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The aim of this study was to examine genetic variations underlying the early neurodevelopmental outcome of developmental disabilities (DDs). The study cohort consisted of 191 children with DDs. Diagnosis was assessed at baseline and at the index age (72-84 months). Exome sequencing was conducted and putative risk variants were identified. According to the diagnostic improvement, children were categorized into the improvement group (n = 19) and the non-improvement group (n = 172). Compared to the non-improvement group, the improvement group had lower number of risk variants in known DD genes and haploinsufficient genes, and lower number of overall putative risk variants. Our results may serve as a preliminary basis for developing a model that informs clinical outcome by sequencing analysis.

Abstract The regeneration of epithelia is crucial for maintaining intestinal homeostasis. Irisin is an exercise-induced hormone originally found to be secreted by skeletal muscles, thereby regulating energy metabolism. Recent studies have revealed that irisin protected against gut inflammation. However, the direct effects of irisin on the intestinal epithelial cells remain to be elucidated. In this study, mouse intestinal organoids were used to assess the effects of irisin on the proliferation of the intestinal epithelial cells. At a concentration of 100 ng/mL irisin significantly increased the growth of the intestinal organoids and upregulated the Wnt/β-catenin and focal adhesion kinase (FAK) signaling pathway genes. Notably, a FAK inhibitor 14 blocked the effects of irisin on the proliferation of the intestinal epithelial cells by inhibiting FAK phosphorylation, as well as the expressions of Wnt target genes. Furthermore, irisin (100 ng/mL) improved the recovery of the intestinal organoids from cellular damages caused by TNF-α, and markedly increased the expression of Wnt target genes in the intestinal epithelial cells. Taken together, irisin activates Wnt/β-catenin and FAK signaling pathways in the intestinal epithelial cells, thereby promoting intestinal epithelial self-renewal under normal homeostatic conditions and intestinal epithelial regeneration upon damages.

To expand the scale of spiking neural networks (SNNs), an interface circuit that supports multiple SNN cores is essential. This circuit should be designed using an asynchronous approach to leverage characteristics of SNNs similar to those of the human brain. However, the absence of a global clock presents tim-ing issues during implementation. Hence, we propose an intermediate latching template to establish asynchronous nonlinear connectivity with multipipeline processing between multiple SNN cores. We design arbitration and distribu-tion blocks in the interface circuit based on the proposed template and fabri-cate an interface circuit that supports four SNN cores using a full-custom approach in a 28-nm CMOS (complementary metal-oxide-semiconductor) FDSOI (fully depleted silicon on insulator) process. The proposed template can enhance throughput in the interface circuit by up to 53% compared with the conventional asynchronous template. The interface circuit transmits spikes while consuming 1.7 and 3.7 pJ of power, supporting 606 and 59 Mevent/s in intrachip and interchip communications, respectively.

Abstract Background Intensive care unit‐acquired weakness (ICU‐AW) is a syndrome characterized by a long‐term muscle weakness often observed in sepsis‐surviving patients during the chronic phase. Although ICU‐AW is independently associated with increased mortality, effective therapies have yet to be established. Programmed death‐1 (PD‐1) inhibitors have attracted attention as potential treatments for reversing immune exhaustion in sepsis; however, its impact on ICU‐AW remains to be elucidated. Here, we study how PD‐1 deficiency affects sepsis‐induced skeletal muscle dysfunction in a preclinical sepsis model. Methods Chronic sepsis model was developed by treating wild‐type (WT) and PD‐1 knockout (KO) mice with caecal slurry, followed by resuscitation with antibiotics and saline. Mice were euthanized on days 15–17. Body weights, muscle weights, and limb muscle strengths were measured. Interleukin 13 (IL‐13) and PD‐1 expressions were examined by flow cytometry. Messenger RNA (mRNA) expressions of slow‐twitch muscles were measured by reverse transcription and quantitative polymerase chain reaction (RT‐qPCR). In an in vitro study, C2C12 myotubes were treated with lipopolysaccharide (LPS) and recombinant IL‐13 followed by gene expression measurements. Results WT septic mice exhibited decreased muscle weight (quadriceps, P

This study, using Korean-English Encyclopedia of Korean Culture as a case, investigates the principled design and methodologies of headwords essential for crafting culturally-informed dictionaries with educational functionalities in the field of Korean studies. In a broader context, this study aims to contribute to the academic discourse surrounding the creation of cultural encyclopedias within the realm of Korean studies. Specifically, it initiates with an analysis of the essence and characteristics of the Korean-English Encyclopedia of Korean Culture. Subsequently, it proceeds to outline the theoretical underpinnings of headword design, offer an overview of the collected data, and delineates the headword extraction methods. Additionally, this study is anticipated to provide inspiration for the scholarly advancement of cultural encyclopedias with educational objectives within the context of Korean studies.

Abstract The advent of artificial intelligence (AI) has enabled a comprehensive exploration of materials for various applications. However, AI models often prioritize frequently encountered material examples in the scientific literature, limiting the selection of suitable candidates based on inherent physical and chemical attributes. To address this imbalance, we generated a dataset consisting of 1,453,493 natural language-material narratives from OQMD, Materials Project, JARVIS, and AFLOW2 databases based on ab initio calculation results that are more evenly distributed across the periodic table. The generated text narratives were then scored by both human experts and GPT-4, based on three rubrics: technical accuracy, language and structure, and relevance and depth of content, showing similar scores but with human-scored depth of content being the most lagging. The integration of multimodal data sources and large language models holds immense potential for AI frameworks to aid the exploration and discovery of solid-state materials for specific applications of interest.

Abstract Low body mass index is closely related to a high risk of Alzheimer’s disease (AD) and related biomarkers including amyloid-β (Aβ) deposition. However, the association between sarcopenia and Aβ-confirmed AD remains controversial. Therefore, we investigated the relationship between sarcopenia and the AD continuum. We explored sarcopenia’s association with clinical implications of participants on the AD continuum. We prospectively enrolled 142 participants on the AD continuum (19 with preclinical AD, 96 with mild cognitive impairment due to AD, and 28 with AD dementia) and 58 Aβ-negative cognitively unimpaired participants. Sarcopenia, assessed using dual-energy X-ray absorptiometry and hand grip measurements, was considered a predictor. AD continuum, defined by Aβ deposition on positron emission tomography served as an outcome. Clinical severity in participants on the AD continuum assessed using hippocampal volume, Mini-Mental State Examination (MMSE), Seoul Verbal Learning Test (SVLT), and Clinical Dementia Rating Scale Sum of Boxes Scores (CDR-SOB) were also considered an outcome. Sarcopenia (odds ratio = 4.99, p = 0.004) was associated independently with the AD continuum after controlling for potential confounders. Moreover, sarcopenia was associated with poor downstream imaging markers (decreased hippocampal volume, β = − 0.206, p = 0.020) and clinical outcomes (low MMSE, β = − 1.364, p = 0.025; low SVLT, β = − 1.077, p = 0.025; and high CDR-SOB scores, β = 0.783, p = 0.022) in participants on the AD continuum. Sarcopenia was associated with the AD continuum and poor clinical outcome in individuals with AD continuum. Therefore, our results provide evidence for future studies to confirm whether proper management of sarcopenia can effective strategies are required for sarcopenia management to prevent the AD continuum and its clinical implications.

ABSTRACTHarmful substances like the cyanotoxin microcystin-leucine-arginine (MC-LR) are commonly found in eutrophic freshwater environments, posing risks to aquatic organisms. The water flea, Daphnia, is a well-established model organism for environmental toxicology research. Nevertheless, there is currently insufficient research on the genes that respond to MC-LR in Daphnia galeata. This study aimed to gain insights into the notable genes that react significantly to MC-LR. In this study, we generated an extensive RNA-Seq sequences isolated from the D. galeata HK strain, Han River in Korea. This strain was nourished with a diet of the green microalga Chlorella vulgaris and treated with pure MC-LR at a concentration of 36 ug/L. The transcriptome profile in response to the MC-LR treatment was obtained and 336 differentially expressed genes were subjected to Gene Ontology (GO) and euKaryotic Orthologous Groups of proteins analyses. GO enrichment analysis showed that chemical stimulus, amino sugar metabolic and catabolic process, oxidative stress, and detoxification were highly enriched, in reverse, proteolysis and fucosylation were underpresented. Detoxification process related genes such as peroxidase-like, chorion, and thyroid peroxidase-like were enriched for eliminating or neutralizing MC_LR from an organism's body. Furthermore, functional protein classification revealed an upregulation of lipid and inorganic ion transport processes, while amino acid and carbohydrate transport processes were found to be downregulated. These findings offer insights into how organisms respond to ecotoxic stimuli, providing valuable information for understanding adaptation or defense pathways.

Purpose This study aimed to evaluate the effectiveness of using the severity of hyperechoic pancreas (HP) observed on preoperative ultrasonography (US) as a predictor of clinically relevant postoperative pancreatic fistula (CR-POPF). Methods A retrospective study was conducted with 94 patients who underwent pancreatectomy between April 2006 and March 2021. The severity of HP on US was classified into two categories (normal to mild vs. moderate to severe [obvious HP]). Multiple preoperative and intraoperative parameters were analyzed to predict CR-POPF. Results Out of the 94 patients, CR-POPF occurred in 21 (22%) patients, and obvious HP was observed in 30 (32%). Univariate analysis revealed that moderate to severe HP (obvious HP) was significantly associated with an increased incidence of CR-POPF (P

Abstract Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.

Metal-organic frameworks (MOFs) are attractive materials with easily tunable porous structures. Their selective carbon dioxide (CO2) capture ability can be varied by altering the functionality of the organic ligands. However, rule-based approaches to tuning and developing MOFs with high CO2 capture and conversion abilities are hindered by the numerous possible combinations of metal ions and organic linkers. Recently, machine learning (ML) has been applied to unravel key descriptors in predicting the performance of MOFs. This review summarizes recent advancements in ML models for MOFs in CO2 capture and utilization, including high-throughput screening, neural network interatomic potential, and generative models. The development of sophisticated ML models for designing high-performance MOFs will play a critical role in addressing climate change in the future. Finally, the main challenges and limitations of current approaches in designing high-performance MOFs are discussed.

Summary: Cannabinoids interact with cannabinoid receptors, influencing diverse central nervous system (CNS) and peripheral functions, including anxiety, depression, and cognition. CB1 and CB2 receptors modulate signaling cascades via G-protein coupling, with anandamide acting as an endogenous ligand for CB1 receptors. LY-2183240, a putative endocannabinoid transport blocker, elevates brain anandamide levels, showing therapeutic potential in pain management and alcohol-related behaviors. LY-2183240 enhances neuronal excitability and is classified as a new psychoactive substance (NPS). However, its precise cellular mechanisms within the CNS remain poorly understood. In this study, the effect of LY-2183240 on cortical neurons and reward-seeking behavior is investigated. Our results indicate enhanced neuronal excitability and reward-seeking behavior induction by LY-2183240, shedding light on its pharmacological profile and NPS-associated risks. Our research underscores the importance of further understanding the cellular mechanisms of LY-2183240 to inform regulatory efforts and mitigate public health risks.

Attending to heartbeats for interoceptive awareness initiates distinct electrophysiological responses synchronized with the R-peaks of an electrocardiogram (ECG), such as the heartbeat-evoked potential (HEP). Beyond HEP, this study proposes heartbeat-related spectral perturbation (HRSP), a time–frequency map of the R-peak locked electroencephalogram (EEG), and explores its characteristics in identifying interoceptive attention states using a classification approach. HRSPs of EEG brain components specified by independent component analysis (ICA) were used for the offline and online classification of interoceptive states. A convolutional neural network (CNN) designed specifically for HRSP was applied to publicly available data from a binary-state experiment (attending to self-heartbeats and white noise) and data from our four-state classification experiment (attending to self-heartbeats, white noise, time passage, and toe) with diverse input feature conditions of HRSP. From the dynamic state perspective, we evaluated the primary frequency bands of HRSP and the minimal number of averaging epochs required to reflect changing interoceptive attention states without compromising accuracy. We also assessed the utility of group ICA and models for classifying HRSP in new participants. The CNN for trial-by-trial HRSP with actual R-peaks demonstrated significantly higher classification accuracy than HRSP with sham, i.e., randomly positioned, R-peaks. Gradient-weighted class activation mapping highlighted the prominent role of theta and alpha bands between 200–600 ms post-R-peak—features absent in classifications using sham HRSPs. Online classification benefits from employing a group ICA and classification model, ensuring reliable accuracy without individual EEG precollection. These results suggest HRSP’s potential to reflect interoceptive attention states, proposing transformative implications for clinical applications.

This study investigates the potential of novel probiotic strains, a 1:1 mix of Bifidobacterium longum RAPO and Lactiplantibacillus plantarum LRCC5264, to alleviate atopic dermatitis (AD). In vitro, the probiotics at 1 × 106 CFU/mL increased anti-inflammatory (interleukin-6; IL6) and reduced pro-inflammatory (IL9) cytokine expression in LPS-stimulated RAW 264.7 cells. In an 2,4-dinitrochlorobenzene-induced AD mouse model, treatment with the probiotics (1 × 106 CFU/day) for eight weeks exhibited significant reductions in dermatitis score, plasma immunoglobulin E, transepidermal water loss, and mRNA expression of ceramidase in the skin. Furthermore, the probiotic consumption suppressed Il9 mRNA expression in the skin and reduced eotaxin-1, eosinophil infiltration, and epidermal thickness. Gut microbiota analysis revealed probiotic consumption increased relative abundances of Alistipes and Ruminococcaceae_uncultured, with a negative association with immune responses and skin barrier functions. These results demonstrate the potential of the probiotic strains in modulating immune responses and the gut microbiota, suggesting their role as a dietary intervention strategy for managing AD.

Purpose Electroencephalography (EEG) is useful for clarifying the association between cortical activity and cognitive processes in children. We investigated whether EEG abnormalities were correlated with developmental delay/intellectual disability (DD/ID) in the absence of clinical seizures. Methods We retrospectively identified 166 children with DD/ID who underwent EEG at Pusan National University Hospital between January 2011 and December 2021. We compared clinical characteristics and test results between those with normal and those with abnormal EEGs. Additionally, we analyzed EEG abnormalities in relation to neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Results Of the 166 patients, 39 (23.5%) displayed abnormal EEGs, while 127 (76.5%) had normal EEGs. Of the former, 25 (64.1%) patients exhibited epileptiform discharges, including 22 (56.3%) with focal and three (7.7%) with generalized discharges. Focal discharges most frequently affected the central area (35.9%). Twenty patients (51.3%) exhibited rhythmic slowing patterns. Epilepsy diagnoses were significantly more common among patients with abnormal EEGs (n=8, 20.5%) than among those with normal EEGs (n=9, 7.1%) (P

Abstract Deformable and miniaturized energy storage devices are essential for powering soft electronics. Herein, we fabricate deformable micro supercapacitors (MSCs) based on eutectic gallium-indium liquid metal (EGaIn) current collectors with integrated graphene. The well-define interdigitated electrode patterning with controlled gap is successfully realized by using the laser ablation because of a strong laser absorption of graphene and EGaIn. By judicious control of gap size between neighboring interdigitated electrodes and mass loading of graphene, we achieve a high areal capacitance (1336 µF cm−2) with reliable rate performance. In addition, owing to the intrinsic liquid characteristics of EGaIn current collector, the areal capacitance of fabricated MSC retains 90% of original value even after repetitive folding and 20% stretching up to 1000 cycles. Finally, we successfully integrate deformable MSC with a commercial light-emitting diode to demonstrate the feasibility of MSC as a deformable power source. The fabricated MSCs operate stably under various mechanical deformations, including stretching, folding, twisting, and wrinkling.

Abstract Background Improving adherence to antihypertensive medication (AHM) is a key challenge in hypertension management. This study aimed to assess the impact of ambulatory blood pressure monitoring (ABPM) on AHM adherence. Methods We utilized the Korean National Health Insurance Service database. Among patients newly diagnosed with hypertension who started AHM between July 2010 and December 2013, we compared clinical characteristics and adherence between 28,116 patients who underwent ABPM prior to starting AHM and 118,594 patients who did not undergo ABPM. Good adherence was defined as a proportion of days covered (PDC) of 0.8 or higher. Results The total study population was 146,710, with a mean age of 50.5 ± 6.4 years; 44.3% were female. Co-morbidities were noted in 4.2%. About a third of patients (33.1%) showed good adherence. The ABPM group had a notably higher PDC (total PDC: 0.64 ± 0.35 vs. 0.45 ± 0.39; P

ObjectiveAcute respiratory distress syndrome (ARDS) presents a global health challenge, characterized by significant morbidity and mortality. However, the role of natural killer T (NKT) cells in human ARDS remains poorly understood. Therefore, this study explored the numerical and functional status of NKT cells in patients with ARDS, examining their clinical relevance and interactions with macrophages and fibroblasts during various stages of the syndrome.MethodsPeripheral blood from 40 ARDS patients and 30 healthy controls was analyzed, with paired samples of peripheral blood and bronchoalveolar lavage fluid (BALF) from seven ARDS patients. We measured levels of NKT cells, cytokines, CD69, programmed death-1 (PD-1), and annexin-V using flow cytometry, and extracellular matrix (ECM) protein expression using real-time PCR.ResultsARDS patients exhibited decreased circulating NKT cells with elevated CD69 expression and enhanced IL-17 production. The reduction in NKT cells correlated with PaO2/FiO2 ratio, albumin, and C-reactive protein levels. Proliferative responses to α-galactosylceramide (α-GalCer) were impaired, and co-culturing NKT cells with monocytes or T cells from ARDS patients resulted in a reduced α-GalCer response. Increased and activated NKT cells in BALF induced proinflammatory cytokine release by macrophages and ECM protein expression in fibroblasts.ConclusionARDS is associated with a numerical deficiency but functional activation of circulating NKT cells, showing impaired responses to α-GalCer and altered interactions with immune cells. The increase in NKT cells within BALF suggests their role in inducing inflammation and remodeling/fibrosis, highlighting the potential of targeting NKT cells as a therapeutic approach for ARDS.

ObjectiveAttention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with developmental coordination disorder (DCD). This study aimed to evaluate the association between DCD symptoms and neuropsychological characteristics in children with and without ADHD.MethodsWe recruited 298 children aged 5–12 years. Motor performance was assessed using the Developmental Coordination Disorder Questionnaire (DCDQ), while ADHD symptoms were assessed using the ADHD Rating Scale (ARS) and the Advanced Test of Attention (ATA). Cognitive characteristics were measured using the Wechsler Intelligence Scale, and behavioral characteristics were assessed using the Korean Personality Rating Scale for Children.ResultsThe children had a mean age of 7.6 ± 1.7 years, with 214 (71.8%) being boys. Among children diagnosed with ADHD (n = 176), 39.2% exceeded the DCDQ cutoff score, compared to 4.1% in the neurotypical group (n = 122). In the correlation analysis, the DCDQ total score was significantly correlated with ARS, omission and commission errors in visual and auditory ATA, and full-scale intellectual quotient. In addition, symptoms of depression, social dysfunction, and psychosis were correlated with the DCDQ total score. In the between-group analysis, children with both ADHD and DCD exhibited more omission errors on the auditory ATA and behavioral problems related to depression, social dysfunction, and psychosis compared to children with ADHD only.ConclusionOur study indicates that children with ADHD exhibit more difficulties in motor performance. Children with both ADHD and DCD may present with a greater burden of psychiatric conditions than children with ADHD only, suggesting the need for careful monitoring in clinical practice.

With the increasing demand for highly efficient lighting in the automotive industry, flip-chip light-emitting diodes (LEDs) have become widely used for both interior and exterior lighting. Solder, serving as a crucial interconnecting material, often develops voids during the reflow process, compromising the integrity and reliability of the connections. Thus, understanding the impact of these voids on the mechanical and thermal properties of the product is vital for improving reliability accuracy. This work employs computational methods alongside experimental approaches to address the challenges of replicating solder voids and controlling the solder void fraction. A comprehensive study investigates the effects of solder voids on shearing properties and thermal conductance. Random voids were introduced into the solder pads of an LED assembly within a finite element model (FEM), leading to predictions of maximum shear stress and LED junction temperature. The findings correlate well with the experimental data, validating the FEM's applicability. Furthermore, a statistical analysis was conducted to explore the relationship between solder void fraction, position, and size, aiming to provide objective guidelines for analyzing soldered assembly tomography in reliability assessments.

AbstractBioluminescence is a type of chemiluminescence that arises from a luciferase-catalyzed oxidation reaction of luciferin. Molecular biology and comparative genomics have recently elucidated the genes involved in fungal bioluminescence and the evolutionary history of their clusters. However, most studies on fungal bioluminescence have been limited to observing the changes in light intensity under various conditions. To understand the molecular basis of bioluminescent responses in Omphalotus guepiniiformis under different environmental conditions, we cloned and sequenced the genes of hispidin synthase, hispidin-3-hydroxylase, and luciferase enzymes, which are pivotal in the fungal bioluminescence pathway. Each gene showed high sequence similarity to that of other luminous fungal species. Furthermore, we investigated their transcriptional changes in response to abiotic stresses. Wound stress enhanced the bioluminescence intensity by increasing the expression of bioluminescence pathway genes, while temperature stress suppressed the bioluminescence intensity via the non-transcriptional pathway. Our data suggested that O. guepiniiformis regulates bioluminescence to respond differentially to specific environmental stresses. To our knowledge, this is the first study on fungal bioluminescence at the gene expression level. Further studies are required to address the biological and ecological meaning of different bioluminescence responses in changing environments, and O. quepiniiformis could be a potential model species.

Background Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults. Methods This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay. Results After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012). Conclusion These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF-1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

Background G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress. Methods Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium. Results In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner. Conclusion GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.

This study provides an updated overview of the clinical characteristics of post-traumatic trigeminal neuropathic pain (PTNP) resulting from dental procedures or facial trauma, addressing its etiology, prevalence, evaluation, management, and prognosis. PTNP arises from injury to the trigeminal nerve, which governs sensory and motor functions in the maxillofacial region. The prevalence and characteristics of PTNP vary considerably across studies, with a reported prevalence ranging from 1.55% to 13%. The predominant causative factors are dental procedures, particularly third molar removal and implant placement. While gender distribution varies, a trend towards higher incidence in females is observed, particularly within the 40–60-year age group. Anatomically, the mandibular nerve is frequently involved. PTNP presents with a spectrum of symptoms ranging from tingling sensations to severe pain. Diagnostic challenges arise due to the lack of standardized criteria and potential overlap with focal neuralgia, necessitating comprehensive evaluation. Misdiagnosis can lead to prolonged patient suffering and unnecessary interventions. Successful management hinges on prompt diagnosis and interdisciplinary collaboration, with early intervention crucial in mitigating progression to chronic pain. Although nerve recovery post-trauma is challenging, preventive measures through accurate evaluation and treatment are paramount. Management strategies for PTNP include non-invasive and surgical interventions, with non-invasive approaches encompassing systemic and local pharmacological management. This narrative review aims to enhance uniformity in PTNP evaluation and treatment approaches, ultimately improving patient care and outcomes.

Background: The incidence of thyroid cancer has increased over the decades, and patients prefer short thin scars after thyroidectomy due to their cosmetic visibility. Several scar assessment methods have been used to determine the most cosmetically optimal surgical method, but a widely accepted measurement tool is still lacking. This study investigates the usage status in the thyroid scar scale according to time, region, and study method. Methods: The authors searched for articles on thyroid scars published between January 2000 and September 2022 in the PubMed database. The study included clinical studies that mentioned thyroid scar and scar scale, excluding articles that did not evaluate neck scars. Statistical analysis was performed using IBM SPSS Statistics 29. Results: A total of 35 studies were included. Among them, 17 used the Vancouver Scar Scale (VSS), 17 used the Patient and Observer Scar Assessment Scale (POSAS), four used the Manchester Scar Scale (MSS), and four used the Stony Brook Scar Evaluation Scale (SBSES). VSS and POSAS were the most commonly used scar evaluation methods. VSS tended to be used frequently in Asia, while POSAS was used frequently in Europe and in randomized controlled trials. Conclusion: VSS and POSAS are popular thyroid scar assessment methods, with regional variations. Standardization is needed for meaningful comparisons. Patient's subjective evaluations should be considered, given the cosmetic importance of thyroid scars.

Coupled electrochemical systems for the direct capture and conversion of CO2 have garnered significant attention owing to their potential to enhance energy- and cost-efficiency by circumventing the amine regeneration step. However, optimizing the coupled system is more challenging than handling separated systems because of its complexity, caused by the incorporation of solvent and heterogeneous catalysts. Nevertheless, the deployment of machine learning can be immensely beneficial, reducing both time and cost owing to its ability to simulate and describe complex systems with numerous parameters involved. In this review, we summarized the machine learning techniques employed in the development of CO2 capture solvents such as amine and ionic liquids, as well as electrochemical CO2 conversion catalysts. To optimize a coupled electrochemical system, these two separately developed systems will need to be combined via machine learning techniques in the future.

In this study, a genus, Achlya longipennis Inoue, 1972, is reported for the first time from Korea with a newly recorded species. The adult and genitalic structures of the newly recorded species are redescribed with illustrations of adult and male genitalia. In addition, an annotated checklist of the genus is provided.

Abstract Background Respiratory support is crucial for newborns with underdeveloped lung. The clinical outcomes of patients depend on the clinician’s ability to recognize the status underlying the presented symptoms and signs. With the increasing number of high-risk infants, artificial intelligence (AI) should be considered as a tool for personalized neonatal care. Continuous monitoring of vital signs is essential in cardiorespiratory care. In this study, we developed deep learning (DL) prediction models for rapid and accurate detection of mechanical ventilation requirements in neonates using electronic health records (EHR). Methods We utilized data from the neonatal intensive care unit in a single center, collected between March 3, 2012, and March 4, 2022, including 1,394 patient records used for model development, consisting of 505 and 889 patients with and without invasive mechanical ventilation (IMV) support, respectively. The proposed model architecture includes feature embedding using feature-wise fully connected (FC) layers, followed by three bidirectional long short-term memory (LSTM) layers. Results A mean gestational age (GA) was 36.61 ± 3.25 weeks, and the mean birth weight was 2,734.01 ± 784.98 g. The IMV group had lower GA, birth weight, and longer hospitalization duration than the non-IMV group (P

Objectives This study aims to assess the feasibility of simultaneously producing hydrogen and hypochlorous acid using a 2-compartment PEM water electrolysis cell with an installed membrane electrode assembly (MEA). Methods External power was applied to the PEM water electrolysis device through a potentiostat to induce the electrolysis reaction and to confirm the production of hydrogen and hypochlorite simultaneously. Linear Sweep Voltammetry (LSV) experiments were conducted, thereby determined the minimum voltage required for the electrolysis. Constant current experiments were performed by applying a fixed current of 1 A for 1 hour, measuring voltage changes every second to evaluate the stability and efficiency of hydrogen production. The hydrogen production rate was measured using a mass flow meter, while the hypochlorite production was determined using a portable free chlorine photometer. Results and Discussion In this study, the minimum voltage required for hydrogen generation in a PEM water electrolysis cell was investigated using LSV with Deionized (DI) water. The results showed that the current increased from around 1.4 V, indicating an approximate voltage efficiency of 82%. NaCl was introduced to the anode in the PEM electrolysis cell to induce electrochemical reactions. When the anolyte was NaCl, the voltage was observed to increase by 0.77 V compared to using DI water. Optimization experiments were conducted to investigate the influence of electrolyte concentration and flow rate on hypochlorite and hydrogen production. As the electrolyte concentration increased, the hypochlorite generation also increased, with a maximum of 104±0.50 mg/L observed with NaCl 10 g/L. Additionally, when the flow rate was reduced, the hypochlorite production increased, and at a reduced flow rate of 5 mL/min compared to 20 mL/min, hypochlorite generation increased by 127.3%. However, the hydrogen production showed no significant variation with NaCl concentration or flow rate. Conclusion This study explores a novel approach using PEM water electrolysis technology to simultaneously produce hydrogen and chlorinated disinfectants. The research employed a PEM electrolysis cell with the MEA to generate both chlorine-based compounds and hydrogen. By varying the concentration and flow rate of the anolyte, the production efficiencies of hypochlorite were compared. This system showed that PEM electrolysis can be a promising alternative for disinfection and energy production in terms of environmental protection and cost-effectiveness.

Abstract Artificial intelligence (AI) using deep learning approaches the capabilities of human experts in medical image diagnosis. However, due to liability issues in medical decisions, AI is often relegated to an assistant role. Based on this responsibility constraint, the effective use of AI to assist human intelligence in real-world clinics remains a challenge. Given the significant inter-individual variations in clinical decisions among physicians based on their expertise, AI needs to adapt to individual experts, complementing weaknesses and enhancing strengths. For this adaptation, AI should not only acquire domain knowledge but also understand the specific human experts it assists. This study introduces a meta-model for human–machine cooperation that first evaluates each expert’s class-specific diagnostic tendencies using conditional probability, based on which the meta-model adjusts the AI’s predictions. This meta-model was applied to ear disease diagnosis using otoendoscopy, highlighting improved performance when incorporating individual diagnostic characteristics, even with limited evaluation data. The highest accuracy was achieved by combining each expert’s conditional probabilities with machine classification probability, using optimal weights specific to each individual’s overall classification accuracy. This tailored model aims to mitigate potential misjudgments due to psychological effects caused by machine suggestions and to capitalize on the unique expertise of individual clinicians.

There are physical, chemical, and biological methods to control algae, and their efficiency requires evaluation. In the field, monitoring and evaluating the overall algal concentration is challenging due to factors such as the flow rate, inhomogeneous distribution of algae in the water body, and limitations in the number of samples for microscopic analysis. In this study, we analyzed total and cyanobacterial chlorophyll a (Chl-a) using a FluoroProbe sensor and microscopic data collected from March to November 2019. The Pearson correlation coefficient of log(x + 1) values revealed a significant positive correlation between four harmful cyanobacteria and cyanobacterial Chl-a (r = 0.618, p < 0.01). Furthermore, we explored the potential of evaluating the efficiency of algal control using sensors by acquiring three-dimensional, spatially continuous data for an algal fence, a physical algae control technology installed at the Daecheong Dam in 2021. The results confirmed that sensors can effectively evaluate algal control technology. This study demonstrates the effectiveness of using sensors to assess the efficiency of physical algal control.

Background/Aims Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) and thiazolidinedione (TZD) can improve nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). However, comprehensive research comparing the effects of GLP-1RA and TZD is limited. Thus, this study aimed to compare the effects of GLP-1RA and TZD on NAFLD or NASH through a network meta-analysis. Methods The PubMed, Embase, Web of Science, and Scopus databases were searched for randomized controlled trials (RCTs) that explored the efficacy of GLP-1RAs or TZDs in adult patients with NAFLD or NASH. The outcomes were liver biopsy-based (NAFLD activity score [NAS], fibrosis stage, and NASH resolution), noninvasive technique-based (liver fat content on proton magnetic resonance spectroscopy [1H-MRS] and controlled attenuation parameter [CAP]), biological, and anthropometric indicators. A random effects model was used to calculate the mean difference (MD) and relative risk with 95% confidence interval (CI). Results Twenty-five RCTs with 2,237 overweight or obese patients were included. GLP-1RA was significantly superior in reducing liver fat content evaluated using 1H-MRS (MD –2.42, 95% CI –3.84 to –1.00), body mass index (MD –1.60, 95% CI –2.41 to –0.80), and waist circumference (MD –4.89, 95% CI –8.17 to –1.61) than TZD. In liver biopsy-based evaluation and liver fat content assessment using CAP, GLP-1RA tended to surpass TZD, albeit not significantly. Sensitivity analysis showed consistent results with the main results. Conclusions Compared with TZD, GLP-1RA had better effects on liver fat content, body mass index, and waist circumference in overweight or obese patients with NAFLD or NASH.

Abstract Owing to the advances in genome editing technologies, research on human pluripotent stem cells (hPSCs) have recently undergone breakthroughs that enable precise alteration of desired nucleotide bases in hPSCs for the creation of isogenic disease models or for autologous ex vivo cell therapy. As pathogenic variants largely consist of point mutations, precise substitution of mutated bases in hPSCs allows researchers study disease mechanisms with “disease-in-a-dish” and provide functionally repaired cells to patients for cell therapy. To this end, in addition to utilizing the conventional homologous directed repair system in the knock-in strategy based on endonuclease activity of Cas9 (i.e., ‘scissors’ like gene editing), diverse toolkits for editing the desirable bases (i.e., ‘pencils’ like gene editing) that avoid the accidental insertion and deletion (indel) mutations as well as large harmful deletions have been developed. In this review, we summarize the recent progress in genome editing methodologies and employment of hPSCs for future translational applications.

Background : As the metabolic significance of sarcopenic obesity (SO) is revealed, finding an appropriate index to detect SO is important, especially for type 2 diabetes mellitus (T2DM) patients with accompanying metabolic dysfunction. Methods : Participants (n=515) from the Korea Guro Diabetes Program were included to compare how well waist circumference (WC), waist hip ratio (WHR), waist height ratio (WHtR), and the weight-adjusted waist index (WWI) predict SO in newly diagnosed T2DM patients. Sarcopenia was defined based on guidelines from the 2019 Asian Working Group for Sarcopenia as both low muscle mass (appendicular skeletal muscle [ASM]/height2

Precise genome editing in human pluripotent stem cells (hPSCs) has potential applications in isogenic disease modeling and ex vivo stem cell therapy, necessitating diverse genome editing tools. However, unlike differentiated somatic cells, hPSCs have unique cellular properties that maintain genome integrity, which largely determine the overall efficiency of an editing tool. Considering the high demand for prime editors (PEs), it is imperative to characterize the key molecular determinants of PE outcomes in hPSCs. Through homozygous knockout (KO) of MMR pathway key proteins MSH2, MSH3, and MSH6, we reveal that MutSα and MutSβ determine PE efficiency in an editing size-dependent manner. Notably, MSH2 perturbation disrupted both MutSα and MutSβ complexes, dramatically escalating PE efficiency from base mispair to 10 bases, up to 50 folds. Similarly, impaired MutSα by MSH6 KO improved editing efficiency from single to three base pairs, while defective MutSβ by MSH3 KO heightened efficiency from three to 10 base pairs. Thus, the size-dependent effect of MutSα and MutSβ on prime editing implies that MMR is a vital PE efficiency determinant in hPSCs and highlights the distinct roles of MutSα and MutSβ in its outcome.

In this study, a series of 2-Aryl-1H-benzo[d]imidazole derivatives were developed to target intra- and extracellular microtubule networks. Compounds O-7 and O-10 showed impressive anti-proliferative activity across various tested cell lines, demonstrating selectivity indexes of 151.7 and 61.9, respectively. O-7 achieved an IC50 value of 0.236 ± 0.096 μM, while O-10 showed an IC50 value of 0.622 ± 0.13 μM against A549 cell lines. The induction of early-stage apoptosis in a dose-dependent manner further underscored the potential of O-7 and O-10 as effective anti-proliferative agents. O-7 and O-10 exhibited substantial inhibition of wound closure, with wound closure percentages decreasing from 23% at 0 μM to 0.43% and 2.62% at 20 μM, respectively. Colony formation reduction rates were impressive, with O-7 at 74.2% and O-10 at 81.2%. These results indicate that the O-7 and O-10 can impede cancer cell migration and have a high potential to curtail colony formation. The mode of action investigations for O-7 and O-10 revealed that O-7 could inhibit in vitro tubulin polymerization and disrupt the intracellular microtubule cytoskeleton. This disruption led to cell cycle arrest in the G2/M phase, indicating that O-7 exerts its anticancer activity through microtubule destabilization. However, O-10 shows a different mode of action than O-7 and requires further investigation. Overall, our study showcases the potential of the synthesized benzimidazole derivatives as novel and selective anticancer agents, motivating further exploration of their pharmacological properties and therapeutic applications.

In this research, we employed functional magnetic resonance imaging (fMRI) to examine the neurological basis for understanding wh-questions in wh-in-situ languages such as Korean, where wh-elements maintain their original positions instead of moving explicitly within the sentence. Our hypothesis centered on the role of the salience and attention network in comprehending wh-questions in wh-in-situ languages, such as the discernment of wh-elements, the demarcation between interrogative types, and the allocation of cognitive resources towards essential constituents vis-à-vis subordinate elements in order to capture the speaker's communicative intent. We explored subject and object wh-questions and scrambled wh-questions, contrasting them with yes/no questions in Korean. Increased activation was observed in the left anterior insula and bilateral frontal operculum, irrespective of the wh-position or scrambling of wh-element. These results suggest the interaction between the salience and attentional system and the syntactic linguistic system, particularly the left anterior insula and bilateral frontal operculum, in comprehending wh-questions in wh-in-situ languages.

The current study investigates the neural correlates when processing prototypicality and simplicity-affecting the preference of product design. Despite its significance, not much is known about how our brain processes these visual qualities of design when forming design preferences. We posit that, although fluency is the perceptual judgment accounting for the positive effects of both prototypicality and simplicity on design preference, the neural substrates for the fluency judgment associated with prototypicality would differ from those associated with simplicity. To investigate these issues, we conducted an fMRI study of preference decisions for actual product designs with different levels of prototypicality and simplicity. The results show a significant functional gradient between the preference processing of simplicity and prototypicality-i.e., involvement of the early ventral stream of visual information processing for simplicity evaluation but recruitment of the late ventral stream and parietal-frontal brain regions for prototypicality evaluation. The interaction between the simplicity and prototypicality evaluations was found in the extrastriate cortex in the right hemisphere. The segregated brain involvements suggest that the fluency judgment for prototypicality and simplicity contribute to preference choice in different levels of cognitive hierarchy in the perceptual mechanism of the design preference.

ABSTRACT In pathogenic bacteria, the flavohemoglobin Hmp is crucial in metabolizing the cytotoxic levels of nitric oxide (NO) produced in phagocytic cells, contributing to bacterial virulence. Hmp expression is predominantly regulated by the Rrf2 family transcription repressor NsrR in an NO-dependent manner; however, the underlying molecular mechanism in enterobacteria remains poorly understood. In this study, we identified Val43 of Salmonella Typhimurium NsrR (StNsrR) as a critical amino acid residue for regulating Hmp expression. The Val43-to-Ala-substituted mutant NsrR isolated through random and site-directed mutagenesis showed high binding affinity to the target DNA irrespective of NO exposure, resulting in a severe reduction in hmp transcription and slow NO metabolism in Salmonella under NO-producing conditions. Conversely, the Val43-to-Glu-substituted NsrR caused effects similar to nsrR null mutation, which directed hmp transcription and NO metabolism in a constitutive way. Comparative analysis of the primary sequences of NsrR and another NO-sensing Rrf2 family regulator, IscR, from diverse bacteria, revealed that Val43 of enterobacterial NsrR corresponds to Ala in Pseudomonas aeruginosa or Streptomyces coelicolor NsrR and Glu in enterobacterial IscR, all of which are located in the DNA recognition helix α3. The predicted structure of StNsrR in complex with the hmp DNA suggests dissimilar spatial stoichiometry in the interactions of Val43 and its substituted residues with the target DNA, consistent with the observed phenotypic changes in StNsrR Val43 mutants. Our findings highlight the discriminative roles of the NsrR recognition helix in regulating species-specific target gene expression, facilitating effective NO detoxification strategies in bacteria across diverse environments. IMPORTANCE The precise regulation of flavohemoglobin Hmp expression by NsrR is critical for bacterial fitness, as excessive Hmp expression in the absence of NO can disturb bacterial redox homeostasis. While the molecular structure of Streptomyces coelicolor NsrR has been recently identified, the specific molecular structures of NsrR proteins in enterobacteria remain unknown. Our discovery of the crucial role of Val43 in the DNA recognition helix α3 of Salmonella NsrR offers valuable insights into the Hmp modulation under NO stress. Furthermore, the observed amino acid polymorphisms in the α3 helices of NsrR proteins across different bacterial species suggest the diverse evolution of NsrR structure and gene regulation in response to varying levels of NO pressure within their ecological niches.

Objectives The COVID-19 pandemic resulted in suboptimal care for ischaemic stroke. Patients with diabetes mellitus (DM), a high-risk group for stroke, had compromised routine care during the pandemic, which increases the chance of stroke. We examined influence of the COVID-19 pandemic on the management of ischaemic stroke in patients with DM in South Korea.Design Retrospective, nationwide, population-based cohort study.Setting Data from the National Emergency Department Information System.Participants We analysed 11 734 patients diagnosed with acute ischaemic stroke who underwent intravenous thrombolysis or endovascular thrombectomy between 2019 (the reference year) and 2020 (the pandemic year). Among them, 1014 subjects with DM were analysed separately.Outcome measures The frequency of emergency department (ED) visits, time from symptom onset to ED, from ED visit to admission and in-hospital mortality were compared between two periods in the overall population and in patients with DM.Results During the pandemic, the incidence of ischaemic stroke requiring urgent procedures increased by 7.57% in total and by 9.03% in patients with DM. Time delay from symptom onset to ED (reference vs pandemic, total: 1.50 vs 1.55 hours; p

Abstract Inorganic–organic hybrid materials have promising properties for bone repair because of the covalent bonding between their inorganic and organic phases. This desirable interaction allows the limitations of composite materials, such as inhomogeneous biodegradation rates and nonbiointeractive surfaces, to be overcome. In this study, a polycaprolactone (PCL)-based polyurethane (PU) with an organosilane functional group was synthesized for the first time. Thereafter, a biodegradable PU-silica hybrid was produced through the sol-gel process. The PU-silica hybrid was not only flexible and fully biodegradable but also possessed shape memory ability. In addition, allophanate bonding enabled the silane coupling agent to induce increased crosslinking between the polymer and silica network, as well as between polymer and polymer. Accordingly, the sol-to-gel gelation time required to produce the hybrids was very short, which allowed the production of 3D porous hybrid scaffolds through a simple salt-leaching process. A hybrid scaffold with a 30 wt. % silica composition was the most ideal bone regenerative scaffold since it was able to withstand thermal deformation with promising mechanical properties. Moreover, the hybrid scaffold induced osteogenic differentiation and angiogenesis to accelerate bone regeneration.

Purpose The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP). Methods The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart. Results PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups. Conclusions Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years.