Publications by authors named "Kyunghoon Lee"

71 Publications

Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study.

Clin Nutr 2021 Jun 9;40(7):4579-4584. Epub 2021 Jun 9.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea; Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, South Korea. Electronic address:

Background: Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia.

Aims: To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults.

Methods: This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models.

Results: During the follow-up period (mean = 5.4 years, SD = 0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6 μmol/L) but also those with low serum tHcy (≤8.9 μmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5 μmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9 μmol/L) were taking vitamin supplements.

Conclusions: Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.
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http://dx.doi.org/10.1016/j.clnu.2021.05.034DOI Listing
June 2021

Evaluation of Heart-type Fatty Acid-binding Protein in Early Diagnosis of Acute Myocardial Infarction.

J Korean Med Sci 2021 Mar 1;36(8):e61. Epub 2021 Mar 1.

Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: Although electrocardiography and cardiac troponin play important roles in the diagnosis of acute coronary syndrome (ACS), there remain unmet clinical needs. Heart-type fatty acid-binding protein (H-FABP) has been identified as an early diagnostic marker of acute myocardial infarction (AMI). In this study, we examined the diagnostic and prognostic value of H-FABP in patients suspected with ACS.

Methods: We conducted an observational single-center cohort study, including 89 adults aged 30 years or older, who presented to the emergency room (ER) within 24 hours after the onset of chest pain and/or dyspnea. We performed laboratory analysis and point-of-care testing (POCT) for cardiac markers, including H-FABP, troponin I, and creatine kinase-myocardial band. We also evaluated the correlation between cardiac markers and left ventricular (LV) dysfunction and extent of coronary artery disease (CAD).

Results: In patients presented to ER within 4 hours after symptom onset (n = 49), the diagnostic accuracy of H-FABP for AMI, as quantified by the area under the receiver operating characteristic curve, was higher (0.738; 95% confidence interval [CI], 0.591-0.885) than other cardiac markers. In POCT, the diagnostic accuracy of H-FABP (56%; 95% CI, 45-67) was significantly higher than other cardiac markers. H-FABP was correlated with not extent of CAD but post-AMI LV dysfunction.

Conclusion: H-FABP is a useful cardiac marker for the early diagnosis of AMI and prediction of myocardia injury. Difference in the circulatory release timeline of cardiac markers could explain its utility in early-stage of myocardial injury.
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http://dx.doi.org/10.3346/jkms.2021.36.e61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921368PMC
March 2021

Development of a limited sampling strategy for the estimation of isoniazid exposure considering N-acetyltransferase 2 genotypes in Korean patients with tuberculosis.

Tuberculosis (Edinb) 2021 03 21;127:102052. Epub 2021 Jan 21.

Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, South Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea. Electronic address:

A limited sampling strategy (LSS) to estimate the exposure to isoniazid was developed considering N-acetyltransferase 2 (NAT2) genotypes in Korean patients with tuberculosis. The influence of the genotypes on the pharmacokinetics of isoniazid was also evaluated. A total of 33 participants participated in the study and received isoniazid 300 mg once daily. Evaluable participants consist of ten slow (SA), fourteen intermediate (IA) and six rapid acetylators (RA). As expected, isoniazid exposure was higher (mean AUC, 28.4 versus 7.6 mg*h/L) and systemic clearance lower (mean apparent clearance, 14.8 versus 50.6 L/h) in SAs than RAs. The formulas to estimate isoniazid exposure were constructed using one or more concentration-time points that correlate with the area under the concentration-time curve (AUC). The LSS using a formula of single concentration-time point at 4 h post dose (C) is applicable for all acetylators to the therapeutic drug monitoring (TDM) of isoniazid in patients with tuberculosis when evaluated using the Deming regression and Bland-Altman plot (AUC = 1.53 + 10.03*C, adjusted r = 0.95, p < 0.001). Considering that SAs are more prone to adverse effects, pre-dose NAT2 genotyping would be valuable for optimal isoniazid dosing in conjunction with TDM.
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http://dx.doi.org/10.1016/j.tube.2021.102052DOI Listing
March 2021

Recent Trends in Creatinine Assays in Korea: Long-Term Accuracy-Based Proficiency Testing Survey Data by the Korean Association of External Quality Assessment Service (2011-2019).

Ann Lab Med 2021 Jul;41(4):372-379

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Background: Accurate serum creatinine (Cr) concentration measurement is essential for evaluating kidney function. In 2011, the Korean Association of External Quality Assessment Service (KEQAS) launched an accuracy-based Cr proficiency testing (ABCr PT) survey. We analyzed long-term data of the KEQAS ABCr PT survey collected between 2011 and 2019 to assess recent trends in Cr assays in Korea.

Methods: The ABCr PT survey including three commutable fresh-frozen serum samples was performed twice a year. The target Cr concentration was assigned using isotope-dilution mass spectrometry. We analyzed data obtained from the participating laboratories, calculated the yearly bias, and evaluated bias trends for the major reagents and instruments. Outliers were excluded from all analysis.

Results: The mean percentage bias based on the total data of all participating laboratories was 10.8% in the 2011-A survey and 0.2% in 2019-B survey. Bias for the major reagents and instruments differed depending on the manufacturer. Enzymatic assays generally showed desirable bias ranging from -3.9% to 3.2% at all Cr concentrations and lower interlaboratory variability than non-enzymatic assays (enzymatic vs. non-enzymatic, 3.3%-7.2% vs. 6.3%-9.1%).

Conclusions: Although the mean percentage bias of Cr assays tends to decrease over time, it is necessary to continuously strive to improve Cr assay accuracy, especially at low concentrations.
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http://dx.doi.org/10.3343/alm.2021.41.4.372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884186PMC
July 2021

Standardization Status of Total Cholesterol Concentration Measurement: Analysis of Korean External Quality Assessment Data.

Ann Lab Med 2021 Jul;41(4):366-371

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Background: Total cholesterol concentration measurement is important in the diagnosis of dyslipidemia and evaluation of cardiovascular disease risk factors. Measurement reliability for obtaining an accurate total cholesterol concentration requires procedure standardization. We evaluated the standardization status for total cholesterol concentration measurement through Korean external quality assessment (EQA) data analysis.

Methods: This study involved 1,670 laboratories that participated in the EQA of total cholesterol concentration measurements in 2019 for 32 products from different manufacturers. The target concentrations of three quality control (QC) materials (samples A, B, and C) were measured using the reference method and compared with EQA data. The performance criteria for total cholesterol concentration measurement were based on the National Cholesterol Education Program guidelines, with ±3% inaccuracy.

Results: The target values and inaccuracies of the QC material based on the reference method measurements were 254.65±7.64, 108.30±3.25, and 256.29±7.69 mg/dL (6.59±0.20, 2.80±0.08, and 6.63±0.20 mmol/L) for samples A, B, and C, respectively. The performance criteria were not met in 42.7% laboratories for sample A, 68.4% of laboratories for sample B, and 38.0% laboratories for sample C.

Conclusions: Despite significant efforts to accurately measure total cholesterol concentrations, further actions are needed for measurement standardization. Manufacturers reporting values that differ from target values should check calibrator traceability; additional efforts to accurately measure total cholesterol concentrations are required for laboratories that use products from these manufacturers.
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http://dx.doi.org/10.3343/alm.2021.41.4.366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884189PMC
July 2021

Analytical performance evaluation of the Norudia HbA assay.

J Clin Lab Anal 2020 Nov 9;34(11):e23504. Epub 2020 Aug 9.

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Hemoglobin A (HbA) is arguably the most important biomarker used in the diagnosis and treatment monitoring of diabetes mellitus. We evaluated the analytical performance of the Norudia HbA assay (Sekisui Medical Co., LTD), which uses an enzymatic method incorporated into a fully automated, high-throughput system.

Methods: The precision, linearity, and carryover of the Norudia HbA assay were evaluated. Using 60 patient samples, comparative analysis of HbA measurements with two commonly used HbA assays, the D100 (Bio-Rad Laboratories, Inc) and HLC-723 G11 (Tosoh), was undergone. Thirteen commutable samples with known HbA concentrations measured using an IFCC reference measurement procedure were used to compare accuracy between methods. Interference of HbA measurement by Hb variants was evaluated using 16 known Hb variant samples.

Results: Repeatability (% CV) for low and high concentrations ranged from 1.12%-1.50% and 0.66%-0.75%, respectively, and within-laboratory precision for low and high concentrations ranged from 1.73%-2.89% and 0.98%-1.64%, respectively. For linearity, the coefficient of determination was 0.9987. No significant carryover was observed. When compared to the D100 and HLC-723 G11 assays, the Norudia HbA assay showed the best accuracy with the lowest mean bias (-1.72%). Furthermore, the Norudia was least affected by Hb variants and gave the most reliable HbA measurements.

Conclusion: The Norudia HbA showed excellent analytical performance with good precision and linearity, and minimal carryover. When compared to other routine HbA methods, the Norudia HbA assay showed the highest accuracy and was least affected by Hb variants.
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http://dx.doi.org/10.1002/jcla.23504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676213PMC
November 2020

Ultrahigh-resolution scanning microwave impedance microscopy of moiré lattices and superstructures.

Sci Adv 2020 Dec 9;6(50). Epub 2020 Dec 9.

Department of Physics, University of California at Berkeley, Berkeley, CA 94720, USA.

Two-dimensional heterostructures composed of layers with slightly different lattice vectors exhibit new periodic structure known as moiré lattices, which, in turn, can support novel correlated and topological phenomena. Moreover, moiré superstructures can emerge from multiple misaligned moiré lattices or inhomogeneous strain distributions, offering additional degrees of freedom in tailoring electronic structure. High-resolution imaging of the moiré lattices and superstructures is critical for understanding the emerging physics. Here, we report the imaging of moiré lattices and superstructures in graphene-based samples under ambient conditions using an ultrahigh-resolution implementation of scanning microwave impedance microscopy. Although the probe tip has a gross radius of ~100 nm, spatial resolution better than 5 nm is achieved, which allows direct visualization of the structural details in moiré lattices and the composite super-moiré. We also demonstrate artificial synthesis of novel superstructures, including the Kagome moiré arising from the interplay between different layers.
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http://dx.doi.org/10.1126/sciadv.abd1919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725474PMC
December 2020

Multiplex LC-MS/MS for simultaneous determination of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, albumin, and vitamin D-binding protein with its isoforms: One-step estimation of bioavailable vitamin D and vitamin D metabolite ratio.

J Steroid Biochem Mol Biol 2021 02 28;206:105796. Epub 2020 Nov 28.

Department of Laboratory Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Bioavailable vitamin D and vitamin D metabolite ratio (VMR) have emerged as potential novel vitamin D markers. We developed a multiplex liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine all elements necessary for the calculation of bioavailable vitamin D and VMR, including 25-hydroxyvitamin D [25-(OH)D] and 24,25-dihydroxyvitamin D [24,25-(OH)D], VDBP and its isoforms, and albumin. Following separate reactions of hexane extraction and trypsin digestion, serum samples were analyzed using LC-MS/MS to measure 25-(OH)D, 25-(OH)D, 24,25-(OH)D, VDBP and its isoforms, and albumin. Analytical performances were assessed. Korean (n = 229), Arab (n = 98), White (n = 99) and Black American (n = 99) samples were analyzed. Bioavailable vitamin D and VMR were calculated. All target molecules were clearly separated and accurately quantified by LC-MS/MS. Analytical performances, including imprecision, accuracy, ion suppression, limit of quantification, linearity, and comparison with existing methods were within acceptable levels. The allele frequencies of VDBP isoforms in various races resulted similar to previously known values. The levels of bioavailable vitamin D were highest in White Americans and lowest in Black Americans. We have successfully developed a multiplex LC-MS/MS-based assay method that can simultaneously perform the measurement of all parameters needed to calculate bioavailable vitamin D and VMR. Our devised method was robust and reliable in terms of analytical performances and could be applied to routine clinical samples in the future to more accurately assess vitamin D status.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105796DOI Listing
February 2021

Evaluation of analytical performance of Alinity i system on 31 measurands.

Pract Lab Med 2020 Nov 20;22:e00185. Epub 2020 Oct 20.

Department of Laboratory Medicine, Seoul National University Hospital, Seoul, South Korea.

Introduction: Accurate, precise and reliable laboratory test results play a critical role in medical decision making. To satisfy the increasing needs in clinical laboratory tests, the analyzers have been advanced. In this study, authors aimed to evaluate the analytical performance of the Alinity i system (Abbott Laboratories, IL, USA) for diverse analytes measured by using immunoassay principle.

Materials And Methods: Analytical performance of recently launched Alinity i system has been evaluated for 31 assays in aspects of precision, linearity and analytical measurement range, correlation with the Architect i2000sr system (Abbott Laboratories), carry-over, and reference interval validation in accordance with CLSI guidelines.

Results: The within-laboratory CVs of the analytes tested in the study ranged between 1.00 and 7.84%, which met vendor claimed value in precision. In linearity test, most assays satisfied acceptable linearity criteria, best-fit first order regression or polynomial regression with nonlinearity smaller than ±10%, compared with linear regression. The recovery of each analyte distributed from 90.1 to 109.7%. The coefficient of determination (R) for each test was larger than 0.95 except for folate when compared to the results obtained from existing routine analyzer and statistically or clinically equivalent. The carry-over rates were acceptable, and reference intervals were validated.

Conclusion: Through this study, acceptable analytical performance of novel Alinity i system has been verified. It is expected to readily replace existing instrument and to be an option for laboratories considering introduction of automated immunoassay analyzer.
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http://dx.doi.org/10.1016/j.plabm.2020.e00185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652776PMC
November 2020

Schemes and Performance Evaluation Criteria of Korean Association of External Quality Assessment (KEQAS) for Improving Laboratory Testing.

Ann Lab Med 2021 Mar;41(2):230-239

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

External quality assessment (EQA) is important for evaluating clinical laboratories and enhancing their testing quality. EQA schemes are variable; thus, it is crucial that the EQA organizers share their experiences to continuously improve the EQA scheme. The Korean Association of External Quality Assessment Service (KEQAS) has been the leading, authorized EQA institute for the standardization and quality management of laboratory testing in Korean medical institutions since 1976. The EQA scheme underwent a major change in 2016, and the number of EQA programs increased significantly since then. The key changes implemented in EQA scheme include a fully computerized assessment to accelerate feedback and unification of the testing and reporting methods. We provide an overview of the EQA schemes and performance evaluation criteria of the KEQAS and suggest directions for achieving the global harmonization of EQA.
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http://dx.doi.org/10.3343/alm.2021.41.2.230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591290PMC
March 2021

High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence.

PLoS One 2020 26;15(8):e0238079. Epub 2020 Aug 26.

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Sitosterolemia is an inherited lipid disorder which presents with elevated serum sitosterol and can result in an increased risk of premature cardiovascular disease. However, sitosterol cannot be accurately measured by routine diagnostic assays, meaning that sitosterolemia diagnosis can often be difficult, especially with many clinical features overlapping with familial hypercholesterolemia. With such complications resulting in increasing reports of misdiagnosis, the prevalence of sitosterolemia is predicted to be much higher than previously reported.

Methods: Gas chromatography-mass spectrometry was utilized to measure sitosterol levels of normocholesterolemic and hypercholesterolemic children. Subsequently, an epidemiologically determined cutoff level of sitosterol was calculated and applied to estimate the prevalence of children with increased sitosterol and identify potential sitosterolemia patients. Massively parallel sequencing was used to confirm the diagnosis in suspected patients.

Results: Samples from 109 normocholesterolemic and 220 hypercholesterolemic were tested for phytosterols. Sitosterol and campesterol levels were significantly increased in hypercholesterolemic children (mean 22.0±45.9 μmol/L for sitosterol and 26.0±32.8 μmol/L for campesterol) compared to normocholesterolemic children (mean 12.1±4.9 μmol/L for sistosterol and 14.8±6.7 μmol/L for campesterol). Via application of a cutoff of 35.9 μmol/L, the prevalence rates for increased and overtly increased sitosterol in hypercholesterolemic children were 6.4% and 1.4% respectively. Furthermore, 3 suspected sitosterolemia patients were identified, with 2 patients receiving molecular confirmation for sitosterolemia diagnosis.

Conclusions: Our findings reaffirm that the prevalence of sitosterolemia is probably much higher than previously reported, which also indicates the significant risk of misdiagnosis of sitosterolemia with familial hypercholesterolemia. Special lipid testing including sitosterol, especially in children with uncontrolled hypercholesterolemia, is recommended in children in order to identify potential sitosterolemia patients that would otherwise be neglected.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238079PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449458PMC
October 2020

Changes in Adrenal Androgens and Steroidogenic Enzyme Activities From Ages 2, 4, to 6 Years: A Prospective Cohort Study.

J Clin Endocrinol Metab 2020 10;105(10)

Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.

Context: The levels of adrenal androgens are increased through the action of steroidogenic enzymes with morphological changes in the adrenal zona reticularis.

Objective: We investigated longitudinal changes in androgen levels and steroidogenic enzyme activities during early childhood.

Design And Participants: From a prospective children's cohort, the Environment and Development of Children cohort, 114 boys and 86 girls with available blood samples from ages 2, 4, and 6 years were included.

Outcome Measurements: Serum concentrations of adrenal androgens using liquid chromatography-tandem mass spectrometry and steroidogenic enzyme activity calculated by the precursor/product ratio.

Results: During ages 2 to 4 years, 17,20-lyase and dehydroepiandrosterone (DHEA) sulfotransferase activities increased (P < 0.01 for both in boys). During ages 4 to 6 years, 17,20-lyase activity persistently increased, but 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD activities decreased (P < 0.01 for all). Serum DHEA sulfate (DHEA-S) levels persistently increased from 2, 4, to 6 years, and DHEA, 17-hydroxyprogesterone, and androstenedione levels increased during ages 4 to 6 years (P < 0.01 for all). Serum DHEA-S levels during early childhood were associated with body mass index z-scores (P = 0.001 in only boys).

Conclusion: This study supports in vivo human evidence of increased 17,20-lyase and DHEA sulfotransferase activities and decreased 3β-HSD activity during early childhood.
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http://dx.doi.org/10.1210/clinem/dgaa498DOI Listing
October 2020

Nationwide External Quality Assessment of SARS-CoV-2 Molecular Testing, South Korea.

Emerg Infect Dis 2020 10 29;26(10):2353-2360. Epub 2020 Jul 29.

External quality assessment (EQA) is essential for ensuring reliable test results, especially when laboratories are using assays authorized for emergency use for newly emerging pathogens. We developed an EQA panel to assess the quality of real-time reverse transcription PCR assays being used in South Korea to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the participation of 23 public health organization laboratories and 95 nongovernmental laboratories involved in SARS-CoV-2 testing, we conducted qualitative and semiquantitative performance assessments by using pooled respiratory samples containing different viral loads of SARS-CoV-2 or human coronavirus OC43. A total of 110 (93.2%) laboratories reported correct results for all qualitative tests; 29 (24.6%) laboratories had >1 outliers according to cycle threshold values. Our EQA panel identified the potential weaknesses of currently available commercial reagent kits. The methodology we used can provide practical experience for those planning to conduct evaluations for testing of SARS-CoV-2 and other emerging pathogens in the future.
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http://dx.doi.org/10.3201/eid2610.202551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510727PMC
October 2020

High-Performance Atomically-Thin Room-Temperature NO Sensor.

Nano Lett 2020 08 24;20(8):6120-6127. Epub 2020 Jul 24.

Department of Physics, University of California at Berkeley, Berkeley, California 94720, United States.

The development of room-temperature sensing devices for detecting small concentrations of molecular species is imperative for a wide range of low-power sensor applications. We demonstrate a room-temperature, highly sensitive, selective, stable, and reversible chemical sensor based on a monolayer of the transition-metal dichalcogenide ReNbS. The sensing device exhibits a thickness-dependent carrier type, and upon exposure to NO molecules, its electrical resistance considerably increases or decreases depending on the layer number. The sensor is selective to NO with only minimal response to other gases such as NH, CHO, and CO. In the presence of humidity, not only are the sensing properties not deteriorated but also the monolayer sensor shows complete reversibility with fast recovery at room temperature. We present a theoretical analysis of the sensing platform and identify the atomically sensitive transduction mechanism.
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http://dx.doi.org/10.1021/acs.nanolett.0c02221DOI Listing
August 2020

Late Diagnosis of Wilson Disease, Initially Presenting as Cerebellar Atrophy Mimicking Spinocerebellar Ataxia, by Multigene Panel Testing.

Ann Lab Med 2020 11 17;40(6):500-503. Epub 2020 Jun 17.

Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2020.40.6.500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295955PMC
November 2020

Development and Validation of a Novel Warfarin Dosing Algorithm for Korean Patients With 1173C.

Ann Lab Med 2020 May;40(3):216-223

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in 1173C carriers. We aimed to develop and validate a new warfarin dosing algorithm for Korean patients with 1173C.

Methods: A total of 109 patients carrying 1173CT (N=105) or 1173CC (N=4) were included in this study. Multiple regression analysis was performed to deduce a new dosing algorithm. Following literature searches for genotype-guided warfarin dosing algorithms, 21 algorithms were selected and evaluated using the correlation coefficient (ρ) of actual dose and estimated dose, mean error, and root mean square error.

Results: The developed algorithm is as follows: maintenance dose (mg/week)=exp [3.223-0.009×(age)+0.577×(body surface area [BSA])+0.178×(sex)-0.481×( genotype)+0.227×( genotype)]. Integrated variables explained 44% of the variance in the maintenance dose. The predicted and actual doses showed moderate correlation (ρ=0.641) with the best performance with a mean error of -1.30 mg/week. The proportion of underestimated groups was 17%, which was lower than with the other algorithms.

Conclusions: This is the first study to develop and validate a warfarin dosing algorithm based on data from 1173C carriers; it showed superior predictive performance compared with previously published algorithms.
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http://dx.doi.org/10.3343/alm.2020.40.3.216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933054PMC
May 2020

Evaluation of Cobas 8000 Analyzer Series Module e801 Analytical Performance.

Ann Clin Lab Sci 2019 May;49(3):372-379

Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Background: Immunoassays are important tests that provide essential information for patient care. The e801, a module of the recently released Cobas 8000 series (Roche Diagnostics, Mannheim, Germany), is an automated immunoassay system based on streptavidin-biotin interactions. In this study, we evaluated the analytical performance of the e801.

Methods: We evaluated the precision, linearity, assay comparison, and reference range validation of 16 analytes (AFP, CA19-9, CA125, CEA, CYFRA, ferritin, NSE, PSA, Vitamin D, E2, fT4, TSH, FSH, insulin, NT-proBNP, and T) according to the guidelines of the Clinical Laboratory Standards Institute.

Results: In precision evaluations, the coefficients of variation were less than each allowable total error for all analytes. Linearity was observed for all analytes over the entire tested analytical range (r≥0.99). Performance comparisons revealed that the two systems are comparable, with correlation coefficients (r)>0.975 for all analytes. The reference range validation was also within the allowable criteria.

Conclusions: In this study, the Cobas 8000 e801 analyzer demonstrated acceptable performance with respect to precision, linearity, reference range validation, and correlation. Therefore, the e801 analyzer is expected to be useful for routine immunoassays in clinical laboratories, although education and awareness about biotin interference is necessary for successful implementation in clinical practice.
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May 2019

Experience with therapeutic drug monitoring of three antifungal agents using an LC-MS/MS method in routine clinical practice.

Clin Biochem 2019 Aug 5;70:14-17. Epub 2019 Jun 5.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Seoul, Republic of Korea. Electronic address:

Therapeutic drug monitoring (TDM) of voriconazole, itraconazole, and posaconazole is a useful tool for treatment of fungal infections. We validated a simple and reliable LC-MS/MS method using simple protein precipitation for simultaneous determination of voriconazole, itraconazole, and posaconazole. The linearity, accuracy, precision, carryover, and matrix effects were validated. Total sample preparation time was <30 min per batch, and analytical run time was 3.8 min per sample. We also presented clinical experience of TDM at 1183 serum concentrations over one year using this validated assay method. About 77%, 85%, and 96% of measured voriconazole, itraconazole, and posaconazole concentrations were within the therapeutic range, respectively. The number of respective measurements per patient was 1-63, 1-8, and 1-4 for voriconazole, itraconazole, and posaconazole. All three antifungal agents showed large intra-individual variability (2 to 181% CV) and drug-drug interaction with proton pump inhibitors or rifampin. In conclusion, we developed and validated a simple and fast method that was successfully applied in a routine clinical setting.
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http://dx.doi.org/10.1016/j.clinbiochem.2019.06.003DOI Listing
August 2019

Performance of ACE-Reaction on 26 Organic Reactions for Fully Automated Reaction Network Construction and Microkinetic Analysis.

J Phys Chem A 2019 Jun 22;123(22):4796-4805. Epub 2019 May 22.

Department of Chemistry , KAIST , 291 Daehak-ro , Yuseong-gu, Daejeon 34141 , Republic of Korea.

Accurate analysis of complex chemical reaction networks is necessary for reliable prediction of reaction mechanism. Though quantum chemical methods provide a desirable accuracy, large computational costs are unavoidable as considering numerous reaction pathways on the networks. We proposed a graph-theoretic approach combined with chemical heuristics (named ACE-Reaction) in previous work [ Chem. Sci. 2018 , 9 , 825 ], which automatically and rapidly finds out the most essential part of reaction networks just from reactants and products, and here we extended it by incorporating a stochastic approach for microkinetic modeling. To show its performance and broad applicability, we applied it to 26 organic reactions, which include 16 common functional groups. As a result, we could demonstrate that ACE-Reaction successfully found the accepted mechanism of all reactions, most within a few hours on a single workstation, and additional microkinetic modeling automatically discovered new competitive paths as well as a major path.
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http://dx.doi.org/10.1021/acs.jpca.9b02161DOI Listing
June 2019

Use of Liquid Chromatography-Tandem Mass Spectrometry for Clinical Testing in Korean Laboratories: a Questionnaire Survey.

Ann Lab Med 2019 Sep;39(5):447-453

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) has substantially increased in clinical laboratories worldwide. To assess the status of clinical LC-MS/MS testing in Korean laboratories, a questionnaire survey was performed by the Clinical Mass Spectrometry Research Committee of the Korean Society of Clinical Chemistry.

Methods: The questionnaire was distributed to 19 clinical laboratories performing clinical LC-MS/MS from April to May 2018. It asked about general characteristics of the laboratory and commonly utilized clinical LC-MS/MS tests: newborn screening, tacrolimus test, vitamin D test, and plasma metanephrine test. Frequency analysis and other statistical analyses were performed.

Results: A total of 17 laboratories responded. The median number of LC-MS/MS instruments, laboratory medicine physicians, and technicians in each laboratory was three, one, and two, respectively. Nine laboratory directors had >10 years of experience with clinical LC-MS/MS. For each LC-MS/MS test, at least two concentrations of QC materials were measured every 24 hours during clinical testing, and all laboratories used QC acceptability criteria based on their established QC means and SDs. All laboratories participated in an external quality assessment program. However, there was inter-laboratory variability in sample preparation methods, instruments, reagents, internal standards, and calibrators.

Conclusions: LC-MS/MS has been successfully introduced in Korean clinical laboratories and is used within a quality framework. Further efforts for harmonization on a nationwide basis could facilitate the widespread use of LC-MS/MS.
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http://dx.doi.org/10.3343/alm.2019.39.5.447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502944PMC
September 2019

Measurement of serum steroid profiles by HPLC-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Jun 3;1117:1-9. Epub 2019 Apr 3.

Department of Laboratory Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Accurate investigations of adrenal hormone levels play a vital role in pediatric endocrinology for the detection of steroid-related disorders. In this study, we developed and validated a simultaneous assay for eight serum steroids, i.e., DHEA, androstenedione, testosterone, progesterone, 17‑hydroxyprogesterone, DHEA‑sulfate, pregnenolone‑sulfate and cholesterol-sulfate, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Serum samples were prepared by liquid-liquid extraction with methyl t‑butyl ether. Quantitation by LC-MS/MS was performed in multiple reaction monitoring mode with an electrospray ionization source. The run time was 10 min. Analytical performance was evaluated, including imprecision, linearity, ion suppression, carry over and detection capabilities. Serum specimens from 59 children and 120 adults were analyzed to compare the distribution of steroid levels between the groups. All hormones were effectively extracted and separated using our method. The method was essentially free from potential interference and ion suppression. Within-run and between-run imprecision values were <20%. The lower limits of quantification varied from 0.025 to 10 ng/mL. The results were generally good and correlated with those obtained using immunoassay techniques. We developed the HPLC-MS/MS method for the simultaneous measurement of free and sulfated steroid hormones. The performance of the developed method was generally acceptable. Thus, this method may provide a novel approach to steroid profiling in children of age before adrenarche.
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http://dx.doi.org/10.1016/j.jchromb.2019.04.001DOI Listing
June 2019

Recent progress in laboratory diagnosis of thalassemia and hemoglobinopathy: a study by the Korean Red Blood Cell Disorder Working Party of the Korean Society of Hematology.

Blood Res 2019 Mar 21;54(1):17-22. Epub 2019 Mar 21.

Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea.

Genetic hemoglobin disorders are caused by mutations and/or deletions in the α-globin or β-globin genes. Thalassemia is caused by quantitative defects and hemoglobinopathies by structural defect of hemoglobin. The incidence of thalassemia and hemoglobinopathy is increased in Korea with rapid influx of people from endemic areas. Thus, the awareness of the disease is needed. α-thalassemias are caused by deletions in α-globin gene, while β-thalassemias are associated with decreased synthesis of β-globin due to β-globin gene mutations. Hemoglobinopathies involve structural defects in hemoglobin due to altered amino acid sequence in the α- or β-globin chains. When the patient is suspected with thalassemia/hemoglobinopathy from abnormal complete blood count findings and/or family history, the next step is detecting hemoglobin abnormality using electrophoresis methods including high performance liquid chromatography and mass spectrometry. The development of novel molecular genetic technologies, such as massively parallel sequencing, facilitates a more precise molecular diagnosis of thalassemia/hemoglobinopathy. Moreover, prenatal diagnosis using genetic testing enables the prevention of thalassemia birth and pregnancy complications. We aimed to review the spectrum and classification of thalassemia/hemoglobinopathy diseases and the diagnostic strategies including screening tests, molecular genetic tests, and prenatal diagnosis.
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http://dx.doi.org/10.5045/br.2019.54.1.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439293PMC
March 2019

Therapeutic drug monitoring of teicoplanin using an LC-MS/MS method: Analysis of 421 measurements in a naturalistic clinical setting.

J Pharm Biomed Anal 2019 Apr 4;167:161-165. Epub 2019 Feb 4.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Seoul, Republic of Korea. Electronic address:

Teicoplanin is a glycopeptide antibiotic used for treatment of severe Gram-positive bacterial infection. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of teicoplanin and to review our clinical experience. We established an LC-MS/MS method to analyze serum concentration of teicoplanin using simple protein precipitation with a 5 min run time for each sample. The linearity, lower limit of quantitation, detection accuracy, precision, carryover, matrix effect, and extraction recovery were evaluated. From September 2014 to June 2017, a total of 421 serum teicoplanin concentrations was measured in 223 patients. We collected demographic and clinical data, medication history, and laboratory findings through retrospective review of medical records. The LC-MS/MS method was linear for serum teicoplanin concentrations in the range of 12.0-89.0 μg/mL. The intra- and inter-assay precisions were below CV 7.5%. The accuracy was less than ±10% bias. The lower limit of quantification was 0.2 μg/mL. The extraction recovery ranged from 88.8% to 96.6%. Of 421 measurements, 87 (20.7%) were subtherapeutic (< 10 μg/mL), and four (0.9%) were above the toxic threshold (≥ 60 μg/mL). Serum teicoplanin concentration was measured once in 140 patients (63%), and multiple measurements were completed for the others (83 patients, 37%). Intra-patient variability in teicoplanin concentration was found (CV 33%, range 2-94%). Our simple and rapid LC-MS/MS method was successfully applied in TDM of teicoplanin in clinical practice. Such TDM of teicoplanin may be useful for individualized dose adjustment.
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http://dx.doi.org/10.1016/j.jpba.2019.02.001DOI Listing
April 2019

Accurate and Rapid Measurement of Glycated Hemoglobin Using HLC-723 G11 Variant Mode.

Ann Lab Med 2019 05;39(3):237-244

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Type II diabetes mellitus causes many complications, and its prevalence continues to increase in Korea. Accurate measurement of glycated Hb (HbA1c) is important because of its usefulness in diagnosis, follow-up, and prediction of prognosis. We tested the analytical performance of the HLC-723 G11 Variant Mode (G11vr; Tosoh Bioscience, Inc., Tokyo, Japan), recently introduced to Korea, in detecting HbA1c.

Methods: We evaluated precision, linearity, carry-over, and turnaround time. Using 208 samples, including 108 flagged samples, we compared HbA1c concentrations from four analyzers through correlation analysis: G11vr, HLC-723 G8 Variant Mode (G8vr, Tosoh Bioscience), HLC-723 G11 Standard Mode (G11st, Tosoh Bioscience), and HLC-723 G8 Standard Mode (G8st, Tosoh Bioscience). We used HPLC mass spectrometry (MS) and capillary electrophoresis (CE) to confirm the HbA1c concentrations of 15 additional known Hb variant samples.

Results: Repeatability (% CV) in measuring low- and high-concentration controls was 0.57% and 0.35%, respectively; within-laboratory precision was 0.86% and 0.69%, respectively. In a linearity test, the coefficient of determination was 0.9999 (measurement range: 3.64% to 18.59%) for HbA1c. The correlations between G11vr and other analyzers were weaker for flagged samples than for non-flagged samples. The carry-over effect was less than 0.4%. Turnaround time for a single sample was lower in G11vr (one minute) than in G8vr (1.6 minutes). For 15 samples with Hb variants, G11vr HbA1c results were more similar than those of other analyzers to HPLC-MS and CE results.

Conclusions: G11vr showed adequate performance and rapid turnaround time in measuring HbA1c.
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http://dx.doi.org/10.3343/alm.2019.39.3.237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340843PMC
May 2019

Quantification of Thiopurine Nucleotides in Erythrocytes and Clinical Application to Pediatric Acute Lymphoblastic Leukemia.

Ther Drug Monit 2019 02;41(1):75-85

Department of Laboratory Medicine, Seoul National University College of Medicine.

Background: Concentrations of 6-thioguanine (6TG) nucleotides and 6-methylmercaptopurine (6MMP) nucleotides in RBCs were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay was validated for clinical use and was applied to blood samples from patients taking mercaptopurine (6MP).

Methods: RBCs were hemolyzed and deproteinized using perchloric acid, followed by heating for the hydrolysis of nucleotides, and the resultant base was measured using LC-MS/MS. Precision, recovery, linearity, matrix effect, and limit of quantification was validated for clinical application. Our results were compared with another institution's established LC-MS/MS assay. We measured the concentrations of 6TG and 6MMP in RBCs of pediatric patients with acute lymphoblastic leukemia (ALL), and the clinical impact of those metabolites was investigated.

Results: The imprecision coefficient of variations of 6TG and 6MMP were 5.7%-8.1%, and the bias was within 5%. Lower limits of quantification were set at 54 ng/mL for 6TG and 1036 ng/mL for 6MMP. Correlation coefficients for 6TG and 6MMP were 0.997 and 1.0 in a comparison study. For clinical proof-of-concept, 74 blood samples were collected from 37 pediatric ALL patients receiving maintenance therapy. Concentration of 6TG ranged from 16.1 to 880 pmol/8 × 10 RBCs and that of 6MMP from 55 to 20,937 pmol/8 × 10 RBCs. The 6MP metabolites were not correlated with WBC or absolute neutrophil count. On the other hand, the higher 6MMP level was associated with elevated alanine aminotransferase and aspartate aminotransferase.

Conclusions: In this study, an assay for the quantification of 6TG and 6MMP in RBCs was established and applied to pediatric ALL patients. Interindividual variability in 6MP metabolite concentrations was considerable and associated with elevation of liver enzymes, which may be useful in the clinical monitoring of 6MP maintenance therapy in pediatric ALL patients.
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http://dx.doi.org/10.1097/FTD.0000000000000575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358190PMC
February 2019

Significant therapeutic effects of adult human multipotent neural cells on spinal cord injury.

Stem Cell Res 2018 08 19;31:71-78. Epub 2018 Jul 19.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, South Korea; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, South Korea; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, South Korea. Electronic address:

Neural stem cells are emerging as a regenerative therapy for spinal cord injury (SCI), since they differentiate into functional neural cells and secrete beneficial paracrine factors into the damaged microenvironment. Previously, we successfully isolated and cultured adult human multipotent neural cells (ahMNCs) from the temporal lobes of epileptic patients. In this study, we investigated the therapeutic efficacy and treatment mechanism of ahMNCs for SCI using rodent models. When 1 × 10 ahMNCs were transplanted into injured spinal cords at 7 days after contusion, the injection group showed significantly better functional recovery than the control group (media injection after contusion), which was determined by the Basso, Beattie and Bresnahan (BBB) score. Although transplanted ahMNCs disappeared continuously, remained cells expressed differentiated neural cell markers (Tuj1) or astrocyte marker (GFAP) in the injured spinal cords. Moreover, the number of CD31-positive microvessels significantly increased in the injection group than that of the control group. The paracrine pro-angiogenic activities of ahMNCs were confirmed by in vitro tube formation assay and in vivo Matrigel plug assay. Together, these results indicate that ahMNCs have significant therapeutic efficacy in SCI via replacement of damaged neural cells and pro-angiogenic effects on the microenvironment of SCI.
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http://dx.doi.org/10.1016/j.scr.2018.07.006DOI Listing
August 2018

The Role of the Signal-to-Cutoff Ratio in Automated Anti-HCV Chemiluminescent Immunoassays by Referring to the Nucleic Acid Amplification Test and the Recombinant Immunoblot Assay.

Ann Lab Med 2018 Sep;38(5):466-472

Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: Following discontinuation of the recombinant immunoblot assay (RIBA), the only available supplementary test for the detection of hepatitis C virus (HCV) is the nucleic acid amplification test (NAAT). However, the NAAT does not adequately detect past HCV. Consequently, it is hard to distinguish between past HCV infection and biological false positivity with an anti-HCV result alone. We assessed the diagnostic performance of two immunoassays: the ARCHITECT anti-HCV chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, Wiesbaden, Germany) and the Access HCV Ab PLUS chemiluminescent immunoassay (CIA; Bio-Rad, Marnes-la-Coquette, France). We also explored an optimized algorithm to determine the anti-HCV results.

Methods: We tested 126,919 patients and 44,556 individuals who underwent a medical checkup. RIBA and NAAT were conducted for samples that tested anti-HCV-positive using CMIA and CIA. We assessed the optimal signal-to-cutoff (S/CO) ratio in HCV-positive samples.

Results: In total, 1,035 blood samples tested anti-HCV-positive. Of these, RIBA was positive in 512, indeterminate in 160, and negative in 363 samples. One hundred sixty-five samples were NAAT-positive. Diagnostic sensitivity and positive predictive value (PPV) were 96.7% and 52.1%, respectively, for CMIA, and 94.7% and 72.3%, respectively, for CIA. The optimal S/CO ratio was 5.2 for CMIA and 2.6 for CIA at 95% PPV. In total, 286 samples tested positive in CMIA and 444 in CIA, while 443 samples tested positive in both assays.

Conclusions: It is hard to determine anti-HCV positivity based on the S/CO ratio alone. However, this study elucidated the role of the S/CO ratio by using the NAAT and RIBA.
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http://dx.doi.org/10.3343/alm.2018.38.5.466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973922PMC
September 2018

Evaluation of Stability of Thiopurine Metabolites Using a Validated LC-MS/MS Method.

Ann Lab Med 2018 May;38(3):255-260

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Measurement of thiopurine metabolites is helpful to monitor adverse effects and assess compliance in patients on thiopurine treatment. The purpose of this study was to develop and validate an analytical method for measurement of thiopurine metabolites, thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN), in RBCs. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of 6-TGN and 6-MMPN and evaluated the stability of the thiopurine metabolites in RBC and whole blood states without any preprocessing at various storage conditions. The linear range was 0.1-10 μmol/L and 0.5-100 μmol/L for 6-TGN and 6-MMPN, respectively. The mean extraction recovery at the two concentrations was 71.0% and 75.0% for 6-TGN, and 102.2% and 96.4% for 6-MMPN. Thiopurine metabolites in preprocessed RBC samples were stable at 25°C and 4°C after storage for 4 hours and at -70°C for up to 6 months. However, 6-TGN decreased by 30% compared with the initial concentration when stored at -20°C for 180 days. In whole blood states, 6-TGN decreased by about 20% at four days after storage at 4°C. We validated a reliable LC-MS/MS method and recommend that the patient's whole blood sample be preprocessed as soon as possible.
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http://dx.doi.org/10.3343/alm.2018.38.3.255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820071PMC
May 2018

Short-channel field-effect transistors with 9-atom and 13-atom wide graphene nanoribbons.

Nat Commun 2017 09 21;8(1):633. Epub 2017 Sep 21.

Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, 94720, USA.

Bottom-up synthesized graphene nanoribbons and graphene nanoribbon heterostructures have promising electronic properties for high-performance field-effect transistors and ultra-low power devices such as tunneling field-effect transistors. However, the short length and wide band gap of these graphene nanoribbons have prevented the fabrication of devices with the desired performance and switching behavior. Here, by fabricating short channel (L  ~ 20 nm) devices with a thin, high-κ gate dielectric and a 9-atom wide (0.95 nm) armchair graphene nanoribbon as the channel material, we demonstrate field-effect transistors with high on-current (I  > 1 μA at V  = -1 V) and high I /I  ~ 10 at room temperature. We find that the performance of these devices is limited by tunneling through the Schottky barrier at the contacts and we observe an increase in the transparency of the barrier by increasing the gate field near the contacts. Our results thus demonstrate successful fabrication of high-performance short-channel field-effect transistors with bottom-up synthesized armchair graphene nanoribbons.Graphene nanoribbons show promise for high-performance field-effect transistors, however they often suffer from short lengths and wide band gaps. Here, the authors use a bottom-up synthesis approach to fabricate 9- and 13-atom wide ribbons, enabling short-channel transistors with 10 on-off current ratio.
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http://dx.doi.org/10.1038/s41467-017-00734-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608806PMC
September 2017
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