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Abstract The widespread use of sulfonamides can result in the residue of sulfonamides in the foods of animal origin that are the major concerns of consumers and regulatory bodies due to their adverse reaction such as the development of antibiotic resistance. A rapid and efficient multi-residue analytical method was developed to screen and confirm 31 sulfonamides in livestock samples in a single run, using ultra-high-performance liquid chromatography combined with comprehensive mass spectrometric approaches. In this study, a novel sample preparation procedure was used, based on a modified QuEChERS method (Quick, Easy, Cheap, Effective, Rugged, and Safe). The linearity, sensitivity, accuracy, and precision of the method were validated according to the Codex guidelines. The response of the detector was linear for each target compound over a wide concentration range, with a correlation coefficient (r2) greater than 0.98. The limit of detection (LOD) and limit of quantification (LOQ) ranged from 0.3 to 5 ng g −1 and from 1 to 19 ng g −1 and the average recoveries (%) for three laboratories ranged from 85 to 109% with a CV (n = 5) below 22%. The applicability of this screening method was verified using real livestock samples. The proposed analytical method achieves identification and quantification of target sulfonamides at trace levels in a short analysis time. None of the samples contained residues that exceeded the maximum residue limit (MRL).

Abstract Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.

Background: Recent research on occupational injuries in companies has faced difficulties in obtaining representative data, leading to studies relying on surveys or case studies. Moreover, it is difficult to find studies on how a company's industry characteristics affect occupational injuries. This study aims to address these limitations. Methods: We collected 11 years of disclosure data from 1,247 listed companies in the Korean stock market and combined it with their occupational injury histories collected by the Republic of Korea Occupational Safety and Health Agency (KOSHA) to build a dataset. We attempted to analyze a linear panel model by dividing the dataset into manufacturing, construction, and other industries. Results: The higher proportion of full-time employees and better job skills correlate with lower occupational injuries in other industries. The wage increase reduces occupational injuries in manufacturing and other industries, but the substitution effect produces the opposite outcome in construction. Also, foreign ownership and credit ratings increase effectively reduce occupational injuries mainly in the manufacturing industry. Conclusion: Our results suggest that in explaining the relationship between corporate characteristics and occupational injuries, it is necessary to consider the nature of the industry more closely, and in particular, employment and labor policies for preventing occupational injuries need to be selectively applied according to industry. In addition, to improve the limitations and increase the usability of the research results, further detailed studies are needed in the future.

This study aims to assess the contamination of water and fish with nine metals (Fe, Al, Pb, Cu, Zn, Cd, Ni, As, and Cr) emitted by four coal-fired power plants in Chungcheongnam-do, Korea. Samples were collected at sites near each coal-fired power plant during the summer and fall. Control samples were also collected for comparison with the study samples. The concentrations of metals ranged from 0.01 to 4,654 μg/L in water. Non-carcinogenic and carcinogenic risks are associated with human exposure to Pb and As. Managing the presence of metals in the water environment is crucial for preserving the aquatic ecosystem.

Objective: This study investigated demographic, sleep related symptoms and mental health status as predictors of clinically significant treatment responses to cognitive behavioral therapy in adults who have good adherence for the cognitive behavioral therapy for insomnia (CBT-I) program in primary insomnia. Methods: A total of 42 adults with primary insomnia disorder were treated with CBT-I at a university hospital from June 2020 to January 2021. Demographic variables were surveyed and sleep-related symptoms were measured using self-reported questionnaires before and after the intervention, comprising a 6-week interval. The treatment responder group was defined as patients with an Insomnia Severity Index change score >7 compared to baseline. Logistic regression and paired t-test examined whether these factors predicted treatment outcomes for CBT-I. Results: Demographic variables did not predict treatment outcomes. Higher levels of anxiety were associated with a higher likelihood of treatment response (odds ratio [OR] = 1.234; confidence interval [CI]: 1.008–1.511). More severe insomnia at baseline was associated with a greater likelihood of treatment response (OR = 1.450; CI: 1.121–1.875). The lesser the dysfunctional beliefs and attitudes about sleep, the more effective the treatment response (OR = 0.943; CI: 0.904–0.984). Unlike the group of treatment responders, daytime function, depressive mood, and anxiety status did not improve in the group of treatment non-responders after CBT-I intervention. Conclusions: Patients with severe insomnia and anxiety at baseline should be treated more aggressively with CBT-I. During treatment, patients’ mental health problems and daytime activities should be continuously monitored, in order to help improve these problems which might strengthen the effectiveness of CBT-I.

AbstractThere has been plenty of observational evidence displaying that L2 English learners whose L1 do not have article systems undergo persistent difficulties. It is known that functional categories of grammar are especially difficult for L2 learners, and the Korean language does not have a functional equivalent to English articles. The current study aims to investigate article usage patterns by L1 Korean L2 English learners by employing a large English interlanguage corpus data; ICNALE written corpus data. Particularly, the current study focuses on the analysis of a specific NP, “part-time jobs”. The current research claims that by narrowing down the scope of analysis to a particular NP, one can expect more reliable and meaningful interpretation from L2 learners’ authentic language production, which can ultimately lead to more effective language instruction and better outcomes for second language learners. The current study seeks to describe patterns of L2 English articles across different proficiency levels. According to the results, it was found that learners’ article usage patterns appeared to be more similar to that of the native speaker in the group with higher English proficiency. One of the interesting findings was the frequent use of bare nominals even in the most advanced learners. Based on the corpus analysis, the current study provides the pedagogical implication that teaching structural differences between learners’ L1 and L2 is very important and article instruction should be emphasized in L2 classrooms in EFL settings.

Abstract Background Fibrosing interstitial lung disease (F-ILD) is a major public health concern due to its poor prognosis. Recent clinical evidence shows that antifibrotic approaches such as pirfenidone and nintedanib provide better clinical outcome prediction in idiopathic pulmonary fibrosis (IPF) as well as selected progressive fibrosing ILD (PF-ILD) patients. Having epidemiologic insight into these diseases will be essential for the efficient utilization of these therapeutic resources. This study aimed to estimate the current prevalence, incidence, and mortality of F-ILD classified as idiopathic pulmonary fibrosis (IPF), PF-ILD other than IPF, and non-progressive F-ILD and their temporal trend in Korea. Methods Population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment (HIRA) database (2011–2018). Patients with IPF were identified using ICD-10 code, RID code, and differential diagnosis approach. By leveraging medical records available from claim data and referencing those used in clinical trials, rigorous diagnostic criteria for PF-ILD detection were implemented. Results For the past eight years, the prevalence of IPF and PF-ILD has progressively increased, while non-progressive F-ILD has remained stable. IPF, PF-ILD, and non-progressive F-ILD prevalence per 100,000 in 2018 were 16.9, 10.4, and 11.7, respectively. The incidence of IPF in 2018 was more than twice that of 2012. The incidence of PF-ILD in 2018 was 1.5 times higher than that in 2012. In 2018, the mortalites were 10.3% and 12.2% for IPF and PF-ILD, respectively. The mortality rate of PF-ILD was greater than that of IPF in all years. Unclassifiable PF-ILD and rheumatoid arthritis-PF-ILD had the highest proportion and mortality among the PF-ILD subtypes. Conclusion The prevalence and incidence of IPF and PF-ILD have been steadily increasing in recent years. The mortality rate of PF-ILD remained consistently high and exceeded those of IPF in all years.

Drawing on social exchange theory and stakeholder responses to corporate social responsibility model, this study aimed to examine if the cross-level impacts of perceived investment in green employee development climate (PIGED) on environmental commitment (EC) and green well-being (GWB) were mediated by green person-job fit and green growth need strength. We collected a total of 412 employees and 80 operating units from a leading palm-oil company in Malaysia. The multilevel regression analysis found the cross-level effects of PIGED on EC and GWB that were partially mediated by green person-job fit and green growth need strength. Due to incomplete understanding of more dynamic relationships at the cross-level analysis, this study contributes a nuanced understanding of psychological mechanism of PIGED and its beneficial values for employees to develop quality of relationships between organizations and employees. Human resource professionals can leverage on PIGED across units at multiple locations to create beneficial values to employees’ jobs and their personal growth desire which can promote EC and GWB.

In recent years, artificial intelligence (AI) has been applied in various fields, with rapid expansion of the scope of AI-human interactions. However, most AI technologies continue to exhibit black-box characteristics, i.e., their decisions and actions are not explainable, degrading user experience (UX). Recently, research on explainable AI (XAI), focusing on both AI performance and UX, has garnered significant attention. However, development of generalizable UX evaluation tools for AI and improvement of AI UX have not been investigated adequately. In this study, a UX evaluation tool is developed for AI based on a systematic literature review and verified using exploratory and confirmatory factor analyses. Subsequently, based on identified AI UX factors, UX of an AI defense system is upgraded. Based on user evaluation, there were significant improvements in eight factors (satisfaction, safety, controllability, trust, causality, efficiency, accountability, and explainability) with the exception of fairness. The proposed evaluation tool is expected to serve as a cornerstone for future evaluation of AI UX advancement.

Abstract Studying seismic wave propagation through complex media is crucial to numerous aspects of geophysics and engineering including seismic hazard assessment. In particular, small-scale structure such as sedimentary basins and their edges can have significant effects on high-frequency earthquake ground motion, which is the main cause for the damage to buildings and infrastructure. However, such structural effects are poorly understood due to limitations in numerical and analytical methods. To overcome this challenge, for the first time, we utilize the 3D printing technique to build a scaled-down physical representation of geological structure and perform lab-scale seismic experiments on it. Specifically, a physical model based on the Los Angeles Basin is printed and used as synthetic medium to propagate ultrasonic waves, to mimic seismic wave propagation from local earthquakes. Our results show clear body and surface waves recorded at expected time and locations, as well as waves that are scattered from the basin edges. We find that high-frequency energies are significantly reduced at the basin, which is at odds with the conventional view of basins as ground motion amplifiers. This novel waveform modeling approach with 3D printed Earth models is largely automated and provides an effective means to tackle geophysical problems of significance.

Background KINE-101, a novel synthetic nonapeptide, is being developed for the treatment of rheumatoid arthritis with a distinctive mode of action. A study using a collagen-induced arthritis (CIA) mouse model showed that KINE-101 suppressed cartilage damage through inhibiting osteoclastogenesis. KINE-101 showed its therapeutic effects in suppressing auto-immune responses by activating Regulatory T cells (Tregs), a specialized subpopulation of T cells, in in-vivo studies using mouse models of RA. Following the in-vivo studies, the phase 1 clinical study for KINE-101 was conducted to assess the safety and tolerability in healthy subjects in the US. Methods Total 40 healthy subjects were enrolled to assign in 5 cohorts. Each cohort included 8 subjects composed of 6 active and 2 placebo treatment. The subjects of first 4 cohorts were administrated with 10, 30, 100, 300 mg of KINE-101 by intravenous (IV) infusion as single ascending doses (SAD), and the Cohort 5 subjects were subcutaneously (SC) injected with 96.8 mg of KINE-101. Results Except for 2 subjects in placebo group, all subjects completed the study. All the randomized subjects were included in the safety evaluation. No deaths, SAEs (Serious Adverse Events), or AEs (Adverse Events) leading to discontinuation were reported during the study periods. While total 9 TEAEs (Treatment-Emergent Adverse Events) were reported, all were assessed as mild. It included 3 headaches, 1 catheter site edema, 1 contusion and 1 nasal congestion in the treatment group, and 1 catheter site pain, 1 oral contusion and 1 COVID-19 infection in the placebo group. Oral contusion and COVID-19 occurred in the same subject, and all the other events were singular TEAEs reported in individual subjects. No injection site reactions were reported and no clinically significant changes in any laboratory values were noted. In terms of pharmacokinetic (PK) profile, KINE-101 was observed in the blood samples during and up to 5 minutes after infusion. Conclusion In the phase I clinical study, Treg activator KINE-101 demonstrated a favorable safety and tolerability profile. The most common AEs were headaches reported in 3 subjects, but all were mild and transient events. As typically seen in peptide drugs, KINE-101 has a short half-life. However, given that KINE-101 uses Treg as a proxy to exerts anti-inflammatory effects, its pharmacodynamic (PD) activity is likely to last longer. The next stage for KINE-101 will proceed to oral formulation and the Phase 2 clinical study in RA patients.

Summary Biofilms are communities of bacteria, fungi or yeasts that form on diverse biotic or abiotic surfaces, and play important roles in pathogenesis and drug resistance. A generic saw palmetto oil inhibited biofilm formation by Staphylococcus aureus, Escherichia coli O157:H7 and fungal Candida albicans without affecting their planktonic cell growth. Two main components of the oil, lauric acid and myristic acid, are responsible for this antibiofilm activity. Their antibiofilm activities were observed in dual‐species biofilms as well as three‐species biofilms of S. aureus, E. coli O157:H7 and C. albicans. Transcriptomic analysis showed that lauric acid and myristic acid repressed the expressions of haemolysin genes (hla and hld) in S. aureus, several biofilm‐related genes (csgAB, fimH and flhD) in E. coli and hypha cell wall gene HWP1 in C. albicans, which supported biofilm inhibition. Also, saw palmetto oil, lauric acid and myristic acid reduced virulence of three microbes in a nematode infection model and exhibited minimal cytotoxicity. Furthermore, combinatorial treatment of fatty acids and antibiotics showed synergistic antibacterial efficacy against S. aureus and E. coli O157:H7. These results demonstrate that saw palmetto oil and its main fatty acids might be useful for controlling bacterial infections as well as multispecies biofilms.

This study presents a novel ship route planning algorithm that takes into account both operational economy and safety by integrating the A∗ algorithm with a collision avoidance algorithm that evaluates the Collision Risk Index (CRI) between the own ship and the target ship. The CRI-based A∗ algorithm defines a penalty zone, allowing the own ship to explore safe routes based on the International Regulations for Preventing Collisions at Sea 1972 (COLREGs) and performs an adaptive and effective node search on an extended local map grid according to various encounter situations. The proposed algorithm is validated through simulations of head-on, fine-broad crossing, converging crossing, and overtaking encounters, indicating an economical and safe optimum route compared to conventional ship domain-based route planning.

Background: We hypothesized that the growing demand of Korean workers for work–life balance would change the factors influencing job satisfaction. We sought to verify our hypothesis by conducting a conjoint analysis based on the Korean Working Conditions Survey (KWCS). Methods: We analyzed the raw data of the KWCS, conducted by the Occupational Safety and Health Research Institute from 2006 to 2017. To complete the analysis, we counted on a conjoint model of analysis, typically used in the analysis of customer satisfaction. The dependent variable was the satisfaction of workers with their working conditions, and the independent variables were the job quality indicators identified by Eurofound. Results: The factors that have the greatest impact on working conditions satisfaction are summarized as follows: “physical environment” for the first wave, “adverse social behavior” for the second wave, “occupational status” for the third and fourth waves, and “management quality” for the fifth wave. “Earnings” were not a major factor in determining employee job satisfaction, and the relative importance index is decreasing. Conclusion: According to the results of the analysis of the tendencies of Korean workers, the factors that affect the satisfaction with the working conditions have changed over time. It is crucial to identify factors that affect working conditions to assure the health and productivity of workers. The results of this study demonstrate that policymakers and employers are required to attentively consider human relations and social environment at work to improve working conditions in the future.

Background and objective: There are limited information about factor associated with linear sequences of suicidal ideation, planning, and attempts among adolescents by gender groups, and those of out-of-linear sequences. The aims of this study was to identify factors associated with typical and atypical patterns of suicidal behaviors by comparing two gender groups of adolescents. Material and methods: This secondary data analysis was conducted based on the 2018 Korea Youth Risk Behavior Survey (N = 65528) by using descriptive statistics and multinomial logistic regression analyses with this complex sample. Results: A total of 12.4% of adolescents were in typical groups, and 1.6% were in atypical groups. Excessive stress and a depressed state were related to typical suicidal behaviors, while violent victimization accounted for atypical suicidal behaviors (all P values < 0.001). In spite of similar degrees and directions in both gender groups, there were some different findings between the gender groups, such as a poor level of academic achievement and stress, as well as living arrangements. Conclusion: Our study findings provide a comprehensive understanding of the risks of typical and atypical suicidal behaviors in adolescents by considering gender differences. Psychological interventions including school violence prevention should be provided to vulnerable adolescents at risk of suicide, specifically tailored to their gender differences.

ABSTRACT Candida albicans is an opportunistic pathogenic fungus responsible for candidiasis. The pathogen readily forms antifungal agent-resistant biofilms on implanted medical devices or human tissue. Morphologic transition from yeast to filamentous cells and subsequent biofilm formation is a key virulence factor and a prerequisite for biofilm development by C. albicans. We investigated the antibiofilm and antifungal activities of 18 hydroquinones against fluconazole-resistant C. albicans. Tetrachlorohydroquinone (TCHQ) at subinhibitory concentrations (2 to 10 μg/mL) significantly inhibited C. albicans biofilm formation with an MIC of 50 μg/mL, whereas the backbone hydroquinone did not (MIC > 400 μg/mL), and it markedly inhibited cell aggregation and hyphal formation. Transcriptomic analyses showed that TCHQ downregulated the expressions of several hyphae-forming and biofilm-related genes (ALS3, ECE1, HWP1, RBT5, and UME6) but upregulated hyphae- and biofilm-inhibitory genes (IFD6 and YWP1). Furthermore, it prevented C. albicans biofilm development on porcine skin and at concentrations of 20 to 50 μg/mL was nontoxic to the nematode Caenorhabditis elegans and did not adversely affect Brassica rapa seed germination and growth. This study indicates that hydroquinones, particularly TCHQ, diminish the virulence, biofilm formation, and animal tissue adhesion of C. albicans, which suggests hydroquinones should be considered potential candidate antifungal agents against drug-resistant C. albicans strains. IMPORTANCE Persistence in chronic infections by Candida albicans is due to its ability of biofilm formation that endures conventional antifungals and host immune systems. Hence, the inhibition of biofilm formation and virulence characteristics is another mean of addressing infections. This study is a distinctive one since 18 hydroquinone analogues were screened and TCHQ efficiently inhibited the biofilm formation by C. albicans with significantly changed expressional profile of hyphae-forming and biofilm-related genes. The antibiofilm efficacy was confirmed using a porcine skin model and chemical toxicity was investigated using plant seed germination and nematode models. Our findings reveal that TCHQ can efficiently control the C. albicans biofilms and virulence characteristics.

Abstract Loss-of-function mutations in the human oligophrenin-1 (OPHN1) gene cause intellectual disability, a prevailing neurodevelopmental condition. However, the role OPHN1 plays during neuronal development is not well understood. We investigated the role of the Drosophila OPHN1 ortholog Graf in the development of the mushroom body (MB), a key brain structure for learning and memory in insects. We show that loss of Graf causes abnormal crossing of the MB β lobe over the brain midline during metamorphosis. This defect in Graf mutants is rescued by MB-specific expression of Graf and OPHN1. Furthermore, MB α/β neuron-specific RNA interference experiments and mosaic analyses indicate that Graf acts via a cell-autonomous mechanism. Consistent with the negative regulation of epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) signaling by Graf, activation of this pathway is required for the β-lobe midline-crossing phenotype of Graf mutants. Finally, Graf mutants have impaired olfactory long-term memory. Our findings reveal a role for Graf in MB axon development and suggest potential neurodevelopmental functions of human OPHN1.

Abstract Although migration has long been an imperative topic in social sciences, there are still needs of study on migrants’ unique and dynamic transnational identity, which heavily influences the social integration in the host society. In Online Social Network (OSN), where the contemporary migrants actively communicate and share their stories the most, different challenges against migrants’ belonging and identity and how they cope or reconcile may evidently exist. This paper aims to scrutinise how migrants are manifesting their belonging and identity via different technological types of online social networks, to understand the relations between online social networks and migrants’ multi-faceted transnational identity. The research introduces a comparative case study on an online social movement led by Koreans in Germany via their online communities, triggered by a German TV advertisement considered as stereotyping East Asians given by white supremacy’s point of view. Starting with virtual ethnography on three OSNs representing each of internet generations (Web 1.0 ~ Web 3.0), two-step Qualitative Data Analysis is carried out to examine how Korean migrants manifest their belonging and identity via their views on “who we are” and “who are others”. The analysis reveals how Korean migrants’ transnational identities differ by their expectation on the audience and the members in each online social network, which indicates that the distinctive features of the online platform may encourage or discourage them in shaping transnational identity as a group identity. The paper concludes with the two main emphases: first, current OSNs comprising different generational technologies play a significant role in understanding the migrants’ dynamic social values, and particularly, transnational identities. Second, the dynamics of migrants’ transnational identity engages diverse social and situational contexts. (keywords: transnational identity, migrants’ online social networks, stereotyping migrants, technological evolution of online social network).

(1) Background: The accurate diagnosis of periodontal disease typically involves complex clinical and radiologic examination. However, recent studies have demonstrated the potential of deep learning in improving diagnostic accuracy and reliability through the development of computer-aided detection and diagnosis algorithms for dental problems using various radiographic sources. This study focuses on the use of panoramic radiographs, which are preferred due to their ability to assess the entire dentition with a single radiation dose. The objective is to evaluate whether panoramic radiographs are a reliable source for the detection of periodontal bone loss using deep learning, and to assess its potential for practical use on a large dataset. (2) Methods: A total of 4083 anonymized digital panoramic radiographs were collected using a Proline XC machine (Planmeca Co., Helsinki, Finland) in accordance with the research ethics protocol. These images were used to train the Faster R-CNN object detection method for detecting periodontally compromised teeth on panoramic radiographs. (3) Results: This study demonstrated a high level of consistency and reproducibility among examiners, with overall inter- and intra-examiner correlation coefficient (ICC) values of 0.94. The Area Under the Curve (AUC) for detecting periodontally compromised and healthy teeth was 0.88 each, and the overall AUC for the entire jaw, including edentulous regions, was 0.91. (4) Conclusions: The regional grouping of teeth exhibited reliable detection performance for periodontal bone loss using a large dataset, indicating the possibility of automating the diagnosis of periodontitis using panoramic radiographs.

Abstract Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo−/− mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.

Fatty acids have diverse functions in the vast majority of cells. At high doses, they act as antimicrobials while, at low doses, they exhibit antibiofilm and antivirulence activities. In this study, the synergistic antibacterial and antibiofilm activities of 30 fatty acids and 11 antibiotics were investigated against methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains. Of the 15 saturated and 15 unsaturated fatty acids examined, 16 enhanced the antibacterial activity of tobramycin. Combinatorial treatment with myristoleic acid (the most active) at 10 μg/ml and tobramycin at 10 μg/ml decreased cell survival by >4 log as compared with tobramycin treatment alone. Notably, aminoglycoside antibiotics, such as tobramycin, kanamycin, gentamicin, and streptomycin exhibited antimicrobial synergy with myristoleic acid. Co-treatment with myristoleic acid and antibiotics markedly decreased biofilm formation. Interestingly, co-treatment with tobramycin and myristoleic acid induced a reduction in S. aureus cell size. These results suggest that fatty acids, particularly myristoleic acid, can be used as aminoglycoside antibiotic adjuvants against recalcitrant S. aureus infections.

Background: Occupational accidents occur for a variety of reasons, such as unsafe behaviors of workers and insufficient safety equipment at the workplace, but there are also various economic and social factors that can impact working conditions and working environment. This study analyzed the relationship between changes in economic factors and the occurrence of occupational accidents in Korea. Methods: Multilinear regression analysis was used as the analysis model. The general to specific method was also used, which consecutively removes statistically insignificant variables from a general model that includes dependent variables and lagged variables of dependent variables. Results: The frequency of occupational accidents was found to have a statistically significant relationship to economic indicators. The monthly number of cases of occupational injury and disease and fatal occupational injuries were found to be closely related to manufacturing capacity utilization, differences in the production index in the services sector, and commencements of building construction. The increase in equipment investment indicators was found to reduce fatal occupational injuries. Conclusion: The results of this study may be used to develop occupational accident trends or leading indicators, which in turn can be used by organizations that manage and monitor occupational accidents toward taking administrative action designed to reduce occupational accidents. The results also imply that short-term and mid- to long-term economic and social changes that can impact workers, workplaces and working conditions, and workplace organizations must be taken into account if more effective government policies are to be established and implemented toward further prevention of occupational accidents.

ABSTRACT The Gram-positive anaerobic bacterium Cutibacterium acnes is a major inhabitant of human skin and has been implicated in acne vulgaris formation and in the formation of multispecies biofilms with other skin-inhabiting organisms like Staphylococcus aureus and Candida albicans. Indoles are widespread in nature (even in human skin) and function as important signaling molecules in diverse prokaryotes and eukaryotes. In the present study, we investigated the antibacterial and antibiofilm activities of 20 indoles against C. acnes. Of the indoles tested, indole-3-carbinol at 0.1 mM significantly inhibited biofilm formation by C. acnes without affecting planktonic cell growth, and the anticancer drug 3,3′-diindolylmethane (DIM) at 0.1 mM (32 μg/mL) also significantly inhibited planktonic cell growth and biofilm formation by C. acnes, whereas the other indoles and indole itself were less effective. Also, DIM at 0.1 mM successfully inhibited multispecies biofilm formation by C. acnes, S. aureus, and C. albicans. Transcriptional analyses showed that DIM inhibited the expressions of several biofilm-related genes in C. acnes, and at 0.05 mM, DIM inhibited hyphal formation and cell aggregation by C. albicans. These results suggest that DIM and other indoles inhibit biofilm formation by C. acnes and have potential use for treating C. acnes associated diseases. IMPORTANCE Since indoles are widespread in nature (even in human skin), we hypothesized that indole and its derivatives might control biofilm formation of acne-causing bacteria (Cutibacterium acnes and Staphylococcus aureus) and fungal Candida albicans. The present study reports for the first time the antibiofilm and antimicrobial activities of several indoles on C. acnes. Of the indoles tested, two anticancer agents, indole-3-carbinol and 3,3′-diindolylmethane found in cruciferous vegetables, significantly inhibited biofilm formation by C. acnes. Furthermore, the most active 3,3′-diindolylmethane successfully inhibited multispecies biofilm formation by C. acnes, S. aureus, and C. albicans. Transcriptional analyses showed that 3,3′-diindolylmethane inhibited the expressions of several biofilm-related genes including lipase, hyaluronate lyase, and virulence-related genes in C. acnes, and 3,3′-diindolylmethane inhibited hyphal formation and cell aggregation by C. albicans. Our findings show that 3,3′-diindolylmethane offers a potential means of controlling acne vulgaris and multispecies biofilm-associated infections due to its antibiofilm and antibiotic properties.

Owing to technological advancements, kiosks have become more prevalent in public places. When using such kiosks, elderly persons and people with disabilities face problems related to accessibility and usability, such as difficulties in kiosk operations such as menu selection and in accessing the kiosk space. Previous studies have usually included accessibility as a subset of usability. However, in this study, we aim to redefine the relationship between these two concepts with a focus on newly emerging kiosk devices. First, we performed a literature review to thoroughly analyze these concepts. Then, we conducted a focus group interview (FGI) targeting people with visual, hearing, and physical impairments to learn about the difficulties that these people face when using kiosks. Finally, we analyzed the characteristics of accessibility and usability related to kiosks and designed a diagram that illustrated the relationship between them. While accessibility and usability shared similarities regarding consistency and user control, they differed deeply regarding their subcategory items; many opinions on accessibility were related to essential functions, whereas many on usability were related to psychological factors such as additional functions or personal preferences. These results can be useful when creating laws and guidelines regarding the accessibility and usability of kiosks or when developing kiosk functions.

Introduction Diagnostic processes in the emergency department (ED) involve multiple interactions among individuals who interface with information systems to access and record information. A better understanding of diagnostic processes is needed to mitigate errors. This paper describes a study protocol to map diagnostic processes in the ED as a foundation for developing future error mitigation strategies.Methods and analysis This study of an adult and a paediatric academic ED uses a prospective mixed methods case study design informed by an ED-specific diagnostic decision-making model (the modified ED-National Academies of Sciences, Engineering and Medicine (NASEM) model) and two cognitive theories (dual process theory and distributed cognition). Data sources include audio recordings of patient and care team interactions, electronic health record data, observer field notes and stakeholder interviews. Multiple qualitative analysis methods will be used to explore diagnostic processes in situ, including systems information flow, human–human and human–system interactions and contextual factors influencing cognition. The study has three parts. Part 1 involves prospective field observations of patients with undifferentiated symptoms at high risk for diagnostic error, where each patient is followed throughout the entire care delivery process. Part 2 involves observing individual care team providers over a 4-hour window to capture their diagnostic workflow, team coordination and communication across multiple patients. Part 3 uses interviews with key stakeholders to understand different perspectives on the diagnostic process, as well as perceived strengths and vulnerabilities, in order to enrich the ED-NASEM diagnostic model.Ethics and dissemination The University of Michigan Institutional Review Board approved this study, HUM00156261. This foundational work will help identify strengths and vulnerabilities in diagnostic processes. Further, it will inform the future development and testing of patient, provider and systems-level interventions for mitigating error and improving patient safety in these and other EDs. The work will be disseminated through journal publications and presentations at national and international meetings.

Spiegelmers are enantiomers of natural D-oligonucleotides that bind to targets with distinct structures such as aptamers. The high susceptibility of natural D-form aptamers to nucleases greatly hinders their application in biological environments. Here, a nonbiodegradable spiegelmer-based platform for the sensitive detection of bisphenol A (BPA) was developed. Due to the symmetric molecule of BPA, the D-form aptamer can be directly converted into mirror forms via chemical synthesis. Aptamer–target interactions that involve chemically synthesized spiegelmers were characterized by biolayer interferometry, and their stabilities were tested in various biological fluids by exposure to nucleases. We demonstrate for the first time the use of a nuclease-resistant spiegelmer in a simple, label-free gold nanoparticle-based colorimetric assay to detect BPA in a highly sensitive and selective manner. The aptasensor exhibits an LOD of 0.057 ng/mL and dynamic range of 105 (100 pg/mL to 10 mg/mL). With sensing capacity and biological stability, the developed aptasensor shows great potential to utilize in in-field applications such as water quality monitoring.

This paper introduces an indoor-monitoring LiDAR sensor for patients with Alzheimer disease residing in long-term care facilities (LTCFs), and this sensor exploits an optoelectronic analog front-end (AFE) to detect light signals from targets by utilizing on-chip avalanche photodiodes (APDs) realized in a 180 nm CMOS process and a neural processing unit (NPU) used for motion detection and decisions, especially for incidents of falls occurring in LTCFs. The AFE consists of an on-chip CMOS P+/N-well APD, a linear-mode transimpedance amplifier, a post-amplifier, and a time-to-digital converter, whereas the NPU exploits network sparsity and approximate processing elements for low-power operation. This work provides a potential solution of low-cost, low-power, indoor-monitoring LiDAR sensors for patients with Alzheimer disease in LTCFs.

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (MTB), is a serious infectious disease with high infection and mortality rates and is a public health problem around the world. According to the World Health Organization (WHO) report, one-third of the world's population is latently infected with MTB, and 5 to 10% of those with latent TB infection (LTBI) have the potential to develop active TB once in their lifetime. Therefore, TB management for promptly distinguishing LTBI from active TB and for proper treatment is important. LTBI is currently diagnosed using the tuberculin skin test (TST) and interferon gamma (IFN-γ) release assay (IGRA). However, this test is substantially limited by its inability to distinguish active TB from LTBI. It is necessary to discover indicators that can be used for effective TB management and to develop diagnostic methods. In the present study, we used IGRA and complete blood count (CBC) analysis for discrimination of active TB, LTBI, and healthy control groups. The results showed that the number of WBC was significantly increased in the group with active TB (p

Abstract Background One-third of cervical cancer patients are still diagnosed at advanced stages. The five-year survival rate is decreased in about 50% of advanced stage cervical cancer patients worldwide, and the clinical outcomes are remarkably varied and difficult to predict. One of the miRNAs known to be associated with cancer tumorigenesis is miR-944. However, the prognostic value of miR-944 in cervical cancer has not been fully investigated. The aim of this study was to analyze clinical significance and prognostic value of miR-944 in cervical cancer. Methods The expression levels of miR-944 were detected using quantitative reverse transcription polymerase chain reaction in five types of cervical cancer cell lines and 116 formalin-fixed paraffin-embedded (FFPE) cervical tissues. The association between the expression levels of miR-944 and prognostic value was analyzed using the Kaplan-Meier analysis and Cox proportional hazards model. Results The expression levels of miR-944 in cervical cancer tissues were significantly higher compared with those in normal tissues (P

This paper examines the history of the ROK Army Motion Picture Production Center (AMPPC), which played a significant role in the Korean film industry from the 1950s to the 1970s. Around this time, the AMPPC was an official film production institute alongside the National Film Production Center, and produced newsreels and culture films as well as fiction films. Starting with the documentary An Assault on Justice, the first film on the Korean War, and the National Defense Series, the AMPPC produced educational short films and many feature-length films. It was a large-scale film production company that produced an average of over 100 films a year until the 1970s. In addition, the military film industry provided workspace for Korean film industry professional and took care of postproduction for commercial films at a time when the film industry was considered nearly impossible. It was also an active producer that recorded significant progress in the Korean film history through technical experiments at a time when the infrastructure for the film industry had collapsed. In addition, many Korean film industry professionals were affiliated with or closely related to the center. Not only directors but also people in photography, editing, and screenwriting worked in both the mainstream film industry and the AMPPC. Moreover, military films also had a certain impact on anti-Communist films and anti-Communist television programs in its early years. Various military films produced from the 1950s to the 1970s, including the anti-Communist films produced in the military since 1948 and the first war documentary An Assault of Justice, were utilized in anti-Communist films for theaters but also television news, drama series, and documentaries, becoming archetypes for each derivative program format. In sum, the AMPPC during this time was closely related to the Korean film industry as well as the television industry in terms of quantity and quality, providing the human resources and physical basis. It is also important to imbue significance into the “militaristic” utilization of military films. Above all, the military films’ most important role in its history since the founding of the government of the Republic of Korea was its utilization as part of the Korean government’s psychological warfare waged against its people between the 1950s and 1970s under the Cold War regime. The role of military films as propaganda warfare, which became much more explicit with the outbreak of the Korean War, became strengthened through the installation of the AMPPC in 1963, dispatch of Korean soldiers for the Vietnam War and the improvement of the film production environment in 1965. Particularly with the sending of Korean troops to Vietnam, it became important for the government to produce and screen military films as propaganda for Korea’s unjustified participation in the war. In the 1970s, the AMPPC, which had to continue the Cold War by continuously placing significance on the Vietnam War throughout and even after the war, was able to produce over 130 films in various genres and lengths every year. This paper is significant in that it systematically organizes the history of the military film industry, which had not been properly explained in the past, and that it discusses the military film industry as a means to examine the overall structure of the film industry and its vibrant activities at the time. This discussion has been performed as a basis for the analysis of specific military films. I hope to delve further into the significance and the role of military films as a tool of propaganda warfare through textual analysis in future studies.

Liquid biopsy has been emerging for early screening and treatment monitoring at each cancer stage. However, the current blood-based diagnostic tools in breast cancer have not been sufficient to understand patient-derived molecular features of aggressive tumors individually. Herein, we aimed to develop a blood test for the early detection of breast cancer with cost-effective and high-throughput considerations in order to combat the challenges associated with precision oncology using mRNA-based tests. We prospectively evaluated 719 blood samples from 404 breast cancer patients and 315 healthy controls, and identified 10 mRNA transcripts whose expression is increased in the blood of breast cancer patients relative to healthy controls. Modeling of the tumor-associated circulating transcripts (TACTs) is performed by means of four different machine learning techniques (artificial neural network (ANN), decision tree (DT), logistic regression (LR), and support vector machine (SVM)). The ANN model had superior sensitivity (90.2%), specificity (80.0%), and accuracy (85.7%) compared with the other three models. Relative to the value of 90.2% achieved using the TACT assay on our test set, the sensitivity values of other conventional assays (mammogram, CEA, and CA 15-3) were comparable or much lower, at 89%, 7%, and 5%, respectively. The sensitivity, specificity, and accuracy of TACTs were appreciably consistent across the different breast cancer stages, suggesting the potential of the TACTs assay as an early diagnosis and prediction of poor outcomes. Our study potentially paves the way for a simple and accurate diagnostic and prognostic tool for liquid biopsy.

Acne vulgaris is a common chronic inflammatory skin disease involving Cutibacterium acnes with other skin commensals such as Staphylococcus aureus and Candida albicans in the anaerobic and lipid-rich conditions of pilosebaceous units. These microbes readily form multispecies biofilms that are tolerant of traditional antibiotics as well as host immune systems. The phytopigment alizarin was previously found to prevent biofilm formation by S. aureus and C. albicans strains under aerobic conditions. Hence, we hypothesized that alizarin might control C. acnes and multispecies biofilm development. We found that under anaerobic conditions, alizarin efficiently inhibited single biofilm formation and multispecies biofilm development by C. acnes, S. aureus, and C. albicans without inhibiting planktonic cell growth. Alizarin increased the hydrophilicities of S. aureus and C. albicans cells, decreased lipase production by S. aureus, diminished agglutination by C. acnes, and inhibited the aggregation of C. albicans cells. Furthermore, the co-administration of alizarin and antibiotics enhanced the antibiofilm efficacies of alizarin against C. acnes. A transcriptomic study showed that alizarin repressed the transcriptions of various biofilm-related genes such as lipase, hyaluronate lyase, adhesin/invasion-related, and virulence-related genes of C. acnes. Furthermore, alizarin at 100 µg/mL prevented C. acnes biofilm development on porcine skin. Our results show that alizarin inhibits multispecies biofilm development by acne-causing microbes and suggest it might be a useful agent for treating or preventing C. acnes-causing skin diseases.

Many universities in Korea have implemented teaching TOEIC based courses in their core curriculums as a result of the increased popularity of the TOEIC test. With the assumption that reading and listening scores are inter-related with each other, a focus of this study is to find the distribution patterns of the reading comprehension (RC) and the listening comprehension (LC) scores with respect to the different levels of the students. More specifically, the present study examines the relationships at the different levels between the RC and the LC scores, the LC scores and the total scores, and the RC scores and the total scores. In order to assist the students with improving their current levels and their TOEIC test scores, determining the particular areas that need to be focused on within each score band was the purpose of the comparison. In this study, 11328 TOEIC test scores were analyzed, and four results are presented. First, during their initial stages of language acquisition, students who are having more difficulty with the RC would benefit from having this area supplemented. The next finding revealed the necessity to implement tailored instruction for the higher levels. After that, it was determined that focusing on the RC would be a worthwhile measure in order to assist the lower level students to increase their overall TOEIC scores. The final result revealed that when the students were grouped in larger score bands, both the RC and the LC should be taught.

Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca2+/NFAT1 signal transduction pathway.

Abstract Background Hepatic steatosis renders hepatocytes vulnerable to injury, resulting in the progression of preexisting liver disease. Previous animal and cell culture studies implicated mammalian target of rapamycin (mTOR), signal transducer and activator of transcription-3 (STAT3), extracellular signal-regulated kinase (ERK) and estrogen-receptor α in the pathogenesis of hepatic steatosis and disease progression. However, to date there have been few studies performed using human liver tissue to study hepatic steatosis. We examined the expression patterns of mTOR, STAT3, ERK and estrogen-receptor α in liver tissues from patients diagnosed with hepatic steatosis. Methods We reviewed the clinical and histomorphological features of 29 patients diagnosed with hepatic steatosis: 18 with non-alcoholic fatty liver disease (NAFLD), 11 with alcoholic fatty acid disease (AFLD), and a control group (16 biliary cysts and 22 hepatolithiasis). Immunohistochemistry was performed on liver tissue using an automated immunostainer. The histologic severity of hepatic steatosis was evaluated by assessing four key histomorphologic parameters common to NAFLD and AFLD: steatosis, lobular inflammation, ballooning degeneration and fibrosis. Results mTOR, phosphorylated STAT3, phosphorylated pERK, estrogen-receptor α were found to be more frequently expressed in the hepatic steatosis group than in the control group. Specifically, mTOR was expressed in 78% of hepatocytes, and ERK in 100% of hepatic stellate cells, respectively, in patients with NAFLD. Interestingly, estrogen-receptor α was diffusely expressed in hepatocytes in all NALFD cases. Phosphorylated (active) STAT3 was expressed in 73% of hepatocytes and 45% of hepatic stellate cells in patients with AFLD, and phosphorylated (active) ERK was expressed in hepatic stellate cells in all AFLD cases. Estrogen-receptor α was expressed in all AFLD cases (focally in 64% of AFLD cases, and diffusely in 36%). Phosphorylated STAT3 expression in hepatocytes and hepatic stellate cells correlated with severe lobular inflammation, severe ballooning degeneration and advanced fibrosis, whereas diffusely expressed estrogen-receptor α correlated with a mild stage of fibrosis. Conclusions Our data indicate ERK activation and estrogen-receptor α may be relevant in the development of hepatic steatosis. However, diffuse expression of estrogen-receptor α would appear to impede disease progression, including hepatic fibrosis. Finally, phosphorylated STAT3 may also contribute to disease progression.

Background Delirium is common among intensive care unit (ICU) patients, so recent clinical guidelines recommended routine delirium monitoring in the ICU. But, its effect on the patient’s clinical outcome is still controversial. In particular, the effect of systems that inform the primary physician of the results of monitoring is largely unknown. Methods The delirium notification program using bedside signs and electronic chart notifications was applied to the pre-existing delirium monitoring protocol. Every patient was routinely evaluated for delirium, pain, and anxiety using validated tools. Clinical outcomes, including duration of delirium, ICU stay, and mortality were reviewed and compared for 3 months before and after the program implementation. Results There was no significant difference between the two periods of delirium, ICU stay, and mortality. However, anxiety, an important prognostic factor in the ICU survivor’s mental health, was significantly reduced and pain tended to decrease. Conclusions Increasing the physician’s awareness of the patient’s mental state by using a notification program could reduce the anxiety of ICU patients even though it may not reduce delirium. The results suggested that the method of delivering the results of monitoring was also an important factor in the success of the delirium monitoring program.

Primary hyperparathyroidism (PHPT) is the leading cause of secondary osteoporosis. Although bone mineral density (BMD) tends to recover after parathyroidectomy in PHPT patients, the degree of recovery varies. Circulating microRNAs (miRNAs) profiles are known to be correlated with osteoporosis and fracture. We aimed to investigate whether osteoporotic fracture-related miRNAs are associated with postoperative BMD recovery in PHPT. Here, 16 previously identified osteoporotic fracture-related miRNAs were selected. We analyzed the association between the preoperative level of each miRNA and total hip (TH) BMD change. All 12 patients (among the 18 patients enrolled) were cured of PHPT after parathyroidectomy as parathyroid hormone (PTH) and calcium levels were restored to the normal range. Preoperative miR-19b-3p, miR-122-5p, and miR-375 showed a negative association with the percent changes in TH BMD from baseline. The association remained robust for miR-122-5p and miR-375 even after adjusting for sex, age, PTH, and procollagen type 1 N-terminal propeptide levels in a multivariable model. In conclusion, preoperative circulating miR-122-5p and miR-375 levels were negatively associated with TH BMD changes after parathyroidectomy in PHPT patients. miRNAs have the potential to serve as predictive biomarkers of treatment response in PHPT patients, which merits further investigation.

Abstract Background Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance. Methods The expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated. Results MiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues (P

Professional pride is a positive emotion that includes self-reflection or evaluation and attitude toward one’s own occupational group. Uniforms can encourage the wearer to have professional pride. The current study aimed to elucidate the neural basis of professional pride using an experimental task related to the self in uniform and functional magnetic resonance imaging (fMRI). The person-adjective matching task, in which a participant or other in uniform or casual wear was presented with positive and negative words, was used for scanning fMRI. Imaging data from 21 adults who had an occupation requiring a uniform were analyzed to identify the main and interaction effects of individual (self vs. other), clothes (uniform vs. casual wear), and valence (positive vs. negative). Identified brain activities were correlated with psychological scales including the Rosenberg Self-esteem Scale and Group Environment Questionnaire. Whole brain analyses found that the interaction between individual and clothes was present in multiple regions such as the right ventrolateral prefrontal cortex (VLPFC), left dorsolateral prefrontal cortex, left middle and inferior temporal gyri, left posterior superior temporal sulcus, right temporoparietal junction, left lingual gyrus, left calcarine cortex, right insula, left caudate, and right putamen. In particular, activities in the right VLPFC, left calcarine cortex, and right putamen in the self/uniform condition were positively correlated with several psychological scales. These results suggest that professional pride may be represented through multiple brain networks related to empathy, reward, and emotion regulation as well as the theory-of-mind network. The neural basis of professional pride is closely related to positive self-evaluation and group cohesion.

After breast and colon cancer, cervical cancer is the third most common cancer of women worldwide. Since human papillomavirus (HPV) infection is known to be the predominant cause of cervical cancer, molecular HPV screening is currently used along with cytological and histological examination methods for precancer diagnosis. Nevertheless, the sensitivity of the current HPV test is less than 80%; thus, many cervical cancer cases are not able to be diagnosed by HPV screening alone, and likewise, patients with cervical cancer are often determined to be HPV-negative by the current screening methods. Therefore, human telomerase reverse transcriptase (hTERT) and Ki67 previously identified as cancer markers were attempted. And cervical exfoliated cells of high-grade squamous intraepithelial lesion (HSIL), the most severe precancerous lesion of cancer, were used in the study. However, it takes a long time to collect enough specimens to conduct statistical analysis. Therefore, in the present study, microscope slides, cervical exfoliated cells on glass slides, were attempted. The results of the analysis demonstrated that hTERT and Ki67 expression levels were useful in distinguishing between cancerous and normal specimens, exhibiting a higher sensitivity and specificity than conventional HPV E6/E7 testing. And the study suggests clinical slide cell samples could be effectively used in the context of retrospective studies to identify novel biomarkers.

p63 is a transcription factor p53 family. Two major isoforms of p63, TAp63 with transactivation (TA) domain and ΔNp63 with truncated TA domain, have been reported to play opposing roles either in tumor suppression or oncogenic function. Little is known about the association of these two isoforms of p63 in the carcinogenesis of cervical cancer. In this study, the mRNA expression levels of TAp63 and ΔNp63 in 40 normal, 30 low-grade squamous intraepithelial lesions (LSIL), 38 high-grade squamous intraepithelial lesions (HSIL), and 52 cervical cancer formalin-fixed paraffin-embedded tissues were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). We analyzed the association between the ΔNp63 and ΔN/TAp63 mRNA expression ratio and clinicopathological parameters and compared disease-specific survival of each ΔNp63 mRNA expression and ΔN/TAp63 mRNA expression ratio. The ΔN/TAp63 mRNA expression ratio in cervical cancer showed higher sensitivity than the mRNA expression levels of ΔNp63 (52.0% vs 44.2%). The level of ΔN/TAp63 mRNA expression ratio in precancerous LSIL and HSIL was higher than in normal tissues (P = 0.01 and P = 0.003) and lower than in cervical cancer tissues (P = 0.03 and P = 0.02). Besides, the positive ΔN/TAp63 mRNA expression ratio was associated with bulky tumor size and high expression of Ki-67, the proliferation marker, in cervical cancer (P = 0.04 and P = 0.02). The cervical cancer patients with the positive ΔN/TAp63 mRNA expression ratio showed worse survival compared to those who with the negative expression ratio of ΔN/TAp63 (HR = 5.7, 95% CI: 1.6-19.9). In conclusion, the balance of TAp63 and ΔNp63 is closely related to the carcinogenesis of cervical cancer. The ΔN/TAp63 mRNA expression ratio could be useful as a diagnostic and prognostic marker of cervical cancer.

[This corrects the article DOI: 10.1371/journal.pone.0214867.].

Peptide materials have recently been considered for use in various industrial fields. Because of their efficacy, safety, and low cost, therapeutic peptides are studied for various diseases, including atopic dermatitis (AD). AD is a common inflammatory skin disease impairing the patient’s quality of life. Various therapies, such as treatments with corticosteroids, calcineurin inhibitors, and antibody drugs, have been applied, but numerous side effects have been reported, including skin atrophy, burning, and infection. In the case of antibody drugs, immunogenicity against the drugs can be a problem. To overcome these side effects, small peptides are considered therapeutic agents. We previously identified the small wound healing peptide AES16-2M with a sequence of REGRT, and examined its effects on AD in this study. Interestingly, the administration of AES16-2M downregulated the AD disease score, ear thickness, serum IgE, and thymic stromal lymphopoietin (TSLP) in AD mice. The thickness of the epidermal layer was also improved by AES16-2M treatment. In addition, quantities of IL-4-, IL-13-, and IL-17-producing CD4 T cells from peripheral lymph nodes and spleens were reduced by injection of AES16-2M. Furthermore, the expression of TSLP was significantly reduced in AES16-2M-treated human keratinocytes. Therefore, these results suggest that AES16-2M can be a novel candidate for AD treatment.

Nogo-A (Rtn 4A), a member of the reticulon 4 (Rtn4) protein family, is a neurite outgrowth inhibitor protein that is primarily expressed in the central nervous system (CNS). However, previous studies revealed that Nogo-A was upregulated in skeletal muscles of Amyotrophic lateral sclerosis (ALS) patients. Additionally, experiments showed that endoplasmic reticulum (ER) stress marker, C/EBP homologous protein (CHOP), was upregulated in gastrocnemius muscle of a murine model of ALS. We therefore hypothesized that Nogo-A might relate to skeletal muscle diseases. According to our knocking down and overexpression results in muscle cell line (C2C12), we have found that upregulation of Nogo-A resulted in upregulation of CHOP, pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while downregulation of Nogo-A led to downregulation of CHOP, IL-6 and TNF-α. Immunofluorescence results showed that Nogo-A and CHOP were expressed by myofibers as well as tissue macrophages. Since resident macrophages share similar functions as bone marrow-derived macrophages (BMDM), we therefore, isolated macrophages from bone marrow to study the role of Nogo-A in activation of these cells. Lipopolysaccharide (LPS)-stimulated BMDM in Nogo-KO mice showed low mRNA expression of CHOP, IL-6 and TNF-α compared to BMDM in wild type (WT) mice. Interestingly, Nogo knockout (KO) BMDM exhibited lower migratory activity and phagocytic ability compared with WT BMDM after LPS treatment. In addition, mice experiments data revealed that upregulation of Nogo-A in notexin- and tunicamycin-treated muscles was associated with upregulation of CHOP, IL-6 and TNF-α in WT group, while in Nogo-KO group resulted in low expression level of CHOP, IL-6 and TNF-α. Furthermore, upregulation of Nogo-A in dystrophin-deficient (mdx) murine model, myopathy and Duchenne muscle dystrophy (DMD) clinical biopsies was associated with upregulation of CHOP, IL-6 and TNF-α. To the best of our knowledge, this is the first study to demonstrate Nogo-A as a regulator of inflammation in diseased muscle and bone marrow macrophages and that deletion of Nogo-A alleviates muscle inflammation and it can be utilized as a therapeutic target for improving muscle diseases.

Erythroid differentiation regulator 1 (Erdr1) has been identified as an anti-inflammatory factor in several disease models, including collagen-induced arthritis (CIA), but its exact mechanisms are still not fully understood. Here, the involvement of regulatory T (Treg) cells in Erdr1-improved CIA was investigated. In the CIA model, Erdr1 was confirmed to reduce collagen-specific IgM in plasma and plasma cells in draining lymph nodes. Importantly, the downregulated Treg cell ratio in draining lymph nodes from CIA mice was recovered by Erdr1 treatment. In addition, administration of Erdr1 improved the CIA score and joint tissue damage, while it revealed no effect in Treg cell-depleted CIA mice, indicating that Treg cells mediate the therapeutic effects of Erdr1 in the CIA model. Results from in vitro experiments also demonstrated that Erdr1 significantly induced Treg cell differentiation and the expression of Treg activation markers, including CD25, CD69, and CTLA4 in CD4+Foxp3+ cells. Furthermore, Erdr1-activated Treg cells dramatically suppressed the proliferation of responder T cells, suggesting that they are functionally active. Taken together, these results show that Erdr1 induces activation of Treg cells and ameliorates rheumatoid arthritis via Treg cells.

Purpose The purpose of this study was to identify the characteristics of chest lesions that are missed in interpretations of neck computed tomography (CT) scans. Materials and Methods A total of 240 consecutive neck CT scans were retrospectively analyzed to determine whether chest lesions were included or not. All missed chest lesions, which had not been described on neck CT reports, were recorded, and classified according to their clinical significance (insignificant, indeterminate, or significant) and awareness (known or unknown) at the time of CT interpretation, and their radiologic patterns were analyzed. Results Eighty seven (36.3%) of 240 neck CT scans had 105 chest lesions, and 88 of these were not described on the neck CT reports. Thirty seven clinically known or insignificant lesions were excluded, resulting in a miss rate for chest lesions of 35.2% (37/105), with six of these (5.7%) being potentially significant. The most common location of missed chest lesions was the lung (56/88, 63.6%), and 45 (80.4%) of these missed lung lesions were visualized only with lung window settings. Conclusion Chest lesions were common and frequently missed on neck CT interpretations. When reviewing neck CT scans, a special attention should be given to lung lesions by using lung window settings.

Water splitting is one of the efficient ways to produce hydrogen with zero carbon dioxide emission. Thus far, Pt has been regarded as a highly reactive catalyst for the hydrogen evolution reaction (HER); however, the high cost and rarity of Pt significantly hinder its commercial use. Herein, we successfully developed an HER catalyst composed of NiSx (x = 1 or 2) on stainless steel (NiSx/SUS) using electrodeposition and sulfurization techniques. Notably, the electrochemical active surface area(ECSA) of NiSx/SUS was improved more than two orders of magnitude, resulting in a considerable improvement in the electrochemical charge transfer and HER activity in comparison with stainless steel (SUS). The long-term HER examination by linear scan voltammetry (LSV) confirmed that NiSx/SUS was stable up to 2000 cycles.

miR-944 is located in an intron of the tumor protein p63 gene (TP63). miR-944 expression levels in cervical cancer tissues are significantly higher than in normal tissues and are associated with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and survival. However, associations of miR-944 with its host gene, TP63, which encodes TAp63 and ΔNp63, in cervical cancer have not been fully investigated. A positive correlation between miR-944 and ΔNp63 mRNA expression was identified in cervical cancer tissues. Furthermore, when the expression of miR-944 and ΔNp63 was simultaneously inhibited, cell proliferation-, differentiation- epithelial–mesenchymal transition (EMT)-, transcription-, and virus-associated gene clusters were shown to be significantly more active according to functional annotation analysis. Cell viability and migration were more reduced upon simultaneous inhibition with anti-miR-944 or ΔNp63 siRNA than with inhibition with anti-miR-944 or ΔNp63 siRNA alone, or scramble. In addition, Western blot analysis showed that the simultaneous inhibition of miR-944 and ΔNp63 reduced EMT by increasing the expression of epithelial markers such as claudin and by decreasing mesenchymal markers such as N-cadherin and vimentin. Slug, an EMT transcription factor, was also decreased by the simultaneous inhibition of miR-944 and ΔNp63. Thus, associations between miR-944 and ΔNp63 in cervical cancer could help to elucidate the function of this intronic microRNA and its role in carcinogenesis.

Non-catalytic and catalytic hydrocracking of C5-isolated asphaltene and its subfractions were performed in batch and semi-batch reactors at various temperatures. Catalyst and H2 played an important role in the hydrocracking of asphaltenes. In the batch system, the catalyst enhanced asphaltene conversion to light liquid products and suppressed coke formation. The coke formation was controlled at a low reaction temperature, but the reaction rate was too low. Light liquid products were also formed at the beginning of the reaction even at high temperatures, but the coke formation was predominant as the reaction time went on due to the decrease in H2 amount in the reactor. To solve these problems, H2 was continuously supplied during the reaction using the semi-batch system. Sufficient supply of H2 improved the conversion of asphaltenes to light liquid products while inhibiting the coke formation. The lightest asphaltene fraction was easily cracked into light products by inhibiting the coke formation, while the heaviest fraction tends to form coke. The lightest asphaltene fraction prolonged the coke induction period of the heaviest fraction during the catalytic hydrocracking because the lightest fraction contained a significant amount of heavy resin close to that which could prevent aggregation of the heaviest asphaltenes.