• Title/Summary/Keyword: adverse outcome pathway

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Trend of In Silico Prediction Research Using Adverse Outcome Pathway (독성발현경로(Adverse Outcome Pathway)를 활용한 In Silico 예측기술 연구동향 분석)

  • Sujin Lee;Jongseo Park;Sunmi Kim;Myungwon Seo
    • Journal of Environmental Health Sciences
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    • v.50 no.2
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    • pp.113-124
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    • 2024
  • Background: The increasing need to minimize animal testing has sparked interest in alternative methods with more humane, cost-effective, and time-saving attributes. In particular, in silico-based computational toxicology is gaining prominence. Adverse outcome pathway (AOP) is a biological map depicting toxicological mechanisms, composed of molecular initiating events (MIEs), key events (KEs), and adverse outcomes (AOs). To understand toxicological mechanisms, predictive models are essential for AOP components in computational toxicology, including molecular structures. Objectives: This study reviewed the literature and investigated previous research cases related to AOP and in silico methodologies. We describe the results obtained from the analysis, including predictive techniques and approaches that can be used for future in silico-based alternative methods to animal testing using AOP. Methods: We analyzed in silico methods and databases used in the literature to identify trends in research on in silico prediction models. Results: We reviewed 26 studies related to AOP and in silico methodologies. The ToxCast/Tox21 database was commonly used for toxicity studies, and MIE was the most frequently used predictive factor among the AOP components. Machine learning was most widely used among prediction techniques, and various in silico methods, such as deep learning, molecular docking, and molecular dynamics, were also utilized. Conclusions: We analyzed the current research trends regarding in silico-based alternative methods for animal testing using AOPs. Developing predictive techniques that reflect toxicological mechanisms will be essential to replace animal testing with in silico methods. In the future, since the applicability of various predictive techniques is increasing, it will be necessary to continue monitoring the trend of predictive techniques and in silico-based approaches.

Adverse Outcome Pathways for Prediction of Chemical Toxicity at Work: Their Applications and Prospects (작업장 화학물질 독성예측을 위한 독성발현경로의 응용과 전망)

  • Rim, Kyung-Taek;Choi, Heung-Koo;Lee, In-Seop
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.29 no.2
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    • pp.141-158
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    • 2019
  • Objectives: An adverse outcome pathway is a biological pathway that disturbs homeostasis and causes toxicity. It is a conceptual framework for organizing existing biological knowledge and consists of the molecular initiating event, key event, and adverse output. The AOP concept provides intuitive risk identification that can be helpful in evaluating the carcinogenicity of chemicals and in the prevention of cancer through the assessment of chemical carcinogenicity predictions. Methods: We reviewed various papers and books related to the application of AOPs for the prevention of occupational cancer. We mainly used the internet to search for the necessary research data and information, such as via Google scholar(http://scholar.google.com), ScienceDirect(www.sciencedirect.com), Scopus(www.scopus. com), NDSL(http: //www.ndsl.kr/index.do) and PubMed(http://www.ncbi.nlm.nih.gov/pubmed). The key terms searched were "adverse outcome pathway," "toxicology," "risk assessment," "human exposure," "worker," "nanoparticle," "applications," and "occupational safety and health," among others. Results: Since it focused on the current state of AOP for the prediction of toxicity from chemical exposure at work and prospects for industrial health in the context of the AOP concept, respiratory and nanomaterial hazard assessments. AOP provides an intuitive understanding of the toxicity of chemicals as a conceptual means, and it works toward accurately predicting chemical toxicity. The AOP technique has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment. AOP can be applied to the assessment of chemical carcinogenicity along with efforts to understand the effects of chronic toxic chemicals in workplaces. Based on these predictive tools, it could be possible to bring about a breakthrough in the prevention of occupational and environmental cancer. Conclusions: The AOP tool has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment and has been widely used in the field of chemical risk assessment and the evaluation of carcinogenicity at work. It will be a useful tool for prediction, and it is possible that it can help bring about a breakthrough in the prevention of occupational and environmental cancer.

Modification of HEART Pathway for Patients With Chest Pain: A Korean Perspective

  • Bora Chae;Shin Ahn;Youn-Jung Kim;Seung Mok Ryoo;Chang Hwan Sohn;Dong-Woo Seo;Won Young Kim
    • Korean Circulation Journal
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    • v.53 no.9
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    • pp.635-644
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    • 2023
  • Background and Objectives: The History, Electrocardiography, Age, Risk factors, and Troponin (HEART) pathway was developed to identify patients at low risk of a major adverse cardiac event (MACE) among patients presenting with chest pain to the emergency department. Methods: We modified the HEART pathway by replacing the Korean cut-off of 25 kg/m2 with the conventional threshold of 30 kg/m2 in the definition of obesity among risk factors. The primary outcome was a MACE within 30 days, which included acute myocardial infarction, primary coronary intervention, coronary artery bypass grafting, and all-cause death. Results: Of the 1,304 patients prospectively enrolled, MACE occurred in 320 (24.5%). The modified HEART pathway identified 37.3% of patients as low-risk compared with 38.3% using the HEART pathway. Of the 500 patients classified as low-risk with HEART pathway, 8 (1.6%) experienced MACE, and of the 486 low-risk patients with modified HEART pathway, 4 (0.8%) experienced MACE. The modified HEART pathway had a sensitivity of 98.8%, a negative predictive value (NPV) of 99.2%, a specificity of 49.0%, and a positive predictive value (PPV) of 38.6%, compared with the original HEART pathway, with a sensitivity of 97.5%, a NPV of 98.4%, a specificity of 50.0%, and a PPV of 38.8%. Conclusions: When applied to Korean population, modified HEART pathway could identify patients safe for early discharge more accurately by using body mass index cut-off levels suggested for Koreans.

A Systematic Review of Toxicological Studies to Identify the Association between Environmental Diseases and Environmental Factors (환경성질환과 환경유해인자의 연관성을 규명하기 위한 독성 연구 고찰)

  • Ka, Yujin;Ji, Kyunghee
    • Journal of Environmental Health Sciences
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    • v.47 no.6
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    • pp.505-512
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    • 2021
  • Background: The occurrence of environmental disease is known to be associated with chronic exposure to toxic chemicals, including waterborne contaminants, air/indoor pollutants, asbestos, ingredients in humidifier disinfectants, etc. Objectives: In this study, we reviewed toxicological studies related to environmental disease as defined by the Environmental Health Act in Korea and toxic chemicals. We also suggested a direction for future toxicological research necessary for the prevention and management of environmental disease. Methods: Trends in previous studies related to environmental disease were investigated through PubMed and Web of Science. A detailed review was provided on toxicological studies related to the humidifier disinfectants. We identified adverse outcome pathways (AOPs) that can be linked to the induction of environmental diseases, and proposed a chemical screening system that uses AOP, chemical toxicity big data, and deep learning models to select chemicals that induce environmental disease. Results: Research on chemical toxicity is increasing every year, but there is a limitation to revealing a clear causal relationship between exposure to chemicals and the occurrence of environmental disease. It is necessary to develop various exposure- and effect-biomarkers related to disease occurrence and to conduct toxicokinetic studies. A novel chemical screening system that uses AOP and chemical toxicity big data could be useful for selecting chemicals that cause environmental diseases. Conclusions: From a toxicological point of view, developing AOP related to environmental diseases and a deep learning-based chemical screening system will contribute to the prevention of environmental diseases in advance.

A Review of Mechanisms of Implantation

  • Kim, Su-Mi;Kim, Jong-Soo
    • Development and Reproduction
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    • v.21 no.4
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    • pp.351-359
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    • 2017
  • Implantation is a highly organized process that involves an interaction between a receptive uterus and a competent blastocyst. In humans, natural fecundity suggests that the chance of conception per cycle is relatively low (~30%) and two-third of lost pregnancies occur because of implantation failure. Defective implantation leads to adverse pregnancy outcomes including infertility, spontaneous miscarriage, intrauterine fetal growth restriction and preeclampsia. With use of advanced scientific technologies, gene expression analysis and genetically-engineered animal models have revealed critical cellular networks and molecular pathways. But, because of ethical restrictions and the lack of a mechanistic experiment, comprehensive steps in human implantation have still not been completely understood. This review primarily focuses on the recent advances in mechanisms of implantation. Because infertility is an emerging issue these days, gaining an understanding the molecular and hormonal signaling pathway will improve the outcome of natural pregnancy and assisted reproductive technology.

Conducting and reporting case series and audits;author guidelines (환자군 연구(Case series) 및 점검(Audit) 연구의 수행과 보고;저자를 위한 지침서)

  • Kim, Song-Yi;Kim, Sang-Woo;Lee, Hyang-Sook;Park, Hi-Joon
    • Korean Journal of Acupuncture
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    • v.24 no.4
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    • pp.13-24
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    • 2007
  • Objectives : This article aims to give guidance on the conduct and reporting of case series and audits of acupuncture, based on common problems that have arisen in the past. This type of project, and particularly the prospective case series or pre- post-intervention study, may give valuable evidence of the overall effectiveness of acupuncture-for example in different situations and in different conditions- and provides one step in the research pathway before generating an hypothesis. Results & Discussion : The project should be designed with the aim of reducing bias as much as possible. Careful and detailed planning is essential for the project to produce worthwhile results that readers can evaluate and replicate. Ethical issues should be considered and formal approval may be necessary. The patient group should be recruited systematically and baseline data obtained. The treatment given should be systematic and decisions to change or end treatment made explicit. The outcome should be measured in ways that are known to be reliable and valid. Musculoskeletal problems can be evaluated with scales for pain and confirmed by measuring one other symptom such as stiffness or one other aspect such as bothersomeness. Global change scores also provide supporting information, and the MYMOP (Measure Yourself Medical Outcome Profile) measure is popular when patients with different conditions are included. The design of questionnaires for beliefs and attitudes is a specialised area that should not be attempted without expert help. Adverse events should also be recorded. Analysis of the data and the best way of summarising and presenting the results are also discussed.

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