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Background Methods Results Conclusions Deprescribing is the planned/supervised method of dose reduction or cessation of medications that might be harmful, or no longer be beneficial. Though benefits of deprescribing are debatable in improving clinical outcomes, it has been associated with decreased number of potentially inappropriate medications, which may potentially reduce the risk of adverse events among hospitalized older adults. With unclear evidence for deprescribing in this population, this study aimed to examine time‐to‐first unplanned healthcare utilization, which included 90‐day emergency department (ED) visits or hospital readmission and associated predictors, during a deprescribing intervention.A secondary data analysis of a clinical trial (Shed‐MEDS NCT02979353) was performed. Cox regression was used to compare the time‐to‐first 90‐day ED visit/readmission/death from hospital discharge for the intervention and control groups. Additionally, we performed exploratory analysis of predictors (comorbidities, functional health status, drug burden index (DBI), hospital length of stay, health literacy, food insecurity, and financial burden) associated with the time‐to‐first 90‐day ED visit/readmission/death.The hazard of first 90‐day ED visits/readmissions/death was 15% lower in the intervention versus the control group (95% CI: 0.61–1.19, p = 0.352, respectively); however, this difference was not statistically significant. For every additional number of comorbidities (Hazard ratio (HR): 1.12, 95% CI: 1.04–1.21) and each additional day of hospital length of stay (HR: 1.04, 95% CI: 1.01–1.07) were significantly associated with a higher hazard of 90‐day ED visit/readmission/death in the intervention group; whereas for each unit of increase in pre‐hospital DBI score (HR: 1.08 and HR 1.16, respectively) was significantly associated with a higher hazard of 90‐day ED visit/readmission/death in the control group.The intervention and control groups had comparable time‐to‐first 90‐day ED visit/readmission/death during a deprescribing intervention. This finding suggests that deprescribing did not result in a higher risk of ED visit/readmission/death during the 90‐day period following hospital discharge. [ABSTRACT FROM AUTHOR]

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]

Drawing on ethnic boundary‐making literature, this study investigates how Korean newspapers and readers adjusted their ethnic boundaries towards Asian migrants in response to the evolving phases of the COVID‐19 pandemic. We analyzed the extent and nature of coverage in five major newspapers on anti‐Asian racism in the US published between January 1 and May 24, 2020, along with associated reader comments. During the maintenance phase, marked by persistent concerns about the resurgence of infections, we observed the highest number of articles and the most significant disparities between the media's portrayal and reader reactions. Contrary to the newspapers, readers perceived the racist threat faced by Asian migrants differently depending on the pandemic circumstances, displaying a more flexible boundary‐making. Despite the general description of Asian diasporas as “innocent comrades” in newspapers, readers viewed the Chinese and Korean diasporas as “blameworthy foreigners,” regarding them as potential threats to the nation. We discuss factors and conditions that might have influenced the formation of transborder ethnic boundaries among Korean newspapers and the public. [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]

Introduction: Lung cancer is one of the most malignant cancers and the leading cause of cancer-related deaths worldwide, while acquired chemoresistance would represent a major problem in the treatment of non-small cell lung cancer (NSCLC) because of the reduced treatment effect and increased rates of recurrence. Methods: To establish the chemoresistant NSCLC cells, doxorubicin was treated to A549 cells over 3 months at gradually increasing concentrations from 0.03 to 0.5 µM. Real-time PCR and Western blotting were employed for investigating mRNA and protein expression of the glutathione peroxidase (GPX) protein family and multidrug resistance protein 1 (MRP1) in A549 and A549/CR cells. We also employed gas chromatography mass-spectrometry and nano electrospray ionization mass-spectrometry coupled with multivariate statistical analysis to characterize the unique metabolic and lipidomic profiles of chemoresistant NSCLC cells in order to identify potential therapeutic targets. Results: Reactive oxygen species levels were decreased, and mRNA and protein levels of GPX2 and multidrug resistance protein 1 (MRP1) were increased in A549/CR. We identified 87 metabolites and intact lipid species in A549 and A549/CR. Among these metabolites, lactic acid, glutamic acid, glycine, proline, aspartic acid, succinic acid, and ceramide, alongside the PC to PE ratio, and arachidonic acid-containing phospholipids were suggested as characteristic features of chemoresistant NSCLC cells (A549/CR). Conclusions: This study reveals characteristic feature differences between drug-resistance NSCLC cells and their parental cells. We suggest potential therapeutic targets in chemoresistant NSCLC. Our results provide new insight into metabolic and lipidomic alterations in chemoresistant NSCLC. This could be used as fundamental information to develop therapeutic strategies for the treatment of chemoresistant NSCLC patients. [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]

The article presents a study which aimed to understand from clinicians and older adults ways to optimize a proposed home-based deprescribing intervention that focuses on tailoring medications based on patient's daily and life goals. Topics include clinicians included in the study, daily activities/goals for older adults, and the need to identify older adults prototypes and design flexible deprescribing interventions that can target a broad range of older adults for maximum impact.

Purpose: Adequate physical activity (PA) can significantly contribute to the prevention of undesirable health outcomes in childhood cancer survivors (CCS). This study aimed to identify the patterns of PA and related factors in Korean CCS. Methods: Study subjects were 184 adolescents selected from an ongoing cohort study of Korean CCS and 1,840 sex- and school grade-matched controls randomly selected from the participants of the 2019 Korea Youth Risk Behavior Web-based Survey. Information on PA and sedentary behaviors was collected by self-administered questionnaire. We estimated body mass index (BMI)-adjusted odds ratio (OR) and 95% confidence interval (CI) for the advisable healthy behaviors of CCS compared with healthy controls using conditional logistic regression analysis. In addition, the associations of advisable healthy behaviors of CCS with sociodemographic and clinical factors were estimated using multiple logistic regression analysis. Results: CCS were less likely to be physically active than controls, but this finding was evident only in males. The ORs (95% CIs) for regular exercise, moderate intensity PA, vigorous intensity PA, and walking were 0.42 (0.27–0.65), 0.39 (0.24–0.63), 0.53 (0.33–0.84), and 0.64 (0.42–0.98), respectively, in male CCS compared with same-sex controls. Compared with same-sex controls, male CCS were 4.60 times and female survivors were 15.19 times more likely to sleep longer than 8 h a day. Among CCS, males were 2.92 times and 3.07 times more likely to perform moderate intensity PA and muscle-strengthening exercise, respectively, than female. Higher BMI (OR: 1.16), highest family income (OR: 3.98), and a caregiver who performed regular exercise (OR: 2.08) were positively associated with vigorous intensity PA of CCS. With increasing time after treatment completion, the probability of engaging in sedentary activity for less than 6 h per day decreased (OR = 0.89, 95% CI 0.79–1.00). Conclusion: Korean adolescent CCS were physically inactive compared with control adolescents. Several sociodemographic factors such as sex, family income, caregiver PA, and obesity level were associated with PA behaviors of CCS. Implications: Strategic effort would be needed to increase physical activity of childhood cancer survivors in adolescent period with consideration of various sociodemographic factors found in this study. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the incidence, risk factors, and clinical outcomes of pleuroparenchymal fibroelastosis (PPFE) in pediatric hematopoietic stem cell transplantation (HSCT) recipients. Methods: This single-center, retrospective, case-control study included 738 consecutive patients who underwent chest CT more than 3 months after HSCT. We identified patients who fulfilled the diagnostic criteria for PPFE and assessed their clinical characteristics and radiologic findings. Propensity score–matched analysis was performed using four covariates (age, sex, HSCT type, and primary disease). The risk factors and clinical outcomes of PPFE were analyzed using the Fine and Gray regression model and stratified log-rank test in the matched groups. Results: PPFE was identified in 4% (31/738, 8.3 ± 3.1 years, 15 males) of the pediatric HSCT recipients with a median time of 2.7 years after HSCT, and it occurred following allogeneic (5%, 15/317), autologous (4%, 15/379), or both (2%, 1/42). Matching yielded 30 and 130 cases in the PPFE and control groups, respectively. The PPFE group showed more frequent late-onset noninfectious pulmonary complications (LONIPCs) and pneumonia more than 3 months after HSCT (p < 0.05). Multivariable analysis showed a significantly higher risk of PPFE in HSCT recipients who had pneumonia more than 3 months after HSCT (hazard ratio = 10.78 [95% confidence interval: 4.29, 27.13], p < 0.001). The PPFE group showed higher mortality (73%, 22/30) and poorer median overall survival (6.8 years [95% confidence interval: 4.1, 9.5]) than the control group (p < 0.001). Conclusions: PPFE represents a severe type of LONIPC after HSCT. HSCT recipients with pneumonia after HSCT may have an increased risk of PPFE. Key Points: • The incidence of pleuroparenchymal fibroelastosis is not negligible (4%), and it can occur after either allogeneic or autologous hematopoietic stem cell transplantation. • Pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation showed poor outcome with a high mortality rate of 73% and median overall survival of 6.8 years. • After hematopoietic stem cell transplantation, pneumonia may increase the risk of pleuroparenchymal fibroelastosis development in children. • Lung biopsy should not be indicated in patients with pleuroparenchymal fibroelastosis findings on chest CT as it can cause refractory pneumothorax without helping the diagnosis. [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]

For the heterojunction composite photocatalyst, the contact interface is the key to charge carrier separation conditions. In order to present novel research through the interaction between these interfaces, the Ti based peroxo complex (TP)/red phosphorus (RP) composite system was introduced and designed to improve carrier separation and transport properties during photocatalytic hydrogen evolution. In this study, we have successfully synthesized TP/RP by facile solution process through stirring at room temperature and pressure. Regarding the specific surface area, which is one of the important factors in the photocatalytic activity, it was confirmed that the specific surface area of the TP (166.4 m2/g) and TP/RP (281.4 m2/g) samples was dramatically improved as the particle surface was oxidized based on TiH 2 (0.613 m2/g), the precursor. And the photo-induced charge carrier life time of the TP/RP was extended by approximately 60% compared to the conventional TP. Finally, excellent research results were obtained in which the photocatalytic hydrogen evolution efficiency (17.05 μmol/h) under visible-light irradiation (200 W Xenon lamp) was improved by about 3 times than that of the conventional TP sample (5.26 μmol/h). • Ti-peroxo complex (TP)/red phosphorus (RP) composite was synthesized by facile solution process at mild conditions. • TP/RP composite was designed and synthesized to improve carrier separation and transport efficiency. • The charge carrier life-time of TP/RP was extended by up to 60% compared to TP. • TP/RP composite showed an excellent hydrogen evolution of 17.05 μmol/h. [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]

Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality post cord blood transplantation (CBT). It has been suggested that the graft-versus-host disease (GVHD) and immunosuppressants have an impact on CMV infection. This study evaluated the incidence, outcomes, and risk factors of CMV infection, while focusing on GVHD and the use of immunosuppressants, in 103 children who had received CBT. Among the patients, 92.2% were positive for CMV serology, while CMV antigenemia was observed in 68.9% and CMV disease developed in 26.2%. CMV enterocolitis was the most common, followed by retinitis and pneumonia. Patients with positive CMV serology and grade II to IV GVHD were independently associated with CMV antigenemia. Recurrent CMV antigenemia was observed significantly more frequently in patients with extensive chronic GVHD. Patients with CMV disease showed significantly worse overall survival, relapse-free survival, and non-relapse mortality than those without CMV disease. In conclusion, CMV infection is common post-CBT in countries with a high rate of CMV seropositivity in the general population and is related to worse outcomes. GVHD severity is associated with the development and recurrence of CMV infection. Thus, efforts need to be made to prevent CMV infection in children post-CBT. [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]

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is a pandemic as of early 2020. Upon infection, SARS‐CoV‐2 attaches to its receptor, that is, angiotensin‐converting enzyme 2 (ACE2), on the surface of host cells and is then internalized into host cells via enzymatic machineries. This subsequently stimulates immune response factors. Since the host immune response and severity of COVID‐19 vary among individuals, genetic risk factors for severe COVID‐19 cases have been investigated. Our research group recently conducted a survey of genetic variants among SARS‐CoV‐2‐interacting molecules across populations, noting near absence of difference in allele frequency spectrum between populations in these genes. Recent genome‐wide association studies have identified genetic risk factors for severe COVID‐19 cases in a segment of chromosome 3 that involves six genes encoding three immune‐regulatory chemokine receptors and another three molecules. The risk haplotype seemed to be inherited from Neanderthals, suggesting genetic adaptation against pathogens in modern human evolution. Therefore, SARS‐CoV‐2 uses highly conserved molecules as its virion interaction, whereas its immune response appears to be genetically biased in individuals to some extent. We herein review the molecular process of SARS‐CoV‐2 infection as well as our further survey of genetic variants of its related immune effectors. We also discuss aspects of modern human evolution. [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]

Purpose: We performed a prospective single-arm trial (NCT02782754) to explore the feasibility of reducing radiation therapy (RT) dose when induction chemotherapy is combined in the treatment of intracranial germinoma with beta-human chorionic gonadotropin levels <200 mIU/mL.Methods and Materials: All patients aged 3 to 35 years from November 2012 to June 2018 were eligible for this study. Four cycles of induction chemotherapy were given before RT. Carboplatin/etoposide and cyclophosphamide/etoposide regimens were used in alternation every 3 weeks. A dose of 18 Gy of craniospinal RT for metastatic tumors, whole brain RT for basal ganglia tumors, or otherwise whole ventricular RT followed by 12.6 Gy of boost RT to the primary tumor bed was administered after induction chemotherapy. The primary endpoint of this study was progression-free survival.Results: A total of 41 consecutive patients were enrolled (location: suprasellar in 12, pineal in 12, both suprasellar and pineal in 11, and basal ganglia in 6 patients). Eleven patients had leptomeningeal seeding. Toxicity during chemotherapy was mild, except for bone marrow suppression. Tumor status after induction chemotherapy was complete response in 33 patients and partial response in 8. All but 2 patients completed the scheduled treatment. All patients but 1 remained event free during a median follow-up of 3.4 (range, 0.3-7.0) years from diagnosis. The 1 patient experienced relapse and died of tumor bleeding. Late effects were not significant except for neuroendocrine dysfunction already present at diagnosis. Vertical growth and cognitive function were not significantly disturbed by treatment.Conclusions: This study showed the feasibility of reducing RT dose/volume with induction chemotherapy in pathologically pure germinoma with elevated beta-human chorionic gonadotropin levels up to 200 mIU/mL. [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]

Objectives: To identify the optimal method for evaluation of coronary artery calcium (CAC) severity on non-electrocardiogram-gated low-dose chest computed tomography (LDCT) in a nationwide lung cancer screening registry.Methods: A total of 256 subjects were retrospectively enrolled from participants of the Korean Lung Cancer Screening (K-LUCAS) project (an LDCT lung cancer screening registry for high-risk individuals). Four board-certified cardiothoracic radiologists independently assessed CAC severity using four different scoring methods (visual assessment, artery-based grading, segment-involvement grading, and segment-based grading) and classified severity for each case using all four methods as none, mild, moderate, or severe. Agreements between the four observers for CAC category classification and between the four different scoring methods for the same observer were assessed by Fleiss kappa statistics. Evaluation time for CAC grading was compared between observers and between grading methods.Results: Interobserver agreement was moderate for visual assessment (Fleiss kappa 0.451) and substantial for the other three methods (Fleiss kappa 0.673-0.704). Agreement between the four grading methods for the same observer was substantial for three observers (Fleiss kappa 0.610-0.705) and moderate for one (Fleiss kappa 0.578). Mean evaluation time differed significantly between methods (visual assessment, 14.3 ± 11.8 s; artery-based grading, 17.6 ± 22.3 s, segment-involvement grading, 19.2 ± 6.8 s; segment-based grading, 34.2 ± 37.4 s; p < 0.01).Conclusion: Artery-based grading could be appropriate with substantial interobserver agreement and an acceptable mean evaluation time.Key Points: • CAC severity grading methods on LDCT show moderate to substantial agreements between grading methods and observers. • Artery-based grading could be appropriate with substantial interobserver agreement and a mean evaluation time of 17.6 s. • Visual assessment is disadvantaged by high interobserver variability despite having the shortest evaluation time. [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]

Long-term complications are becoming more important as the survival rate of breast cancer improves. Treatment-related myeloid neoplasm is an important long-term complication in breast cancer survivors as it has a poor prognosis. We evaluated the incidence and risk factors for the development of treatment-related acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) in patients treated with early breast cancer. We accessed the national Korean database to identify 153,565 patients diagnosed with breast cancer between January 2007 and October 2016 who underwent surgery for breast cancer. We estimated the cumulative incidence of AML/MDS and analysed the risk factors for developing AML/MDS. Of 153,575 patients, 79,321 received anthracycline-based adjuvant therapy, 14,317 received adjuvant therapy without anthracyclines and 46,657 did not receive adjuvant chemotherapy. Overall, 120 developed AML (105 in the anthracycline group, 9 in the non-anthracycline group and 6 in the control group), and 128 developed MDS (96, 9 and 23 in each group). The 10-year cumulative incidence of AML/MDS was the highest in the anthracycline group (0.221% and 0.199%), followed by the non-anthracycline group (0.122% and 0.163%) and the control group (0.024% and 0.089%). The risk of developing AML/MDS was significantly higher in patients treated with anthracyclines (hazard ratio [HR] 9.531; p < 0.0001 for AML and HR 2.559; p < 0.0001 for MDS) compared to patients in the control group. This study found that anthracycline-based adjuvant therapy significantly increased the risk of AML/MDS in Korean breast cancer patients, with the risk persisting for at least 10 years. While the cumulative incidence was low, the long-term risks of AML/MDS should be taken into account considering the poor outcomes associated with these neoplasms. • Therapy-related myeloid neoplasms are increasing as survival rates for breast cancer improve. • Anthracyclines increased the risk of AML/MDS in breast cancer patients. • Chemotherapy without anthracycline also increased the risk of AML. • Despite the low incidence, therapy-related AML/MDS should be kept in mind. [ABSTRACT FROM AUTHOR]

• pH-swing chlorination from acidic to neutral conditions effectively degraded urea. • Urea degradation was accelerated with increasing the second-stage pH. • Deprotonation of chloroureas is responsible for the accelerated urea degradation. • pH-swing chlorination successfully reduced total nitrogen during urea degradation. Urea reacts with chlorine to form chlorinated ureas (chloroureas), and fully chlorinated urea (tetrachlorourea) is further hydrolyzed into CO 2 and chloramines. This study found that the oxidative degradation of urea by chlorination was enhanced by the pH swing, wherein the reaction proceeded under an acidic pH (e.g., pH = 3) in the first stage, and the solution pH was subsequently increased to a neutral or alkaline value (e.g., pH > 7) in the second-stage reaction. The degradation rate of urea by pH-swing chlorination increased with increasing chlorine dose and pH during the second-stage reaction. The pH-swing chlorination was based on the opposite pH dependence of sub-processes comprising urea chlorination. The formation of monochlorourea was favored under acidic pH conditions; however, the subsequent conversion into di- and trichloroureas was favored under neutral or alkaline pH conditions. The deprotonation of monochlorourea (pK a = 9.7 ± 1.1) and dichlorourea (pK a = 5.1 ± 1.4) was suggested to be responsible for the accelerated reaction in the second stage under increased pH conditions. pH-swing chlorination was also effective in degrading urea at low concentrations (micromolar levels). In addition, the total nitrogen concentration significantly decreased during the degradation of urea because of the volatilization of chloramines and the release of other gaseous nitrogen compounds. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Urchin-like hollow sphere shaped ZnSn(OH) 6 particles were synthesized by 2-step hydrothermal method. • Zn 2 SnO 4 /SnO 2 phase were obtained by annealing process at 800 °C. • Rod-shaped SnO 2 were located outside of hollow sphere. • We conducted photocatalyst and quartz crystal microbalance (QCM) experiments. Abstract In this paper, we successfully synthesized urchin-like hollow sphere shaped ZnSn(OH) 6 by a 2-step hydrothermal synthesis process. During the synthesis process, the sphere shape was used as a template and formed based on Pearson's hard and soft acid and base (HSABs) theory. The rod shape on the outside of sphere is SnO 2 , it was characterized by energy dispersive spectrometer (EDS), X-ray diffraction (XRD) and Raman spectrum. The crystal phase of ZnSn(OH) 6 with different shape changes to Zn 2 SnO 4 /SnO 2 through annealing process at 800 °C. Finally, we measured photocatalyst and quartz crystal microbalance (QCM) based on the advantages of composite material and morphology-modulation. As a result, urchin-like hollow sphere shaped Zn 2 SnO 4 /SnO 2 achieved the best efficiency in all applications. [ABSTRACT FROM AUTHOR]

Abstract Efficient perovskite solar cell was achieved using a small hole transport material, Spiro-OMeTAD, after oxygen plasma treatment. It was demonstrated that the plasma treatment of hole transport layer for the solids state perovskite solar cell was enhanced power conversion efficiency. Reason for enhancing the cell performance of solar cell was good match of homo energy level between perovskite and Spiro-OMeTAD. It leads to transfer well hole carrier at Active/HTL interface. This study obtained highly improved performance by a current density of 25.4 mA/cm2, an open-circuit voltage of 1.02 V, and a fill factor of 60.2%, which resulted showed above 15% of cell efficiency. Graphical abstract Unlabelled Image Highlights • We applied the O 2 plasma treatment at Spiro-OMeTAD of HTM. • The rate of recombination reduced after plasma process due to the energy level was good matched mutually. • We achieved 15.6% power conversion efficiency and this process will be useful for solar cell industry. [ABSTRACT FROM AUTHOR]

Although progressive cardiac dysfunction is the leading cause of death in patients with Duchenne muscular dystrophy (DMD), their cardiac function measured by conventional echocardiography has been generally interpreted as normal at a young age. We aimed to determine whether two-dimensional speckle tracking echocardiography (STE) or tissue Doppler imaging (TDI) could be used for early identification and detection of cardiac dysfunction in young patients with DMD. Thirteen pediatric patients (mean age, 9.69 ± 2.2 years) with DMD and 26 age-matched healthy children (mean age, 9.65 ± 2.2 years) were included in the study. All patients were examined via conventional echocardiography, TDI, and STE. Standard echocardiographic measurements of left ventricular (LV) systolic and diastolic function were obtained. Myocardial velocities including peak-systolic and early- and late-diastolic myocardial velocities were calculated in longitudinal direction in the interventricular septum, using TDI. Speckle tracking analyses were performed by acquiring apical four-, three-, and two-chamber views with the highest possible frame rates. Conventional parameters were similar between the two groups, but heart rates were higher in patients with DMD than in controls. The results of LV diastolic function evaluated using TDI showed that annular peak velocity during early diastole (e′; 10.9 ± 1.7 vs. 14.6 ± 1.7 cm/s), e′/a′ ratio (2.0 ± 0.5 vs. 3.0 ± 0.5), E/e′ ratio (9.4 ± 1.4 vs. 7.3 ± 0.8), and myocardial performance index (0.46 ± 0.05 vs. 0.36 ± 0.06) of the mitral septal annulus among patients with DMD differed significantly from those of healthy children. A significant decrease in global longitudinal systolic strain was found in patients with DMD (− 16.6 ± 3.7 vs. − 21.2 ± 2.1), with a marked decrease in the LV basal inferolateral and basal inferior walls. In young patients with DMD who have global normal systolic function, reductions in systolic deformation parameters as well as reduced early diastolic myocardial velocities can be detected particularly in the basal inferolateral LV walls. The prognostic significance of these findings warrants further longitudinal follow-up. [ABSTRACT FROM AUTHOR]

Abstract: A simple and scalable method to fabricate a yarn‐type supercapacitor with a large specific capacitance without the aid of traditional pseudocapacitive electrode materials such as conducting polymers and metal oxides is reported. The yarn‐type supercapacitors are made from twisting reduced graphene oxide (rGO) or/and single‐walled carbon nanotubes (SWNTs)‐coated Korean traditional paper (KTP). The yarn‐type paper supercapacitor displays surprisingly enhanced electrochemical capacitance values, showing synergistic effect between rGO and SWNTs (500 times larger than performance of yarn‐type rGO‐coated paper supercapacitors). Coating rGO or/and SWNTs on KTP gives good morphology to the composite film, in which porosity increases and mean pore diameter decreases. The yarn‐type rGO/SWNT paper supercapacitor shows good mechanical strength, high flexibility, excellent electrochemical performance, and long‐life operation. The yarn‐type supercapacitor has an excellent electrochemical performance with a specific capacitance of 366 F g−1 at scan rate of 25 mV s−1 and high stability without any degradation in electrical performance up to 10 000 charge–discharge cycles. The average capacitance of rGO/SWNT@KTP yarn‐type supercapacitors is seven times higher than that of sheet‐type supercapacitors at scan rate of 500 mV s−1. The lighting of a red light‐emitting diode (LED) is demonstrated by the yarn‐type paper supercapacitor without connecting supercapacitors in series. [ABSTRACT FROM AUTHOR]

The authors discuss a study on dentin dysplasia type II caused by novel frameshift mutations in dentin sialophosphoprotein (DSPP). Highlights include genotype-phenotype correlation concerning the frameshift mutations in the dentin phosphoprotein region, gene diagram of DSPP, and Sanger sequencing chromatograms of the mutations identified.

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]

Characterization of microstructures and creep fracture characteristics of dissimilar welds between Ni-based Inconel 740H superalloy and ferritic/martensitic P92 steel has been investigated. The welds were produced by shielded metal arc (SMA) welding process with the AWS A5.11 Class ENiCrFe-3 filler metal, commonly known as Inconel 182 superalloy. Postweld heat treatment (PWHT) at 760 °C for 4 h was conducted to temper the martensite in heat-affected zone (HAZ) of P92 and to form γ′ strengthener in Inconel 740H. The deposited Inconel 182 austenitic weld metal had a columnar microstructure, and grew epitaxially from the Inconel 740H base metal. The weld interface between P92 and weld metal was characterized by the discrete line with a minimal inter-diffusion, where the fresh untempered martensite was found to be formed during PWHT due to higher Ni contents diffused from Inconel 182 into P92. The P92 base metal and Inconel 182 weld metal displayed low hardness values (~240 Hv), and the sharp hardness increase was detected at coarse-grained HAZ of P92 while the hardness minimum occurred at the fine-grained HAZ (FGHAZ). Fracture location after creep was found to shift from the P92-sided fusion line to the FGHAZ of P92 with increasing creep temperature. The carbon migration from the P92 into the weld metal was not significant at lower creep temperature (600 °C), where the crack initiation at the P92-sided fusion line appeared to be related with a significant strain incompatibility across the fusion line. At both 650 °C and 700 °C where diffusion-controlled creep was more pronounced, the type IV cracking was observed. This may be attributed to the strain localization at the weak grain boundaries of FGHAZ due to the smaller grain size as well as the lack of grain boundary strengthening by carbides. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto‐SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto‐SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto‐SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto‐SCT, and 13 subsequently underwent the second HDCT/auto‐SCT. One patient died from hepatic VOD during the second HDCT/auto‐SCT; other toxicities occurring during tandem HDCT/auto‐SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5‐year overall and event‐free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto‐SCT could be a feasible option for improving survival in children with anaplastic ependymomas. [ABSTRACT FROM AUTHOR]

Tooth and bone are major tissues involved in physiological calcification in the body, and they use similar molecular pathways for development, homeostasis, and regeneration. Harmine (HMN) is a natural small compound that stimulates osteoblast differentiation in vitro and in vivo . Here we examined the biological effect of HMN on the postnatal development of molar tooth roots and periodontal tissues. HMN supported the formation of tooth roots and periodontal tissues in developing tooth germs. In tooth germ organ culture, HMN promoted the elongation of Hertwig's epithelial root sheath (HERS) and stimulated cell proliferation in HERS and dental follicle-derived tissues, including dental papillae and dental follicles. HMN stimulated cell proliferation and cell movement of HERS-derived cells without mesenchymal cells in vitro and directly induced the phosphorylation of SMAD1/5/8 protein in HERS-derived cells. Our results indicated that HMN was the first natural small compound to stimulate postnatal development of tooth germs. [ABSTRACT FROM AUTHOR]

The effects of Ti and Ta addition on microstructure stability and tensile properties of a reduced activation ferritic/martensitic (RAFM) steel have been investigated. Ti addition of 0.06 wt% to conventional RAFM reference base steel (Fe-9.3Cr-0.93W-0.22V-0.094Ta-0.1C) was intended to promote the precipitation of nano-sized (Ti,W) carbides with a high resistance to coarsening. In addition, the Ti addition was substituted for 0.094 wt% Ta. The Ti-added RAFM steel (Ti-RAFM) exhibited a higher yield strength ( Δ YS = 32 MPa) at 600 °C than the reference base steel due to additional precipitation hardening by (Ti,W)-rich MX with an average size of 6.1 nm and the area fraction of 2.39%. However, after thermal exposure at 600 °C for 1000 h, this Ti-RAFM was more susceptible to degradation than the reference base steel; the block width increased by 77.6% in Ti-RAFM after thermal exposure while the reference base steel showed only 9.1% increase. In order to suppress diffusion rate during thermal exposure, the large-sized Ta element with low activation was added to Ti-RAFM. The Ta-added Ti-RAFM steel exhibited good properties with outstanding microstructure stability. Quantitative comparison in microstructures was discussed with a consideration of Ti and Ta addition. [ABSTRACT FROM AUTHOR]