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BackgroundTramadol is known to cause fewer adverse events (AEs) than other opioids. However, recent research has raised concerns about various safety issues. ObjectiveWe aimed to explore these new AEs related to tramadol using social media and conventional pharmacovigilance data. MethodsThis study used 2 data sets, 1 from patients’ drug reviews on WebMD (January 2007 to January 2021) and 1 from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS; January 2016 to December 2020). We analyzed 2062 and 29,350 patient reports from WebMD and FAERS, respectively. Patient posts on WebMD were manually assigned the preferred terms of the Medical Dictionary for Regulatory Activities. To analyze AEs from FAERS, a disproportionality analysis was performed with 3 measures: proportional reporting ratio, reporting odds ratio, and information component. ResultsFrom the 869 AEs reported, we identified 125 new signals related to tramadol use not listed on the drug label that satisfied all 3 signal detection criteria. In addition, 20 serious AEs were selected from new signals. Among new serious AEs, vascular disorders had the largest signal detection criteria value. Based on the disproportionality analysis and patients’ symptom descriptions, tramadol-induced pain might also be an unexpected AE. ConclusionsThis study detected several novel signals related to tramadol use, suggesting newly identified possible AEs. Additionally, this study indicates that unexpected AEs can be detected using social media analysis alongside traditional pharmacovigilance data.

Abstract Background The Korean government implemented mandatory hospital isolation in the early phase of the COVID-19 pandemic. This study investigated the mental health of children and caregivers who underwent mandatory hospital isolation due to COVID-19. Methods This prospective study examined the physical condition and mental health of children under 7 years of age with COVID-19 and the mental health of their caregivers who underwent isolation in negative pressure rooms at two hospitals in Korea from April to September 2021. Caregivers received a self-report questionnaire via text message. Their responses were analyzed to compare the physical condition and mental health of children with COVID-19 and the mental health of their caregivers during and after isolation and identify factors influencing caregivers’ mental health. Results Sixty caregivers participated in the study. More than half of the caregivers perceived their children’s disease severity as mild. During hospital isolation, 36.4% of the children experienced decreased oral intake, which improved significantly post-isolation (8.7%, P = 0.014). During isolation, approximately 22.2% of the children frequently awoke from sleep, 20.0% displayed irritability, and 70.8% had symptoms of depression. Approximately 36.7% of caregivers showed at least moderate levels of depression during isolation, which significantly decreased to 14.3% three months after discharge (P = 0.032). Factors associated with caregivers’ mental health included child-related issues, such as difficulty concentrating, frequent awakenings, and irritability. Conclusion Mandatory hospital isolation has a significantly negative psychological impact on children and caregivers during pandemics. Isolation decisions must be carefully considered during pandemics, especially those concerning young children. Heightened vigilance is warranted for the early detection and intervention of mental health issues in children and their caregivers.

Sargassum fusiforme, a brown alga, has been traditionally used as an herbal remedy. While previous studies have reported its immunomodulatory properties, the specific immune-modulating effects of fucoidan extracted from S. fusiforme remain underexplored. This study aimed to assess the immune-enhancing properties of S. fusiforme fucoidan (SFF) using the RAW 264.7 macrophage model. SFF significantly increased nitric oxide (NO) production and phagocytic activity at 25–100 μg/mL concentrations, without exhibiting cytotoxicity. RAW 264.7 macrophages treated with SFF adopted a spindle shape with elongated pseudopodia, indicating an activated state. Additionally, SFF upregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), while promoting the secretion of cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in a dose-dependent manner. SFF also promoted the activation of nuclear factor kappa B and mitogen-activated protein kinase signaling pathways. These findings suggest that SFF exhibits potent immunomodulatory activity in the RAW 264.7 macrophage model and holds potential as a functional food to support immune health.

Taste buds, the neuroepithelial organs responsible for the detection of gustatory stimuli in the oral cavity, arise from stem/progenitor cells among nearby basal keratinocytes. Using genetic lineage tracing, Lgr5 and Lgr6 were suggested as the specific markers for the stem/progenitor cells of taste buds, but recent evidence implied that taste buds may arise even in the absence of these markers. Thus, we wanted to verify the genetic lineage tracing of lingual Lgr5- and Lgr6-expressing cells. Unexpectedly, we found that antibody staining revealed more diverse Lgr5-expressing cells inside and outside the taste buds of circumvallate papillae than was previously suggested. We also found that, while tamoxifen-induced genetic recombination occurred only in cells expressing the Lgr5 reporter GFP, we did not see any increase in the number of recombined daughter cells induced by consecutive injections of tamoxifen. Similarly, we found that cells expressing Lgr6, another stem/progenitor cell marker candidate and an analog of Lgr5, also do not generate recombined clones. In contrast, Lgr5-expressing cells in fungiform papillae can transform into Lgr5-negative progeny. Together, our data indicate that lingual Lgr5- and Lgr6-expressing cells exhibit diversity in their capacity to transform into Lgr5- and Lgr6-negative cells, depending on their location. Our results complement previous findings that did not distinguish this diversity.

In this study, effect of an ethanol extract of Euodia rutaecarpa fruit (EER), known to have various pharmacological effects, on benign prostatic hyperplasia (BPH) was evaluated. To induce BPH in an in vivo animal model, testosterone propionate (TP) was injected to rats. EER was administered orally with TP injection. Finasteride, a 5α-reductase inhibitor, was used as a positive control. After all mice were sacrificed at the end of the experiment, pathological changes in prostate tissues and levels of key biomarkers involved in BPH development were assessed. Oral administration of EER significantly suppressed TP-induced BPH by diminishing prostate weight, lumen size and epithelial thickness. EER also abrogated the expression of prostate-specific antigen, proliferating cell nuclear antigen, and 5α-reductase type 2 induced by TP. In addition, serum levels of testosterone, dihydrotestosterone (DHT) and prostate specific antigen were elevated in TP challenged rats but decreased in EER-administered rats. Moreover, the improvement effect of EER on TP-induced BPH was associated with decreased expression of androgen receptor (AR) and its coactivators. The current findings show that EER can protect against BPH by attenuating the activation of 5α-reductase and inhibiting the AR signaling pathway, suggesting that EER has great potential in blocking BPH pathogenesis.

Objective: To elucidate the anti-melanogenic potential of Carex pumila Thunb. extract (FBCC-EP850). Methods: A collection of 180 plant extracts was tested for inhibition of mushroom tyrosinase activity using an in vitro assay. Among them, FBCC-EP850 exhibited the most promising inhibitory activity. Further analysis was conducted to investigate its mechanisms and therapeutic potential in reducing melanogenesis in B16F10 melanoma cells and zebrafish larvae. Results: FBCC-EP850 inhibited mushroom tyrosinase activity in a dose-dependent manner, with a half-maximal inhibitory concentration of 45.83 μg/mL. FBCC-EP850 at concentrations up to 50 pg/mL demonstrated minimal cytotoxicity against B16F10 melanoma cells and no adverse effects on zebrafish larvae. Treatment with 50 μg/mL of FBCC-EP850 significantly reduced α-melanocyte stimulating hormone-induced melanin production and suppressed cellular tyrosinase activity in B16F10 melanoma cells. Additionally, FBCC-EP850 at 25 and 50 μg/mL effectively diminished hyperpigmentation in α-melanocyte stimulating hormone-stimulated zebrafish larvae. Its anti-melanogenic action could be attributed to modulation of the cAMP-CREB-MITF signaling pathway. Conclusions: Carex pumila extract can inhibit melanogenesis by modulating the cAMP-CREB-MITF signaling pathway, which can be used as a promising candidate for treating hyperpigmentation disorders.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Its treatment is complicated due to the development of resistance to conventional chemotherapy and targeted therapy. Deoxybouvardin and related cyclic hexapeptides reportedly exhibit antitumor activities, but their mechanisms of action remain unclear. This study aimed to investigate the anticancer mechanisms of deoxybouvardin glucoside (DBG), a glucosidic form of deoxybouvardin from Rubia species, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. The effects of DBG treatment on cell proliferation were evaluated using a viability assay. The inhibitory effects of DBG treatment on the activities and phosphorylation of the protein kinases epidermal growth factor receptor (EGFR), MET, and AKTs were assessed using in vitro kinase assay and western blot, respectively. DBG treatment inhibited the growth of HCC827 cells in a concentration- and time-dependent manner. Results of in vitro kinase assay and western blotting showed that DBG treatment significantly inhibited the activities and phosphorylation of the protein kinases EGFR, MET, and AKT. Prediction using molecular docking showed that DBG is located in the ATP-binding pockets of these kinases, supporting the kinase inhibition by DBG treatment. Moreover, DBG treatment induced reactive oxygen species (ROS) generation and cell cycle arrest in the cells. The induction of apoptosis by DBG through caspase activation was confirmed by Z-VAD-FMK treatment. In summary, DBG treatment inhibited the growth of GEF-sensitive and -resistant NSCLC cells by targeting EGFR, MET, and AKTs. Moreover, it induced apoptosis by inducing ROS generation and caspase activation. These results indicate that DBG is a potential therapeutic agent for the treatment of GEF-resistant NSCLC.

Purpose: The aim of this study was to investigate the efficacy of ethanol extracts of Cornus alba (ECA) against benign prostatic hyperplasia (BPH) in vitro and in vivo. Materials and Methods: The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH in vitro. ECA efficacy was evaluated in vivo using a testosterone propionate (TP)-induced BPH rat model. Results: Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogenactivated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels. Conclusions: These results demonstrated that ECA exerted beneficial effects on BPH both in vitro and in vivo and might provide valuable information in the development of preventive or therapeutic agents for improving BPH.

Abstract This study aimed to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with central retinal artery occlusion (CRAO) by analyzing changes in visual acuity (VA) and enhanced depth imaging optical coherence tomography (EDI-OCT) parameters. A comparative retrospective study was conducted by reviewing the medical records of all HBO-treated RAO patients in our department and comparing them with matched RAO patients who did not receive HBO treatment. All patients treated with HBO received treatment within 7 days of the onset of visual symptoms. Baseline characteristics were compared, and VA and OCT parameters were evaluated at baseline and follow-up visits. A total of 50 eyes from 50 patients were included, with 29 eyes in the HBOT group and 21 eyes in the control group. The mean BCVA of the HBOT group at the initial visit was 2.03 logMAR, which improved to 1.55 logMAR at 6 months, with the change being statistically significant (P

Abstract Several studies have investigated whether sarcopenia is associated with diabetic microvascular complications, but very few have examined associations between sarcopenia and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Therefore, we investigated associations of muscle strength (handgrip strength [HGS]) and mass (appendicular skeletal muscle mass index [ASMI]) and CAN in patients with T2DM. We enrolled 342 patients in this retrospective, cross-sectional study. Cardiovascular reflex tests were used to assess CAN according to Ewing’s protocol. Relative HGS was determined after normalizing absolute HGS to body weight (HGS/body weight [kg]). We defined low HGS and low ASMI according to a consensus report of the Asian Group for Sarcopenia. Logistic regression analyses were carried out to assess the associations between relative HGS or ASMI quartiles and the presence of CAN in patients with T2DM. The prevalence rates of CAN, low HGS, and low ASMI in the study subjects were 34.8%, 17.3%, and 18.7%, respectively. Low HGS was significantly more prevalent in patients with CAN than those without CAN (23.5% vs. 13.9%, p = 0.025). The CAN scores were significantly and negatively correlated with relative HGS but not with ASMI. Relative HGS was negative correlated with age, glycated hemoglobin, fasting plasma glucose, hsCRP, body mass index, and HOMA-IR and positively correlated with ASMI. The prevalence of CAN gradually increased with decreasing quartile of relative HGS (28.4% in Q4, 31.8% in Q3, 34.2% in Q2, and 45.3% in Q1, p = 0.02 for trend). Multivariable-adjusted prevalence ratios (PRs) for CAN, determined by comparing the first, second, and third quartiles with the fourth quartile of relative HGS, were 4.4 with a 95% confidence interval (95% CI) of [1.1 to 17.3]), 2.3 (95% CI [0.8 to 6.9]), and 1.2 (95% CI [0.4 to 3.7]), respectively. The prevalence of CAN and the PRs (95% [CI]) for CAN based on ASMI were not statistically significant. Our findings suggest that low muscle strength rather than low muscle mass was significantly associated with the presence of CAN. Therefore, HGS testing could help identify patients who would benefit from screening for earlier diagnosis of CAN.

Abstract On-scene resuscitation time is associated with out-of-hospital cardiac arrest (OHCA) outcomes. We developed and validated reinforcement learning models for individualized on-scene resuscitation times, leveraging nationwide Korean data. Adult OHCA patients with a medical cause of arrest were included (N = 73,905). The optimal policy was derived from conservative Q-learning to maximize survival. The on-scene return of spontaneous circulation hazard rates estimated from the Random Survival Forest were used as intermediate rewards to handle sparse rewards, while patients’ historical survival was reflected in the terminal rewards. The optimal policy increased the survival to hospital discharge rate from 9.6% to 12.5% (95% CI: 12.2–12.8) and the good neurological recovery rate from 5.4% to 7.5% (95% CI: 7.3–7.7). The recommended maximum on-scene resuscitation times for patients demonstrated a bimodal distribution, varying with patient, emergency medical services, and OHCA characteristics. Our survival analysis-based approach generates explainable rewards, reducing subjectivity in reinforcement learning.

Abstract Background Shock is a life‐threatening condition that is associated with high mortality and morbidity. Therefore, the timely identification and management of this condition are important. We aimed to develop a prediction model for vasopressor use based on concise serial arterial blood pressure data. Methods We collected continuous arterial blood pressure from patients admitted to the emergency department (ED) resuscitation room. Patients with an initial systolic blood pressure lower than 90 mmHg were included in the study. We developed prediction models using convolutional neural networks (CNNs) and long short‐term memory (LSTM) networks. Discrimination performance was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision–recall curve (AUPRC). Results A total of 120 patients were enrolled in the study. The CNN and LSTM models yielded AUROCs ranging from 0.731 to 0.834 for predicting the need for vasopressor infusion within different time frames (30 min, 1 h, and 6 h). LSTM outperformed the CNN in terms of predicting vasopressor infusion within 30 min and 1 h (p value

Abstract This study aimed to observe the impact of pure Binaural Beats (BB) stimulation in the inaudible frequency range, excluding the influence of sound, on visuospatial memory. Additionally, we investigated whether the brainwave changes induced by BB stimulation directly affect brain activation. The experiment involved 17 participants (12 males with a mean age of 23.2 ± 1.7 and 5 females with a mean age of 21.0 ± 0.7) in their 20s. Each participant received 10 Hz BB stimulation by presenting frequencies of 18,000 Hz and 18,010 Hz to the left and right ears, respectively. The experiment consisted of Rest phase (5 min), Task phase (5 min), and Rest phase (5 min). The Task phase included conditions where participants performed the task either without BB stimulation “Task only” or with BB stimulation “Task + BB”. Visuospatial memory was evaluated using the 3-back task. To observe brain activation, functional Near Infrared Spectroscopy (fNIRS) was employed to measure hemodynamic responses in all phases. The cognitive task performance (Accuracy, Reaction time) and oxyhemoglobin (HbO) concentration during the Task phase were compared between conditions with and without BB stimulation using paired t-tests. Results indicated a significantly shorter Reaction time in the Task + BB condition compared to the Task only condition. Moreover, an increase in HbO concentration was observed in the F1-F3, F2-F4, and P2-P4 regions during the Task + BB condition. In conclusion, the observed increase in HbO concentration suggests a positive influence on task performance. This study is meaningful in objectively demonstrating the impact of inaudible BB stimulation on visuospatial memory, utilizing both behavioral data and direct neural activation reflected in hemodynamic responses.

Abstract Non-suicidal self-injury (NSSI) among adolescents continues to be a significant public health concern worldwide. A recent systematic review and meta-analysis found that the global prevalence of NSSI in adolescents aged 12–18 years was 17.2%, with higher rates reported among females (19.7%) than males (14.8%). This behavior has been linked to several negative outcomes, such as depression, anxiety, substance abuse, and suicidal ideation. The present study aimed to classify adolescents based on intrapersonal and interpersonal factors associated with NSSI proposed in Nock’s (2009) integrated model of NSSI, to identify distinct clusters targeting specific risk factors. This encompassed negative cognition, emotional vulnerability, poor coping skill, peer-victimization, family adaptability, and perceived stress. A total of 881 adolescents aged 11–16 years in South Korea completed self-reported questionnaires on automatic thoughts, depression, emotional regulation, peer victimization, family adaptability and perceived stress. Latent profile analysis (LPA) revealed three distinct classes: “the severe group”, “the moderate group”, “the mild group”. Class 3 (“severe group”: N = 127) exhibited greater severity related to NSSI, including negative cognition, emotional vulnerability, poor coping skills, peer victimization, and perceived stress, with weaker levels of factors that can prevent NSSI compared to class 1 (“mild group”: N = 416) and class 2 (“moderated group”: N = 338). The present study emphasizes the importance of considering both intrapersonal (e.g., negative automatic thoughts & emotional dysregulation) and interpersonal factors (i.e., peer victimization) when understanding NSSI - among adolescents. These findings can be utilized to develop interventions aimed at reducing the prevalence and severity of NSSI among adolescents.

Backgrounds/Aims To systematically evaluate inter-reader agreement in the assessment of individual liver imaging reporting and data system (LI-RADS) category M (LR-M) imaging features in computed tomography/magnetic resonance imaging (CT/MRI) LIRADS v2018, and to explore the causes of poor agreement in LR-M assignment. Methods Original studies reporting inter-reader agreement for LR-M features on multiphasic CT or MRI were identified using the MEDLINE, EMBASE, and Cochrane databases. The pooled kappa coefficient (κ) was calculated using the DerSimonian-Laird random-effects model. Heterogeneity was assessed using Cochran’s Q test and I2 statistics. Subgroup meta-regression analyses were conducted to explore the study heterogeneity. Results In total, 24 eligible studies with 5,163 hepatic observations were included. The pooled κ values were 0.72 (95% confidence interval [CI], 0.65-0.78) for rim arterial phase hyperenhancement, 0.52 (95% CI, 0.39-0.65) for peripheral washout, 0.60 (95% CI, 0.50-0.70) for delayed central enhancement, 0.68 (95% CI, 0.57-0.78) for targetoid restriction, 0.74 (95% CI, 0.65-0.83) for targetoid transitional phase/hepatobiliary phase appearance, 0.64 (95% CI, 0.49-0.78) for infiltrative appearance, 0.49 (95% CI, 0.30-0.68) for marked diffusion restriction, and 0.61 (95% CI, 0.48-0.73) for necrosis or severe ischemia. Substantial study heterogeneity was observed for all LR-M features (Cochran’s Q test, P

Background : Since 1992, over 800 pancreas transplants have been performed in Korea. However, this number is significantly lower compared to the number of kidney or liver transplants. Methods : Between 2015 and July 2023, Pusan National University Yangsan Hospital conducted 100 pancreas transplants, accounting for about 20% of all transplants performed in Korea during this period. The study comprised 27 simultaneous pancreas and kidney (SPK) transplants, 23 pancreas after kidney (PAK) transplants, and 50 pancreas transplant alone (PTA) cases. Duodenoduodenostomy was the primary surgical technique employed for exocrine drainage, along with various modifications of the venous outflow anastomosis. Results : The availability of brain-dead donors for kidney transplants was lower compared to isolated pancreas transplants. Patients undergoing SPK transplants faced significantly longer waiting times than those receiving PTA or PAK transplants. The rate of surgical complications was acceptable, with a notably low thrombotic graft failure rate of 1.0%. In the PTA group, acute rejection of the graft pancreas occurred frequently (18.0%), though this was not statistically significant (P=0.328). The pancreas transplantation survival rates were 91.0%, 78.5%, and 75.4% at 1, 5, and 9 years, respectively. The PTA group exhibited a lower graft survival rate than the SPK and PAK groups, with marginal statistical significance (P=0.059). Conclusion : s: Graft survival rates have improved over time due to advancements in surgical techniques and immunosuppressant strategies. By sharing our experiences, we aim to enhance the activity and success of pancreas transplantation in Korea.

AbstractIntroduction A change from the supine to prone position causes hemodynamic alterations. We aimed to evaluate the effect of fluid preloading in the supine position, the subsequent hemodynamic changes in the prone position and postoperative outcomes.Patients and methods This prospective, assessor-blind, randomized controlled trial was conducted between March and June 2023. Adults scheduled for elective orthopaedic lumbar surgery under general anaesthesia were enrolled. In total, 80 participants were randomly assigned to fluid maintenance (M) or loading (L) groups. Both groups were administered intravenous fluid at a rate of 2 ml/kg/h until surgical incision; Group L was loaded with an additional 5 ml/kg intravenous fluid for 10 min after anaesthesia induction. The primary outcome was incidence of hypotension before surgical incision. Secondary outcomes included differences in the mean blood pressure (mBP), heart rate, pleth variability index (PVi), stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index and cardiac index before surgical incision between the two groups. Additionally, postoperative complications until postoperative day 2 and postoperative hospital length of stay were investigated.Results Hypotension was prevalent in Group M before surgical incision and could be predicted by a baseline PVi >16. The mBP was significantly higher in Group L immediately after fluid loading. The PVi, SVV and PPV were lower in Group L after fluid loading, with continued differences at 2–3 time points for SVV and PPV. Other outcomes did not differ between the two groups.Conclusion Fluid loading after inducing general anaesthesia could reduce the occurrence of hypotension until surgical incision in patients scheduled for surgery in the prone position. Additionally, hypotension could be predicted in patients with a baseline PVi >16. Therefore, intravenous fluid loading is strongly recommended in patients with high baseline PVi to prevent hypotension after anaesthesia induction and in the prone position.Trial number KCT0008294 (date of registration: 16 March 2023)

Abstract Aims Frailty is an obstacle to performing cardiopulmonary exercise test (CPET) in patients with chronic heart failure (CHF). We evaluated the usefulness of oxygen uptake efficiency slope (OUES) using a 6 min walk test (6MWT) with portable gas analysis compared with CPET‐derived parameters in patients with CHF. Methods and results Patients with CHF who underwent both the 6MWT with portable gas analysis and CPET between December 2016 and May 2020 were retrospectively investigated. The 6MWT‐derived and echocardiographic parameters were compared with the OUES and peak oxygen consumption (VO2) from the CPET. Forty patients were analysed; 50% were male with a mean age of 55.45 ± 14.70 years. Twenty‐six patients (65%) had New York Heart Association Functional Classification II or III dyspnoea. Twenty‐five patients (62.5%) had heart failure (HF) with preserved ejection fraction (EF) (left ventricular EF > 50%), and nine patients (22.5%) had HF with reduced EF (EF

Abstract Responding to threats in the real world demands a sophisticated orchestration of freeze and flight behaviors dynamically modulated by the neural activity. While the medial prefrontal cortex-basolateral amygdala (mPFC-BLA) network is known to play a pivotal role in coordinating these responses, the mechanisms underlying its population dynamics remain vague. As traditional Pavlovian fear conditioning models fall short in encapsulating the breadth of natural escape behaviors, we introduce a novel dataset to bridge this gap, capturing the defensive strategies of mice against a spider robot in a natural-like environment. The adaptive escape behaviors and concurrent mPFC-BLA activity in eight mice were monitored using wireless local field potential (LFP) and video recordings, both individually and in groups. Our data offers a unique avenue to explore the neural dynamics that govern fear- and vigilance-induced threat responses in isolated and social contexts. Supplemented by detailed methodologies and validation, the dataset allows for the analysis of the transient neural oscillatory dynamics, with prospective implications for the fields of neuroscience, robotics, and artificial intelligence.

Abstract Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

It has been reported that the administration of Limosilactobacillus fermentum alleviates diseases such as osteoporosis and colitis. In this study, we report the complete genome sequence of Limosilactobacillus fermentum KUFM407, a probiotic strain of LAB isolated from Korean traditional fermented food, Kimchi. Whole genome sequencing of L. fermentum KUFM407 was performed on the Illumina MiSeq and Oxford Nanopore MinION platform. The genome consisted of one circular chromosome (2,077,616 base pair [bp]) with a guanine cytosine (GC) content of 51.5% and one circular plasmid sequence (13,931 bp). Genome annotation identified 1,932 protein-coding genes, 15 rRNAs, and 58 tRNAs in the assembly. The function annotation of the predicted proteins revealed genes involved in the biosynthesis of bacteriocin and fatty acids. The complete genome of L. fermentum KUFM407 could provide valuable information for the development of new probiotic food and health supplements.

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1β and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

Introduction: The Liver Imaging Reporting and Data System (LI-RADS) categorization has been proposed as a potential prognostic indicator for primary liver neoplasms in patients with liver cirrhosis or chronic hepatitis B. This multicenter study aimed to determine whether LI-RADS categorization can offer additional post-surgical prognostic value for intrahepatic cholangiocarcinoma (ICCA) when used in conjunction with the American Joint Committee on Cancer (AJCC) guidelines. Methods: Patients with high risk for hepatocellular carcinoma, surgically confirmed ICCAs, and available preoperative MRI were enrolled. LI-RADS categorization of ICCAs was performed using MRI features, and multivariate analyses were conducted incorporating LI-RADS category, AJCC staging, and clinicopathologic factors to evaluate their predictive value for postoperative recurrence-free survival (RFS) and overall survival (OS). In patients with early recurrence (

The motor is essential for manufacturing industries, but wear can cause unexpected failure. Predictive and health management (PHM) for motors is critical in manufacturing sites. In particular, data-driven PHM using deep learning methods has gained popularity because it reduces the need for domain expertise. However, the massive amount of data poses challenges to traditional cloud-based PHM, making edge computing a promising solution. This study proposes a novel approach to motor PHM in edge devices. Our approach integrates principal component analysis (PCA) and an autoencoder (AE) encoder achieving effective data compression while preserving fault detection and severity estimation integrity. The compressed data is visualized using t-SNE, and its ability to retain information is assessed through clustering performance metrics. The proposed method is tested on a custom-made experimental platform dataset, demonstrating robustness across various fault scenarios and providing valuable insights for practical applications in manufacturing.

Background Nurses are crucial for enhancing patient safety due to their continuous presence at patients’ bedsides and close interactions with families and other healthcare providers. This study aims to examine the relationships among safety education, perception of patient safety culture, safety control, and patient safety competence in clinical nurses, while also exploring the mediating effect of perceptions on patient safety culture and safety control. Methods The study involved 165 nurses, including 10 males (6.1%) and 155 females (93.9%). Structural equation modeling (SEM) was used to test the hypothesized model, and data were analyzed using SPSS and AMOS programs. Results Significant positive correlations were among the frequency of attending safety education, the perception of patient safety culture, safety control, and patient safety competency. The number of safety education briefings attended did not directly influence patient safety competence; however, safety education for nurses indirectly influenced patient safety competence via the perception of patient safety culture and safety control. These findings suggest that enhancing safety education for nurses can improve patient safety competence by shaping their perceptions of patient safety culture and safety control.

Study region: The Seohwa watershed, South Korea. Study focus: Agricultural practices and urbanization in watersheds increase nutrient loads (total nitrogen (TN), total phosphorus (TP), and nitrate-nitrogen (NO3--N)) in streams and deteriorate water quality. Between October 2017 and October 2018, water samples were collected from a small stream (MS), main tributary (TS), and sub-tributaries (ST) characterized by different land-use patterns. The objective of this study was to identify the sources that determine water quality in the respective streams and to estimate whether water quality was dependent on land-use patterns. New hydrological insights for the region: TN in MS progressively decreased downstream, whereas such spatial variation was not observed in TS and ST. For TP, TS and ST samples showed elevated concentrations during storm events, but not in MS. These observations resulted from TN and TP derived from natural and anthropogenic sources associated with land-use patterns. Interestingly, TN/TP ratios were strongly negatively correlated with the proportion of residential area (R2 = 0.92) rather than other land-use patterns such as agricultural area and forest. In addition, statistical analysis and dual isotopes of nitrate (NO3-) showed that the water quality in MS and the one in TS and ST were predominantly affected by natural sources and anthropogenic sources, respectively. Considering the effects of land-use patterns and rainfall on water quality, anthropogenic sources should be precisely identified to manage stream water in small watersheds more effectively.

IntroductionThis study created and validated a scale to measure the level of suicide crisis among international students attending South Korean universities.MethodsStudy 1 developed questions and constructed the components of the scale using an initial survey of 248 people and exploratory factor analysis. Study 2 validated the scale using a second survey of 340 participants and confirmatory factor analysis.ResultsThe results showed that 21 items were confirmed in six factors, which include lack of social support, burdensomeness, maladaptation to Korean culture, academic maladjustment, suicidal thoughts, and suicide risk.DiscussionWe verified the convergent validity, criterion validity, and reliability of the scale. The significance and implications of this study are presented, along with suggestions for future research.

Abstract Although mice are social, multiple animals’ neural activities are rarely explored. To characterise the neural activities during multi-brain interaction, we simultaneously recorded local field potentials (LFP) in the prefrontal cortex of four mice. The social context and locomotive states predominately modulated the entire LFP structure. The power of lower frequency bands—delta to alpha—were correlated with each other and anti-correlated with gamma power. The high-to-low-power ratio (HLR) provided a useful measure to understand LFP changes along the change of behavioural and locomotive states. The HLR during huddled conditions was lower than that during non-huddled conditions, dividing the social context into two. Multi-brain analyses of HLR indicated that the mice in the group displayed high cross-correlation. The mice in the group often showed unilateral precedence of HLR by Granger causality analysis, possibly comprising a hierarchical social structure. Overall, this study shows the importance of the social environment in brain dynamics and emphasises the simultaneous multi-brain recordings in social neuroscience.

Abstract Background Alcohol-related liver disease (ALD) is a major health concern worldwide, but effective therapeutics for ALD are still lacking. Tumor necrosis factor-inducible gene 6 protein (TSG-6), a cytokine released from mesenchymal stem cells, was shown to reduce liver fibrosis and promote successful liver repair in mice with chronically damaged livers. However, the effect of TSG-6 and the mechanism underlying its activity in ALD remain poorly understood. Methods To investigate its function in ALD mice with fibrosis, male mice chronically fed an ethanol (EtOH)-containing diet for 9 weeks were treated with TSG-6 (EtOH + TSG-6) or PBS (EtOH + Veh) for an additional 3 weeks. Results Severe hepatic injury in EtOH-treated mice was markedly decreased in TSG-6-treated mice fed EtOH. The EtOH + TSG-6 group had less fibrosis than the EtOH + Veh group. Activation of cluster of differentiation 44 (CD44) was reported to promote HSC activation. CD44 and nuclear CD44 intracellular domain (ICD), a CD44 activator which were upregulated in activated HSCs and ALD mice were significantly downregulated in TSG-6-exposed mice fed EtOH. TSG-6 interacted directly with the catalytic site of MMP14, a proteolytic enzyme that cleaves CD44, inhibited CD44 cleavage to CD44ICD, and reduced HSC activation and liver fibrosis in ALD mice. In addition, a novel peptide designed to include a region that binds to the catalytic site of MMP14 suppressed CD44 activation and attenuated alcohol-induced liver injury, including fibrosis, in mice. Conclusions These results demonstrate that TSG-6 attenuates alcohol-induced liver damage and fibrosis by blocking CD44 cleavage to CD44ICD and suggest that TSG-6 and TSG-6-mimicking peptide could be used as therapeutics for ALD with fibrosis.

Abstract Mouse models expressing human ACE2 for coronavirus disease 2019 have been frequently used to understand its pathogenesis and develop therapeutic strategies against SARS-CoV-2. Given that human TMPRSS2 supports viral entry, replication, and pathogenesis, we established a double-transgenic mouse model expressing both human ACE2 and TMPRSS2 for SARS-CoV-2 infection. Co-overexpression of both genes increased viral infectivity in vitro and in vivo. Double-transgenic mice showed significant body weight loss, clinical disease symptoms, acute lung injury, lung inflammation, and lethality in response to viral infection, indicating that they were highly susceptible to SARS-CoV-2. Pretreatment with the TMPRSS2 inhibitor, nafamostat, effectively reduced virus-induced weight loss, viral replication, and mortality in the double-transgenic mice. Moreover, the susceptibility and differential pathogenesis of SARS-CoV-2 variants were demonstrated in this animal model. Together, our results demonstrate that double-transgenic mice could provide a highly susceptible mouse model for viral infection to understand SARS-CoV-2 pathogenesis and evaluate antiviral therapeutics against coronavirus disease 2019.

Abstract This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol‐lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash‐out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low‐density lipoprotein‐C (LDL‐C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were −23.02 (3.04) versus −7.18 (3.09) mmHg in the TRE and RE groups, respectively (p

Abstract Despite the proposal of numerous advanced materials for batteries, there remains a notable lack of comprehensive assessment protocols that facilitate direct comparisons between laboratory-scale research and industrial trials. Here, we introduce a standardized method coined as extremely lean electrolytic testing (ELET), designed as a uniform framework for evaluating the performance across different battery systems. This approach replicates the cycling behaviour of larger pouch cells within the more manageable format of coin cells under ELET conditions. Employing ELET, we develop quantitative models to create contour maps that standardize cell performance metrics. To demonstrate the ELET efficacy, we explore the mitigation of electrolyte decomposition in lithium-ion batteries through applying polydopamine coatings on silicon/carbon composite anodes, achieving a 150% decrease in electrolyte decomposition compared to uncoated ones. Additionally, we employ the ELET method to compare the performance of various post-secondary and commercial batteries, demonstrating its full utility in battery evaluation.

Abstract The ability to modulate optical and electrical properties of two-dimensional (2D) semiconductors has sparked considerable interest in transition metal dichalcogenides (TMDs). Herein, we introduce a facile strategy for modulating optoelectronic properties of monolayer MoSe2 with external light. Photochromic diarylethene (DAE) molecules formed a 2-nm-thick uniform layer on MoSe2, switching between its closed- and open-form isomers under UV and visible irradiation, respectively. We have discovered that the closed DAE conformation under UV has its lowest unoccupied molecular orbital energy level lower than the conduction band minimum of MoSe2, which facilitates photoinduced charge separation at the hybrid interface and quenches photoluminescence (PL) from monolayer flakes. In contrast, open isomers under visible light prevent photoexcited electron transfer from MoSe2 to DAE, thus retaining PL emission properties. Alternating UV and visible light repeatedly show a dynamic modulation of optoelectronic signatures of MoSe2. Conductive atomic force microscopy and Kelvin probe force microscopy also reveal an increase in conductivity and work function of MoSe2/DAE with photoswitched closed-form DAE. These results may open new opportunities for designing new phototransistors and other 2D optoelectronic devices.

(1) Background: the objective of this study was to examine the impact of defatted mealworm hydrolysate (DMH), formulated through protein hydrolysis, on muscle protein synthesis in C2C12 cells and rats; (2) Methods: C2C12 cells were treated with dexamethasone and DMH, and cell viability was quantified using the MTT assay. Twenty-four Sprague–Dawley rats were divided into three groups (control, DEX, and DEX + DMH) and treated for 8 weeks. The DEX and DEX + DMH groups were administered intraperitoneal injections of DEX at a concentration of 2.25 mg/kg over a 3-d period. The control and DEX groups were fed a control diet, whereas the DMH group had part of the protein composition of the control diet replaced with 3.5% of DMH. The impact of DMH on muscle protein synthesis was evaluated through the measurement of grip strength, gastrocnemius and tibialis anterior muscle weights, and the investigation of muscle protein synthesis and degradation factor mRNA expression utilising the real-time PCR method; (3) Results: in vitro experiments demonstrated that treatment with DMH at concentrations greater than 5 mg/mL markedly alleviated DEX-induced injury in C2C12 cells. In vivo experiments demonstrated that the mRNA expression levels of myogenin and myoblast determination proteins, which promote muscle protein synthesis, were significantly increased. Furthermore, rats fed DMH exhibited significantly enhanced grip strength and tibialis anterior weight; (4) Conclusions: these findings indicate that DMH may serve as a functional material capable of promoting muscle protein synthesis and that the utilization of proteolytic enzymes is advantageous for the effective utilization of mealworms.

Purpose: To effectively operate river water quality under current fourth-phase Total Maximum Daily Load (TMDL) management system, we built a machine learning model that predicts whether water quality goals are achieved for the entire Nakdong river watershed in Korea. Methods: First, to consider the effects of land use type on the runoff characteristics of pollutants, K-means clustering was used to classify the watershed into three areas: agricultural areas, forest areas, and urban areas. Next, we developed a machine learning model to predict the achievement of BOD, TP, and TOC water quality goals in the different rainfall seasons. At this time, the Isolated Forest and ADASYN machine learning techniques were used to preprocess the training data. Finally, SHAP was used to find the factors with the greatest effects on the achievement of water quality goals. Results: This model’s average prediction results for TP, BOD, and TOC showed accuracy ranging from 0.6 to 1.0. Meteorological factors, particularly monthly precipitation and average temperature, were found to highly influence the model predictions for all land use types. In the landscape metrics, ED showed a high level of importance in all land use types. CONTAG was the main factor in agricultural areas; ED, LPI, CONTAG, COHESION and SHDI were the main factors in forest areas; and PD, ED, SHDI, and COHESION were the main factors in urban areas. Conclusion: The monthly precipitation and average temperature significantly affected whether the TMDL water quality goals were achieved in all sub watersheds, and the landscape metrics calculated as highly influenced factors differed depending on the land use type. Therefore, customized watershed management according to land use characteristics is necessary. These results provide valuable ideas for land use managers and landscape planners to achieve water quality goals through the management of non-point source pollution.

Abstract The sustained water repellency of interconnected micropatterned surfaces is explored over an extended duration, with a focus on their resilience during a 90‐day water‐immersion test. Initially, the microstructure surfaces exhibit high water repellency, a characteristic of the Cassie–Baxter state. However, subsequent detailed temporal analyses reveal varying responses depending on the structural topology. The interconnected micropatterned surfaces exhibit remarkable long‐term resistance to water; this is attributed to the formation of large and stable air pockets enabled by their unique microcavity structures. In comparison, hierarchical microcavity surfaces with micropillars exhibit a notable decrease in water repellency, as evidenced by reduced contact angles, suggesting a transition to a wetting state owing to the emergence of surface hydrophilicity during long‐term water exposure. This study demonstrates the importance of stable air‐pocket effects, particularly in applications where the long‐term stability of liquid repellency is critical, and suggests the role of interconnected structures in maintaining water repellency over time.

Objectives To construct a new scoring system utilizing biomarkers, vitals, and imaging data to predict 30-day mortality in acute pulmonary embolism (PE). Background Acute PE, a well-known manifestation of venous thromboembolic disease, is responsible for over 100,000 deaths worldwide yearly. Contemporary management algorithms rely on a multidisciplinary approach to care via PE response teams (PERT) in the identification of low, intermediate, and high-risk patients. The PESI and sPESI scores have been used as cornerstones of the triage process in assigning risk of 30-day mortality for patients presenting with acute PE; however, the specificity of these scoring systems has often come into question. Methods This study retrospectively analyzed 488 patients with acute PE who were managed at a tertiary care institution with either conservative therapy consisting of low molecular weight or unfractionated heparin, advanced therapies consisting of catheter directed therapies, aspiration thrombectomy, or a combination of these therapies, or surgical embolectomy. The CLOT-5 score was designed to include vital signs, biomarkers, and imaging data to predict 30-day mortality in patients presenting with acute PE. Results The CLOT-5 score had an area under the curve (AUC) of 0.901 with a standard error of 0.29, while the PESI and sPESI scores had an AUC and standard errors of 0.793 ±­ 0.43 and 0.728 ± 0.55, respectively. Conclusions When incorporated into the management algorithms of national PERT programs, the CLOT-5 score may allow for rapid and comprehensive assessment of patients with acute PE at high risk for clinical decompensation, leading to early escalation of care where appropriate.

The study investigates the medicinal properties of Tagetes erecta L. (marigold) in combating inflammation and toxicity induced by lipopolysaccharides (LPS). The polyphenol-enriched extract from T. erecta L. petals (TE) exhibited significant anti-inflammatory effects by targeting the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex, as evidenced in cellular and animal models. In vitro, TE effectively inhibited LPS-induced proinflammatory mediators and key genes associated with inflammation. Molecular docking analyses suggested that constituents of TE, such as patulitrin, quercetagetin, kaempferol, patuletin, and isorhamnetin, have the potential to bind to the TLR4/MD2 complex, therefore supporting its anti-inflammatory effects. Experiments on zebrafish larvae revealed that TE mitigates LPS-induced abnormalities and mortality, as well as attenuates the expression of proinflammatory genes, highlighting its therapeutic potential. Overall, the study underscores the promising medicinal value of T. erecta L., particularly TE, in addressing LPS-induced inflammation and associated disorders, thus warranting further exploration in clinical applications.

This study conducted sterilization testing under different conditions using different strains for sterilization and crushing, the intermediate healthcare waste treatment phase, and proposed strategies for diversifying corresponding facilities in addition to promoting their installation. Five indicator microorganisms were selected to test the sterilization efficiency of steam, microwave, and chemical methods. Steam sterilization testing was conducted in accordance with legal and technological standards, microwave testing was carried out according to the legal standard, and chemical sterilization employed three typical compounds. Steam and microwave sterilization achieved 99.9999 % inactivation rates for all five strains under both conditions used; whereas under the chemical sterilization analyses, sodium hypochlorite (1000 ppm) failed to meet the inactivation requirement of the fungal strain Candida albicans, requiring further investigation. Based on these findings, this study presents strategies for diversifying sterilization·crushing facilities and promoting their installation.

Safe and effective sedation depends on various factors, such as the choice of sedatives, sedation techniques used, experience of the sedation provider, degree of sedation-related education and training, equipment and healthcare worker availability, the patient’s underlying diseases, and the procedure being performed. The purpose of these evidence-based multidisciplinary clinical practice guidelines is to ensure the safety and efficacy of sedation, thereby contributing to patient safety and ultimately improving public health. These clinical practice guidelines comprise 15 key questions covering various topics related to the following: the sedation providers; medications and equipment available; appropriate patient selection; anesthesiologist referrals for high-risk patients; pre-sedation fasting; comparison of representative drugs used in adult and pediatric patients; respiratory system, cardiovascular system, and sedation depth monitoring during sedation; management of respiratory complications during pediatric sedation; and discharge criteria. The recommendations in these clinical practice guidelines were systematically developed to assist providers and patients in sedation-related decision making for diagnostic and therapeutic examinations or procedures. Depending on the characteristics of primary, secondary, and tertiary care institutions as well as the clinical needs and limitations, sedation providers at each medical institution may choose to apply the recommendations as they are, modify them appropriately, or reject them completely.