Best-response dynamics, playing sequences, and convergence to equilibrium in random games.

We analyze the performance of the best-response dynamic across all normal-form games using a random games approach. The playing sequence-the order in which players update their actions-is essentially irrelevant in determining whether the dynamic converges to a Nash equilibrium in certain classes of games (e.g. in potential games) but, when evaluated across all possible games, convergence to equilibrium depends on the playing sequence in an extreme way. Our main asymptotic result shows that the best-response dynamic converges to a pure Nash equilibrium in a vanishingly small fraction of all (large) games when players take turns according to a fixed cyclic order. By contrast, when the playing sequence is random, the dynamic converges to a pure Nash equilibrium if one exists in almost all (large) games.

Chemoenzymatic Synthesis of Select Intermediates and Natural Products of the Desferrioxamine E Siderophore Pathway.

The NIS synthetase family of enzymes responsible for the biosynthesis of siderophores is increasingly associated with bacterial virulence. Proteins in this class represent outstanding potential drug targets, assuming that basic biochemical and structural characterizations can be completed. Towards this goal, we have mated an improved synthesis of the non-commercial amino acid N-hydroxy-N-succinylcadaverine (HSC, 6) with an isothermal titration calorimetry (ITC) assay that profiles the iterative stages of HSC trimerization and macrocyclization by NIS synthetase DesD from Streptomyces coelicolor. HSC synthesis begins with multigram-scale Gabrielle and tert-butyl N-(benzyloxy)carbamate alkylations of 1-bromo-5-chloropentane following prior literature, but the end-game reported herein has two advantages for greater material throughput: (1) hydrogenolysis of benzyl ether and Cbz blocking groups is best accomplished with Pearlman's catalyst at 40 psi of H2 and (2) purification of neutral (zwitterionic) HSC is effected by simple flash chromatography over silica gel in MeOH. HSC is subsequently shown to be a substrate for NIS synthetase DesD, which catalyzes three successive amide bond syntheses via adenyl monophosphate ester intermediates. We quantify and present the iterative and overall enzyme kinetic constants associated with formation of the cyclotrimeric siderophore desferrioxamine E (dfoE, 1).

Preventive Effect of Vitamin C on Dextran Sulfate Sodium (DSS)-Induced Colitis via the Regulation of IL-22 and IL-6 Production in Gulo(-/-) Mice.

Reactive oxygen species (ROS), which are exceptionally high in IBD lesions, are known to cause abnormal immune responses to inflammatory reactions in inflammatory bowel diseases (IBD) through damage to the intestinal mucosal linings. Moreover, they are theorized to be an agent of IBD development. Vitamin C is widely known to be an effective antioxidant for its ability to regulate inflammatory responses through its ROS scavenging effect. Therefore, we examined vitamin C's influence on the development and progression of IBD in Gulo(-/-) mice, which cannot synthesize vitamin C like humans due to a defect in the expression of L-gulono-γ-lactone oxidase, an essential enzyme for vitamin C production. First, we found extensive oxidative stress and an inflammation increase in the colon of vitamin C-insufficient Gulo(-/-) mice. We also found decreased IL-22 production and NKp46(+) cell recruitment and the impaired activation of the p38MAPK pathway. Additionally, comparing vitamin C-insufficient Gulo(-/-) mice to vitamin C-sufficient Gulo(-/-) mice and wild-type mice, the insufficient group faced a decrease in mucin-1 expression, accompanied by an increase in IL-6 production, followed by the activation of the STAT3 and Akt pathways. The results suggest that vitamin C insufficiency induces severe colitis, meaning vitamin C could also take on a preventative role by regulating the production of cytokines and the induction of inflammation.

Polyphenol-Incorporated Composite Nanogels of Multimodal Interactions for Enhanced Gel Stability and Cisplatin Delivery.

Naturally abundant polyphenols that can readily undergo the facile cross-linking of polymer chains have been of great interest for functional hydrogel formation and its potential biomedical applications. Herein, we report that the internal incorporation of tannic acid (TA) as a natural polyphenol additive at the chitosan-based nanogel templates can enhance the self-association of physically cross-linked polymer networks upon dilution, as well as the colloidal gel stability in protein solution. This is driven by the multivalent hydrogen bonding and π-stacking capability of TA, as verified by the viscosity estimation of diluted nanogel solution, coupled to the conformation-dependent excimer emission of stacked fluorophores in polymer networks, which also allows for the Stern-Volmer analysis of the TA-induced quenching property. Furthermore, the excellent coordination generality of TA for versatile metallic cations enables the facile immobilization of a cisplatin pharmacophore inside the nanogels for acid-sensitive drug release and the potential delivery of metallic components.

Mental Stress Assessment Using Ultra Short Term HRV Analysis Based on Non-Linear Method.

Mental stress is on the rise as one of the major health problems in modern society. It is important to detect and manage mental stress to prevent various diseases caused by stress and to maintain a healthy life. The purpose of this paper is to present new heart rate variability (HRV) features based on empirical mode decomposition and to detect acute mental stress through short-term HRV (5 min) and ultra-short-term HRV (under 5 min) analysis. HRV signals were acquired from 74 young police officers using acute stressors, including the Trier Social Stress Test and horror movie viewing, and a total of 26 features, including the proposed IMF energy features and general HRV features, were extracted. A support vector machine (SVM) classification model is used to classify the stress and non-stress states through leave-one-subject-out cross-validation. The classification accuracies of short-term HRV and ultra-short-term HRV analysis are 86.5% and 90.5%, respectively. In the results of ultra-short-term HRV analysis using various time lengths, we suggest the optimal duration to detect mental stress, which can be applied to wearable devices or healthcare systems.

Alloferon Affects the Chemosensitivity of Pancreatic Cancer by Regulating the Expression of SLC6A14.

Pancreatic cancer (PCa), one of the most malignant solid tumors, has a high mortality rate. Although there have been many trials of chemotherapeutic drugs such as gemcitabine, the mortality rates remain significantly higher than for other types of cancer. Therefore, more effective ways of improving conventional therapy for PCa are needed. Cancer cells take up large amounts of glutamine to drive their rapid proliferation. Recent studies show that the amino acid transporter SLC6A14 is upregulated in some cancers alongside glutamine metabolism. Alloferon, a peptide isolated from the insect immune system, exerts anti-viral and anti-inflammatory effects via its immunomodulatory function. In addition, it has anti-tumoral effects, although the underlying mechanisms are largely unknown. Therefore, we investigated the effects of alloferon on the PCa cell lines Panc-1 and AsPC-1. Exposure of these cells to alloferon for 3 weeks led to the downregulation of SLC6A14 expression and decreased glutamine uptake. Given that SLC6A14 plays a role in tumor progression and survival by promoting glutamine uptake into cancer cells, alloferon could be a potential adjuvant for the chemotherapeutic drug gemcitabine.

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain.

Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rß subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.

Study on the use of standard 12-lead ECG data for rhythm-type ECG classification problems.

BACKGROUND AND OBJECTIVES: Most deep-learning-related methodologies for electrocardiogram (ECG) classification are focused on finding an optimal deep-learning architecture to improve classification performance. However, in this study, we proposed a methodology for fusion of various single-lead ECG data as training data in the single-lead ECG classification problem. METHODS: We used a squeeze-and-excitation residual network (SE-ResNet) with 152 layers as the baseline model. We compared the performance of a 152-layer SE-ResNet trained on ECG signals from various leads of a standard 12-lead ECG system to that of a 152-layer SE-ResNet trained on only single-lead ECG data with the same lead information as the test set. The experiments were performed using five different types of rhythm-type single-lead ECG data obtained from Konkuk University Hospital in South Korea. RESULTS: Experiment results based on the combination from the relationship experiments of the leads showed that lead -aVR or II revealed the best classification performance. In case of -aVR, this model achieved a high F1 score for normal (98.7%), AF (98.2%), APC (95.1%), and VPC (97.4%), indicating its potential for practical use in the medical field. CONCLUSION: We concluded that the 152-layer SE-ResNet trained by fusion of single-lead ECGs had better classification performance than the 152-layer SE-ResNet trained on only single-lead ECG data, regardless of the single-lead ECG signal type. We also found that the best performance directions for single-lead ECG classification are Lead -aVR and II.

Alloferon and Zanamivir Show Effective Antiviral Activity against Influenza A Virus (H1N1) Infection In Vitro and In Vivo.

The use of vaccines is the most effective and reliable method for the prevention of viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after infection is necessary. Zanamivir was administered through inhalation for treatment of pandemic influenza A/H1N1 in 2009. However, the emergence of drug-resistant strains can occur rapidly. Alloferon, an immunomodulatory drug developed as an NK cell activator, exerts antiviral effects against various viruses, particularly influenza viruses. Therefore, alloferon and zanamivir were administered in combination in an effort to improve the antiviral effect of zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of IL-6 and MIP-1α in these cells and the activity of p38 MAPK and c-Jun that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the antiviral efficacy of the alloferon/zanamivir combination was performed. The results showed that combined treatment after infection with H1N1 prevented weight loss, increased the survival rate, and improved lung fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of p38 MAPK and c-Jun in lung tissue, which was increased by infection with H1N1. Therefore, the combination of alloferon/zanamivir effectively prevents the development of H1N1-mediated inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.

Delays in the diagnosis and treatment of tuberculosis during the COVID-19 outbreak in the Republic of Korea in 2020.

OBJECTIVE: We investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on tuberculosis (TB) "diagnosis and" management in the Republic of Korea (ROK). METHODS: This retrospective cross-sectional study used nationwide ROK TB notification data (98,346 cases) from 2017 to 2020. The median time from the onset of TB symptoms to treatment initiation and the compliance rates with the required timing for notification and individual case investigations were measured and compared across periods and regions affected by the COVID-19 epidemic. RESULTS: TB diagnosis during the COVID-19 pandemic was delayed. The median time to TB treatment initiation (25 days) in 2020 increased by 3 days compared to that of the previous 3 years (22 days) (p<0.0001). In the outbreak in Seoul, Incheon, and Gyeonggi province during August, the time to TB diagnosis was 4 days longer than in the previous 3 years (p=0.0303). In the outbreak in Daegu and Gyeongbuk province from February to March 2020, the compliance rate with the required timing for individual case investigations was 2.2%p lower than in other areas in 2020 (p=0.0148). For public health centers, the rate was 13%p lower than in other areas (80.3% vs. 93.3%, p=0.0003). CONCLUSION: TB diagnoses during the COVID-19 pandemic in the ROK were delayed nationwide, especially for patients notified by public-private mix TB control hospitals. TB individual case investigations were delayed in regional COVID-19 outbreak areas (Daegu and Gyeongbuk province), especially in public health centers. Developing strategies to address this issue will be helpful for sustainable TB management during future outbreaks.

The Anti-Inflammatory Effect of Aptamin C on House Dust Mite Extract-Induced Inflammation in Keratinocytes via Regulation of IL-22 and GDNF Production.

Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by eczemous lesions on the skin that manifest as severe itching and last a long time. AD is thought to be a response to local allergens, including house dust mites (HDMs). Aptamin C is a modified form of vitamin C comprised of aptamers (DNA fragments) that bind specifically to vitamin C and inhibit its oxidation, thereby increasing its stability and antioxidant effects. It is already known that vitamin C shows an anti-inflammatory effect on skin inflammation. Oxidative stress is one of the major causes of inflammatory diseases, including HDM-induced skin inflammation, suggesting that the antioxidant activity of Aptamin C could regulate inflammatory responses to HDMs in the skin keratinocyte cell line HaCaT and primary skin keratinocytes. Aptamin C not only inhibited HDM-induced proliferation of both type of cells, but suppressed HDM-induced increases in interleukin (IL)-1α and IL-6 production by these cells. In addition, Aptamin C suppressed the production of IL-17 and IL-22 by T cells, which are closely associated with AD pathogenesis, as well as HDM-induced IL-22Rα expression. Aptamin C also reduced the production of thymus and activation-regulated chemokine (TARC) by suppressing the interaction between IL-22 and IL-22Rα, as well as reducing T cell migration. Although HDM treatment markedly increased the expression of glial cell line-derived neurotrophic factor (GDNF), which is associated with itching in AD skin lesions, this increase was reduced by Aptamin C treatment. Taken together, these results suggest that Aptamin C can effectively regulate inflammatory lesions, such as AD, by regulating the production of inflammatory cytokines and GDNF induced by HDM.

Eu(III)-Chelated Polymeric Hybrid Nanoplatform for Luminescence Resonance Energy Transfer (LRET)-Based Real-Time Monitoring of Organic Cargo Release.

The real-time monitoring of specific guest release from nanoscale assemblies has been of great interest for the potential application in nanomedicine. Herein, we present a facile one-pot strategy to achieve a metal-chelated nanoscale platform that enables a highly efficient luminescence resonance energy transfer (LRET) for the monitoring of hydrophobic cargo release. To this end, Eu(III) as a lanthanide luminophore was employed to induce the metal-mediated self-assembly of chelating block copolymers in the presence of fluorescent Nile Blue (NB) as an organic cargo, which can then produce a nanoscale assembly containing a hybrid polyionic complex (HPIC) of Eu(III) and NB as LRET pairs. Exploiting this Eu(III)-chelated, NB-incorporated polymeric assembly as a luminescent platform that allows for the intermolecular distance-sensitive LRET, we further demonstrate that the facile monitoring of NB release from the carriers was made possible upon the addition of serum albumin as a protein reservoir for the released hydrophobic guest molecules.

A Content Analysis of the Counseling Literature on Technology Integration: American Counseling Association (ACA) Counseling Journals between 2000 and 2018.

This content analysis provides an overview of articles specific to technology integration in the field of counseling published in American Counseling Association (ACA) journals between the years 2000 and 2018. In addition to the number of articles on this topic published during this time period, the study identified other aspects such as authors and institutional affiliations; methodology, study locations, and application settings; target populations and sample characteristics; and areas and types of technology integration. Recommendations are provided for counseling research in general and for future research extending from specific circumstances such as the COVID-19 pandemic.

The Relationship Between Army Soldiers' Perceived Stress and Army Life Adjustment: Focusing on the Mediating Effect of Stress Response and the Moderating Effect of Cohesion.

INTRODUCTION: South Korea maintains a mandatory military duty, and high percentage of conscript soldiers have difficulty adjusting to military life. The purpose of this study is to investigate the mediating effect of the stress response on the relationship between soldiers' perceived stress and military life adjustment and to clarify the moderating effect of cohesion on this relationship. MATERIALS AND METHODS: The study's participants were 285 Korean military soldiers who are obliged to serve in the military and they completed the Perceived Stress Scale, the Stress Response Scale, the Military Life Adjustment, and the Group Cohesion Scale. Analysis methods included descriptive statistics, correlation analysis, path analysis, bootstrapping, collinearity statistic, and hierarchical regression analysis. This research obtained the approval of the institutional review board of the university (HYI-18-229-1). RESULTS: First, a partial mediation effect of the stress response was found in the relationship between soldiers' perceived stress and military life adjustment. That is, a high level of soldiers' perceived stress was related to their military life maladjustment. Moreover, the greater the level of soldiers' perceived stress, the greater the stress response, and, in turn, the greater the military life maladjustment. Second, we found the moderating effect of cohesion in the relationship between stress perception and military life adjustment. CONCLUSIONS: The stress perceived by soldiers not only directly affects their military life adjustment but also indirectly affects their adjustment through the stress responses. In addition, soldiers' levels of adjustment to military life change significantly based on cohesion levels only when they perceive less stress.

CD80CD86 deficiency disrupts regulatory CD4+FoxP3+T cell homoeostasis and induces autoimmune-like alopecia.

Alopecia areata (AA) is an autoimmune disease that results in spot baldness in humans. Adequate animal models for AA are currently lacking. The objective of this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in C57BL/6.CD80CD86-deficient (B6.CD80CD86-/- ) mice. Incidence and severity of alopecia were analysed in 58 B6.CD80CD86-/- mice using histological examination, flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR and CD25 inhibition test. Both male and female B6.CD80CD86-/- mice showed almost 100% incidence of hair loss at 40 weeks of age. Moreover, CD4+FoxP3+Treg (Treg) cell population in B6.CD80CD86-/- mice was significantly lower than in B6 mice, which presumably underlined autoimmune reaction. Histologically, B6.CD80CD86-/- mice showed CD4+ and CD8+ T-cell infiltration around terminal follicle region and exhibited hair follicle destruction in the anagen or catagen stage. Negative correlation between the number of CD4+FoxP3+ Tregs and ALA was confirmed by the CD25 depletion test in B6 mice, as follicle destruction was similar to that observed in B6.CD80CD86-/- animals. CD80CD86 deficiency disrupted CD4+FoxP3+ Treg homoeostasis and prompted the development of ALA. We demonstrated that B6.CD80CD86-/- mice might have several advantages as an ALA model, because they exhibited high incidence of disease phenotype and epipathogenesis similar to that observed in human AA.

Suppressor Effects of Positive and Negative Religious Coping on Academic Burnout Among Korean Middle School Students.

Statistical suppressor effects in prediction models can provide evidence of the interdependent relationship of independent variables. In this study, the suppressor effects of positive and negative religious coping on academic burnout were examined using longitudinal data. First, 388 middle school students reported their type of religion and use of positive and negative religious coping strategies. Four months later, they also reported their level of academic burnout. From structural equation modeling, significant suppressor effects were found among religious students. That is, the coefficients became larger when both positive and negative religious coping predicted academic burnout simultaneously, compared to when each religious coping predicted academic burnout alone. However, suppressor effects were not found among non-religious students.