Computational analysis of a collaboration network on human-computer interaction in Korea.

Since information and communication technology (ICT) has become one of the leading and essential fields for allowing developing countries to have the major growth engines, the majority of the countries have promoted collaboration in every ICT-related topics. In this study, we performed the trend and collaboration network analysis (CNA) in Korea for 2010-2019 among researchers who are related to human-computer interaction, one of the hottest research areas in ICT. Publication data were collected from SciVal, and the collaboration network was determined using degree, closeness, betweenness centralities, and PageRank. Hence, key researchers were identified based on their centrality metrics. The dataset contained 7,155 publications, thus reflecting the contributions of a total of 243 authors. The results of our data analysis demonstrated that key researchers can be identified via CNA; this aspect was not evident from the results of the most productive researchers. Additionally, on the basis of the results, the implications and limitations of this study were analyzed.

Revealing Metabolic Perturbation Following Heavy Methamphetamine Abuse by Human Hair Metabolomics and Network Analysis.

Methamphetamine (MA) is a highly addictive central nervous system stimulant. Drug addiction is not a static condition but rather a chronically relapsing disorder. Hair is a valuable and stable specimen for chronic toxicological monitoring as it retains toxicants and metabolites. The primary focus of this study was to discover the metabolic effects encompassing diverse pathological symptoms of MA addiction. Therefore, metabolic alterations were investigated in human hair following heavy MA abuse using both targeted and untargeted mass spectrometry and through integrated network analysis. The statistical analyses (t-test, variable importance on projection score, and receiver-operator characteristic curve) demonstrated that 32 metabolites (in targeted metabolomics) as well as 417 and 224 ion features (in positive and negative ionization modes of untargeted metabolomics, respectively) were critically dysregulated. The network analysis showed that the biosynthesis or metabolism of lipids, such as glycosphingolipids, sphingolipids, glycerophospholipids, and ether lipids, as well as the metabolism of amino acids (glycine, serine and threonine; cysteine and methionine) is affected by heavy MA abuse. These findings reveal crucial metabolic effects caused by MA addiction, with emphasis on the value of human hair as a diagnostic specimen for determining drug addiction, and will aid in identifying robust diagnostic markers and therapeutic targets.

Integrated Non-targeted and Targeted Metabolomics Uncovers Dynamic Metabolic Effects during Short-Term Abstinence in Methamphetamine Self-Administering Rats.

Persistent neurochemical disturbances by repeating drug reward and withdrawal lead to addiction. Particularly, drug withdrawal, usually starting within hours of the last dose, is considered as a critical step in the transition to addiction and a treatment clue. The aim of this study was to uncover metabolic effects associated with methamphetamine (MA) short-term abstinence using both non-targeted and targeted metabolomics. Metabolic alterations were investigated in rat plasma collected immediately after 16 days of MA self-administration and after 12 and 24 h of abstinence. Principal component analysis revealed that the highest level of separation occurred between the 24 h and saline (control) groups based on the significantly changed ion features, 257/320/333 and 331/409/388, in the SA/12 h/24 h groups in positive and negative modes of UPLC-QTOF-ESI-MS, respectively. Targeted metabolomics revealed dynamic changes in the biosynthesis/metabolism of amino acids, including the phenylalanine, tyrosine, and tryptophan biosynthesis and the valine, leucine, and isoleucine biosynthesis. Integrating non-targeted and targeted metabolomics data uncovered rapid and distinct changes in the metabolic pathways involved in energy metabolism, the nervous system, and membrane lipid metabolism. These findings provide essential knowledge of the dynamic metabolic effects associated with short-term MA abstinence and may help identify early warning signs of MA dependence.

Correction to: Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study.

In the original version of the article titled "Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study", published in 41(5):554-563 (https://doi.org/10.1007/s12272-018-1013-7), unfortunately an important statement was missing in the Clinical study section by the author.

Correction to: Development of a linear dual column HPLC-MS/MS method and clinical genetic evaluation for tramadol and its phase I and II metabolites in oral fluid.

In the original version of the article titled "Development of a linear dual column HPLC-MS/MS method and clinical genetic evaluation for tramadol and its phase I and II metabolites in oral fluid", published in 41(3):288-298 ( https://doi.org/10.1007/s12272-017-0993-z ), unfortunately an important statement was missing in the Clinical study section by the author. The following statement: "The clinical study was approved by the Institutional Review Board of Keimyung University (Deagu, Republic of Korea, approval number: 40525-201509-BR-70-02) and Kyungpook National University Hospital (Daegu, Republic of Korea, approval number of clinical trial: 2016-08-005) and carried out at the Kyungpook National University Hospital Clinical Trial Center (Daegu, Republic of Korea)." Should read: "Written informed consent was obtained from all subjects. The study was performed in accordance with the guidelines of the Declaration of Helsinki on biomedical research involving human subjects and was approved by the Institutional Review Board of Keimyung University (Deagu, Republic of Korea, approval number: 40525-201509-BR-70-02) and Kyungpook National University Hospital (Daegu, Republic of Korea, approval number of clinical trial: 2016-08-005) and carried out at the Kyungpook National University Hospital Clinical Trial Center (Daegu, Republic of Korea)."

Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study.

Hair is a valuable specimen for monitoring long-term drug use. Tramadol is an effective opioid analgesic but is associated with risks such as drug dependence and unexpected toxicity arising from genetic differences in metabolism. However, few studies have been performed on the distribution of tramadol and its metabolites in hair. In the present study, a column-switching LC-MS/MS method was developed and fully validated for the simultaneous determination of tramadol and its phase I and II metabolites in hair. Furthermore, the distribution of tramadol and its metabolites in hair was investigated in a pharmacogenetic study. Tramadol and its metabolites were extracted from hair using methanol and injected onto LC-MS/MS. The validation results of selectivity, matrix effect, linearity, precision and accuracy were satisfactory. The (mean) concentrations of O-desmethyltramadol (ODMT) and N,O-didesmethyltramadol (NODMT) in the CYP2D6*10/*10 and CYP2D6*5/*5 groups were lower than those in the CYP2D6*wt/*wt group, while the (mean) concentrations of N-desmethyltramadol (NDMT) were higher. Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT were well correlated with the CYP2D6 genotypes. The developed method was successfully applied to the clinical study, which demonstrated that the concentrations of a drug and its metabolites in hair were dependent on the polymorphism of its metabolizing enzyme.

Development of a linear dual column HPLC-MS/MS method and clinical genetic evaluation for tramadol and its phase I and II metabolites in oral fluid.

Tramadol is a centrally acting synthetic opioid analgesic and has received special attention due to its abuse potential and unexpected responses induced by CYP2D6 polymorphism. Oral fluid is an advantageous biofluid for drug analysis due to non-invasive sampling and high correlation of drug concentrations with plasma. However, few studies have been performed on distribution of tramadol and its metabolites in oral fluid. In the present study, a linear dual column HPLC-MS/MS method was developed and fully validated for the simultaneous determination of tramadol and its phase I [O-desmethyltramadol (ODMT), N-desmethyltramadol (NDMT) and N,O-didesmethyltramadol (NODMT)] and II metabolites in oral fluid. Furthermore, the distribution of tramadol and its metabolites, in relation to CYP2D6 genetic variations, in oral fluid was investigated following a clinical study including 23 subjects with CYP2D6*wt/*wt, CYP2D6*10/*10 or CYP2D6*5/*5. The validation results of selectivity, matrix effect, linearity, precision and accuracy were satisfactory. Pharmacokinetic parameters, such as Css,max and AUC0-τ of tramadol, NDMT and NODMT, in the CYP2D6*10/*10 group were significantly higher than those in the CYP2D6*wt/*wt group. Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT correlated well with the CYP2D6 genotypes. We demonstrated that oral fluid is a promising biofluid for pharmacokinetic evaluation in relation to genetic variations.

Role of hair pigmentation in drug incorporation into hair.

Hair analysis has notably expanded its application as a bio-monitor for drug or toxicant exposure. Hair pigmentation is proposed as a major factor affecting drug incorporation into hair; however, the mechanisms underlying the incorporation of drugs into hair are still unclear. In the present study, the effect of hair pigmentation on drug incorporation into hair was examined using rats carrying hair with different melanin status and human cells (SK-Mel-28 cells, HaCaT cells and the co-cultured HaCaT cells with SK-Mel-28 cells) representing the main pigmentary unit in hair. Tramadol, a synthetic opioid analgesic, was selected as a model drug. The distribution of tramadol and its phase I (O-desmethyltramadol [ODMT], N-desmethyltramadol [NDMT] and N,O-didesmethyltramadol [NODMT]) and phase II metabolites (ODMT-glucuronide and NODMT-glucuronide) was investigated in non-pigmented and pigmented hair from Long-Evans rats. Moreover, the incorporation levels of ODMT and ODMT-glucuronide were compared in hair cells. The concentrations of tramadol and its phase I metabolites were significantly higher in pigmented rat hair while those of phase II metabolites did not showed any consistent significant difference depending on the status of hair pigmentation. ODMT was taken up to a greater extent than ODMT-glucuronide by SK-Mel-28 cells, HaCaT cells and the co-cultured HaCaT cells with SK-Mel-28 cells. Notably, the incorporated level of ODMT was higher in SK-Mel-28 cells than HaCaT cells and the concentration difference of ODMT was significantly larger than that of ODMT-glucuronide. This study clearly demonstrated that hair pigmentation played a role as a facilitating factor for the incorporation of basic compounds and provided insight into the drug incorporation process into hair.