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Purpose: We aimed to assess the effects of different exercise modalities on cardiometabolic risk factors within a comprehensive, representative sample of the Korean population. Methods: We categorized 13,971 adult participants into aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (TE), insufficient exercise, and inactive groups. Multivariable regressions were conducted to compare the incidence of chronic diseases across the groups before and after propensity score matching (PSM). Results: The TE and RE groups had significantly lower waist circumference (WC), mean blood pressure (BP), glucose and insulin-related indices, and white blood cell count (WBC) measures, with TE showing the most significant differences. The TE group had significantly lower triglyceride levels and higher high-density lipoprotein-cholesterol levels. Post-PSM, the TE group had the lowest risk for metabolic syndrome, hypertension, and diabetes, closely followed by the RE group when compared with the inactive group. In a subgroup analysis, RE consistently exhibited benefits including lower body mass index, WC, BP, total cholesterol, glucose and insulin-related indices, and WBC count when compared with AE. RE may be associated with reduced incidence of cardiometabolic diseases compared to AE alone. Conclusion: TE appears to be associated with significant reduction in cardiometabolic risk in Korean adults. RE possibly provides a more favorable cardiometabolic effect than AE. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether amplitude modulation (A-mode) ultrasound (US) provides accurate and reliable measurements comparable to those obtained using brightness modulation (B-mode) US under diverse conditions. Thirty healthy participants (15 women and 15 men) underwent measurements of subcutaneous fat thickness (SFT), muscle thickness (MT), and muscle quality (MQ) in the trapezius and biceps brachii muscles using both US modes before and after exercises designed to stimulate the respective muscles. Among the three key indices, the results demonstrated the high validity of the A-mode, with minimal mean differences (MDs) between the two devices less than 0.91 mm and intra-class correlation coefficients (ICCs) exceeding 0.95 for all measures. In addition, the correlation coefficients between the error scores and average scores for the trapezius and biceps brachii suggested no evidence of systematic error. The trapezius MT and MQ significantly increased, and the biceps brachii MT significantly increased after the exercises (p < 0.05). Notably, both the A- and B-modes exhibited the same trend in these post-exercise changes in the muscle. This study suggests that low-cost and low-resolution A-mode US provides measurements of SFT, MT, and MQ similar to the more expensive, high-resolution B-mode imaging. A-mode US is an affordable and portable alternative for muscle assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: This study addresses the limited understanding of the molecular consequences of low-dose ionizing radiation (LDIR), a relatively unexplored area compared to high-dose radiation methods. The research focuses on profiling RNA species crosslinked to the RNA-binding protein human antigen R (HuR) using LDIR and high throughput RNA sequencing. The developed method involves isolating RNA fragments crosslinked to HuR through LDIR and immunoprecipitation followed by RNA sequencing, revealing rapid degradation of target mRNAs (e.g., PAX6, ZFP91, NR2F6, and CAND2) in human cell lines. Notably, the downregulation of PAX6 and NR2F6 is identified as a protein mediating the beneficial effects of LDIR on cell viability. The findings underscore the significance of investigating post-transcriptional gene regulation under LDIR conditions. Overall, this research introduces a valuable approach for understanding the impact of LDIR on RNA dynamics, shedding light on the molecular consequences and potential therapeutic applications of low-dose ionizing radiation. Although ionizing radiation (IR) is widely used for therapeutic and research purposes, studies on low-dose ionizing radiation (LDIR) are limited compared with those on other IR approaches, such as high-dose gamma irradiation and ultraviolet irradiation. High-dose IR affects DNA damage response and nucleotide–protein crosslinking, among other processes; however, the molecular consequences of LDIR have been poorly investigated. Here, we developed a method to profile RNA species crosslinked to an RNA-binding protein, namely, human antigen R (HuR), using LDIR and high-throughput RNA sequencing. The RNA fragments isolated via LDIR-crosslinking and immunoprecipitation sequencing were crosslinked to HuR and protected from RNase-mediated digestion. Upon crosslinking HuR to target mRNAs such as PAX6, ZFP91, NR2F6, and CAND2, the transcripts degraded rapidly in human cell lines. Additionally, PAX6 and NR2F6 downregulation mediated the beneficial effects of LDIR on cell viability. Thus, our approach provides a method for investigating post-transcriptional gene regulation using LDIR. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the association between methionine (MET) metabolism and endocrine function of the pituitary gland in patients with suprasellar region tumor. Materials and methods: Twenty patients with intracranial germinoma were included in this study. Initial staging and all surveillance MET PET/CT scans and comparable serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid stimulating hormone (TSH) were analyzed. The patients were divided into two groups according to tumor location, with tumors in the suprasellar region (condition) or not (control). MET uptake of the pituitary gland (i.e., SUVR [standardized uptake value ratio]) and levels of FSH, LH, TSH were compared in the condition and control groups and in the before and after treatment phases of each group. Results: The SUVR in the control group was like that found in normal pituitary glands in previous studies, whereas the SUVR of the untreated condition group was high and that of treated condition group was low with significance compared to the control group. Serum levels of pituitary hormones in before and after treatment condition groups were significantly lower than those in the control group. The FSH and LH levels of curatively treated patients in the control group were positively correlated with SUVR with respective ß values of 3.71 and 0.98 (p <.001). The TSH level of the treated condition group was negatively correlated with SUVR (ß = -1.02, p <.001). Conclusion: This study is the first known investigation to examine the association between MET metabolism and endocrine function of the pituitary gland, and it confirmed that MET metabolism reflects endocrine function. A future study validating the result of correlation analysis is warranted. [ABSTRACT FROM AUTHOR]

Background: Small dense low-density lipoprotein cholesterol (sdLDL-C) is the lipoprotein marker among the various lipoproteins that is most strongly related to atherosclerosis. Insulin resistance (IR) can alter lipid metabolism, and sdLDL-C is characteristic of diabetic dyslipidemia. Therefore, this study sought to inspect the relationship between the triglyceride-glucose (TyG) index and mean low-density lipoprotein (LDL) particle size. Methods: In this study, a total of 128 adults participated. The correlation coefficients between various lipoproteins and the TyG index were compared using Steiger's Z test and the Spearman correlation. The independent link between the TyG index and mean LDL particle size was demonstrated by multiple linear regression analysis. To identify the TyG index cutoff value for the predominance of sdLDL particles, receiver operating characteristic curves were plotted. Results: Mean LDL particle size correlated more strongly with the TyG index than did very low-density lipoprotein, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Regression analysis demonstrated that mean LDL particle size had a strong association with the TyG index (β coefficient = -0.038, P-value < 0.001). The TyG index optimal cutoff value for sdLDL particle predominance and the corresponding area under the curve (standard error: 0.028, 95% confidence interval: 0.842–0.952) were 8.72 and 0.897, respectively, which were close to the cutoff value of diabetes risk in Koreans. Conclusions: Mean LDL particle size is more strongly correlated with the TyG index than do other lipid parameters. After correcting for confounding variables, mean LDL particle size is independently linked with the TyG index. The study indicates that the TyG index is strongly related to atherogenic sdLDL particles predominance. [ABSTRACT FROM AUTHOR]

We synthesized an amorphous Ti-based hydroperoxo complex (ATPC) using a facile method involvingonly titanium hydride (TiH2) and H2O2 under mild conditions. We chose TiH2 as the precursor because it has more reactive sites than metal oxides such as TiO2. Qualitative and quantitative optical measurements showed that our synthesized ATPC photocatalysts contained many hydroperoxo groups and various oxidation states of Ti (Ti2+, Ti3+, and Ti4+). Thus, the synthesized ATPC exhibits excellent photocatalytic properties with very fast rates of organic decolorization compared to other conventional visiblelight catalysts. The presence of many hydroperoxo complexes increases the formation of active radicals, which can degrade VOCs such as acetaldehyde in a gas phase. To test the application of the synthesized ATPC, we fabricated a filter system in an air purifier using ATPC coating layers and successfully removed the VOCs. We also proposed a possible photocatalytic oxidation mechanism with ATPC based on this study. It is important to conduct application tests as well as commercialization in photocatalytic experiments. [ABSTRACT FROM AUTHOR]

We proposed a wearable drone controller with hand gesture recognition and vibrotactile feedback. The intended hand motions of the user are sensed by an inertial measurement unit (IMU) placed on the back of the hand, and the signals are analyzed and classified using machine learning models. The recognized hand gestures control the drone, and the obstacle information in the heading direction of the drone is fed back to the user by activating the vibration motor attached to the wrist. Simulation experiments for drone operation were performed, and the participants' subjective evaluations regarding the controller's convenience and effectiveness were investigated. Finally, experiments with a real drone were conducted and discussed to validate the proposed controller. [ABSTRACT FROM AUTHOR]

In recent years, the boom of the quadcopter industry resulted in a broad range of real-world applications which highlighted the urgent need to improve quadcopter control quality. Typically, external disturbances, such as wind, parameter uncertainties caused by payload variations, or the ground effect, can severely degrade the quadcopter's altitude control performance. Meanwhile, widely used controllers like the proportional-integral-derivative control cannot guarantee control performance when the system is critically affected by factors that exhibit a high degree of variability with time. In this paper, an adaptive control algorithm is proposed to improve quadcopter altitude tracking performance in the presence of both the ground effect and a time-varying payload. First, we derive an adaptive altitude control algorithm using the sliding mode control technique to account for these uncertainties in the quadcopter dynamics model. Second, we apply Lyapunov theory to analyze the stability of the closed-loop system. Finally, we conduct several numerical simulations and experiments to validate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Background: We report dose-escalation results from an open-label, phase 1/2 trial evaluating avelumab (anti-PD-L1) in paediatric patients with refractory/relapsed solid tumours. Methods: In phase 1, patients aged < 18 years with solid (including central nervous system [CNS]) tumours for which standard therapy did not exist or had failed were enrolled in sequential cohorts of 3–6 patients. Patients received avelumab 10 or 20 mg/kg intravenously every 2 weeks. Primary endpoints were dose-limiting toxicities (DLTs) and grade ≥ 3 treatment-emergent adverse events (AEs). Results: At data cut-off (27 July 2021), 21 patients aged 3–17 years had received avelumab 10 mg/kg (n = 6) or 20 mg/kg (n = 15). One patient had three events that were classified as a DLT (fatigue with hemiparesis and muscular weakness associated with pseudoprogression; 20 mg/kg cohort). Grade ≥ 3 AEs occurred in five (83%) and 11 (73%) patients in the 10 and 20 mg/kg cohorts, respectively, and were treatment-related in one patient (7%; grade 3 [DLT]) in the 20 mg/kg cohort. Avelumab exposure in paediatric patients receiving 20 mg/kg dosing, but not 10 mg/kg, was comparable or higher compared with approved adult dosing (10 mg/kg or 800 mg flat dose). No objective responses were observed. Four patients with CNS tumours (20 mg/kg cohort) achieved stable disease, which was ongoing in two patients with astrocytoma at cut-off (for 24.7 and 30.3 months). Conclusion: In paediatric patients with refractory/relapsed solid tumours, avelumab monotherapy showed a safety profile consistent with previous adult studies, but clinical benefits were limited. [ABSTRACT FROM AUTHOR]

Studies investigating the relationship between germline telomere length and the clinical characteristics of tumors are very limited. This study evaluated the relationship between germline telomere length and the clinical characteristics of neuroblastoma. In addition, a genome-wide association study (GWAS) was performed to investigate the genetic factors associated with germline telomere length. The germline telomere length of peripheral blood mononuclear cells from 186 patients with neuroblastoma was measured by quantitative polymerase chain reaction. The association between germline telomere length and clinical characteristics, including long-term survival, was investigated. For the GWAS, genotyping was performed with a high-density bead chip (Illumina, San Diego, CA, USA). After strict quality-control checks of the samples, an association analysis was conducted. The result showed that longer germline telomeres were significantly associated with longer event-free survival (P = 0.032). To identify significantly assocated genetic markers for germline telomere length, genome wide association analysis was performed. As a result, several single nucleotide polymorphisms located in HIVEP3, LRRTM4, ADGRV1, RAB30, and CHRNA4 genes were discovered. During gene-based analysis (VEGAS2 tool), the CNTN4 gene had the most significant association with germline telomere length (P = 1.0E−06). During gene ontology analysis, susceptible genes associated with germline telomere length were mainly distributed in neurite morphogenesis and neuron development. A longer germline telomere length is associated with favorable prognostic factors at diagnosis and eventually better event-free survival in patients with neuroblastoma. In addition, the GWAS demonstrated that genetic markers and genes related to germline telomere length are associated with neurite morphogenesis and neuron development. Further research with larger cohorts of patients and functional investigations are needed. [ABSTRACT FROM AUTHOR]

Studies investigating the relationship between germline telomere length and the clinical characteristics of tumors are very limited. This study evaluated the relationship between germline telomere length and the clinical characteristics of neuroblastoma. In addition, a genome-wide association study (GWAS) was performed to investigate the genetic factors associated with germline telomere length. The germline telomere length of peripheral blood mononuclear cells from 186 patients with neuroblastoma was measured by quantitative polymerase chain reaction. The association between germline telomere length and clinical characteristics, including long-term survival, was investigated. For the GWAS, genotyping was performed with a high-density bead chip (Illumina, San Diego, CA, USA). After strict quality-control checks of the samples, an association analysis was conducted. The result showed that longer germline telomeres were significantly associated with longer event-free survival (P = 0.032). To identify significantly assocated genetic markers for germline telomere length, genome wide association analysis was performed. As a result, several single nucleotide polymorphisms located in HIVEP3, LRRTM4, ADGRV1, RAB30, and CHRNA4 genes were discovered. During gene-based analysis (VEGAS2 tool), the CNTN4 gene had the most significant association with germline telomere length (P = 1.0E−06). During gene ontology analysis, susceptible genes associated with germline telomere length were mainly distributed in neurite morphogenesis and neuron development. A longer germline telomere length is associated with favorable prognostic factors at diagnosis and eventually better event-free survival in patients with neuroblastoma. In addition, the GWAS demonstrated that genetic markers and genes related to germline telomere length are associated with neurite morphogenesis and neuron development. Further research with larger cohorts of patients and functional investigations are needed. [ABSTRACT FROM AUTHOR]

The study aimed to develop and validate whether the computed tomography (CT) radiomics analysis is effective in differentiating cardiac tumors and thrombi. For this retrospective study, a radiomics model was developed on the basis of a training dataset of 192 patients (61.9 ± 13.3 years, 90 men) with cardiac masses detected in cardiac CT from January 2010 to September 2019. We constructed three models for discriminating between a cardiac tumor and a thrombus: a radiomics model, a clinical model, which included clinical and conventional CT variables, and a model that combined clinical and radiomics models. In the training dataset, the radiomics model and the combined model yielded significantly higher differentiation performance between cardiac tumors and cardiac thrombi than the clinical model (AUC 0.973 vs 0.870, p < 0.001 and AUC 0.983 vs 0.870, p < 0.001, respectively). In the external validation dataset with 63 patients (59.8 ± 13.2 years, 26 men), the combined model yielded a larger AUC compared to the clinical model (AUC 0.911 vs 0.802, p = 0.037). CT radiomics analysis is effective in differentiating cardiac tumors and thrombi. In conclusion, the combination of clinical, conventional CT, and radiomics features demonstrated an additional benefit in differentiating between cardiac tumor and thrombi compared to clinical data and conventional CT features alone. [ABSTRACT FROM AUTHOR]

The study aimed to develop and validate whether the computed tomography (CT) radiomics analysis is effective in differentiating cardiac tumors and thrombi. For this retrospective study, a radiomics model was developed on the basis of a training dataset of 192 patients (61.9 ± 13.3 years, 90 men) with cardiac masses detected in cardiac CT from January 2010 to September 2019. We constructed three models for discriminating between a cardiac tumor and a thrombus: a radiomics model, a clinical model, which included clinical and conventional CT variables, and a model that combined clinical and radiomics models. In the training dataset, the radiomics model and the combined model yielded significantly higher differentiation performance between cardiac tumors and cardiac thrombi than the clinical model (AUC 0.973 vs 0.870, p < 0.001 and AUC 0.983 vs 0.870, p < 0.001, respectively). In the external validation dataset with 63 patients (59.8 ± 13.2 years, 26 men), the combined model yielded a larger AUC compared to the clinical model (AUC 0.911 vs 0.802, p = 0.037). CT radiomics analysis is effective in differentiating cardiac tumors and thrombi. In conclusion, the combination of clinical, conventional CT, and radiomics features demonstrated an additional benefit in differentiating between cardiac tumor and thrombi compared to clinical data and conventional CT features alone. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the value of C-11 methionine (MET) positron emission tomography (PET)/computed tomography (CT) in patients with intracranial germinoma (IG). Material and methods: We conducted a retrospective analysis of 21 consecutive patients with pathologically confirmed IGs and eight patients with intracranial non-germinomas (INGs) located in a similar region. Clinical characteristics, imaging findings, and tumor markers such as α-fetoprotein (AFP) and β-human chorionic gonadotropin (HCG) were used as clinical variables. Maximum standardized uptake value (SUVmax), tumor-to-normal tissue (T/N) ratio, and visual scoring of tumor were used as MET PET parameters. Results: All IGs were well visualized on MET PET with a three-grade visual scoring system. In addition, SUVmax of IGs was higher than that of INGs (P = 0.005). Pre-treatment (Pre-Tx) T/N ratio was significantly correlated with pre-Tx serum HCG (P = 0.031). Moreover, MET PET parameters showed significant associations with tumor location, sex, KRAS variant, and symptoms. Conclusion: MET PET/CT could be a useful diagnostic tool in patients suspected of having IGs. In addition, the MET avidity of tumor is a potential surrogate biomarker of HCG, which has been used as a diagnostic marker for IGs. Tumor MET parameters also had significant differences according to tumor locations, sex, symptoms, and KRAS mutation. However, MET avidity of tumors had no significant prognostic value. [ABSTRACT FROM AUTHOR]

Radio-resistant triple negative breast cancer (TNBC) is resistant to conventional drugs and radiation therapy. ortho-topolin riboside (oTR) has been evaluated for its anticancer activity in several types of cancer cells. However, its anti-proliferative activity in radio-resistant TNBC cells has not yet been reported. Therefore, we investigated the anti-proliferative activity of oTR in radio-resistant TNBC cells, and performed metabolome, lipidome, transcriptome, and proteome profiling to reveal the mechanisms of the anticancer activity of oTR. oTR showed cytotoxicity against radio-resistant TNBC cells with an inhibitory concentration (IC 50) value of 7.78 μM. Significantly decreased (p value < 0.05) basal and compensatory glycolysis were observed in the oTR-treated group than untreated group. Mitochondrial spare respiratory capacity, which is relevant to cell fitness and flexibility, was significantly decreased (p value < 0.05) in the oTR-treated group. The major metabolic pathways significantly altered by oTR according to metabolome, transcriptome, and proteome profiles were the glycerolipid/glycerophospholipid pathway (log 2 (FC) of MGLL = −0.13, log 2 (FC) of acylglycerol lipase = −1.35, log 2 (FC) of glycerol = −0.81), glycolysis (log 2 (FC) of EGLN1 = 0.16, log 2 (FC) of EGLN1 = 0.62, log 2 (FC) of glucose = −0.76, log 2 (FC) of lactate = −0.81), and kynurenine pathway (log 2 (FC) of KYNU = 0.29, log 2 (FC) of kynureninase = 0.55, log 2 (FC) of alanine = 0.72). Additionally, proline metabolism (log 2 (FC) of PYCR1 = −0.17, log 2 (FC) of proline = −0.73) was significantly altered in the metabolomic and transcriptomic profiles. The MAPK signaling pathway (log 2 (FC) of CCN1 = −0.15, log 2 (FC) of CCN family member 1 = −1.02) and Rap 1 signaling pathway (log 2 (FC) of PARD6B = −0.28, log 2 (FC) of PAR6B = −3.13) were also significantly altered in transcriptomic and proteomic profiles. The findings of this study revealed that oTR has anticancer activity in radio-resistant TNBC cells by affecting various metabolic pathways, suggesting the potential of oTR as a novel anticancer agent for radio-resistant TNBC patients. [Display omitted] • OTR exhibited anti-proliferative activity against MDA-MB-231/RR cells. • Three pathways were significantly altered in metabolomic, transcriptomic, and proteomic profiles by the oTR. • The proline pathway was altered in the metabolomic and transcriptomic profiles by the oTR. • The MAPK and Rap 1 signaling pathways were altered in the transcriptomic and proteomic profiles by the oTR. [ABSTRACT FROM AUTHOR]

Lung cancer is a highly prevalent and lethal malignancy worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of cancer-related deaths. In this study, the effects of co-treatment with melatonin and ortho-topolin riboside (oTR) on the cell viability and alteration of metabolites and transcripts were investigated in NSCLC cells using gas chromatography-mass spectrometry (GC-MS) and next-generation sequencing (NGS). The co-treatment of melatonin and oTR exhibited synergistic effects on the reduction of cell viability and alteration of metabolic and transcriptomic profiles in NSCLC cells. We observed that the co-treatment inhibited glycolytic function and mitochondria respiration, and downregulated glycine, serine and threonine metabolism alongside tyrosine metabolism in NSCLC cells. In the glycine, serine and threonine metabolism pathway, the co-treatment resulted in a significant 8.4-fold reduction in the expression level of the SDS gene, which encodes the enzyme responsible for the breakdown of serine to pyruvate. Moreover, co-treatment decreased the gene expression of TH, DDC, and CYP1A1 in tyrosine metabolism. Additionally, we observed that the co-treatment resulted in a significant 146.9-fold reduction in the expression of the DISC1 gene. The alteration in metabolites and transcript expressions might provide information to explain the cytotoxicity of co-treatment of melatonin and oTR in NSCLC cells. Our study presents insights into the synergistic anticancer effect of the co-treatment of melatonin and oTR, which could be a potential future therapeutic strategy for the treatment of NSCLC patients. [Display omitted] • The co-treatment of melatonin and oTR exhibits synergistic cytotoxicity in NSCLC cells. • The co-treatment of melatonin and oTR inhibits glycolytic and mitochondrial functions. • The co-treatment of melatonin and oTR downregulates glycine, serine and threonine metabolism and tyrosine metabolism. • The co-treatment of melatonin and oTR significantly reduced the expression of the DISC1 gene. [ABSTRACT FROM AUTHOR]

Over the past number of years, the power conversion efficiency of perovskite solar cells has remained at 25.5%, reflecting a respectable result for the general incorporation of organometallic trihalide perovskite solar cells. However, perovskite solar cells still suffer from long-term stability issues. Perovskite decomposes upon exposure to moisture, thermal, and UV-A light. Studies related to this context have remained ongoing. Recently, research was mainly conducted on the stability of perovskite against non-radiative recombination. This study improved a critical instability in perovskite solar cells arising from non-radiative recombination and UV-A light using a passivation layer. The passivation layer comprised a polyaniline (PANI) polymer as an interfacial modifier inserted between the active layer and the electron transport layer. Accordingly, the UV-A light did not reach the active layer and confined the Pb2+ ions at PANI passivation layer. This study optimized the perovskite solar cells by controlling the concentration, thickness and drying conditions of the PANI passivation layer. As a result, the efficiency of the perovskite solar cell was achieved 15.1% and showed over 84% maintain in efficiency in the ambient air for one month using the 65 nm PANI passivation layer. [ABSTRACT FROM AUTHOR]

Background: The triglyceride glucose (TyG) index is a noninsulin-based marker for insulin resistance (IR) in general practice. Although smoking and heavy drinking have been regarded as major risk factors for various chronic diseases, there is limited evidence regarding the combined effects of smoking and alcohol consumption on IR. This study aimed to investigate the relationship between the TyG index and smoking and alcohol consumption using two Korean population-based datasets. Methods: This study included 10,568 adults in the Korean National Health and Nutrition Examination Survey (KNHANES) and 9586 adults in the Korean Initiatives on Coronary Artery Calcification (KOICA) registry datasets. Multivariate logistic analysis was conducted to explore the relationship between smoking and alcohol consumption and the TyG index. To assess the predictive value of smoking and alcohol consumption on high TyG index, the area under the curve (AUC) were compared and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were derived. Results: The combined effect of smoking and alcohol consumption was an independent risk factor of a higher TyG index in the KNHANES (adjusted odds ratio: 4.33, P <.001) and KOICA (adjusted odds ratio: 1.94, P <.001) datasets. Adding smoking and alcohol consumption to the multivariate logistic models improved the model performance for the TyG index in the KNHANES (AUC: from 0.817 to 0.829, P <.001; NRI: 0.040, P <.001; IDI: 0.017, P <.001) and KOICA (AUC: from 0.822 to 0.826, P <.001; NRI: 0.025, P =.006; IDI: 0.005, P <.001) datasets. Conclusions: Smoking and alcohol consumption were independently associated with the TyG index. Concurrent smokers and alcohol consumers were more likely to have a TyG index that was ≥8.8 and higher than the TyG indices of non-users and those who exclusively consumed alcohol or smoking tobacco. [ABSTRACT FROM AUTHOR]

This study demonstrates a novel type of biphasic calcium phosphate (BCP) gyroid scaffolds featuring of gyroid macroporous structure and micropous BCP walls using poly(methyl methacrylate) (PMMA) microspheres as the porogen for ceramic digital light processing (DLP) technique. To tailor the microporosity of the BCP walls and the overall porosity of the dual-scale porous BCP scaffolds, the PMMA content with regard to the BCP powder was controlled in the range of 40 vol% to 70 vol%. After debinding at 600 °C and sintering at 1200 °C for 3 h, micropores were uniformly created throughout each BCP framework, while preserving 3−dimensional gyroid macroporous structures. As the PMMA content increased from 40 vol% to 70 vol%, the microporosity remarkably increased from 31.9 (±2.5) vol% to 55.2 (±1.4) vol%. This approach allowed the achievement of very high overall porosities (82.2–89.7 vol%) for the dual-scale porous scaffolds. However, all the scaffolds showed reasonable compressive strengths (0.8 MPa −2.1 MPa), which are comparable to those of cancellous bones. [ABSTRACT FROM AUTHOR]

The present study reports the manufacturing of a novel type of porous calcium phosphate scaffolds with elongated gyroid structures using digital light processing (DLP), in order to offer significantly enhanced mechanical properties. In particular, solid camphor was employed as the diluent, in order to offer sufficiently low viscosity at high solid loading for conventional layer-by-layer DLP process. Four types of porous CaP scaffolds with different percent elongation (%EL = 0, 20, 40, and 60) were manufactured, and their porous structures and mechanical properties were characterized. All porous CaP scaffolds showed that CaP walls were elongated along the z-direction, while the degree of pore elongation increased with an increase in the designed %EL. Owing to the use of controlled processing parameters, such as layer thickness and exposure time for layer-by-layer photocuring process, and carefully designed debinding process, the photocured layers could be completely bonded together with high densification after sintering at 1,200 °C for 3 h. Such elongation of a gyroid structure offered significantly enhanced mechanical properties − compressive strengths of 4.33 ± 0.26 MPa and 11.51 ± 1.75 MPa were obtained for the porous CaP scaffold with the %EL of 0 and 60, respectively. [ABSTRACT FROM AUTHOR]

Background: Large inter-individual variations in drug metabolism pose a challenge in determining 6-mercaptopurine (6MP) doses. As the last product of 6MP metabolism, DNA-thioguanine nucleotide (DNA-TGN) could reflect the efficacy of 6MP, especially in patients harboring variants in the 6MP metabolism pathway. The aim of this study was to investigate the clinical significance of DNA-TGN monitoring in Korean pediatric acute lymphoblastic leukemia (ALL) patients, focusing on the NUDT15 genotype. Methods: The subjects of this study were patients who underwent ALL treatment with 6MP. Tests for the NUDT15 and TPMT genotypes were performed, and prospective DNA-TGN and erythrocyte TGN samples were collected after two weeks or more of 6MP treatment. DNA-TGN was quantified using the liquid chromatography-tandem mass spectrometry method. Results: A total of 471 DNA-TGN measurements in 71 patients were analyzed, which ranged from 1.0 to 903.1 fmol thioguanine/μg DNA. The 6MP intensity demonstrated a significant relationship with DNA-TGN concentration (P<0.001). Patients harboring NUDT15 variants were treated with a lower dose of 6MP (P<0.001); however, there was no significant difference in DNA-TGN concentration when compared to patients carrying wild-type NUDT15 (P = 0.261). These patients also presented higher variation in DNA-TGN levels (P = 0.002) and DNA-TGN/6MP intensity (P = 0.019) compared to patients carrying wild-type NUDT15. DNA-TGN concentration did not show a significant correlation with WBC count (P = 0.093). Conclusions: Patients harboring NUDT15 variants demonstrated similar DNA-TGN concentrations even at low doses of 6MP and showed high variability in DNA-TGN. Particularly in patients with NUDT15 variants who need a reduced 6MP dose, DNA-TGN could be applied as a useful marker to monitor the therapeutic effect of 6MP. [ABSTRACT FROM AUTHOR]

Background: MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification. Methods: Fifty-eight whole exome sequencing (WES) and forty-eight whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. Results: In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients. Conclusions: This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB. [ABSTRACT FROM AUTHOR]

Background: In this study, we report the follow‐up results of reduced dose of craniospinal radiotherapy (CSRT) followed by tandem high‐dose chemotherapy (HDCT) in patients with high‐risk medulloblastoma (MB). Methods: Newly diagnosed high‐risk MB patients (metastatic disease, postoperative residual tumor >1.5 cm2, or large cell/anaplastic histology) over 3 years of age were enrolled in this study. Two cycles of pre‐RT chemotherapy, radiotherapy (RT) including reduced‐dose CSRT (23.4 or 30.6 Gy), four cycles of post‐RT chemotherapy, and tandem HDCT were administered. NanoString and DNA sequencing were performed using archival tissues. Results: In all, 40 patients were enrolled, and molecular subgrouping was possible in 21 patients (2 wingless, 3 sonic hedgehog, 8 Group 3, and 8 group 4). All patients including two patients who experienced progression during the induction chemotherapy underwent HDCT. Relapse/progression occurred only in four patients (5‐year cumulative incidence [CI] 10.4 ± 0.3%). However, six patients died from treatment‐related mortality (TRM) (four acute TRMs and two late TRMs) resulting in 18.5 ± 0.5% of 5‐year CI. Taken together, the 5‐year event‐free survival and overall survival were 71.1 ± 8.0% and 73.2 ± 7.9%, respectively. Late effects were evaluated in 25 patients and high‐tone hearing loss, endocrine dysfunction, dyslipidemia, and growth retardation were common. Conclusions: The strategy using tandem HDCT following reduced‐dose CSRT showed promising results in terms of low relapse/progression rate; however, the high TRM rate indicates that modification of HDCT regimen and careful selection of patients who can benefit from HDCT will be needed in the future study. [ABSTRACT FROM AUTHOR]

mRNA vaccines have emerged as a pivotal tool in combating COVID-19, offering an advanced approach to immunization. A key challenge with these vaccines is their need for extremely-low-temperature storage, which affects their stability and shelf life. Our research addresses this issue by enhancing the stability of mRNA vaccines through a novel cationic lipid, O,O′-dimyristyl-N-lysyl aspartate (DMKD). DMKD effectively binds with mRNA, improving vaccine stability. We also integrated phosphatidylserine (PS) into the formulation to boost immune response by promoting the uptake of these nanoparticles by immune cells. Our findings reveal that DMKD-PS nanoparticles maintain structural integrity under long-term refrigeration and effectively protect mRNA. When tested, these nanoparticles containing green fluorescent protein (GFP) mRNA outperformed other commercial lipid nanoparticles in protein expression, both in immune cells (RAW 264.7 mouse macrophage) and non-immune cells (CT26 mouse colorectal carcinoma cells). Importantly, in vivo studies show that DMKD-PS nanoparticles are safely eliminated from the body within 48 h. The results suggest that DMKD-PS nanoparticles present a promising alternative for mRNA vaccine delivery, enhancing both the stability and effectiveness of these vaccines. [ABSTRACT FROM AUTHOR]

Microglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a Gαi-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1CreERT2 mice express Cre recombinase in a tamoxifen-inducible manner and have been widely used to delete target genes in microglia, since microglia are long-lived cells and outlive peripheral macrophages, which continuously turn over and lose their gene modification over time. ATG7 is an E1-like enzyme that plays an essential role in two ubiquitin-like reactions, ATG12-ATG5 conjugation and LC3-lipidation in autophagy. To study the role of ATG7 in adult microglia, we generated Cx3cr1CreERT2:Atg7fl/fl mice and deleted Atg7 at the age of 8 weeks, and found induction of intestinal adhesion. Since intestinal adhesion is caused by excessive inflammation, these results suggest that deletion of Atg7 in intestinal macrophages even for a short time results in inflammation that cannot be rescued by replenishment with wild-type intestinal macrophages. Our finding suggests that, depending on the roles of the gene, Cx3cr1-Cre-mediated gene deletion may yield unanticipated physiological outcomes outside the central nervous system, and careful necropsy is necessary to assure the microglia-specific roles of the target gene. [ABSTRACT FROM AUTHOR]

Advances in genomic technologies and the development of targeted therapeutics are making the use of precision medicine increasingly possible. In this study, we explored whether precision medicine can be applied for the management of refractory/relapsed pediatric solid tumors by discovering actionable alterations using targeted panel sequencing. Samples of refractory/relapsed pediatric solid tumors were tested using a targeted sequencing panel covering the exonic DNA sequences of 381 cancer genes and introns across 22 genes to detect clinically significant genomic aberrations in tumors. The molecular targets were tiered from 1 to 5 based on the presence of actionable genetic alterations, strength of supporting evidence, and drug availability in the Republic of Korea. From January 2016 to October 2018, 55 patients were enrolled. The median time from tissue acquisition to drug selection was 29 d (range 14–39), and tumor profiling was successful in 53 (96.4%) patients. A total of 27 actionable alterations in tiers 1–4 were detected in 20 patients (36.4%), and the majority of actionable alterations were copy number variations. The tiers of molecular alterations were tier 1 (clinical evidence) in 4 variants, tier 2 (preclinical evidence) in 8 variants, tier 3 (consensus opinion) in 2 variants, and tier 4 (actionable variants with a drug that is available in other countries but not in the Republic of Korea) in 9 variants. In one patient with relapsed neuroblastoma with ALK F1174L mutation and ALK amplification, lorlatinib was used in a compassionate use program, and it showed some efficacy. In conclusion, using a targeted sequencing panel to discover actionable alterations in relapsed/refractory pediatric solid tumors was practical and feasible. [ABSTRACT FROM AUTHOR]

Background: Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC.Methods: In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification. Heightened levels of cancer-related genes expressed in concert with LYL1 amplification were similarly investigated through differentially expressed gene and gene set enrichment analyses. Factors associated with survival outcomes were also identified.Results: Somatic LYL1 gene amplification was observed in 22 patients (5.9%) with UCEC. Patients displaying amplification (vs. non-amplification) were significantly older at the time of diagnosis and more often were marked by non-endometrioid, high-grade, or advanced disease. In survival analysis, the amplification subset showed poorer progression-free survival (PFS) and overall survival (OS) rates (3-year PFS: 34.4% vs. 79.9%, P = 0.031; 5-year OS: 25.1% vs. 84.9%, P = 0.014). However, multivariate analyses adjusted for tumor histologic type, grade, and stage did not confirm LYL1 gene amplification as an independent prognostic factor for either PFS or OS. Nevertheless, MAPK, WNT, and cell cycle pathways were significantly enriched by LYL1 gene amplification (P < 0.001, P = 0.002, and P = 0.004, respectively).Conclusions: Despite not being identified as an independent prognostic factor in UCEC, LYL1 gene amplification is associated with other poor prognostic factors and correlated with upregulation of cancer-related pathways. [ABSTRACT FROM AUTHOR]

Ag-doped CaCu 3 Ti 4 O 12 powders were subjected to high-energy milling to produce nano-sized particles, and the resulting ceramics were analyzed in terms of the dielectric properties and sintering temperature. Ag dopant was added to CaCu 3 Ti 4 O 12 powders to reduce the sintering temperature, and the Ag-doped CaCu 3 Ti 4 O 12 ceramics were sintered at temperatures from 975 to 1125 °C to determine the optimum sintering temperature according to the various dopant ratios. The relative dielectric permittivity at a frequency of 1 kHz of the 2 mol% Ag-doped CaCu 3 Ti 4 O 12 ceramics was higher than that of undoped CaCu 3 Ti 4 O 12 ceramics. The addition of Ag to the CaCu 3 Ti 4 O 12 ceramics was observed to lower the sintering temperature from 1125 to 1075 °C. Moreover, the 2 mol% Ag-doped CaCu 3 Ti 4 O 12 ceramics prepared from nano-size particles exhibited an improved relative dielectric permittivity. These results suggest that Ag-doping and reducing the particle size of the CaCu 3 Ti 4 O 12 ceramics decreases their sintering temperature and improves their dielectric properties. [ABSTRACT FROM AUTHOR]

The article discusses the diagnosis of sulfite hypersensitivity, hypereosinophilia, using stimulation assays of dobutamine infusion, in a patient of blood eosinophil count variation history.

Assimilating the proper amount of water vapor into a numerical weather prediction (NWP) model is essential in accurately forecasting a heavy rainfall. Radar data assimilation can effectively initialize the three-dimensional structure, intensity, and movement of precipitation fields to an NWP at a high resolution (±250 m). However, the in-cloud water vapor amount estimated from radar reflectivity is empirical and assumes that the air is saturated when the reflectivity exceeds a certain threshold. Previous studies show that this assumption tends to overpredict the rainfall intensity in the early hours of the prediction. The purpose of this study is to reduce the initial value error associated with the amount of water vapor in radar reflectivity by introducing advanced remote sensing data. The ongoing research shows that errors can be largely solved by assimilating satellite all-sky radiances and global positioning system radio occultation (GPSRO) refractivity to enhance the moisture analysis during the cycling period. The impacts of assimilating moisture variables from satellite all-sky radiances and GPSRO refractivity in addition to hydrometeor variables from radar reflectivity generate proper amounts of moisture and hydrometeors at all levels of the initial state. Additionally, the assimilation of satellite atmospheric motion vectors (AMVs) improves wind information and the atmospheric dynamics driving the moisture field which, in turn, increase the accuracy of the moisture convergence and fluxes at the core of the convection. As a result, the accuracy of the timing and intensity of a heavy rainfall prediction is improved, and the hourly and accumulated forecast errors are reduced. [ABSTRACT FROM AUTHOR]

The supercapacitor based piezoelectric material composite (Na,K)NbO 3 –CaCu 3 Ti 4 O 12 (NKN–CCTO) is investigated for possible application in piezoelectric devices. (1− x )NKN– x CCTO (0.015≤ x ≤0.06) with different sintering conditions is researched for supercapacitor based piezoelectric applications. The 0.94NKN–0.06CCTO composite sintered at 975 °C shows the highest dielectric permittivity of 796. Clear SEM images of (1− x )NKN– x CCTO reveal that these compositions have high density well-crystallized structures. The composition and sintering temperature dependence of dielectric permittivities and piezoelectric coefficients, plotted in three dimensions, show that the 0.985NKN–0.015CCTO composite sintered at 1025 °C has a moderate dielectric permittivity of 405 and a piezoelectric constant of 98 pC/N. [ABSTRACT FROM AUTHOR]

CaCu 3 Ti 4 O 12 ceramic specimens for supercapacitor applications were prepared by the conventional mixed oxide method. The specimens were prepared under different sintering conditions at 1125 °C. The SEM results indicated that the mean grain size of CaCu 3 Ti 4 O 12 increased with increasing sintering time (30 min–12 h). Using SEM analysis, it was observed that at a sintering time of 2 h, CaCu 3 Ti 4 O 12 ceramic specimens had large-sized grains and the agglomerated parts consisted of small-sized grains and grain boundaries. The X-ray diffraction patterns showed single-phase ceramics with a cubic structure. Increasing sintering times led to substantial improvements in permittivity. The different spectra of frequency dependent impedance spectroscopy for large grains and small grains were compared and analyzed using Cole–Cole plots. AC conductivity as a function of the as a function of sintering times of CaCu 3 Ti 4 O 12 ceramics was investigated. [ABSTRACT FROM AUTHOR]

Radar data are assimilated into numerical prediction models to improve precipitation forecasts using three-dimensional (3D) variational (VAR) and hybrid data assimilation (DA) methods. The effect of radar DA (RDA) and prediction accuracy according to DA methods are evaluated by conducting experiments of three heavy rainfall events and analyzing the spatial pattern of accumulated precipitation, profiles of hydrometeors, and cloud microphysical processes. Increments of the initial analysis revealed that the hybrid method simulated the convective band, wind convergence in front of the cold front and a higher amount of water vapor mixing ratio compared to 3DVAR. Based on numerical experiments, the root mean square error of the total cumulative precipitation in 3DVAR was 9.68 mm lower than that of the no-RDA experiment (CTRL), whereas that of the Hybrid was 11.12 mm lower than that of CTRL. RDA improved precipitation forecasts, and Hybrid showed better precipitation forecast accuracy than 3DVAR. Although RDA indirectly changed the water vapor, rain, snow, and graupel mixing ratios, the change in the water vapor amount was the major factor affecting microphysical processes. The increase (decrease) in the water vapor mixing ratio had the greatest impact on precipitation formation (dissipation), whereas the effect of snow, rain, and graupel mixing ratios was relatively small. The results indicate that it is critical to create an environment in which water vapor can transform into precipitating hydrometeors and the hydrometeors can grow through cloud microphysical processes. The accuracy of heavy rain forecast can be improved by hybrid DA method, which can consider the model error in real time, making it more adaptable to the day-to-day changing weather conditions. • The precipitation forecast accuracy is improved through Hybrid radar data assimilation compared to 3DVAR. • The change in water vapor amount through radar data assimilaton was the major factor in affecting microphysical processes. • The increase in water vapor amount provided an environment in which it can grow into hydrometeors or supply moisture. [ABSTRACT FROM AUTHOR]

Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae. Busulfan and cyclophosphamide have been used as an alternative to TBI. Etoposide also has been widely used to enhance antileukemic effect. However, toxicities have been reported in some studies using busulfan, cyclophosphamide, and etoposide regimen. A reduced toxicity myeloablative regimen using busulfan and fludarabine showed promising results. Also, therapeutic drug monitoring (TDM) and administration of targeted doses of busulfan have been recommended to improve the outcome of hematopoietic stem cell transplantation (HSCT). In this study, we evaluated the outcome of HSCT using a targeted once-daily i.v. busulfan–fludarabine–etoposide (BuFluVP) regimen in pediatric and infant ALL. Busulfan (age ≥ 1 year, 120 mg/m 2 ; age < 1 year, 80 mg/m 2 ) was administered once daily as the first dose on day −8, and a targeted dose of busulfan was used according to the TDM results on days −7 to −5. Forty-four patients were evaluated. Donor-type neutrophil engraftment was achieved in all patients. Veno-occlusive disease occurred in 7 patients (15.9%), but all patients were successfully treated. Cumulative incidence of treatment-related mortality and relapse were 9.1% and 9.9%, respectively. One-year overall survival and event-free survival rates of all patients were 86.2% and 83.8%, respectively. Twelve patients (27.3%) were infants at diagnosis, and their 1-year overall survival rate was 83.3%. Our study demonstrated that HSCT using a targeted once-daily i.v. BuFluVP regimen showed favorable outcomes and could be an option for HSCT in pediatric and infant ALL. [ABSTRACT FROM AUTHOR]

Degenerative joint disease of the temporomandibular joints (DJD-TMJ) clinically manifests with symptoms such as orofacial pain, joint sounds and limited jaw movements. Our research group previously reported the functional necessity of a chemokine-chemokine receptor axis of CCL5-CCR5 in osteoclasts. Accumulated studies reported that this axis was involved in the pathogenesis of bone and joint destructive diseases, suggesting CCL5 as a potent biomarker. This study investigated whether or not the serum level of CCL5 can be a biomarker of DJD-TMJ and concomitantly analyzed changes in the serum and urine levels of bone markers to see whether or not changes in the rate of bone metabolism were predisposing. We enrolled 17 female subjects with diagnosed DJD-TMJ and sexually and age-matched 17 controls. The serum CCL5 level in DJD-TMJ subjects was significantly higher than that in the control subjects. Multivariate analyses indicated an association between an augmented CCL5 level and the rate of bone metabolism, especially in relatively young DJD-TMJ subjects without other systemic symptoms. A principal component analysis of serum markers and our pharmacological experiment using a postmenopausal model of ovariectomized rats suggested that an augmented serum CCL5 level specifically reflected DJD-TMJ and that covert changes in the rate of bone metabolism predisposed individuals to DJD-TMJ. [ABSTRACT FROM AUTHOR]

Objective: Aortic unfolding occurs with aging and reflects proximal aortic dilation, aortic arch widening, and decreased curvature. This study 1) evaluated the relationship between aortic unfolding measured using non-contrast cardiac-gated computed tomography (CT) and age, 2) assessed factors influencing aortic unfolding, and 3) determined the association of this measurement with coronary artery calcium (CAC) score. Methods: We reviewed the charts of 219 subjects (142 men, 77 women; mean age 54.2±9.3 years) who underwent coronary artery calcium scanning during routine health screening from December 2010 to May 2011. Multivariate regression analysis according to cardiovascular risk factors was performed. We also analyzed the relationship between aortic unfolding measurements and CAC score using stepwise multiple linear regression. Results: Mean aortic unfolding was 103.7±13.9 mm (men, 106.5±13.5 mm; women, 98.4±12.9 mm). Age, body surface area, and hypertension were exclusively associated with aortic unfolding. The association between aortic unfolding and CAC score was significant after adjustment for age and gender (β = 1.89, p = 0.017) and for Framingham risk score (β = 2.83, p<0.001). Conclusions: Aortic unfolding defined by measuring aortic width was a reproducible and practical method with non-contrast cardiac CT and associated with age, body surface area, and hypertension. CAC score, a well-established surrogate marker of cardiovascular disease, is positively associated with aortic unfolding. Further study to evaluate aortic unfolding as a potential predictor of cardiovascular risk is warranted. [ABSTRACT FROM AUTHOR]

Anticancer effects of dendropanoxide (DP) newly isolated from leaves and stem of Dendropanax morbifera Leveille were firstly investigated in this study. DP inhibited cell proliferation and induced apoptosis in dose- and time-dependent manner in MG-63 human osteosarcoma cells, which was dependent on the release of cytochrome c to the cytosol and the activation of caspases. Moreover, the DP-treated cells exhibited autophagy, as characterized by the punctuate patterns of microtubule-associated protein 1 light chain 3 (LC3) by confocal microscopy and the appearance of autophagic vacuoles by MDC staining. The expression levels of ATG7, Beclin-1 and LC3-II were also increased by DP treatment. Inhibition of autophagy by 3-methyladenine (3-MA) and wortmannin (Wort) significantly enhanced DP-induced apoptosis. DP treatment also caused a time-dependent increase in protein levels of extracellular signal-regulated kinase 1 and 2 (ERK1/2), and inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased DP-induced autophagy that was accompanied by an increased apoptosis and a decreased cell viability. These results indicate a cytoprotective function of autophagy against DP-induced apoptosis and suggest that the combination of DP treatment with autophagy inhibition may be a promising strategy for human osteosarcoma control. Taken together, this study demonstrated for the first time that DP could induce autophagy through ERK1/2 activation in human osteosarcoma cells and autophagy inhibition enhanced DP-induced apoptosis. [ABSTRACT FROM AUTHOR]

Various cancer therapies, such as surgery, radiotherapy, chemotherapy, and immunotherapy, have been used to treat cancer. Among cancer immunotherapies, stimulators of interferon genes (STING) activate various immune cells and induce them to attack cancer cells. However, the secretion of type I interferon (IFN α and β) increases after stimulation of the immune cell as a side effect of STING agonist, thereby increasing the expression of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Therefore, it is necessary to reduce the side effects of STING agonists and maximize cancer treatment by administering combination therapy. Tumor-bearing mice were treated with cisplatin, tumor-specific peptide, neoantigen, DMXAA (STING agonist), and immune checkpoint inhibitor (ICI). The combination vaccine group showed a reduction in tumor mass, an increased survival rate, and IFN-γ+ (interferon gamma) CD8+ (cluster of differentiation 8) T cells in the spleen and TME. The distribution of immune cells in the spleen and TME was confirmed, and the number of active immune cells increased, whereas that of immunosuppressive cells decreased. When measuring cytokine levels in the tumor and serum, the levels of pro-inflammatory cytokines increased and anti-inflammatory cytokines decreased. This study demonstrated that when various cancer therapies are combined to treat cancer, it can lead to an anticancer immune synergistic effect by increasing the immune response and reducing side effects. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a deadly disease regardless of sex, and a few therapeutic approaches have been fully developed at advanced stages, even if some strategies have durable clinical benefits, such as immunotherapy and chemotherapy. Ganoderma lucidum has been recognized as an organism that suppresses tumors and inflammation; however, the molecular mechanisms induced by a triterpenoid in Ganoderma lucidum, Lucidumol A, have not yet been fully explored in CRC and inflammatory responses. To this end, we extracted Lucidumol A from Ganoderma lucidum and analyzed its anticancer effect and anti-inflammatory potential in CRC cell lines and RAW264.7 macrophage-derived cell lines, respectively. A series of in vitro experiments including cell survival, wound healing, and migration assays were performed to determine the role of Lucidumol A in the CRC cell line. We also analyzed inflammatory responses using qRT-PCR, Western Blot, and ELISA in RAW 264.7 macrophaged-derived cell lines exposed to various concentrations of Lucidumol A. Lucidumol A efficiently suppressed the metastatic potential of CRC at very low concentrations. Furthermore, significant anti-inflammatory activities were observed in Lucidumol A-treated RAW264.7 cells through modulation of inflammation-associated marker genes and cytokines. In conclusion, Lucidumol A plays an important role in Ganoderma lucidum-dependent tumor suppression and anti-inflammation, suggesting different strategies to treat CRC patients, and other diseases evoked by proinflammatory cytokines, despite the need to explore further its mechanism of action. [ABSTRACT FROM AUTHOR]

Research on layered two-dimensional (2D) materials is at the forefront of material science. Because 2D materialshave variousplate shapes, there is a great deal of research on the layer-by-layer-type junction structure. In this study, we designed a composite catalyst with a dimension lower than two dimensions and with catalysts that canbe combined so that the band structures can be designed to suit various applications and cover for each other's disadvantages. Among transition metal dichalcogenides, 1T-WS2 can be a promising catalytic material because of its unique electrical properties. Black phosphorus with properly controlled surface oxidation can act as a redox functional group. We synthesized black phosphorus that was properly surface oxidized by oxygen plasma treatment and made a catalyst for water quality improvement through composite with 1T-WS2. This photocatalytic activity was highly efficient such that the reaction rate constant k was 10.31 × 10−2 min−1. In addition, a high-concentration methylene blue solution (20 ppm) was rapidly decomposed after more than 10 cycles and showed photo stability. Designing and fabricating bandgap energy-matching nanocomposite photocatalysts could provide a fundamental direction in solving the future's clean energy problem. [ABSTRACT FROM AUTHOR]

Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3%) patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing −1774 del and/or −24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR = 7.17, 95% CI = 1.79–28.67, P = 0.005). Creatinine elevation was observed in 9 patients (9.2%). Body weight ≥40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR = 8.48, 95% CI = 1.7–43.57, P = 0.010 and OR = 14.17, 95% CI = 1.34–150.35, P = 0.028). Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox. [ABSTRACT FROM AUTHOR]

The popularity of 3D content is on the rise since it provides an immersive experience to viewers. In this situation, depth-image-based rendering (DIBR) has taken on an important role in 3D technology due to its low bandwidth cost and ease of depth configuration. Noting that the viewer could record provided center view or synthesized views for illegal distribution, it is clear that copyright protection must be taken into account for the DIBR 3D content, including the possibility that one single view could be illegally distributed as 2D content. In this paper, we propose a robust watermarking scheme for DIBR 3D images by quantization on dual-tree complex wavelet transform (DT-CWT) coefficients with consideration of imperceptibility. To make the proposed scheme robust to DIBR process, two characteristics of DT-CWT are employed: approximate shift invariance and directional selectivity. We select certain coefficient sub-blocks and group the coefficient rows based on the properties of DIBR. On the extraction side, the threshold is carefully chosen with a low false positive rate. The simulation results show that the embedded watermark is stably extracted from the center view and the synthesized left and right views. In addition, even if the synthesized left and right views are distorted by general attacks, the watermark is successfully extracted. Furthermore, the proposed scheme is robust to pre-processing of the depth image and baseline adjusting, which are common processing on the DIBR system for better quality of 3D views. [ABSTRACT FROM AUTHOR]

Backgrounds: Metabolic dysfunction-associated steatotic liver disease (MASLD) has gained attention owing to its severe complications. This study aimed to explore the interaction between Mediterranean-diet (MD) adherence, genetic factors, and MASLD risk in a Korean population. Methods: In total, 33,133 individuals aged 40 years and older from the Korean Genome and Epidemiology Study (KoGES) were analyzed. Participants were assessed for MASLD based on criteria and MD adherence measured by the Korean version of the Mediterranean-Diet Adherence Screener (K-MEDAS). Individuals were categorized into two groups based on their MD adherence: high adherence (K-MEDAS > 6) and low adherence (K-MEDAS < 5). Single nucleotide polymorphism (SNP) genotypes were obtained using the Korea Biobank array. Logistic regression was used to examine the single-marker variants for genetic associations with MASLD prevalence. Results: Individuals were categorized into MASLD (10,018 [30.2%]) and non-MASLD (23,115 [69.8%]) groups. A significant interaction was observed between the rs780094 glucokinase regulatory protein (GCKR) gene and K-MEDAS on MASLD (p < 10 - 2 ). Of individuals with K-MEDAS > 6, those carrying the minor allele (C) of the GCKR gene rs780094 exhibited a lower risk of MASLD compared to those without the allele (odds ratio [OR] = 0.88 [0.85–0.91], p-value = 5.54e−13). Conclusion: The study identified a significant interaction involving the rs780094 variant near the GCKR gene, with carriers of the minor allele exhibiting a lower MASLD risk among those adhering well to the MD. Dietary habits influence the MASLD risk associated with the rs780094 allele, emphasizing the need for personalized nutrition recommendations. [ABSTRACT FROM AUTHOR]

Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level. [ABSTRACT FROM AUTHOR]

Busulfan has a narrow therapeutic range, and in children, pharmacokinetic variability has been found to be high even after the use of intravenous (i.v.) busulfan. Recently, a reduced toxicity myeloablative regimen showed promising results, but the data of busulfan pharmacokinetics in hematopoietic stem cell transplantation (HSCT) using a targeted busulfan/fludarabine regimen in children has not yet been reported. We performed therapeutic drug monitoring (TDM) after once-daily i.v. busulfan combined with fludarabine and analyzed the outcomes. Busulfan (i.v.) was administered once daily for 4 consecutive days. The daily target area under the curve (AUC) was 18,125-20,000 μg∗h/L/day (4415-4872 μmol∗min/L/day), which was reduced to 18,000-19,000 μg∗h/L/day (4384-4628 μmol∗min/L/day) after a high incidence of toxicity was observed. A total of 24 patients were enrolled. After infusion of busulfan on the first day, patients showed AUC that ranged from 12,079 to 31,660 μg∗h/L (2942 to 7712 μmol∗min/L) (median 16,824 μg∗h/L, percent coefficient of variation (%CV) = 26.5%), with clearance of 1.74-6.94 mL/min/kg (median 4.03 mL/min/kg). We performed daily TDM in 20 patients, and during the daily TDM, the actual AUC ranged from 73% to 146% of the target AUC, showing high intraindividual variability. The %CV of busulfan clearance of each individual ranged from 7.7% to 38.7%. The total dose of busulfan administered for 4 days ranged from 287.3 mg/m2 to 689.3 mg/m2. Graft failure occurred in 3 patients with total AUC less than 74,000 μg∗h/L (18,026 μmol∗min/L), and 2 patients with relatively high total AUC experienced veno-occlusive disease. Busulfan pharmacokinetics showed high inter- and intraindividual variability in HSCT using a targeted busulfan/fludarabine regimen, which indicates the need for intensive monitoring and dose adjustment to improve the outcome of HSCT. Currently, we are performing a newly designed phase II study to decrease regimen-related toxicities and reduce graft failure by setting an optimal target AUC based on this study. [Copyright &y& Elsevier]

The purpose of this study was to investigate associations between combinations of body mass index (BMI) categories plus non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) among Korean adults. We prepared the data of 5665 subjects aged 20 years and over who had visited a health promotion center. We excluded 582 subjects as they had a viral or alcoholic liver disease. According to BMI-NAFLD status, the subjects were categorized as non-obese (BMI<25 kg/m2) without NAFLD (n=2568), obese (BMI>=25 kg/m2) without NAFLD (n=572), non-obese with NAFLD (n=748), or obese with NAFLD (n=1195). The prevalence of NAFLD was highest in the obese subjects with DM (87.9%). In non-obese and non-DM subjects, the prevalence of NAFLD was lowest (18.4%). After adjustment of age, gender, waist circumference, smoking status, alcohol drinking, regular exercise, the odd ratios for DM or DM plus impaired fasting glucose (IFG) of subjects with mild NAFLD regardless of obesity were almost 2-fold compared to non-obese subjects without NAFLD. Moreover, those of subjects with moderate or severe NAFLD regardless of obesity were about 4- fold. Clinicians and investigators need to pay attention to non-obese patients with fatty liver. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine trends in the prevalence of type 2 diabetes and related conditions in Asian Americans compared with non-Hispanic whites. RESEARCH DESIGN AND METHODS--We analyzed data from the National Health Interview Survey (NHIS) from 1997 to 2008 to construct a nationally representative sample of 230,503 U.S. adults aged ≥18 years. Of these adults, 11,056 identified themselves as Asian Americans and 219,447 as non-Hispanic whites. RESULTS--The age- and sex-adjusted prevalence of type 2 diabetes was higher in Asian Americans than in whites throughout the study period (4.3-8.2% vs. 3.8-6.0%), and there was a significant upward trend in both ethnic groups (P < 0.01). BMI also was increased in both groups, but age- and sex-adjusted BMI was consistently lower in Asian Americans. In fully adjusted logistic regression models, Asian Americans remained 30-50% more likely to have diabetes than their white counterparts. In addition, Asian Indians had the highest odds of prevalent type 2 diabetes, followed by Filipinos, other Asians, and Chinese. CONCLUSIONS--Compared with their white counterparts, Asian Americans have a significantly higher risk for type 2 diabetes, despite having substantially lower BMI. Additional investigation of this disparity is warranted, with the aim of tailoring optimal diabetes prevention strategies to Asian Americans. [ABSTRACT FROM AUTHOR]

Osteoporosis is an age-related disorder that is characterized by reduced bone mass. Its prevention and treatment are important healthcare issues for maintaining social activity in aged societies. Although bone fractures mostly occur at sites of weakened cortical bone, pathophysiological and pharmacological evaluations of bone mass have tended to be predominantly assessed in trabecular bone. To statistically characterize cortical bone remodeling, we originally established multimode fluorescence imaging and artificial intelligence (AI)-driven morphometric analyses in six-month-old female rabbits with well-defined cortical remodeling, similar to that in humans. We evaluated three distinct administration frequencies of teriparatide [TPTD; human parathyroid hormone, hPTH (1–34)]: once (1/w), twice (2/w), and seven times (7/w) a week, with the same total dose (140 μg/kg/week). Our analyses revealed significant expansions of the osteocytic lacunar-canalicular system and Haversian canals accompanied by the development of cortical porosity and endosteal naïve bone formation induced by a frequent administration regimen (7/w) of TPTD; however, once-weekly (1/w) and twice-weekly (2/w) administration of TPTD showed little effect. These findings demonstrate a clear contrast between the effects of frequent and infrequent administration of TPTD on cortical bone metabolism and suggest that osteocytic bone remodeling is involved in the pharmacological action of PTH. [ABSTRACT FROM AUTHOR]