good self-rated health was 0.795 (0.676-0.935; P = 0.006). However, the renal hazard of good self-rated health did not differ from that of fair self-rated health. In the fully adjusted model, the HR (95% CI) of poor self-rated health compared to non-poor self-rated health for incident CKD was 1.278 (1.114-1.465, P < 0.001). Old age, smoking, cardiovascular disease, diabetes, hypertension, impaired sleep, and high levels of C-reactive protein and white blood cell counts were associated with increased odds of poor self-rated health, whereas male sex, college graduate level of education, and alcohol consumption were associated with decreased odds of poor self-rated health., Conclusion: Poor self-rated health is independently associated with CKD development. Therefore, the early detection of potential CKD patients through a brief questionnaire assessment may help control the incidence of CKD., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Introduction: Patients with acute kidney injury (AKI) receiving renal replacement therapy constitute the subgroup of AKI with the highest risk of mortality. Despite recent promising findings on the neutrophil-to-lymphocyte ratio (NLR) in AKI, studies have not yet addressed the clinical implication of the NLR in this population. Therefore, we aimed to examine the prognostic value of NLR in critically ill patients requiring continuous renal replacement therapy (CRRT), especially focusing on temporal changes in NLR., Methods: We enrolled 1,494 patients with AKI who received CRRT in five university hospitals in Korea between 2006 and 2021. NLR fold changes were calculated as the NLR on each day divided by the NLR value on the first day. We performed a multivariable Cox proportional hazard analysis to assess the association between the NLR fold change and 30-day mortality., Results: The NLR on day 1 did not differ between survivors and non-survivors; however, the NLR fold change on day 5 was significantly different. The highest quartile of NLR fold change during the first 5 days after CRRT initiation showed a significantly increased risk of death (hazard ratio [HR], 1.65; 95% confidence intervals (CI), 1.27-2.15) compared to the lowest quartile. NLR fold change as a continuous variable was an independent predictor of 30-day mortality (HR, 1.14; 95% CI, 1.05-1.23)., Conclusion: In this study, we demonstrated an independent association between changes in NLR and mortality during the initial phase of CRRT in AKI patients receiving CRRT. Our findings provide evidence for the predictive role of changes in the NLR in this high-risk subgroup of AKI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ko, Jung, Lee, Lim, Im, Kim, Paek, Park, Kim, Lee, Lee, Shin, Kim, Han, Baek, Kim, Park, Ban and Kim.)

Immune diversification helps protect the host against a myriad of pathogens. CD8 + T cells are essential adaptive immune cells that inhibit the spread of pathogens by inducing apoptosis in infected host cells, ultimately ensuring complete elimination of infectious pathogens and suppressing disease development. Accordingly, numerous studies have been conducted to elucidate the mechanisms underlying CD8 + T cell activation, proliferation, and differentiation into effector and memory cells, and to identify various intrinsic and extrinsic factors regulating these processes. The current knowledge accumulated through these studies has led to a huge breakthrough in understanding the existence of heterogeneity in CD8 + T cell populations during immune response and the principles underlying this heterogeneity. As the heterogeneity in effector/memory phases has been extensively reviewed elsewhere, in the current review, we focus on CD8 + T cells in a "naïve" state, introducing recent studies dealing with the heterogeneity of naive CD8 + T cells and discussing the factors that contribute to such heterogeneity. We also discuss how this heterogeneity contributes to establishing the immense complexity of antigen-specific CD8 + T cell response., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2023. The Korean Association of Immunologists.)

We recruited 50 patients with unresectable stage III NSCLC who received CCRT between March 2020 and March 2021. Durvalumab consolidation (DC) was administered to patients ( n = 23) without progression after CCRT and programmed death-ligand 1 (PD-L1) ≥ 1%. Blood samples were collected before (C0) and after CCRT (C1) to calculate PBC counts and analyze CTCs. CTCs, isolated by the CD-PRIME TM system, exhibited EpCAM/CK+/CD45- phenotype in BioViewCCBS TM . At median follow-up of 27.4 months, patients with residual CTC clusters at C1 had worse median PFS than those without a detectable CTC cluster (11.0 vs. 27.8 months, p = 0.032), and this trend was noted only in the DC group ( p = 0.034). Patients with high platelets at C1 (PLT hi , >252 × 10 3 /µL) had worse median PFS than those with low platelets (PLT lo ) (5.9 vs. 17.1 months, p < 0.001). In multivariable analysis, PLT hi and residual CTC clusters at C1 were independent risk factors for PFS, and DC group with PLT hi and residual CTC clusters at C1 showed the worst median PFS (2.6 months, HR 45.16, p = 0.001), even worse than that of the CCRT alone group with PLT hi (5.9 months, HR 15.39, p = 0.001). The comprehensive analysis of CTCs and PBCs before and after CCRT revealed that the clearance of CTC clusters and platelet counts at C1 might be potential biomarkers for predicting survival.

Background: In the Republic of Korea, a trauma care system was not created until 2012, at which point regional trauma centers (RTCs) were established nationwide. In accordance with the national emergency care system and legislation, regional and local emergency medical centers (EMCs) also treat patients presenting with trauma. The aim of the present study was to assess whether treatment in RTCs is truly associated with better patient outcomes than that in EMCs by means of propensity score-matched comparisons and to identify populations that would benefit from treatment in RTCs., Methods: This study analyzed the data of patients with consecutive emergency visits between January 1, 2018, and December 31, 2018, collected in the National Emergency Department Information System registry. Data from RTCs, designated regional EMCs, or local EMCs were included; data from smaller emergency departments were excluded because, in Korea, dedicated RTCs are established only in hospitals with regional or local EMCs. Propensity scores for treatment in RTCs or EMCs were estimated by logistic regression using linear terms. Mortality rates in RTCs and EMCs were compared between the matched samples., Results: The in-hospital mortality rates in the matched cases treated in RTCs and EMCs were 1.4% and 1.6%, respectively. The odds ratio for in-hospital mortality in RTCs over EMCs was 0.984 (95% confidence interval: 0.813-1.191). Among the subgroups evaluated, the subgroup of patients with injuries involving the chest or lower limbs showed a significant difference in the in-hospital mortality rate., Conclusion: There was no significant difference in the overall severity-adjusted mortality rate between patients treated in RTCs and EMCs. Treatment in an RTC might benefit those with injuries involving the chest or lower limbs., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yuri Choi et al.)

Endosulfan was widely used as an insecticide in the agricultural sector before its environmental persistence was fully understood. Although its fate and transport in the environment have been studied, the effects of historic endosulfan residues in soil and its bioaccumulation in crops are not well understood. This knowledge gap was addressed by investigating the dissipation and bioaccumulation of endosulfan in ginseng as a perennial crop in fresh and aged endosulfan-contaminated fields. In addition, the effect of granular biochar (GBC) treatment on the bioaccumulation factor (BAF) of endosulfan residue in ginseng was assessed. The 50% dissipation time (DT 50 ) of the total endosulfan was over 770 days in both the fresh and aged soils under mulching conditions. This was at least twofold greater than the reported (6- > 200 days) in arable soil. Among the endosulfan congeners, the main contributor to the soil residue was endosulfan sulfate, as observed from 150 days after treatment. The BAF for the 2-year-old ginseng was similar in the fresh (1.682-2.055) and aged (1.372-2.570) soils, whereas the BAF for the 3-year-old ginseng in the aged soil (1.087-1.137) was lower than that in the fresh soil (1.771-2.387). The treatment with 0.3 wt% GBC extended the DT 50 of endosulfan in soil; however, this could successfully suppress endosulfan uptake, and reduced the BAFs by 66.5-67.7% in the freshly contaminated soil and 32.3-41.4% in the aged soil. Thus, this adsorbent treatment could be an effective, financially viable, and sustainable option to protect human health by reducing plant uptake of endosulfan from contaminated soils., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Practical guidelines that are not explicit in the TG-51 protocol and its Addendum for photon beam dosimetry are presented for the implementation of the TG-51 protocol for reference dosimetry of external high-energy photon and electron beams. These guidelines pertain to: (i) measurement of depth-ionization curves required to obtain beam quality specifiers for the selection of beam quality conversion factors, (ii) considerations for the dosimetry system and specifications of a reference-class ionization chamber, (iii) commissioning a dosimetry system and frequency of measurements, (iv) positioning/aligning the water tank and ionization chamber for depth ionization and reference dose measurements, (v) requirements for ancillary equipment needed to measure charge (triaxial cables and electrometers) and to correct for environmental conditions, and (vi) translation from dose at the reference depth to that at the depth required by the treatment planning system. Procedures are identified to achieve the most accurate results (errors up to 8% have been observed) and, where applicable, a commonly used simplified procedure is described and the impact on reference dosimetry measurements is discussed so that the medical physicist can be informed on where to allocate resources., (© 2022 American Association of Physicists in Medicine.)

In Alzheimer's disease, reactive oxygen species (ROS) are generated by the deposition of amyloid-beta oligomers (AβOs), which represent one of the important causes of neuronal cell death. Additionally, AβOs are known to induce autophagy via ROS induction. Previous studies have shown that autophagy upregulation aggravates neuronal cell death. In this study, the effects of peroxiredoxin 2 (Prx2), a member of the peroxidase family of antioxidant enzymes, on regulating AβO-mediated autophagy were investigated. Prx2 decreased AβO-mediated oxidative stress and autophagy in N2a-APPswe cells. Further, we examined the relationship between the neuronal protective effect of Prx2 and a decrease in autophagy. Similar to the effects of N-acetyl cysteine, Prx2 decreased AβO-induced ROS and inhibited p62 protein expression levels by downregulating the activation of NRF2 and its translocation to the nucleus. In addition, treatment with 3-methyladenine, an autophagy inhibitor, ameliorates neuronal cell death. Overall, these results demonstrate that the Prx2-induced decrease in autophagy was associated with the inhibition of ROS via the ROS-NRF2-p62 pathway in N2a-APPswe cells. Therefore, our results revealed that Prx2 is a potential therapeutic target in anti-Alzheimer therapy.

Purpose: Cyberattacks on health care systems have been on the rise over the past 5 years. Formulation and implementation of a robust postattack business continuity plan and/or contingency plan (CP) is essential for minimal disruption to patient care. The level of awareness and planning within the radiation oncology community for cyberattacks is not clear. This study was undertaken to survey and assess cyberattack CP awareness and preparedness., Methods and Materials: A survey instrument comprising 5 questions on awareness and preparedness of cyberattack CPs was e-mailed to 150 radiation oncology departments. Recipients included 105 institutions with residency programs in therapeutic medical physics, as listed by the Commission on Accreditation of Medical Physics Education Program (usually either school-based or large institutional settings), and 45 additional smaller settings within the United States, representing community practices., Results: Forty-three responses were deemed evaluable for analysis. Forty-two percent (18 respondents) of respondents responded that they are well-aware of the concept of a cyberattack CP. A large discrepancy in awareness exists between larger hospitals (LH) that have 5 or more treatment machines and smaller hospitals (SH) that have 4 or fewer, 54% versus 24 % ( P < .05). Fifty-eight percent of respondents considered it "essential" to have such a plan in place, and 28% considered it "desirable" to do so but not practical. Nine percent regarded a cyberattack CP as unnecessary. No significant differences in responses were noted among different types or sizes of institutions on this issue. Sixty-two percent of LH responded that they were either preparing or evaluating a CP, compared with only 29% of SH ( P  = .03). However, no respondents explicitly replied that they already had a CP in place in their practices., Conclusions: The importance of cyberattack preparedness and implementation does not seem to be well-recognized in radiation oncology. Both the awareness and the preparedness of SH are substantially less than those of LH. Specific and ongoing education efforts in parallel with development of appropriate programs are needed to counter the increasingly pervasive and complex threat of cyberattacks., (© 2022 The Author(s).)

Objective: This study aimed to elucidate whether direct transport of out-of-hospital cardiac arrest (OHCA) patients to higher-level emergency medical centres (EMCs) would result in better survival compared to resuscitation in smaller local emergency departments (EDs) and subsequent transfer., Methods: This study was a retrospective population-based analysis of cases registered in the national database of 2019. This study investigated the immediate results of cardiopulmonary resuscitation for OHCA compared between EMCs and EDs and the results of therapeutic temperature management (TTM) compared between the patients directly transported from the field and those transferred from other hospitals. In-hospital mortality was compared using multivariate logistic regression., Results: From the population dataset, 11,493 OHCA patients were extracted. (8,912 in the EMC group vs. 2,581 in the ED group). Multivariate logistic regression revealed that the odds for ED mortality were lower with treatment in EDs than with treatment in EMCs. (odds ratio 0.712 (95% confidence interval (CI): 0.638-0.796)). From the study dataset, 1,798 patients who received TTM were extracted. (1,164 in the direct visit group vs. 634 in the transferred group). Multivariate regression analysis showed that the odds ratio for overall mortality was 1.411 (95% CI: 0.809-2.446) in the transferred group. ( p = 0.220)., Conclusion: The immediate outcome of OHCA patients who were transported to EDs was not inferior to that of EMCs. Therefore, it would be acceptable to transport OHCA patients to the nearest emergency facilities rather than to the specialized centres in distant areas., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Je Young Chung et al.)

Purpose: Well-designed routine multileaf collimator (MLC) quality assurance (QA) is important to assure external-beam radiation treatment delivery accuracy. This study evaluates the clinical necessity of a comprehensive weekly (C-Weekly) MLC QA program compared to the American Association of Physics in Medicinerecommended weekly picket fence test (PF-Weekly), based on our seven-year experience with weekly MLC QA., Methods: The C-Weekly MLC QA program used in this study includes 5 tests to analyze: (1) absolute MLC leaf position; (2) interdigitation MLC leaf position; (3) picket fence MLC leaf positions at static gantry angle; (4) minimum leaf-gap setting; and (5) volumetric-modulated arc therapy delivery. A total of 20,226 QA images from 16,855 tests (3,371 tests × 5) for 11 linacs at 5 photon clinical sites from May 2014 to June 2021 were analyzed. Failure mode and effects analysis was performed with 5 failure modes related to the 5 tests. For each failure mode, a risk probability number (RPN) was calculated for a C-Weekly and a PF-Weekly MLC QA program. The probability of occurrence was evaluated from statistical analyses of the C-Weekly MLC QA., Results: The total number of failures for these 16,855 tests was 143 (0.9%): 39 (27.3%) for absolute MLC leaf position, 13 (9.1%) for interdigitation position, 9 (6.3%) for static gantry picket fence, 2 (1.4%) for minimum leaf-gap setting, and 80 (55.9%) for VMAT delivery. RPN scores for PF-Weekly MLC QA ranged from 60 to 192 and from 48 to 96 for C-Weekly MLC QA., Conclusion: RPNs for the 5 failure modes of MLC QA tests were quantitatively determined and analyzed. A comprehensive weekly MLC QA is imperative to lower the RPNs of the 5 failure modes to the desired level (<125); those from the PF-Weekly MLC QA program were found to be higher (>125). This supports the clinical necessity for comprehensive weekly MLC QA., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

The utilization of the emergency department (ED) has been continuously increasing and has become a burden for ED resources. The aim of this study was to describe the characteristics, outcomes, common diagnoses, and disease classifications of patients who were referred to the ED. This nationwide epidemiologic study examined the data from adult patients (>18 years) who visited EDs from 1 January 2016 to 31 December 2018. Most EDs in Korea provide data from ED patients to the National Emergency Medical Center (NEMC). The disposition of ED patients was classified as discharge, admission, death, and re-transfer. From 2016 to 2018, the proportion of referred patients out of the total ED visits increased from 7.3% to 7.8%. The referred patients were older (61.1 vs. 50.5 years), had worse vital signs, longer ED lengths of stay (409.1 vs. 153.3 min), and higher admission (62.3 vs. 16.9%) and re-transfer rates (4.4 vs. 1.9%) than the direct-visit patients. Among the referred patients in the 3 years, 62.3% were hospitalized, and the most common disease classification was “disease of the digestive system” (19.8%). The most common diagnosis was pneumonia (6.0%), followed by urinary tract infection, gastrointestinal bleeding, and hepatobiliary infection. The number of patients referred to EDs is increasing, and more than 60% of referred patients are hospitalized. Detailed characteristics of these patients will be helpful for improving ED management and the distribution of medical resources.

Background Few studies have examined the association between the early diastolic mitral inflow velocity/early diastolic mitral annulus velocity ratio (E/e') and chronic kidney disease progression. Methods and Results We reviewed data from 2238 patients with nondialysis chronic kidney disease from the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease); data from 163 patients were excluded because of missing content. A >50% decrease in estimated glomerular filtration rate from baseline, doubling of serum creatinine, or dialysis initiation and/or kidney transplantation were considered renal events. At baseline, median (interquartile range) ejection fraction and E/e' were 64.0% (60.0%-68.0%) and 9.1 (7.4-11.9), respectively. Proportions of ejection fraction <50% and E/e' ≥15 were 1.3% and 9.6%, respectively. More than one quarter of patients (27.2%) had an estimated glomerular filtration rate <30 mL/min per 1.73 m 2 . During the mean 59.1-month follow-up period, 724 patients (34.9%) experienced renal events. In multivariable Cox proportional hazard regression analysis, the hazard ratio with 95% CI per 1-unit increase in E/e' was 1.027 (1.005-1.050; P =0.016). Penalized spline curve analysis yielded a suggested threshold of E/e' for renal events of 12; in our data set, the proportion of E/e' ≥12 was 4.1%. Conclusions Increased E/e' was associated with an increased hazard of renal events, suggesting that diastolic heart dysfunction is a novel risk factor for chronic kidney disease progression.

Background: The relationship between orthostatic blood pressure (BP) changes and incident chronic kidney disease (CKD) has not been explored in Asian populations., Methods: We reviewed the data of 7,039 participants from the Ansung-Ansan cohort study. BP was measured in the supine position and 2 minutes after standing. The change in BP from the supine to upright position was defined as orthostatic BP change. Orthostatic systolic BP (SBP) decline was defined as an orthostatic SBP change of <-2 mm Hg. The primary outcome was the development of CKD, defined as the first event of an estimated glomerular filtration rate <60 ml/min/1.73 m2 at least twice during the follow-up period., Results: Of 7,039 participants, 949 (13.5 %) developed incident CKD over a mean of 11.9 years. Although orthostatic diastolic BP change was not associated with incident CKD, every 1 mm Hg increase in orthostatic SBP change was associated with a decreased risk of incident CKD (HR, 0.989; 95% CI, 0.982-0.995; P = 0.001). Orthostatic SBP decline was associated with an increased risk of incident CKD (HR, 1.337; 95% CI, 1.163-1.537; P < 0.001). Older age and diabetes were associated with increased odds of orthostatic SBP decline, whereas male sex and high body mass index were associated with decreased odds of orthostatic SBP decline. Subgroup analysis revealed that orthostatic SBP decline was associated with incident CKD only in non-diabetic participants., Conclusions: Orthostatic SBP decline was independently associated with an increased risk of future incident CKD, whereas orthostatic DBP decline was not., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A favorable neurological outcome is closely related to patient characteristics and total cardiopulmonary resuscitation (CPR) duration. The total CPR duration consists of pre-hospital and in-hospital durations. To date, consensus is lacking on the optimal total CPR duration. Therefore, this study aimed to determine the upper limit of total CPR duration, the optimal cut-off time at the pre-hospital level, and the time to switch from conventional CPR to alternative CPR such as extracorporeal CPR., Methods: We conducted a retrospective observational study using prospective, multi-center registry of out-of-hospital cardiac arrest (OHCA) patients between October 2015 and June 2019. Emergency medical service-assessed adult patients (aged ≥ 18 years) with non-traumatic OHCA were included. The primary endpoint was a favorable neurological outcome at hospital discharge., Results: Among 7914 patients with OHCA, 577 had favorable neurological outcomes. The optimal cut-off for pre-hospital CPR duration in patients with OHCA was 12 min regardless of the initial rhythm. The optimal cut-offs for total CPR duration that transitioned from conventional CPR to an alternative CPR method were 25 and 21 min in patients with initial shockable and non-shockable rhythms, respectively. In the two groups, the upper limits of total CPR duration for achieving a probability of favorable neurological outcomes < 1% were 55-62 and 24-34 min, respectively, while those for a cumulative proportion of favorable neurological outcome > 99% were 43-53 and 45-71 min, respectively., Conclusions: Herein, we identified the optimal cut-off time for transitioning from pre-hospital to in-hospital settings and from conventional CPR to alternative resuscitation. Although there is an upper limit of CPR duration, favorable neurological outcomes can be expected according to each patient's resuscitation-related factors, despite prolonged CPR duration., (© 2022. The Author(s).)

Background: Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels., Methods: We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays., Results: During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function., Conclusion: Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise function and underlying mechanisms are unclear. Here, we demonstrate that naive CD8 + T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon, resulting in three distinct subsets, CD5 lo Ly6C - , CD5 hi Ly6C - , and CD5 hi Ly6C + cells. CD5 hi Ly6C + cells differ from CD5 lo Ly6C - and CD5 hi Ly6C - cells in terms of gene expression profiles and functional properties. Moreover, CD5 hi Ly6C + cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such features of CD5 hi Ly6C + cells are imprinted in a steady-state and type I interferon dependence is observed even for monoclonal CD8 + T cell populations. These findings demonstrate that self-reactivity controls the functional diversity of naive CD8 + T cells by co-opting tonic type I interferon signaling., (© 2021. The Author(s).)

Naïve CD8 + T cell quiescence is maintained at a steady state. Although this state of quiescence involves various cell-intrinsic and cell-extrinsic regulators, the mechanisms underlying this regulation remain incompletely understood. Here, we found that signal transducer and activator of transcription 1 (STAT1), a key transcription factor downstream of interferon receptor (IFNR) signaling, plays a cell-intrinsic role in maintaining naïve CD8 + T cell quiescence. STAT1-deficient mice showed enhanced proliferation of peripheral naïve CD8 + T cells, which resulted in an abnormal increase in the number of CD44 hi memory/activated phenotype cells and an enlargement of secondary lymphoid tissues. This phenomenon was not observed in IFNR-deficient mice but was paradoxically dependent on type I interferon and its alternative signaling pathway via the STAT4–RagD–lysosomal mTORC1 axis. Collectively, these findings underline the importance of STAT1 in regulating the homeostasis of peripheral naïve CD8 + T cells by suppressing their responsiveness to homeostatic cues at a steady state.

Background: CD8 + tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA re-expressing CD8 + T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood., Methods: We analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics., Results: We found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27 - CD28 - double-negative (DN), a large fraction of tilTemra population was CD27 + CD28 + double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8 + TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8 + TILs., Conclusions: These data suggest a complex interplay between CD8 + T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8 + TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8 + TIL counts, a reliable biomarker for successful cancer immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

The health benefits of physical activity (PA) are well known. However, the association between an adequate amount of moderate-vigorous PA (MVPA) and clinical outcomes has limited evidence in chronic kidney disease (CKD). We assessed PA using a self-administered questionnaire. The amount of MVPA was categorized into four groups: none, low, moderate, and high (0, <7.5, 7.5-14.9, and 15.0-29.9 metabolic equivalent-hours/week, respectively). We analyzed the association between the amount of MVPA and clinical outcomes. Among a total of 1909 adults with CKD, adults with MVPA showed various beneficial outcomes compared to those with no MVPA in a Kaplan-Meier curve followed over a median of 5.9 years. In multivariable-adjusted Cox proportional hazard models, a low and a moderate amount of MVPA was associated with a lower risk of all-cause death. A moderate amount of MVPA was associated with a lower risk of cardiovascular events. A high amount of MVPA was associated with a lower risk of end-stage kidney disease in ESKD in 1324 adults with eGFR <60 mL/min/1.73 m 2 . Age and sex modified the relationships between MVPA and clinical outcomes. MVPA is associated with various beneficial outcomes across the amount of MVPA. PA plans should be tailored for individual adults with CKD.

Objectives: There do not appear to be many studies which have examined the socio-economic burden and medical factors influencing the mortality and hospital costs incurred by patients with cardiac arrest in South Korea. We analyzed the differences in characteristics, medical factors, mortality, and costs between patients with national health insurance and those on a medical aid program., Methods: We selected patients (≥20 years old) who experienced their first episode of cardiac arrest from 2004 to 2015 using data from the National Health Insurance Service database. We analyzed demographic characteristics, insurance type, urbanization of residential area, comorbidities, treatments, hospital costs, and mortality within 30 days and one year for each group. A multiple regression analysis was used to identify an association between insurance type and outcomes., Results: Among the 487,442 patients with cardiac arrest, the medical aid group (13.3% of the total) had a higher proportion of females, rural residents, and patients treated in low-level hospitals. The patients in the medical aid group also reported a higher rate of non-shockable conditions; a high Charlson Comorbidity Index; and pre-existing comorbidities, such as hypertension, diabetes mellitus, and renal failure with a lower rate of providing a coronary angiography. The national health insurance group reported a lower one-year mortality rate (91.2%), compared to the medical aid group (94%), and a negative association with one-year mortality (Adjusted OR 0.74, 95% CI 0.71-0.76). While there was no significant difference in short-term costs between the two groups, the medical aid group reported lower long-term costs, despite a higher rate of readmission., Conclusions: Medical aid coverage was an associated factor for one-year mortality, and may be the result of an insufficient delivery of long-term services as reflected by the lower long-term costs and higher readmission rates. There were differences of characteristics, comorbidities, medical and hospital factors and treatments in two groups. These differences in medical and hospital factors may display discrepancies by type of insurance in the delivery of services, especially in chronic healthcare services., Competing Interests: The authors have declared that no competing interests exist.

Background: Inter-hospital transfer (IHT) for emergency department (ED) admission is a burden to high-level EDs. This study aimed to evaluate the prevalence and ED utilization patterns of patients who underwent single and double IHTs at high-level EDs in South Korea., Methods: This nationwide cross-sectional study analyzed data from the National Emergency Department Information System for the period of 2016-2018. All the patients who underwent IHT at Level I and II emergency centers during this time period were included. The patients were categorized into the single-transfer and double-transfer groups. The clinical characteristics and ED utilization patterns were compared between the two groups., Results: We found that 2.1% of the patients in the ED (n = 265,046) underwent IHTs; 18.1% of the pediatric patients (n = 3,556), and 24.2% of the adult patients (n = 59,498) underwent double transfers. Both pediatric (median, 141.0 vs. 208.0 minutes, P < 0.001) and adult (median, 189.0 vs. 308.0 minutes, P < 0.001) patients in the double-transfer group had longer duration of stay in the EDs. Patient's request was the reason for transfer in 41.9% of all IHTs (111,076 of 265,046). Unavailability of medical resources was the reason for transfer in 30.0% of the double transfers (18,920 of 64,054)., Conclusion: The incidence of double-transfer of patients is increasing. The main reasons for double transfers were patient's request and unavailability of medical resources at the first-transfer hospitals. Emergency physicians and policymakers should focus on lowering the number of preventable double transfers., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: Survival and post-cardiac arrest care vary considerably by hospital, region, and country. In the current study, we aimed to analyze mortality in patients who underwent cardiac arrest by hospital level, and to reveal differences in patient characteristics and hospital factors, including post-cardiac arrest care, hospital costs, and adherence to changes in resuscitation guidelines., Methods: We enrolled adult patients (≥ 20 years) who suffered non-traumatic cardiac arrest from 2006 to 2015. Patient demographics, insurance type, admission route, comorbidities, treatments, and hospital costs were extracted from the National Health Insurance Service database. We categorized patients into tertiary hospital, general hospital, and hospital groups according to the level of the hospital where they were treated. We analyzed the patients' characteristics, hospital factors, and mortalities among the three groups. We also analyzed post-cardiac arrest care before and after the 2010 guideline changes. The primary end-point was 30 days and 1 year mortality rates., Results: The tertiary hospital, general hospital, and hospital groups represented 32.6%, 49.6%, and 17.8% of 337,042 patients, respectively. The tertiary and general hospital groups were younger, had a lower proportion of medical aid coverage, and fewer comorbidities, compared to the hospital group. Post-cardiac arrest care, such as percutaneous coronary intervention, targeted temperature management, and extracorporeal membrane oxygenation, were provided more frequently in the tertiary and general hospital groups. After adjusting for age, sex, insurance type, urbanization level, admission route, comorbidities, defibrillation, resuscitation medications, angiography, and guideline changes, the tertiary and general hospital groups showed lower 1-year mortality (tertiary hospital vs. general hospital vs. hospital, adjusted odds ratios, 0.538 vs. 0.604 vs. 1; P < 0.001). After 2010 guideline changes, a marked decline in atropine use and an increase in post-cardiac arrest care were observed in the tertiary and general hospital groups., Conclusion: The tertiary and general hospital groups showed lower 30 days and 1 year mortality rates than the hospital group, after adjusting for patient characteristics and hospital factors. Higher-level hospitals provided more post-cardiac arrest care, which led to high hospital costs, and showed good adherence to the guideline change after 2010., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: In-hospital mortality and short-term mortality are indicators that are commonly used to evaluate the outcome of emergency department (ED) treatment. Although several scoring systems and machine learning-based approaches have been suggested to grade the severity of the condition of ED patients, methods for comparing severity-adjusted mortality in general ED patients between different systems have yet to be developed. The aim of the present study was to develop a scoring system to predict mortality in ED patients using data collected at the initial evaluation and to validate the usefulness of the scoring system for comparing severity-adjusted mortality between institutions with different severity distributions., Methods: The study was based on the registry of the National Emergency Department Information System, which is maintained by the National Emergency Medical Center of the Republic of Korea. Data from 2016 were used to construct the prediction model, and data from 2017 were used for validation. Logistic regression was used to build the mortality prediction model. Receiver operating characteristic curves were used to evaluate the performance of the prediction model. We calculated the standardized W statistic and its 95% confidence intervals using the newly developed mortality prediction model., Results: The area under the receiver operating characteristic curve of the developed scoring system for the prediction of mortality was 0.883 (95% confidence interval [CI]: 0.882-0.884). The Ws score calculated from the 2016 dataset was 0.000 (95% CI: - 0.021 - 0.021). The Ws score calculated from the 2017 dataset was 0.049 (95% CI: 0.030-0.069)., Conclusions: The scoring system developed in the present study utilizing the parameters gathered in initial ED evaluations has acceptable performance for the prediction of in-hospital mortality. Standardized W statistics based on this scoring system can be used to compare the performance of an ED with the reference data or with the performance of other institutions.

Objective: With trends in population aging an increasing number of older patients are visiting the emergency department (ED). This study aimed to identify the characteristics of ED utilization and risk factors for in-hospital mortality in older patients who visited EDs., Methods: This nationwide observational study used National Emergency Department Information System data collected during a 2-year period from January 2016 to December 2017. The characteristics of older patients aged 70 years or older were compared with those of younger patients aged 20 to 69 years. Risk factors associated with in-hospital mortality were analyzed by multivariable logistic regression., Results: A total of 6,596,423 younger patients and 1,737,799 older patients were included. In the medical and nonmedical older patient groups, significantly higher proportions of patients were transferred from another hospital, utilized emergency medical services, had Korean Triage and Acuity Scale scores of 1 and 2, required hospitalization, and required intensive care unit admission in the older patient group than in the younger patient group. ED and post-hospitalization mortality rates increased with age; in particular, older medical patients aged 90 or older had an in-hospital mortality rate of 9%. Older age, male sex, transfer from another hospital, emergency medical service utilization, a high Korean Triage and Acuity Scale score, systolic blood pressure <100 mmHg, respiratory rate >20/min, heart rate >100/min, body temperature <36°C, and altered mental status were associated with in-hospital mortality., Conclusion: Development of appropriate decision-making algorithms and treatment protocols for high risk older patients visiting the ED might facilitate appropriate allocation of medical resources to optimize outcomes.

(1) Background: The emergency department provides lifesaving treatment and has become an entry point to hospital admission. The purpose of our study was to describe the characteristics and outcomes of patients who were admitted through the emergency department to the intensive care unit or general ward. (2) Methods: We performed a retrospective, cross-sectional, descriptive analysis using the National Emergency Department Information System, analyzing patient data including disease category, diagnosis, and mortality from 1 January 2016, to 31 December 2018. (3) Results: During the study period, about 13.6% were admitted through the emergency department. Of these, the overall in-hospital mortality was 4.6%. The frequent disease class for the intensive care unit admissions was the cardiovascular system, and the classes for the general ward admissions were as follows: injury and toxicology, digestive system, and respiratory system. Cardiovascular system-related emergencies were the predominant cause of death among patients admitted to the intensive care unit; however, oncologic complications were the leading cause of death in the general ward. (4) Conclusions: Emergency departments are incrementally utilized as the entry point for hospital admission. Health care providers need to understand emergency department admission epidemiology and prepare for managing patients with certain common diagnoses.

Background: Hyperglycemic conditions are associated with respiratory dysfunction. Although several studies have reported that insulin resistance (IR) is related to decreased lung function, the association between IR and change in lung function has been rarely studied. This study aimed to investigate the potential association of IR on annual change in lung function using a community-based prospective cohort in Korea., Methods: We selected 4827 Korean participants whose serial lung functions were assessed over 4 years using 1:3 propensity score matching. Exposure was baseline IR estimated with homeostatic model assessment (HOMA-IR), and outcomes were annual changes in lung function determined by calculating the regression coefficient using least-square linear regression analysis., Results: In the multivariate linear regression, per one unit increased log transformed HOMA-IR was associated with decline in FEV 1 %-predicted (β: - 0.23, 95% CI: - 0.36 to - 0.11) and FVC %-predicted (β: - 0.20, 95% CI: - 0.33 to - 0.08), respectively. In the generalized additive model plot, HOMA-IR showed a negative linear association with annual changes in FEV 1 %-predicted and FVC %-predicted. The suggested threshold of HOMA-IR for decline in lung function was 1.0 unit for annual change in FEV 1 %-predicted and 2.2 unit for annual change in FVC %-predicted. Age showed statistically significant effect modification on the relationship between HOMA-IR and annual change in FEV 1 %-predicted. Increased HOMA-IR was associated with the decreased annual change in FEV 1 %-predicted, particularly in older people., Conclusions: In South Korea, increased HOMA-IR was associated with decline in lung function. Since IR was related to decline in FEV 1 %-predicted, particularly in older people, tailored approaches are needed in these populations. The potential pulmonary hazard of IR needs to be confirmed in future studies.