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Artificial intelligence (AI) in radiology is a rapidly developing field with several prospective clinical studies demonstrating its benefits in clinical practice. In 2022, the Korean Society of Radiology held a forum to discuss the challenges and drawbacks in AI development and implementation. Various barriers hinder the successful application and widespread adoption of AI in radiology, such as limited annotated data, data privacy and security, data heterogeneity, imbalanced data, model interpretability, overfitting, and integration with clinical workflows. In this review, some of the various possible solutions to these challenges are presented and discussed; these include training with longitudinal and multimodal datasets, dense training with multitask learning and multimodal learning, self-supervised contrastive learning, various image modifications and syntheses using generative models, explainable AI, causal learning, federated learning with large data models, and digital twins., Competing Interests: Joon Beom Seo and Namkug Kim, editorial board members of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. All authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Vitamin D is known for its immunosuppressive effects on T cells, suppressing Th1 and Th17 and promoting Treg differentiation. Th1 cells contribute to inflammatory responses such as inflammatory cytokine production and macrophage activation, which accelerate the progression of atherosclerosis. However, the mechanisms underlying the modulation of T cell functions by vitamin D in atherosclerosis have not been investigated. This study analyzed the gene expression profiles of T cells, using RNA-seq transcriptome analysis, to investigate the effects of in vitro vitamin D treatment on T cell differentiation and signal transduction pathways in Ldlr knock-out (Ldlr -/- ) mice. C57BL/6 mice were randomly assigned to two groups and fed a control diet (CON) or a Western diet (WD) for 16 weeks, while Ldlr -/- mice (LDLR -/- ) were fed a Western diet. Splenic T cells were isolated and stimulated with anti-CD3e and anti-CD28 mAb for 48 hours with or without 10 nM 1,25(OH) 2 D 3 . RNA sequencing was performed, followed by KEGG and GO enrichment analyses. Populations of T cell subsets and cytokine production were measured to assess T cell lineage differentiation. The JAK-STAT, HIF-1, and calcium signaling pathways of Ldlr -/- mice significantly differed from those of control mice, and 1,25(OH) 2 D 3 treatment affected MAPKKK binding molecular function of Ldlr -/- mice. Percentages of Th1 cells and IL-17 production were significantly reduced by 1,25(OH) 2 D 3 treatment in all three mouse groups. These results suggest that 1,25(OH) 2 D 3 has anti-inflammatory effects in atherosclerosis and is involved in cell signaling pathways that could prevent disease progression by regulating T cell differentiation and effector functions., Competing Interests: Declaration of Competing Interest The authors confirm that they have no conflicts of interest concerning the contents of this research., (Copyright © 2023. Published by Elsevier Inc.)

In this study, the high isoflavone-enriched soy leaves (IESLs) were manufactured by treating with the chemical inducer ethephon, a plant growth regulator, to confirm changes in the properties of soy leaves (SLs), which are underutilized. Ethephon treatment concentrations consisted of 0 (SL1), 150 (SL2), and 300 (SL3) μg/mL. The composition analysis and physiological activity were conducted according to the ethephon treatment concentration of SLs. There was no significant difference in the proximate composition and fatty acids, except for an increase with increasing ethephon treatment concentrations. Depending on the ethephon treatment concentration, free amino acids increased to 1413.0, 1569.8, and 2100.4 mg/100 g, and water-soluble vitamins increased to 246.7, 244.7, and 501.6 mg/100 g. In particular, the functional substance isoflavone increased significantly to 1430.11, 7806.42, and 14,968.00 μg/g. Through this study, it was confirmed that the nutritional components and isoflavones of SLs increased according to the ethephon treatment concentration, a chemical inducer treatment agent. This can be used as a high-value-added biosubstance for raw materials for functional foods, cosmetics, and for natural drugs.

We present a new type of torsional soft morphing actuator designed and fabricated by twisted shape memory alloy (SMA) wires embedded in polydimethylsiloxane matrix. The design and fabrication process of the proposed soft morphing actuator are presented with investigations of its working mechanism. Actuation performance was evaluated with respect to the temporal response, the maximum torsional deformation under an applied electric current, and various design parameters including the twist direction, wire diameter, helical pitch of the SMA wire, and the actuator's thickness and length. We demonstrate potential applications of the proposed soft morphing actuator as a soft morphing wing and airfoil. The proposed actuator will aid in the development of soft actuators, soft robotics, and other relevant scientific and engineering applications., (© 2023. Springer Nature Limited.)

Colorectal cancers (CRC) are classified into consensus molecular subtypes (CMS) based on gene expression profiles. The revised classification system iCMS was proposed by considering intrinsic epithelial status, microsatellite instability (MSI), and fibrosis. This study aimed to provide molecular evidence for the adenoma-carcinoma sequence concept by examining CRC and synchronous adenomas using iCMS. Epithelial CMS cell proportion was estimated using CiberSortx, an in silico cell fractionation method that included CMS cell types among the reference cell types. A random forest (RF) model estimated the posterior probabilities of CMS classes, which were compared with the CiberSortx results. Gene expression profiles of the published iCMS signature panel were retrieved from our dataset and subjected to heatmap clustering for classification. Bulk RNA sequencing data were collected from 29 adenocarcinomas and 11 adenoma samples. CiberSortx showed all CRC contained either CMS2 or CMS3 as the major epithelial cancer cell type. The RF model classified approximately half of the CRC as CMS4, whereas CMS4 was hardly detected by CiberSortx. Because they were enriched with myofibroblasts as per the CiberSortx classification, we tentatively designated them as iCMS2-F/iCMS3-F. iCMS coupled with the application of an in silico cell fractionation method can provide the molecular dissection of CRC and adenoma.

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

We analyzed the virulence traits and azole resistance mechanisms of 104 Candida auris isolates collected from 13 Korean hospitals from 1996 to 2022. Of these 104 isolates, 96 (5 blood and 91 ear isolates) belonged to clade II, and 8 (6 blood and 2 other isolates) belonged to clade I. Fluconazole resistance (minimum inhibitory concentration ≥32 mg/L) was observed in 68.8% of clade II and 25.0% of clade I isolates. All 104 isolates were susceptible to amphotericin B and three echinocandins. In 2022, six clade I isolates indicated the first nosocomial C. auris cluster in Korea. Clade II C. auris isolates exhibited reduced thermotolerance at 42 °C, with diminished in vitro competitive growth and lower virulence in the Galleria mellonella model compared to non-clade II isolates. Of the 66 fluconazole-resistant clade II isolates, several amino acid substitutions were identified: Erg11p in 14 (21.2%), Tac1Ap in 2 (3.0%), Tac1Bp in 62 (93.9%), and Tac1Bp F214S in 33 (50.0%). Although there were a limited number of non-clade II isolates studied, our results suggest that clade II C. auris isolates from Korean hospitals might display lower virulence traits than non-clade II isolates, and their primary fluconazole resistance mechanism is linked to Tac1Bp mutations.

In this study, we investigated the effect of cycloastragenol (CAG), a triterpenoid isolated from Astragalus membranaceus roots, on regulating the adipogenesis and fat accumulation in vitro and in vivo. During the adipogenesis of 3T3-L1 cells, CAG inhibited lipid accumulation and the expression of key adipogenic factors, proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding protein α (C/EBPα) and increased the expression of Gli1, a key mediator in Hedgehog (Hh) signaling. In HFD-induced animal experiment, CAG significantly reduced body weight gain without affecting brown fat weight. In addition, CAG regulated the expression of PPARγ, C/EBPα, and Gli1 in visceral white adipose tissue (vWAT). We also confirmed the inhibitory effect of CAG on specifically targeting white adipose tissue (WAT) formation in stromal vascular fraction (SVF) cell differentiation. Taken together, these results suggest that CAG may be a potent phytochemical preventing adipogenesis and obesity via Hh signaling., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01403-0., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Psychological status affects dietary intake, and recognizing genetic information can lead to behavior changes by influencing psychological factors such as anxiety or depression., Objectives: In this study, we examined the effects of disclosing genetic information on anxiety or depression levels and the association between these psychological factors and dietary intake., Methods: A total of 100 healthy adults were randomly assigned to an intervention group (n = 65) informed about their genetic test results regarding body mass index and lipid profiles (triglyceride and cholesterol concentrations) and a not-informed control group (CON, n = 35). Based on polygenic risk scores, participants in the intervention group were subclassified into an intervention-low risk (ILR, n = 32) and an intervention-high risk (IHR, n = 33) group. Nutrient and food intakes were assessed via a 3-day dietary record at baseline and at 3 and 6 months. Depression and anxiety levels were measured using PHQ-9 and GAD-7 questionnaires, and the relative levels of blood metabolites were measure using GC-MS/MS analysis., Results: Noticeable changes in dietary intake as well as psychological factors were observed in male subjects, with those perceiving their genetic risks as low (ILR) showing a significant increase in protein intake at 3 months compared to baseline (ILR: 3.9 ± 1.4, p<0.05). Meat intake also increased significantly in males in the ILR group at 3 months, but not in the IHR and CON groups (ILR: 49.4 ± 30.8, IHR: -52.2 ± 25.4, CON: -5.3 ± 30.3 g/d). ILR group showed a significant decrease in anxiety levels at 3 months, and their anxiety scores showed a negative association with meat intake (standardized β = -0.321, p<0.05). The meat intake at 3 months was associated with the relative levels of arginine and ornithine (standardized β = 0.452, p<0.05 and standardized β = 0.474, p<0.05, respectively)., Conclusions: Taken together, anxiety levels were decreased in male subjects who perceived their genetic risk to be low, and the decrease in anxiety levels was associated with an increase in meat intake. This suggests that recognizing genetic information may affect psychological factors and dietary intake., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Non- aureus staphylococci (NAS), particularly antimicrobial-resistant NAS, have a substantial impact on human and animal health. In the current study, we investigated (1) the species profiles of NAS isolates collected from healthy broilers, farm environments, and farm workers in Korea, (2) the occurrence of antimicrobial-resistant NAS isolates, especially methicillin resistance, and (3) the genetic factors involved in the methicillin and fluoroquinolone resistance. In total, 216 NAS isolates of 16 different species were collected from healthy broilers (n=178), broiler farm environments (n=18), and farm workers (n=20) of 20 different broiler farms. The two most dominant broiler-associated NAS species were Staphylococcus agnetis (23.6%) and Staphylococcus xylosus (22.9%). Six NAS isolates were mecA -positive carrying staphylococcal cassette chromosome mec (SCC mec ) II (n=1), SCC mec IV (n=1), SCC mec V (n=2), or non-typeable SCC mec element (n=2). While two mecA -positive Staphylococcus epidermidis isolates from farm workers had SCC mec II and IV, a mecA -positive S. epidermidis isolate from broiler and a Staphylococcus haemolyticus isolate farm environment carried SCC mec V. The occurrence of multidrug resistance was observed in 48.1% (104/216 isolates) of NAS isolates with high resistance rates to β-lactams (>40%) and fusidic acid (59.7%). Fluoroquinolone resistance was confirmed in 59 NAS isolates (27.3%), and diverse mutations in the quinolone resistance determining regions of gyrA , gyrB , parC , and parE were identified. These findings suggest that NAS in broiler farms may have a potential role in the acquisition, amplification, and transmission of antimicrobial resistance., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases., Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables., Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P < 7.94E-04) that can be explored as potential therapeutic targets., Interpretation: By integrating eQTM and MR analyses in general and clinical asthma populations, our findings provide a deeper understanding of the multidimensional inter-relations of DNA methylation, gene expression, and IgE levels., Funding: US NIH/NHLBI grants: P01HL132825, K99HL159234. N01-HC-25195 and HHSN268201500001I., Competing Interests: Declaration of interests DLD has received grants from Bayer and honoraria from Novartis. STW has received royalties from UpToDate and served on the Board of Histolix, a digital pathology company. Rest authors declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Osteonecrosis of the femoral head (ONFH) is characterized as bone cell death in the hip joint, involving a severe pain in the groin. The staging of ONFH is commonly based on Magnetic resonance imaging and computed tomography (CT), which are important for establishing effective treatment plans. There have been some attempts to automate ONFH staging using deep learning, but few of them used only MR images., Purpose: To propose a deep learning model for MR-only ONFH staging, which can reduce additional cost and radiation exposure from the acquisition of CT images., Methods: We integrated information from the MR images of five different imaging protocols by a newly proposed attention fusion method, which was composed of intra-modality attention and inter-modality attention. In addition, a self-supervised learning was used to learn deep representations from a large amount of paired MR-CT dataset. The encoder part of the MR-CT translation network was used as a pretraining network for the staging, which aimed to overcome the lack of annotated data for staging. Ablation studies were performed to investigate the contributions of each proposed method. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of the networks., Results: Our model improved the performance of the four-way classification of the association research circulation osseous (ARCO) stage using MR images of the multiple protocols by 6.8%p in AUROC over a plain VGG network. Each proposed method increased the performance by 4.7%p (self-supervised learning) and 2.6%p (attention fusion) in AUROC, which was demonstrated by the ablation experiments., Conclusions: We have shown the feasibility of the MR-only ONFH staging by using self-supervised learning and attention fusion. A large amount of paired MR-CT data in hospitals can be used to further improve the performance of the staging, and the proposed method has potential to be used in the diagnosis of various diseases that require staging from multiple MR protocols., (© 2023 American Association of Physicists in Medicine.)

Individuals with end-stage kidney disease (ESKD) on dialysis are at a high risk of developing foot ulcerations and undergoing subsequent lower extremity amputation (LEA), which can exert significant impacts on their quality of life and contribute to rising healthcare costs. We aimed to identify risk factors associated with LEA in patients with ESKD to predict LEA progression and eventually prevent it. We used 18 years (2002-2019) of data from the Korean National Health Insurance Service (KNHIS). Data were collected from patients with ESKD who underwent renal replacement therapy (RRT) and had no history of amputation caused by trauma or toxins. The risk factors were compared between patients with or without LEA. We collected data from 220,838 patients newly diagnosed with ESKD, including 6348 in the LEA group and 214,490 in the non-LEA group. The total incidence of LEA was 2.9%. Older age, male gender, lower income, non-metropolitan residence, diabetes mellitus, dialysis treatment (compared to kidney transplantation), microvascular disease, peripheral vascular disease, endovascular procedure, and endovascular operation were associated with an increased risk of LEA. Thus, individuals with ESKD who are at a higher risk for LEA should be closely monitored, and kidney transplantation should be considered as a preventative measure.

Background: Despite increasing support for stakeholder inclusion in research, there is limited evaluative research to guide safe (i.e., youth-friendly) and meaningful (i.e., non-tokenistic) partnerships with young people with lived experience of mental ill-health in research. This paper describes a pilot evaluation and iterative design of a Youth Lived Experience Working Group (LEWG) protocol that was established by the Youth Mental Health and Technology team at The University of Sydney's Brain and Mind Centre, based on the results of two studies., Methods: Study one consisted of a pilot evaluation of the extent to which youth partners felt empowered to contribute, to qualitatively explore how LEWG processes could be improved. Youth partners completed online surveys, and results were shared over two LEWG meetings in 2021 to empower youth partners to collectively identify actions of positive change regarding LEWG processes. These meetings were audio-recorded and transcripts were subsequently coded using thematic analysis. Study two assessed whether LEWG processes and proposed improvements were acceptable and feasible from the perspective of academic researchers via an online survey in 2022., Results: Quantitative and qualitative data collected from nine youth partners and 42 academic researchers uncovered initial learnings regarding facilitators, motivators, and barriers to partnering with young people with lived experience in research. Implementing clear processes for youth partners and academic researchers on effective partnership strategies, providing training opportunities for youth partners to develop research skills, and providing regular updates on how youth partner contributions led to research outcomes were identified as key facilitators., Conclusions: This pilot study provides insight into a growing international field on how to optimise participatory processes so that researchers and young people with lived experience can be better supported and engaged to make meaningful contributions to mental health research. We argue that more transparency is needed around participatory research processes so that partnerships with young people with lived experience are not merely tokenistic., Consumer Contributions: Our study has also been approved by and reflects the concepts and priorities of our youth lived experience partners and lived experience researchers, all of whom are authors of this paper., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Objective: ASTHMAXcel © is a mobile application previously shown to improve asthma knowledge, control, and quality of life. In this study, we translated the application to Marathi for pilot testing in Pune, India in order to evaluate its impact on user satisfaction and asthma knowledge among adult asthma patients., Methods: ASTHMAXcel © was adapted to Marathi with the help of asthma patients and clinicians from Bharati Hospital. 57 different asthma patients were then recruited and received the Asthma Knowledge Questionnaire (AKQ), Asthma Control Questionnaire (ACQ), and Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) to complete at baseline. Study participants then completed the adapted ASTHMAXcel © application. Post-intervention, participants filled out a post-AKQ and Questionnaire for User Interface Satisfaction (QUIS). A subset of participants was also interviewed for qualitative feedback. Paired t-tests and Pearson's correlation were used for statistical analysis., Results: Mean AKQ improved from 5.0+/-2.4 to 12.4+/-1.6 ( p  = 0.0001). QUIS results revealed that participants were highly satisfied with the application, scoring an average of 50 out of 54 maximum points. Better baseline asthma control was correlated with greater overall experience with the application (-0.110, p  = 0.0417). Finally, the qualitative feedback revealed four themes for future refinement., Conclusion: The adapted version of ASTHMAXcel © was linked to significant improvement in patient asthma knowledge and a high level of user satisfaction. These results support the potential utility of mHealth applications in promoting guideline-based asthma care in India. However, further studies are needed to establish a causal relationship between ASTHMAXcel © and improved clinical outcomes.

Aims and Objectives: To determine the effectiveness of nurse-led interventions on medication adherence, medication knowledge and clinical outcomes in adults taking medication for metabolic syndrome., Background: Despite the significance of interventions designed to improve medication adherence, a systematic review of nurse-led intervention studies for metabolic syndrome is lacking., Design: A systematic review and meta-analysis of randomised controlled trials., Methods: The study was conducted following the PRISMA guidelines checklist. PubMed, EMBASE, PsychINFO, CINAHL, Cochrane CENTRAL and other manual sources were searched in May 2021.The quality assessment was conducted using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Comprehensive Meta-Analysis 3.0 was used to calculate the pooled effect sizes with 95% confidence intervals., Results: This review included 20 studies of nurse-led medication adherence interventions in 6017 adults at risk for metabolic syndrome. The pooled effect size using the random effects model indicated that nurse-led interventions had a significantly moderate impact on enhancing medication adherence and medication knowledge and improving selected clinical outcomes of available studies in nurse-led intervention groups compared with control groups. Duration of intervention (median 12 weeks), mode of delivery (group vs. individual) and using multiple strategies influenced outcomes of nurse-led medication adherence interventions. The results revealed that interventions of moderate- to high-quality studies were more likely to show significant improvements in medication adherence than those of low-quality studies., Conclusion: The meta-analyses showed that nurse-led interventions may enhance medication adherence and knowledge and improve clinical outcomes of this population., Relevance to Clinical Practice: The findings may contribute to evidence-based information about nurse-led intervention and its selection of appropriate interventions for improving medication adherence in this population., Patient or Public Contribution: Patients or the public were not directly involved in this review., (© 2022 John Wiley & Sons Ltd.)

The conversion of cellular prion protein (PrP C ) into pathogenic prion isoforms (PrP Sc ) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga 20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrP Sc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg/kg) exhibited prolonged survival times (159 ± 28.6 days) compared to nontreated hamsters (135 ± 9.9 days) as well as reduced PrP Sc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood-brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.

Fatty acid binding protein 4 (FABP4) is a lipid chaperone secreted from adipocytes upon stimulation of lipolysis. Circulating FABP4 levels strongly correlate with obesity and metabolic pathologies in experimental models and humans. While adipocytes have been presumed to be the major source of hormonal FABP4, this question has not been addressed definitively in vivo. We generated mice with Fabp4 deletion in cells known to express the gene - adipocytes (Adipo-KO), endothelial cells (Endo-KO), myeloid cells (Myeloid-KO), and the whole body (Total-KO) - to examine the contribution of these cell types to basal and stimulated plasma FABP4 levels. Unexpectedly, baseline plasma FABP4 was not significantly reduced in Adipo-KO mice, whereas Endo-KO mice showed ~87% reduction versus WT controls. In contrast, Adipo-KO mice exhibited ~62% decreased induction of FABP4 responses to lipolysis, while Endo-KO mice showed only mildly decreased induction, indicating that adipocytes are the main source of increases in FABP4 during lipolysis. We did not detect any myeloid contribution to circulating FABP4. Surprisingly, despite the nearly intact induction of FABP4, Endo-KO mice showed blunted lipolysis-induced insulin secretion, identical to Total-KO mice. We conclude that the endothelium is the major source of baseline hormonal FABP4 and is required for the insulin response to lipolysis.

High-throughput sequencing is a robust tool used for identifying and tracking pathogen outbreaks. Whole-genome sequencing of hepatitis A virus (HAV) remains poor due to ultra-low viral loads, limitations of next-generation sequencing technology, and its high costs in clinical applications. This study evaluated multiplex polymerase chain reaction (PCR)-based nanopore sequencing to obtain whole-genome sequences of HAV. The HAV genomes were obtained directly from patient specimens for a rapid molecular diagnosis of viral genotypes. Serum and stool samples were collected from six patients with hepatitis A infection. Amplicon-based nanopore sequencing was performed from the clinical specimens to identify HAV genotypes by acquiring nearly complete-genome sequences. TaqMan-based quantitative PCR (qPCR) was conducted to detect and quantify multiple HAV genes. Singleplex-based nanopore sequencing demonstrated high genome coverage rates (90.4-99.5%) of HAV within 8 h, at viral RNA loads of 10 to 105 copies/μL. TaqMan qPCR showed multiplex quantification of HAV genes namely, VP0, VP3, and 3C. This study provides useful insights into rapid molecular diagnosis during hepatitis A outbreaks and may ultimately augment public health disease surveillance in the hospital and epidemiology field., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [ 18 F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [ 18 F]FDG PET literature in this area.

Livestock-associated coagulase-negative staphylococci (CoNS), such as Staphylococcus (S.) epidermidis, have emerged as a significant reservoir of antimicrobial resistance (AMR). In the current study, the AMR profiles and genetic diversity of S. epidermidis isolates obtained from pig farms, slaughterhouses, and retail pork were analyzed. A total of 89 S. epidermidis isolates, comprising 22 methicillin-resistant (MRSE) and 67 methicillin-susceptible S. epidermidis (MSSE) isolates, were assessed to determine (i) the clonal lineages of the isolates [multilocus sequence (MLST), agr, and staphylococcal cassette chromosome mec (SCCmec) types], (ii) the profiles of AMR phenotypes, and (iii) the carriage of genetic factors associated with major AMR phenotypes and zinc chloride resistance. Two dominant clonal lineages of S. epidermidis, ST100 and ST570, were observed on pig farms, especially in healthy pigs. In addition, potential transmission of pig-associated ST100 MRSE-SCCmec V and ST100 MSSE to farm workers was identified. The high prevalence of ST100 and ST570 isolates in pig farms was associated with high levels of AMR and zinc chloride resistance. In relation to resistance phenotypes, higher carriage rates of resistance genes, such as β-lactams (mecA), phenicols (fexA), and tetracyclines [tet(K), tet(L), tet(S), tet(M), and tet(O)], were identified in pig farm-associated isolates. Furthermore, cfr-mediated linezolid resistance was detected in 14 MSSE isolates from pig farms. This study is the first to provide important insights into the clonal structures and AMR profiles of S. epidermidis isolates collected from healthy pigs, carcass/pork samples, and human workers in Korea., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Transsphenoidal surgery is one of the important treatment options in the management of prolactinomas; however, complete resection of the tumor does not always lead to endocrinological remission. While many studies have investigated preoperative factors associated with surgical outcome, little has been known about the relationship between postoperative factors and long-term surgical outcomes; moreover, there is no consistency in results. The aim of this study was to demonstrate the reliability of immediate postoperative prolactin levels as predictors of long-term outcomes., Methods: A total of 105 female patients who underwent complete removal of their histologically confirmed prolactinomas were included, and their medical records were retrospectively reviewed. To evaluate the predictability of immediate postoperative prolactin levels for long-term remission, prolactin levels were measured at 2, 6, 12, 18, 24, 48, and 72 h after surgery., Results: From the 105 included patients, 95 (90.5%) and 10 (9.5%) belonged to the remission and non-remission groups, respectively. A significant difference was observed in the prolactin level measured 6 h after surgery between the remission and non-remission groups, and this difference stayed apparent until 72 h after surgery. We derived a cut-off value for every postoperative time point that showed a significant relationship with disease remission., Conclusion: Our study suggests that immediate postoperative measurement of prolactin levels is a reliable predictor of long-term remission and can contribute to early identification of patients who require adjuvant treatment after surgery., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Vaping is an increasing health threat in the US and worldwide. The damaging impact of vaping on the human distal lung has been highlighted by the recent epidemic of electronic cigarette or vaping use-associated lung injury (EVALI). The pathogenesis of EVALI remains incompletely understood, due to a paucity of models that recapitulate the structural and functional complexity of the human distal lung and the still poorly defined culprit exposures to vaping products and respiratory viral infections. Our aim was to establish the feasibility of using single cell RNA-sequencing (scRNA-seq) technology in human precision-cut lung slices (PCLS) as a more physiologically relevant model to better understand how vaping regulates the antiviral and pro-inflammatory response to influenza A virus infection. Normal healthy donor PCLS were treated with vaping extract and influenza A viruses for scRNA-seq analysis. Vaping extract augmented host antiviral and pro-inflammatory responses in structural cells such as lung epithelial cells and fibroblasts, as well as in immune cells such as macrophages and monocytes. Our findings suggest that human distal lung slice model is useful to study the heterogeneous responses of immune and structural cells under EVALI conditions, such as vaping and respiratory viral infection.

We newly detected two (sinking and floating) phenotypes of Candida parapsilosis among bloodstream infection (BSI) isolates from Korean hospitals and assessed their microbiological and clinical characteristics. During the performance of a Clinical and Laboratory Standards Institute (CLSI) broth microdilution antifungal susceptibility testing, the sinking phenotype had a characteristic smaller button-like appearance because all yeast cells sank to the bottoms of the CLSI U-shaped round-bottom wells, whereas the floating phenotype comprised dispersed cells. Phenotypic analysis, antifungal susceptibility testing, ERG11 sequencing, microsatellite genotyping, and clinical analysis were performed on C. parapsilosis isolates from 197 patients with BSI at a university hospital during 2006 to 2018. The sinking phenotype was detected in 86.7% (65/75) of the fluconazole-nonsusceptible (FNS) isolates, 92.9% (65/70) of the isolates harboring the Y132F ERG11 gene substitution, and 49.7% (98/197) of all isolates. Clonality was more frequently observed for the Y132F-sinking isolates (84.6% [55/65]) than for all other isolates (26.5% [35/132]; P <  0.0001). Annual incidence of Y132F-sinking isolates increased 4.5-fold after 2014, and two dominant genotypes, persistently recovered for 6 and 10 years, accounted for 69.2% of all Y132F-sinking isolates. Azole breakthrough fungemia (odds ratio [OR], 6.540), admission to the intensive care unit (OR, 5.044), and urinary catheter placement (OR, 6.918) were independent risk factors for BSIs with Y132F-sinking isolates. The Y132F-sinking isolates exhibited fewer pseudohyphae, a higher chitin content, and lower virulence in the Galleria mellonella model than the floating isolates. These long-term results illustrate the increasing BSIs caused by clonal transmission of the Y132F-sinking isolates of C. parapsilosis. IMPORTANCE We believe that this is the first study describe the microbiological and molecular characteristics of bloodstream isolates of C. parapsilosis in Korea exhibiting two phenotypes (sinking and floating). An important aspect of our findings is that the sinking phenotype was observed predominantly in isolates harboring a Y132F substitution in the ERG11 gene (92.9%), fluconazole-nonsusceptible (FNS) isolates (86.7%), and clonal BSI isolates (74.4%) of C. parapsilosis. Although the increase in the prevalence of FNS C. parapsilosis isolates has been a major threat in developing countries, in which the vast majority of candidemia cases are treated with fluconazole, our long-term results show increasing numbers of BSIs caused by clonal transmission of Y132F-sinking isolates of C. parapsilosis in the period with an increased echinocandin use for candidemia treatment in Korea, which suggests that C. parapsilosis isolates with the sinking phenotype continue to be a nosocomial threat in the era of echinocandin therapy., Competing Interests: The authors declare no conflict of interest.

Novel barium heteroleptic complexes were synthesized through the substitution of the bis(trimethylsilyl)amide of Ba(btsa) 2 ·2DME with aminoalkoxide and β-diketonate ligands. Compounds [Ba(ddemap)(tmhd)] 2 ( 1 ) and [Ba(ddemmp)(tmhd)] 2 ( 2 ) were obtained and analyzed through Fourier transform infrared spectroscopy, nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis (ddemapH = 1-(dimethylamino)-5-((2-(dimethylamino)ethyl) (methyl)amino)pentan-3-ol and ddemmpH = 1-(dimethylamino)-5-((2-(dimethylamino)ethyl) (methyl)amino)-3-methylpentan-3-ol). In single-crystal X-ray crystallography, complex 1 exhibited a dimeric structure with μ 2 -O bonds of the ddemap ligand. All complexes exhibited high volatility and could be sublimed under reduced pressure (0.5 Torr) at 160 °C, indicating that these complexes are promising candidates as atomic layer deposition or chemical vapor deposition precursors for the growth of barium-containing thin films., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Employing affordable and uncomplicated sample preparation techniques to recommend the most efficient antibacterial therapy could help reduce antibiotic-resistant bacteria. This study evaluated the suitability of immunoassays and microbiological assays as alternatives for liquid chromatography/mass spectrometry (LC/MS) in determining plasma tylosin concentrations after intramuscular administration at a dose of 20 mg/kg to both healthy and diseased pigs in clinical veterinary practice. The diseased pigs were confirmed using the target genes Actinobacillus pleuropneumoniae ( apxIVA ) and Pasteurella multocida ( kmt1 ). The methods showed good linearity, precision, and accuracy. In both healthy and diseased pigs, a significant correlation was observed between LC/MS and the microbiological assay (Pearson correlation coefficient: 0.930, p < 0.001 vs. Pearson correlation coefficient: 0.950, p < 0.001) and between LC/MS and the enzyme-linked immunosorbent assay (ELISA) (Pearson correlation coefficient: 0.933; p < 0.001 vs. Pearson correlation coefficient: 0.976, p < 0.001). A strong correlation was observed between the microbiological assay and the ELISA in both healthy and diseased pigs (Pearson correlation coefficient: 0.911; p < 0.001 vs. Pearson correlation coefficient: 0.908, p < 0.001). A Bland-Altman analysis revealed good agreement between the methods, i.e., 95% of the differences were within the limits of agreement. Therefore, the microbiological assay and the ELISA, which demonstrated sufficient precision and accuracy, can be viable alternatives to LC/MS when it is unavailable.

Background: Although autophagy is an important mediator of metformin antitumor activity, the role of metformin in the crosstalk between autophagy and apoptosis remains unclear. The aim was to confirm the anticancer effect by inducing apoptosis by co-treatment with metformin and OSMI-1, an inhibitor of O-GlcNAcylation, in colon cancer cells., Methods: Cell viability was measured by MTT in colon cancer cell lines HCT116 and SW620 cells. Co-treatment with metformin and OSMI-1 induced autophagy and apoptosis, which was analyzed using western blot, reverse transcription-polymerase chain reaction (RT-PCR) analysis, and fluorescence-activated cell sorting (FACS). Combined treatment with metformin and OSMI-1 synergistically inhibit the growth of HCT116 was confirmed by xenograft tumors., Results: We showed that metformin inhibited mammalian target of rapamycin (mTOR) activity by inducing high levels of C/EBP homologous protein (CHOP) expression through endoplasmic reticulum (ER) stress and activating adenosine monophosphate-activated protein kinase (AMPK) to induce autophagy in HCT116 cells. Interestingly, metformin increased O-GlcNAcylation and glutamine:fructose-6-phosphate amidotransferase (GFAT) levels in HCT116 cells. Thus, metformin also blocks autophagy by enhancing O-GlcNAcylation, whereas OSMI-1 increases autophagy via ER stress. In contrast, combined metformin and OSMI-1 treatment resulted in continuous induction of autophagy and disruption of O-GlcNAcylation homeostasis, resulting in excessive autophagic flux, which synergistically induced apoptosis. Downregulation of Bcl2 promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and CHOP overexpression, synergistically inducing apoptosis. The activation of IRE1α/JNK signaling by OSMI-1 and PERK/CHOP signaling by metformin combined to inhibit Bcl2 activity, ultimately leading to the upregulation of cytochrome c release and activation of caspase-3., Conclusions: In conclusion, combinatorial treatment of HCT116 cells with metformin and OSMI-1 resulted in more synergistic apoptosis being induced by enhancement of signal activation through ER stress-induced signaling rather than the cell protective autophagy function. These results in HCT116 cells were also confirmed in xenograft models, suggesting that this combination strategy could be utilized for colon cancer treatment., (© 2023. The Author(s).)

Levels of circulating fatty acid binding protein 4 (FABP4) protein are strongly associated with obesity and metabolic disease in both mice and humans, and secretion is stimulated by β-adrenergic stimulation both in vivo and in vitro. Previously, lipolysis-induced FABP4 secretion was found to be significantly reduced upon pharmacological inhibition of adipose triglyceride lipase (ATGL) and was absent from adipose tissue explants from mice specifically lacking ATGL in their adipocytes (ATGL AdpKO ). Here, we find that upon activation of β-adrenergic receptors in vivo, ATGL AdpKO mice unexpectedly exhibited significantly higher levels of circulating FABP4 as compared with ATGL fl/fl controls, despite no corresponding induction of lipolysis. We generated an additional model with adipocyte-specific deletion of both FABP4 and ATGL (ATGL/FABP4 AdpKO ) to evaluate the cellular source of this circulating FABP4. In these animals, there was no evidence of lipolysis-induced FABP4 secretion, indicating that the source of elevated FABP4 levels in ATGL AdpKO mice was indeed from the adipocytes. ATGL AdpKO mice exhibited significantly elevated corticosterone levels, which positively correlated with plasma FABP4 levels. Pharmacological inhibition of sympathetic signaling during lipolysis using hexamethonium or housing mice at thermoneutrality to chronically reduce sympathetic tone significantly reduced FABP4 secretion in ATGL AdpKO mice compared with controls. Therefore, activity of a key enzymatic step of lipolysis mediated by ATGL, per se, is not required for in vivo stimulation of FABP4 secretion from adipocytes, which can be induced through sympathetic signaling., Competing Interests: Conflict of interest G. S. H. is in the Scientific Advisory Board of Crescenta Biosciences and holds equity. The Hotamisligil laboratory holds intellectual property related to hormonal FABP4 and its therapeutic targeting. All other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rheumatoid arthritis (RA) is a risk factor for atherosclerotic cardiovascular diseases (CVD). Given the critical roles of the immune system and inflammatory signals in the pathogenesis of CVD, we hypothesized that interrogation of CVD-related proteins using integrative genomics might provide new insights into the pathophysiology of RA. We utilized two-sample Mendelian randomization (MR) for causal inference between circulating protein levels and RA by incorporating genetic variants, followed by colocalization to characterize the causal associations. Genetic variants from three sources were obtained: those associated with 71 CVD-related proteins measured in nearly 7000 Framingham Heart Study participants, a published genome-wide association study (GWAS) of RA (19 234 cases, 61 565 controls), and GWAS of rheumatoid factor (RF) levels from the UK Biobank (n = 30 565). We identified the soluble receptor for advanced glycation end products (sRAGE), a critical inflammatory pathway protein, as putatively causal and protective for both RA (odds ratio per 1-standard deviation increment in inverse-rank normalized sRAGE level = 0.364; 95% confidence interval 0.342-0.385; P = 6.40 × 10 -241 ) and RF levels (β [change in RF level per sRAGE increment] = - 1.318; SE = 0.434; P = 0.002). Using an integrative genomic approach, we highlight the AGER/RAGE axis as a putatively causal and promising therapeutic target for RA., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Following 3R (reduction, refinement, and replacement) principles, we employed the rat liver S9 fraction to mimic liver metabolism of curcumol having high in vitro IC 50 on cancer cells. In HCT116 and HT29 colon cancer cells, the metabolites of curcumol by S9 fraction exerted more enhanced activity in inducing cell cycle arrest and apoptosis via regulating the expression of cyclin D1, CDK1, p21, PARP and Bcl-2 than curcumol. In addition, oral administration of curcumol at 4 mg/kg BW significantly suppressed the development of colon tumor induced by azoxymethane/dextran sulfate sodium, and induced cell cycle arrest and apoptosis in tumor tissues. In mass analysis, curcumenol and curzerene were identified as the metabolites of curcumol by S9 fraction metabolism. Taken together, curcumol metabolites showed the enhanced suppressive effect on colon cancer, suggesting that S9 fraction can be considered as simple, fast, and bio-mimicking platform for the screening of chemical libraries on different chronic diseases., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Competing Interests: The authors have nothing to disclose.

Strontium β-diketonate complexes were synthesized by the substitution reaction of the bis(trimethylsilyl) amide of Sr(btsa) 2 ·2DME with an ethereal group and β-diketonate ligands. The compounds [Sr(tmge)(btsa)] 2 ( 1 ), [Sr(tod)(btsa)] 2 ( 2 ), Sr(tmgeH)(tfac) 2 ( 3 ), Sr(tmgeH)(acac) 2 ( 4 ), Sr(tmgeH)(tmhd) 2 ( 5 ), Sr(todH)(tfac) 2 ( 6 ), Sr(todH)(acac) 2 ( 7 ), Sr(todH)(tmhd) 2 ( 8 ), Sr(todH)(hfac) 2 ( 9 ), Sr(dmts)(hfac) 2 ( 10 ), [Sr(mee)(tmhd) 2 ] 2 ( 11 ), and Sr(dts)(hfac) 2 ·DME ( 12 ) were obtained and analyzed by various techniques, including FT-IR, NMR, TGA (thermogravimetric analyses), and elemental analysis. Complexes 1 , 3 , 8 , 9 , 10 , 11 , and 12 were further structurally confirmed by single-crystal X-ray crystallography, where complexes 1 and 11 showed dimeric structures with μ 2 -O bonds of ethereal groups or tmhd ligands, and complexes 3 , 8 , 9 , 10 , and 12 displayed monomeric structures. Interestingly, compounds 10 and 12 , which preceded trimethylsilylation of the coordinating ethereal alcohols such as tmhgeH and meeH in the presence of HMDS as by-products due to highly increasing acidity of them, originated from electron-withdrawing two hfac ligands., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In this study, the physicochemical properties (pH, acidity, salinity, and soluble protein), bacterial diversities, isoflavone contents, and antioxidant activities of doenjang (fermented soy paste), household doenjang (HDJ), and commercial doenjang (CDJ), were assessed and compared. The values of pH 5.14-5.94 and acidity 1.36-3.03%, indicated a similar level in all doenjang. The salinity was high in CDJ at 12.8-14.6%, and the protein contents (25.69-37.54 mg/g) were generally high in HDJ. Forty-three species were identified from the HDJ and CDJ. The main species were verified to be Bacillus amyloliquefaciens ( B. amyloliquefaciens ), B . amyloliquefaciens subsp. plantarum , Bacillus licheniformis , Bacillus sp. and Bacillus subtilis . Comparing the ratios of isoflavone types, the HDJ has an aglycone ratio of >80%, and 3HDJ indicates a ratio of isoflavone to aglycone of 100%. In the CDJ, except 4CDJ, glycosides account for a high proportion of more than 50%. The results of antioxidant activities and DNA protection effects were variedly confirmed regardless of HDJs and CDJs. Through these results, it is judged that HDJs have a variety of bacterial species compared to CDJs, and these are biologically active and converted from glycoside to aglycone. Bacterial distribution and isoflavone contents could be used as basic data.

Metalenses are attractive alternatives to conventional bulky refractive lenses owing to their superior light-modulating performance and sub-micrometre-scale thicknesses; however, limitations in existing fabrication techniques, including high cost, low throughput and small patterning area, have hindered their mass production. Here we demonstrate low-cost and high-throughput mass production of large-aperture visible metalenses using deep-ultraviolet argon fluoride immersion lithography and wafer-scale nanoimprint lithography. Once a 12″ master stamp is imprinted, hundreds of centimetre-scale metalenses can be fabricated using a thinly coated high-index film to enhance light confinement, resulting in a substantial increase in conversion efficiency. As a proof of concept, an ultrathin virtual reality device created with the printed metalens demonstrates its potential towards the scalable manufacturing of metaphotonic devices., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To evaluate the diagnostic performance of hip magnetic resonance (MR) arthrography with a gadolinium-based contrast agent (GBCA) or normal saline (NS) for intra-articular pathologies., Methods: This retrospective study was approved by the institutional review board of our hospital, and the requirement for informed consent was waived. The study included 37 consecutive patients (38 hips; 21 right hips; 24 males; mean age, 33 years) who underwent GBCA-hip MR arthrography from July 2011 to January 2020 and 30 consecutive patients (30 hips; 20 right hips; 21 males; mean age, 40 years) who underwent NS-hip MR arthrography from January 2018 to June 2020. All images were evaluated twice independently by two radiologists blinded to the arthroscopic findings for the presence of labral tears, cartilage abnormalities, or ligamentum teres tears. Intrareader and interreader reliabilities were determined by kappa values (k) using the chi-squared test, and diagnostic performance was evaluated based on the arthroscopic findings. A P value less than .05 was considered to indicate statistical significance., Results: Intra-reader reliability in the detection of intra-articular pathologies ranged from moderate to almost perfect (k = 0.510-0.840) and inter-reader reliability ranged from moderate to substantial (k = 0.441-0.695) for GBCA- and NS-hip MR arthrography. The diagnostic accuracy of GBCA- and NS-hip MR arthrography was as follows: 81.6-92.1% and 66.7-73.3% for labral tears, respectively; 68.4-86.8% and 63.3-70.0% for cartilage abnormality, respectively; and 68.4-76.3% and 50.0-56.7% for ligamentum teres tears, respectively., Conclusion: NS-hip MR arthrography may be less accurate than GBCA-hip MR arthrography. LEVEL OF EVIDENCE: Level II of development of diagnostic criteria (consecutive patients with consistently applied reference standard and blinding)., (Copyright © 2022 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: The supramaximal stimulation (SMS) of the TOF test causes uncomfortable sensations in patients. We aimed to determine whether the submaximal stimulation would be reliable in TOF tests with reduced painful sensation., Methods: The accelomyography (AMG) and electromyography (EMG) monitor was applied at each arm and general anesthesia was induced and maintained by total intravenous anesthesia. At extubation, we conducted TOF test three times at each of four different currents: SMS, 70% SMS, 50% SMS, and 30% SMS. The same procedure was performed in the postanesthesia care unit (PACU) only with EMG, and the pain scores on the numerical rating scale (NRS) during the tests were recorded., Results: A total of 36 patients were enrolled. At extubation, TOF ratios with SMS in AMG and EMG were 112.0 ± 13.1% and 93.7 ± 8.9%, respectively. There were no significant differences in TOF ratios between the SMS and lower stimulation intensities. However, 30% and 50% SMS showed significantly higher rates of the unmeasurable results of tests in the PACU. In terms of the stimulation pain, NRS showed a downward pattern as the current decreased and was significantly lower at 50% and 30% SMS than the NRS at SMS., Conclusion: The TOF test with submaximal stimulation is still reliable and can reduce stimulation pain. Considering the importance of the TOF results in determining extubation, the authors suggest the minimal current for the TOF test as 70% SMS., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

This paper reports the synthesis of three novel titanium complexes containing amidoxime ligands as potential precursors for titanium nitride (TiN) thin films fabricated using atomic layer deposition (ALD). A series of ligands, viz ., N '-methoxy- N -methylacetimidamide (mnnoH), N '-ethoxy- N -methylacetimidamide (ennoH), and N '-methoxy- N -methylbenzimidamide (pnnoH), were successfully synthesized and used to produce Ti(mnno)(NMe 2 ) 3 ( 4 ), Ti(enno)(NMe 2 ) 3 ( 5 ), and Ti(pnno)(NMe 2 ) 3 ( 6 ). Thermogravimetric analysis curves of complexes 4 - 6 revealed a single-step weight loss up to 200 °C. Pyrolysis occurred beyond 200 °C. Among the three new complexes, 5 was liquid at room temperature. Therefore, TiN was synthesized by ALD using Ti(enno)(NMe 2 ) 3 ( 5 ) as a novel precursor. A TiN thin film was deposited from the Ti(enno)(NMe 2 ) 3 ( 5) precursor and NH 3 plasma, and self-limiting growth was achieved by varying the injection/purge duration. TiN thin film growths were observed with a growth per cycle (GPC) of 0.05-0.13 nm·cy -1 at deposition temperatures between 150 and 300 °C, while the measured resistivity was as low as 420 μΩ·cm. The high reactivity of the precursor promotes nucleation, resulting in TiN thin films with smooth, good step coverage and preferentially orientated microstructure.

Background: Remimazolam is a new anesthetic drug developed and is an ultra-short-acting agent with rapid onset and offset. The pharmacology of this drug seems to be ideal for short surgeries eligible for I-gel insertion. Therefore, this study aimed to determine the optimal bolus dose of remimazolam for I-gel insertion when co-administered with remifentanil without neuromuscular blocking agents (NMBAs)., Methods: Patients aged 19-65 years with American Society of Anesthesiologists physical status I or II scheduled for general anesthesia were enrolled. The first dose of remimazolam was 0.15 mg/kg and remifentanil was co-administered at an effect-site concentration (Ce) of 3.0 ng/mL. The dose of remimazolam for the following patient was decreased or increased by 0.05 mg/kg depending on the success or failure of I-gel insertion in the previous patient., Results: The remimazolam bolus dose required for successful I-gel insertion in 50% of adult patients using modified Dixon's up-and-down method with remifentanil Ce 3.0 ng/mL and no NMBAs was 0.280 ± 0.048 mg/kg. Isotonic regression analysis showed that the 50% and 95% effective doses were 0.244 (83% confidence interval [CI] 0.213-0.313) mg/kg and 0.444 (95% CI 0.436-0.448) mg/kg, respectively. The mean time to loss of consciousness (Modified Observer's Assessment of Alertness/Sedation score < 2) was 52.2 s. Three patients (12.0%) showed a reduction in systolic blood pressure of more than 30% from baseline., Conclusions: Selecting the appropriate dose of remimazolam/remifentanil without NMBAs makes it feasible to insert the I-gel., Trial Registration: This study protocol was registered at http://cris.nih.go.kr (KCT0007801, 12th, October, 2022)., (© 2023. The Author(s).)

An electrochemical immunoassay based on the redox cycling method was presented using vertically paired electrodes (VPEs), which were fabricated using poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as an electrode material and parylene-C as a dielectric layer. For the application to immunoassays, different electrochemical properties of PEDOT:PSS were analyzed for the redox reaction of 3,3',5,5'-tetramethylbenzidine (TMB, the chromogenic substrate for enzyme-immunoassays) at different pH conditions, including the conductivity ( σ ), electron transfer rate constant ( k app ), and double-layer capacitance ( C dl ). The influencing factors on the sensitivity of redox cycling based on VPE based on PEDOT:PSS were analyzed for the redox reaction of TMB, such as the electrode gap and number of electrode pairs. Computer simulation was also performed for the redox cycling results based on VPEs, which had limitations in fabrication, such as VPEs with an electrode gap of less than 100 nm and more than five electrode pairs. Finally, the redox cycling based on VPE was applied to the medical diagnosis of human hepatitis-C virus (hHCV) using a commercial ELISA kit. The sensitivity of the redox cycling method for the medical diagnosis of hHCV was compared with conventional assay methods, such as TMB-based chromogenic detection, luminol-based chemiluminescence assay, and a rapid test kit (lateral flow immunoassay).

High prevalence of livestock-associated methicillin-susceptible and -resistant Staphylococcus aureus (LA-MSSA and LA-MRSA, respectively) in livestock farms, particularly pig farms, is an increasingly serious threat to food safety and public health. In this study, 173 S. aureus (84 MRSA and 89 MSSA) isolates from healthy pigs, farm environments, and farm workers in Korea were examined to determine the (1) genetic diversity of S. aureus isolates (sequence type [ST], spa , and agr types), (2) staphylococcal cassette chromosome mec (SCC mec ) types of MRSA isolates, and (3) multidrug resistance (MDR) phenotypes of MRSA and MSSA isolates. Clonal complex 398 (CC398) genotypes of MRSA and MSSA isolates, particularly CC398- spa type t571- agr I lineages, displaying MDR phenotypes were highly prevalent in pig farms. High prevalence of CC398-t571 MRSA and MSSA was more frequently associated with weaning piglets and growing pigs. Moreover, the same clonal lineages of S. aureus isolates colonized both pigs and farm workers, suggesting the transmission of antimicrobial-resistant CC398 MRSA and MSSA between pigs and humans in the pig farms. Furthermore, two dominant SCC mec types, SCC mec V and SCC mec IX, were identified in CC398 MRSA isolates colonizing healthy pigs. To the best of our knowledge, this is the first report of a CC398 LA-MRSA isolate carrying SCC mec IX in Korea. Collectively, these results suggest widespread distribution of the CC398 lineage among MRSA and MSSA isolates in pigs, farm environments, and farm workers in Korea.

The emergence and spread of cfr -mediated resistance to linezolid in staphylococci have become a serious global concern. The acquisition of cfr confers multidrug resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A (PhLOPS A phenotype). However, occurrence of cfr -positive and linezolid-susceptible staphylococci has been identified. To investigate the mechanism underlying linezolid susceptibility in cfr -positive Staphylococcus aureus and non- aureus staphylococci (NAS) isolates from pig farms in Korea. Eleven cfr -positive and linezolid-susceptible staphylococci were analyzed for mutations in domain V of 23S rRNA, ribosomal proteins (L3, L4, and L22), cfr open reading frames (ORFs), and cfr promoter regions. The effect of the cfr mutation (Q148K) on the PhLOPS A phenotype was determined using plasmid constructs expressing either the mutated ( cfr Q148K ) or nonmutated cfr genes. All 11 (six S. aureus and five NAS) cfr -positive and linezolid-susceptible isolates had a point mutation at position 442 in cfr ORFs (C to A) that resulted in the Q148K mutation. No mutations were detected in 23S rRNA, L3, L4, or L22. The Q148K mutation in Cfr is responsible for phenotypes susceptible to PhLOPS A antimicrobial agents. To our knowledge, this is the first study to report the causal role of a single nucleotide mutation (Q148K) in cfr of S. aureus and NAS isolates in PhLOPS A resistance. Continued nationwide surveillance is necessary to monitor the occurrence and dissemination of mutations in cfr that affect resistance phenotypes in staphylococci of human and animal origin.

Recently, various commercial ark shell products were being sold, and in the case of processed foods, the loss of morphological traits makes species identification visually challenging, which can lead to seafood fraud. Therefore, a multiplex polymerase chain reaction (PCR) assay was developed to simultaneously identify three ark shells. The specific PCR amplicon sizes of the generated species-specific primer pairs were observed to be 99 bp for Anadara kagoshimensis , 148 bp for Anadara broughtonii , and 207 bp for Tegillarca granosa . Specificity was confirmed for 17 fish and shellfish, and only the target was amplified without cross-reactivity. The detection limit for the multiplex PCR assay was 1 pg. Furthermore, 31 commercial products were evaluated to assess the developed assay's applicability. Therefore, the analytical approach used in this study can rapidly and accurately identify ark shells in commercial food, and may be used as an authentication tool in the seafood industry., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01269-2., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. To this end, we performed a discovery transcriptome-wide association study to identify differentially expressed genes associated with circulating IgE levels in whole-blood derived RNA from 5,345 participants in the Framingham Heart Study across 17,873 mRNA gene-level transcripts. We identified 216 significant transcripts at a false discovery rate <0.05. We conducted replication using the meta-analysis of two independent external studies: the Childhood Asthma Management Program (n=610) and the Genetic Epidemiology of Asthma in Costa Rica Study (n=326); we then reversed the discovery and replication cohorts, which revealed 59 significant genes that replicated in both directions. Gene ontology analysis revealed that many of these genes were implicated in immune function pathways, including defense response, inflammatory response, and cytokine production. Mendelian randomization (MR) analysis revealed four genes ( CLC , CCDC21 , S100A13 , and GCNT1 ) as putatively causal ( p <0.05) regulators of IgE levels. GCNT1 (beta=1.5, p =0.01)-which is a top result in the MR analysis of expression in relation to asthma and allergic diseases-plays a role in regulating T helper type 1 cell homing, lymphocyte trafficking, and B cell differentiation. Our findings build upon prior knowledge of IgE regulation and provide a deeper understanding of underlying molecular mechanisms. The IgE-associated genes that we identified-particularly those implicated in MR analysis-can be explored as promising therapeutic targets for asthma and IgE-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Recto, Huan, Lee, Lee, Gereige, Yao, Hwang, Joehanes, Kelly, Lasky-Su, O’Connor and Levy.)