• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.354-361
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• 2002

Purpose : Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma. Methods : To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect. Results : A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model. Conclusion : We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.

• Journal of Korean Academic Society of Home Health Care Nursing
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• v.30 no.1
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• pp.15-25
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• 2023

Purpose: This study describes the associations between shift work factors, workplace violence bystander types, and the missed nursing care of hospital nurses. Methods: A cross-sectional survey was conducted among hospital nurses using structured questionnaires related to shift work factors, workplace violence bystander types, and missed nursing care. The study participants were 199 nurses caring for adult patients and working in two tertiary hospitals. Results: The missed nursing care of the participants showed a statistically significant positive correlation with the facilitating bystander (r=.40, p<.001) and abdicating bystander (r=.28, p<.001) among the workplace violence bystander types. However, rest time during duty showed a significant negative correlation (r=-.16, p=.026). A regression model with control variables (department and clinical career), shift work factors, and workplace violence bystander types explained approximately 25% of missed nursing care of the study participants. Further, the facilitating bystander type influenced the missed nursing care of hospital nurses. Conclusion: As a result of examining the associations between shift work factors, workplace violence bystander types, and missed nursing care of hospital nurses, it was confirmed that missed nursing care was influenced by the facilitating bystander type. It is necessary to improve the nursing culture within the department so that nurses do not behave as negative bystanders to workplace violence.

• BMB Reports
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• v.55 no.2
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• pp.57-64
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• 2022

Autoimmune disease is known to be caused by unregulated self-antigen-specific T cells, causing tissue damage. Although antigen specificity is an important mechanism of the adaptive immune system, antigen non-related T cells have been found in the inflamed tissues in various conditions. Bystander T cell activation refers to the activation of T cells without antigen recognition. During an immune response to a pathogen, bystander activation of self-reactive T cells via inflammatory mediators such as cytokines can trigger autoimmune diseases. Other antigen-specific T cells can also be bystander-activated to induce innate immune response resulting in autoimmune disease pathogenesis along with self-antigen-specific T cells. In this review, we summarize previous studies investigating bystander activation of various T cell types (NKT, γδ T cells, MAIT cells, conventional CD4⁺, and CD8⁺ T cells) and discuss the role of innate-like T cell response in autoimmune diseases. In addition, we also review previous findings of bystander T cell function in infection and cancer. A better understanding of bystander-activated T cells versus antigen-stimulated T cells provides a novel insight to control autoimmune disease pathogenesis.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.162-174
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• 1997

Background : Metabolic cooperation via gap junctional intercellular communication (GJIC) is an important mechanism of the bystander effect in gene therapy using the Herpes Simplex Virus thymidine kinase/ganciclovir (HSVtk) "prodrug" system. Since retinoids have been reported to increase GJIC by induction of connexin 43 expression, we hyporthesized that treatment of tumor cells with retinoic acid could augment the bystander effect of the HSVtk/GCV system and result in improved tumor cell killing by enhancing GJIC. Methods : We transferred HSVtk gene to SKHep-J cell line that does not express connexin43, and also transferred the gene to human and murine mesothelioma cell lines that express connexin43. We verified that retinoic acid enhanced GJIC utilizing a functional double-dye transfer study and evaluated the effects of retinoic acid on the growth rate of tumor cells. We then tested the effects of retinoic acid on bystander-mediated cell killing. Results : Addition of all-trans retinoic acid (RA) increased GJIC in cell lines expressing connexin 43 and was asspciated with more efficient in vitro bystander killing in cells transduced with HSVtk via adenoviral and retroviral vectors. In contrast, there was no increase in the efficiency of the bystander effect after exposure to RA in a cell line which had no delectable connexin 43. Conclusion : These results provide evidence that retinoids can augment the efficiency of cell killing with the HSVtk/GCV system by enhancing bystander effect and may thus be a promising new approach to improve responses in gene therapy utilizing the HSVtk system to treat tumors.

• Molecules and Cells
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• v.21 no.1
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• pp.7-20
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• 2006

The major event in human immunodeficiency virus type 1 (HIV-1) infection is the death of many cells related to host immune response. The demise of these cells is normally explained by cell suicide mechanism, apoptosis. Interestingly, the decrease in the number of immune cells, such as non-CD4+ cells as well as CD4+ T cells, in HIV infection usually occurs in uninfected bystander cells, not in directly infected cells. It has, therefore, been suggested that several soluble factors, including viral protein R (Vpr), are released from the infected cells and induce the death of bystander cells. Some studies show that Vpr interacts directly with adenine nucleotide translocator (ANT) to induce mitochondrial membrane permeabilization (MMP). The MMP results in release of some apoptogenic factors such as cytochrome-c (cyt-c) and apoptosis-inducing factor (AIF). Vpr also has indirect effect on mitochondria through enhancing the level of caspase-9 transcription and suppressing nuclear factor-kappa B (NF-${\kappa}B$). The involvement of p53 in Vpr-induced apoptosis remains to be studied. On the other hand, low level of Vpr expression has anti-apoptotic effect, whereas it's high level of expression induces apoptosis. Extracellular Vpr also exhibits cytotoxicity to uninfected bystander cells through apoptotic or necrotic mechanism. The facts that Vpr has cytotoxic effect on both infected cells and bystander cells, and that it exhibits both proand anti-apoptotic activity may explain its role in viral survival and disease progression.

• Asia pacific journal of information systems
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• v.31 no.1
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• pp.1-16
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• 2021

Cyberbullying has become a social problem as malicious text messages and online comments among teenagers have increased in the late 2000s. Some serious reporting has attempted to impress on us the need to pay more attention to reducing malicious online content as a typical type of cyberbullying. Meanwhile, despite environmental changes that have made it easier to report perpetrators of such messages, it is often the case that the crime occurs in a public place and is tolerated. However, there is a growing tendency for people to exhibit the bystander effect, the problem of personal indifference to witnessing or knowing about crimes, but individuals do not offer any means of help to a victim when other people are present. This effect is rampant in the case of cybercrimes. This study aims to extract the motivations behind posting malicious comments through in-depth interviews and to suggest recommendations for relative issues by demonstrating how the bystander effect can be reduced using causal relationship diagrams of the system dynamics methodology. Hopefully, this work will contribute to a better understanding of factors that could cause a decrease in malicious online comments.

• Journal of Korean Medical Science
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• v.33 no.51
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• pp.328.1-328.12
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• 2018

Background: In cardiac arrest, the survival rate increases with the provision of bystander cardiopulmonary resuscitation (CPR), of which the initial response and treatment are critical. Telephone CPR is among the effective methods that might increase the provision of bystander CPR. This study aimed to describe and examine the improvement of neurological outcomes in individuals with out-of-hospital acute cardiac arrest by implementing the nationwide, standardized telephone CPR program. Methods: Data from the emergency medical service-based cardiac arrest registry that were collected between 2009 and 2014 were used. The effectiveness of the intervention in the interrupted time-series study was determined via a segmented regression analysis, which showed the risk ratio and risk difference in good neurological outcomes before and after the intervention. Results: Of 164,221 patients, 148,403 were analyzed. However, patients with unknown sex and limited data on treatment outcomes were excluded. Approximately 64.3% patients were men, with an average age of 63.7 years. The number of bystander CPR increased by 3.3 times (95% confidence interval [CI], 3.1-3.5) after the intervention, whereas the rate of good neurological outcomes increased by 2.6 times (95% CI, 2.3-2.9 [1.6%]; 1.4-1.7). The excess number was identified based on the differences between the observed and predicted trends. In total, 2,127 cases of out-of-hospital cardiac arrest (OHCA) after the intervention period received additional bystander CPR, and 339 cases of OHCA had good neurological outcomes. Conclusion: The nationwide implementation of the standardized telephone CPR program increased the number of bystander CPR and improved good neurological outcomes.

• Korean Journal of Culture and Social Issue
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• v.28 no.2
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• pp.107-131
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• 2022

This study was conducted with the aim of developing and validating a measure of the workplace bullying bystander behavior. For the purpose, items were developed by referring to previous studies related to workplace bullying, and behavior subtypes were defined as pro-bullying, defending, and bystander behaviors. After confirming the content validity with the help of experts, a total of 31 preliminary items were composed. The final 26 items were selected by conducting an exploratory factor analysis and verifying the validity and reliability of the scale with a survey of 288 office workers who have directly or indirectly witnessed workplace bullying over the past three years. In this process, it was confirmed that defense behavior was distinguished into two types: Active and supportive. Confirmatory factor analysis was conducted with data from 518 office workers who have directly or indirectly witnessed workplace bullying over the past year, and the validity and reliability of the developed scale were confirmed. As a result of comparing the competing models to reconfirm the subtypes, it was confirmed again that active defense behavior and supportive defense behavior were distinguished. The criterion-related validity of all subtypes was confirmed by setting the criterion variables for workplace bullying behavior, altruistic behavior, pro-social behavior, fear of intervention, moral disengagement, guilt, and moral identity. Based on the result of this study, follow-up research tasks related to workplace bullying bystander behavior scale were suggested and the methods to prevent and intervene in workplace bullying while utilizing workplace bullying bystander behaviors were discussed.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.298-309
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• 2000

Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

• Korean Journal of School Psychology
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• v.16 no.3
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• pp.453-470
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• 2019

This study aimed to investigate how teacher's attitude toward violence affect students who experienced bullying victim in their role in making peer-to-peer violence deepen, and how students who experienced the bullying victim react to show aggression, and the aggression is blocked by teacher's attitude toward violence, resulting in decrease of doing the bystander's negative behavior. By conducing this study, this study ultimately aimed to ensure that the teacher's attitude toward violence is very important in preventing peer bullying in the classroom. To achieve this aims, this study conducted a survey of 820 fourth, fifth and sixth graders in 40 classes at 10 elementary schools and limited only 365 of the respondents who reported experiencing peer bullying victim. This study utilized the structural equation modeling method to analyze the data. The results were as follows. First, it showed that the lower the bystander's negative behavior in victims who experienced peer bullying, and the lower the responsive aggression reacted from the peer bullying, when the teacher shows an unacceptable attitude toward violence. Teacher's attitude toward violence also appears to affect peer bystander's negative behavior by mediating peer bullying victim's reactive aggression, indicating that the teacher's attitude toward classroom violence may reduce the aggression of students from the experience of victimization, and consequently prevent the classroom from becoming more leprosy by reducing peer bullying.