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This study introduces a deep-learning-based automatic sleep scoring system to detect sleep apnea using a single-lead electrocardiography (ECG) signal, focusing on accurately estimating the apnea–hypopnea index (AHI). Unlike other research, this work emphasizes AHI estimation, crucial for the diagnosis and severity evaluation of sleep apnea. The suggested model, trained on 1465 ECG recordings, combines the deep-shallow fusion network for sleep apnea detection network (DSF-SANet) and gated recurrent units (GRUs) to analyze ECG signals at 1-min intervals, capturing sleep-related respiratory disturbances. Achieving a 0.87 correlation coefficient with actual AHI values, an accuracy of 0.82, an F1 score of 0.71, and an area under the receiver operating characteristic curve of 0.88 for per-segment classification, our model was effective in identifying sleep-breathing events and estimating the AHI, offering a promising tool for medical professionals. [ABSTRACT FROM AUTHOR]

Deficiencies in DNA mismatch repair (MMRd) leave characteristic footprints of microsatellite instability (MSI) in cancer genomes. We used data from the Cancer Genome Atlas and International Cancer Genome Consortium to conduct a comprehensive analysis of MSI-associated cancers, focusing on indel mutational signatures. We classified MSI-high genomes into two subtypes based on their indel profiles: deletion-dominant (MMRd-del) and insertion-dominant (MMRd-ins). Compared with MMRd-del genomes, MMRd-ins genomes exhibit distinct mutational and transcriptomic features, including a higher prevalence of T>C substitutions and related mutation signatures. Short insertions and deletions in MMRd-ins and MMRd-del genomes target different sets of genes, resulting in distinct indel profiles between the two subtypes. In addition, indels in the MMRd-ins genomes are enriched with subclonal alterations that provide clues about a distinct evolutionary relationship between the MMRd-ins and MMRd-del genomes. Notably, the transcriptome analysis indicated that MMRd-ins cancers upregulate immune-related genes, show a high level of immune cell infiltration, and display an elevated neoantigen burden. The genomic and transcriptomic distinctions between the two types of MMRd genomes highlight the heterogeneity of genetic mechanisms and resulting genomic footprints and transcriptomic changes in cancers, which has potential clinical implications. [ABSTRACT FROM AUTHOR]

We characterized the therapeutic biological modes of action of several terpenes in Poria cocos F.A Wolf (PC) and proposed a broad therapeutic mode of action for PC. Molecular docking and drug-induced transcriptome analysis were performed to confirm the pharmacological mechanism of PC terpene, and a new analysis method, namely diffusion network analysis, was proposed to verify the mechanism of action against Alzheimer's disease. We confirmed that the compound that exists only in PC has a unique mechanism through statistical-based docking analysis. Also, docking and transcriptomic analysis results could reflect results in clinical practice when used complementarily. The detailed pharmacological mechanism of PC was confirmed by constructing and analyzing the Alzheimer's disease diffusion network, and the antioxidant activity based on microglial cells was verified. In this study, we used two bioinformatics approaches to reveal PC's broad mode of action while also using diffusion networks to identify its detailed pharmacological mechanisms of action. The results of this study provide evidence that future pharmacological mechanism analysis should simultaneously consider complementary docking and transcriptomics and suggest diffusion network analysis, a new method to derive pharmacological mechanisms based on natural complex compounds. [ABSTRACT FROM AUTHOR]

The growing demand for electricity, driven by factors such as the shift to carbon neutrality and economic growth, is a challenge shared by South Korea and Japan. South Korea, a peninsula nation, and Japan, an island country, which are both heavily dependent on foreign energy sources and have manufacturing-based industrial structures, are actively working to secure stable power supplies for their economic development. This article carries out a quantitative analysis of the roles of the South Korean and Japanese electric power sectors (EPSs) in their respective economies, seeking to identify differences and generate actionable insights for decision making and policy formulation. Utilizing the input–output (IO) technique with the latest available data, the analysis includes a demand-side model, a supply-side model, and a price-side model to examine various effects of the EPSs. The key findings reveal differences in the production-inducing, value-added creation, and job-creation effects between the two countries, highlighting operational disparities in their electricity sectors. Additionally, South Korea exhibits higher wage-inducing, supply shortage, and price-side effects than Japan, because of its public enterprise-oriented high-wage structure and a substantial manufacturing sector. These quantitative results provide valuable reference material for future government decisions and policy development in the EPS and emphasize the significant role and impact of the power sector in both countries. [ABSTRACT FROM AUTHOR]

Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients. [ABSTRACT FROM AUTHOR]

In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issue in iPSC-based cell therapy, it is essential to selectively remove undifferentiated iPSCs remaining in the iPSC-derived differentiated cell product prior to in vivo transplantation. In this study, we explored whether an ethanol extract of coptidis rhizoma (ECR) exhibited anti-teratoma activity and identified the active components involved in the selective elimination of undifferentiated iPSCs. Transcriptome analysis of iPSCs confirmed that cell death-related pathways were significantly altered by ECR treatment. Our results demonstrate that ECR effectively induced apoptotic cell death and DNA damage in iPSCs, and that reactive oxygen species generation, mitochondrial damage, caspase activation, and p53 activation were involved in ECR-mediated iPSC death. However, in iPSC-derived differentiated cells (iPSC-Diff), reduced cell viability and the DNA damage response were not observed after ECR treatment. We co-cultured iPSCs and iPSC-Diff and found that ECR treatment selectively removed iPSCs, whereas iPSC-Diff remained intact. Prior to in ovo implantation, ECR treatment of a mixed cell culture of iPSCs and iPSC-Diff significantly suppressed iPSC-derived teratoma formation. Among the main components of the ECR, berberine and coptisine showed selective cytotoxicity to iPSCs but not to iPSC-Diff. Together, these results indicate the usefulness of ECRs in preparing safe and effective iPSC-based therapeutic cell products with no risk of teratoma formation. [ABSTRACT FROM AUTHOR]

Background: Currently, information on sleep and circadian patterns in relation to COVID-19 or vaccination remains limited. We aimed to investigate sleep and circadian patterns according to history of COVID-19 and COVID-19 vaccination side effects. Methods: We used data from the National Sleep Survey of South Korea 2022, a nationwide cross-sectional population-based survey regarding sleep–wake behaviors and sleep problems among Korean adults. Analysis of covariance (ANCOVA) and logistic regression analyses were performed to explore the different sleep and circadian patterns according to the history of COVID-19 or self-reported side effects of the COVID-19 vaccination. Results: The ANCOVA showed that individuals with a history of COVID-19 presented a later chronotype than individuals without a history of COVID-19. Individuals who had experienced vaccine-related side effects had a shorter sleep duration, poorer sleep efficiency, and worse insomnia severity. Multivariable logistic regression analysis showed a later chronotype related to COVID-19. A short sleep duration, poorer sleep efficiency, and worse insomnia severity were associated with self-reported side effects of the COVID-19 vaccination. Conclusions: Individuals who recovered from COVID-19 had a later chronotype than those without a history of COVID-19. Individuals who had experienced vaccine-related side effects presented with poorer sleep than those without side effects. [ABSTRACT FROM AUTHOR]

Featured Application: This work assesses and compares the respective economic effects of the same amount of production or investment in the natural gas supply sector in South Korea and Japan. This study examines the role of the natural gas supply sector in the national economy by applying input–output analysis to South Korea and Japan. Specifically, the production-inducing effect, value-added creation effect, wage-inducing effect, employment-inducing effect, supply shortage effect, and price-inducing effect were analyzed using an input–output table of South Korea and Japan. As a result, the production-inducing effect, value-added creation effect, and employment-inducing effect of same investment amount in the natural gas supply sector were greater in Japan than in South Korea. On the other hand, the wage-inducing effect of an investment of USD 1 in the natural gas supply sector was found to be greater in South Korea than in Japan. In addition, the supply shortage effect and price-inducing effect in the natural gas supply sector were greater in South Korea than in Japan. The causes of differences in analysis results for each country and their implications were discussed. The results of this study could be a useful reference for the government to establish policies related to natural gas supply in the future. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated. A cell viability assay showed that LCD had anti-apoptotic properties in MG132-induced oxidative-stressed pNSCs. It was confirmed that apoptosis was reduced in pNSCs treated with LCD through 7-AAD/Annexin Ⅴ staining and cleaved caspase3. These effects of LCD were mediated through an interaction with JunD and through the EGFR/AKT and JNK signaling pathways. These findings suggest that LCD could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat kinase 2 (LRRK2) gene mutation is an autosomal dominant mutation associated with Parkinson's disease (PD). Among LRRK2 gene mutations, the LRRK2 G2019S mutation is frequently involved in PD onset. Currently, diverse gene correction tools such as zinc finger nucleases (ZFNs), helper-dependent adenoviral vector (HDAdV), the bacterial artificial chromosome-based homologous recombination (BAC-based HR) system, and CRISPR/Cas9-homology-directed repair (HDR) or adenine base editor (ABE) are used in genome editing. Gene correction of the LRRK2 G2019S mutation has been applied whenever new gene therapy tools emerge, being mainly applied to induced pluripotent stem cells (LRRK2 G2019S-mutant iPSCs). Here, we comprehensively introduce the principles and methods of each programmable nuclease such as ZFN, CRISPR/Cas9-HDR or ABE applied to LRRK2 G2019S, as well as those of HDAdV or BAC-based HR systems used as nonprogrammable nuclease systems. [ABSTRACT FROM AUTHOR]

Muscle atrophy in postmenopausal women is caused by estrogen deficiency and a variety of inflammatory factors, including tumor necrosis factor alpha (TNFα). Paeoniflorin (PNF), a natural compound with anti-inflammatory properties, improves estradiol synthesis. Here, we demonstrate that PNF inhibits the progression of TNFα-induced skeletal muscle atrophy after menopause by restoring mitochondrial biosynthesis. Differentiated myoblasts damaged by TNFα were restored by PNF, as evident by the increase in the expression of myogenin (MyoG) and myosin heavy chain 3 (Myh3)—the markers of muscle differentiation. Moreover, diameter of atrophied myotubes was restored by PNF treatment. TNFα-repressed nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) (a major regulator of mitochondrial biosynthesis) were restored by PNF, via regulation by estrogen receptor alpha (ERα), an upregulator of NRF1. This mechanism was confirmed in ovariectomized (OVX) mice with a ~40% reduction in the cross-sectional area of the anterior tibialis muscle. OVX mice administered PNF (100, 300 mg/kg/day) for 12 weeks recovered more than ~20%. Behavioral, rotarod, and inverted screen tests showed that PNF enhances reduced muscle function in OVX mice. ERα restored expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) (mitochondrial fusion markers) and dynamin-related protein (DRP1) and fission 1 (FIS1) (mitochondrial fission markers). Therefore, PNF can prevent muscle atrophy in postmenopausal women by inhibiting dysfunctional mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

p53 is a transcription factor that is activated under DNA damage stress and regulates the expression of proapoptotic genes including the expression of growth arrest genes to subsequently determine the fate of cells. To investigate the functional differences of polymorphic p53 codon 72, we constructed isogenic lines encoding each polymorphic p53 codon 72 based on induced pluripotent stem cells, which can endogenously express each polymorphic p53 protein only, encoding either the arginine 72 (R72) variant or proline 72 (P72) variant, respectively. We found that there was no significant functional difference between P72 and R72 cells in growth arrest or apoptosis as a representative function of p53. In the comprehensive analysis, the expression pattern of the common p53 target genes, including cell cycle arrest or apoptosis, was also increased regardless of the polymorphic p53 codon 72 status, whereas the expression pattern involved in metabolism was decreased and more significant in R72 than in P72 cells. This study noted that polymorphic p53 codon 72 differentially regulated the functional categories of metabolism and not the pathways that determine cell fate, such as growth arrest and apoptosis in cells exposed to genotoxic stress. [ABSTRACT FROM AUTHOR]

An interrelationship between psychological and physical health is generally accepted in the field of sports medicine. This preliminary study explored the association between emotional changes and functional outcomes and aimed to describe how each aspect progresses during postoperative rehabilitation. Four collegiate student-athletes (1 female and 3 males) who underwent supervised postoperative rehabilitation due to a lower-extremity injury volunteered for participation in the study. Emotion was quantified using a visual analogue scale prior to and after each session while self-reported function using the Lower-extremity Functional Scale was assessed every eight sessions throughout rehabilitation. There was a moderate correlation between emotional changes and functional outcomes (r = 0.58, p < 0.0001). After the first emotional improvement, patients experienced six emotional deteriorations (28% of the entire rehabilitation period; F49,297 = 2.25, p < 0.0001), while their function consistently increased (F49,147 = 17.39, p < 0.0001). Clinicians should be aware of the relationship between emotional changes and functional progression as well as the occurrence of emotional fluctuations when supervising and consulting patients during postoperative rehabilitation. A larger study is warranted to generalize the results. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in reprogramming techniques, a primitive neural stem cell (pNSC) derived from PD patient induced pluripotent stem cells (iPSCs) could be potentially used as a reproducible and reliable experimental system to analyze the effect of the leucine-rich repeat kinase 2 G2019S mutation (LK2GS) in neural cells. Here, we investigated the advantages of such a model system through quantitative proteomic analysis of pNSCs from normal control iPSCs and familial PD patient iPSCs harboring LK2GS. We confirmed that the expression of molecules known to be involved in PD pathogenesis, such as oxidative stress-, cell adhesion-, and cytoskeleton-related proteins, were altered in the LK2GS pNSC. In addition, we showed that down-regulation of Ku80, which was found in the proteomic analysis with LK2GS pNSCs, resulted in apoptosis induced by DNA damage response. Taken together, we suggest that pNSCs from PD iPSCs could provide a reliable and useful model system to study PD. Moreover, the highly expandable pNSC is suitable for multi-omics approaches to understand PD pathologies and discover therapeutic targets for PD. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) are regarded as a promising option for cell-based regenerative medicine. To obtain safe and efficient iPSC-based cell products, it is necessary to selectively eliminate the residual iPSCs prior to in vivo implantation due to the risk of teratoma formation. Bee venom (BV) has long been used in traditional Chinese medicine to treat inflammatory diseases and relieve pain, and has been shown to exhibit anti-cancer, anti-mutagenic, anti-nociceptive, and radioprotective activities. However, the potential benefits of BV in iPSC therapy, particularly its anti-teratoma activity, have not been examined. In this study, we found that BV selectively induced cell death in iPSCs, but not in iPSC-derived differentiated cells (iPSCs-Diff). BV rapidly disrupted cell membrane integrity and focal adhesions, followed by induction of apoptosis and necroptosis in iPSCs. We also found that BV remarkably enhanced intracellular calcium levels, calpain activation, and reactive oxygen speciesgeneration in iPSCs. BV treatment before in ovo grafting efficiently prevented iPSC-derived teratoma formation. In contrast, no DNA damage was observed in iPSCs-Diff following BV treatment, further demonstrating the safety of BV for use with iPSCs-Diff. Taken together, these findings show that BV has potent anti-teratoma activity by eliminating residual iPSCs, and can be used for the development of effective and safe iPSC-based cell therapies. [ABSTRACT FROM AUTHOR]

We aimed to describe temporal trends in emergency department (ED) visits of patients with atrial fibrillation (AF) over 12 years. A repeated cross-sectional analysis of ED visits in AF patients using the Korean nationwide claims database between 2006 and 2017 were conducted. We identified AF patients who had ≥1 ED visits. The incidence of ED visits among total AF population, cause of ED visit, and clinical outcomes were evaluated. During 12 years, the annual numbers of AF patients who attended ED at least once a year continuously increased (40,425 to 99,763). However, the annual incidence of ED visits of AF patients was stationary at about 30% because the number of total AF patients also increased during the same period. The most common cause of ED visits was cerebral infarction. Although patients had a higher risk profile over time, the 30-day and 90-day mortality after ED visit decreased over time. ED visits due to ischemic stroke, intracranial hemorrhage, and myocardial infarction decreased, whereas ED visits due to AF, gastrointestinal bleeding, and other major bleeding slightly increased among total AF population over 12 years. A substantial proportion of AF patients attended ED every year, and the annual numbers of AF patients who visited the ED significantly increased over 12 years. Optimized management approaches in a holistic and integrated manner should be provided to reduce ED visits of AF patients. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) have similar properties to embryonic stem cells in terms of indefinite self-renewal and differentiation capacity. After in vitro differentiation of iPSCs, undifferentiated iPSCs (USCs) may exist in cell therapy material and can form teratomas after in vivo transplantation. Selective elimination of residual USCs is, therefore, very important. Prunellae Spica (PS) is a traditional medicinal plant that has been shown to exert anti-cancer, antioxidant, and anti-inflammatory activities; however, its effects on iPSCs have not been previously characterized. In this study, we find that ethanol extract of PS (EPS) effectively induces apoptotic cell death of USCs through G2/M cell cycle arrest, generation of intracellular reactive oxygen species, alteration of mitochondrial membrane potentials, and caspase activation of USCs. In addition, EPS increases p53 accumulation and expression of its downstream targets. In p53 knockout (KO) iPSCs, the EPS did not induce apoptosis, indicating that EPS-mediated apoptosis of USCs was p53-dependent. In addition, EPS was not genotoxic towards iPSCs-derived differentiated cells. EPS treatment before injection efficiently prevented in ovo teratoma formation of p53 wild-type (WT) iPSCs but not p53KO iPSCs. Collectively, these results indicate that EPS has potent anti-teratoma activity and no genotoxicity to differentiated cells. It can, therefore, be used in the development of safe and efficient iPSC-based cell therapies. [ABSTRACT FROM AUTHOR]

As the uses of conversational agents increase, the affective and social abilities of agents become important with their functional abilities. Agents that lack affective abilities could frustrate users during interaction. This study applied personality to implement the natural feedback of conversational agents referring to the concept of affective computing. Two types of feedback were used to express conversational agents' personality: (1) visual feedback and (2) verbal cues. For visual feedback, participants (N = 45) watched visual feedback with different colors and motions. For verbal cues, participants (N = 60) heard different conditions of agents' voices with different scripts. The results indicated that the motions of visual feedback were more significant than colors. Fast motions could express distinct and positive personalities. Different verbal cues were perceived as different personalities. The perceptions of personalities differed according to the vocal gender. This study provided design implications for personality expressions applicable to diverse interfaces. [ABSTRACT FROM AUTHOR]

We evaluate the accuracy of whole body muscle mass (WBMM) and appendicular skeletal muscle mass (ASMM) assessed by bioelectrical impedance analysis (BIA) using an InBody770 machine (InBody, Seoul, Korea) referenced to dual-energy X-ray absorptiometry (DXA) in 507 people (mean age 63.7 ± 10.8 years, body mass index (BMI) 25.2 ± 3.5 kg/m2). Mean WBMMs measured by BIA and DXA were 49.3 ± 6.6 kg and 46.8 ± 6.5 kg in men and 36.1 ± 4.7 kg and 34.0 ± 4.8 kg in women, respectively. The respective effect sizes and 95% confidence intervals (CIs) for the difference were 2.49 (2.22–2.76) for men, and 2.12 (1.91–2.33) for women. Mean ASMMs measured by BIA and DXA were 22.1 ± 3.3 kg and 19.9 ± 3.2 kg in men, and 15.3 ± 2.5 kg and 13.5 ± 2.2 kg in women, respectively. The respective effect sizes and 95% CIs for the difference were 2.26 (2.10–2.41) for men and 1.75 (1.65–1.87) for women. The BIA clearly overestimated WBMM by 2.28 kg and ASMM by 1.97 kg compared with DXA. Using BMI, gender, and fat percentage, we derive equations that improved the residuals to <2 kg between methods from 38.29% to 85.91% for WBMM and 52.78% to 97.02% for ASMM. [ABSTRACT FROM AUTHOR]