571 results on '"Lee TG"'
Search Results
2. Pure dysarthria due to small cortical stroke.
- Author
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Kim JS, Kwon SU, Lee TG, Kim, Jong S, Kwon, Sun U, and Lee, Te G
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- 2003
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3. The temporal dynamics of visual attention.
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Zhang H, Sellers J, Lee TG, and Jonides J
- Abstract
Researchers have long debated how humans select relevant objects amid physically salient distractions. An increasingly popular view holds that the key to avoiding distractions lies in suppressing the attentional priority of a salient distractor. However, the precise mechanisms of distractor suppression remain elusive. Because the computation of attentional priority is a time-dependent process, distractor suppression must be understood within these temporal dynamics. In four experiments, we tracked the temporal dynamics of visual attention using a novel forced-response method, by which participants were required to express their latent attentional priority at varying processing times via saccades. We show that attention could be biased either toward or away from a salient distractor depending on the timing of observation, with these temporal dynamics varying substantially across experiments. These dynamics were explained by a computational model assuming the distractor and target priority signals arrive asynchronously in time and with different influences on saccadic behavior. The model suggests that distractor signal suppression can be achieved via a "slow" mechanism in which the distractor priority signal dictates saccadic behavior until a late-arriving priority signal overrides it, or a "fast" mechanism which directly suppresses the distractor priority signal's behavioral expression. The two mechanisms are temporally dissociable and can work collaboratively, resulting in time-dependent patterns of attentional allocation. The current work underscores the importance of considering the temporal dynamics of visual attention and provides a computational architecture for understanding the mechanisms of distractor suppression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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- 2024
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4. Repeated spaced cortical paired associative stimulation promotes additive plasticity in the human parietal-motor circuit.
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Goldenkoff ER, Deluisi JA, Lee TG, Hampstead BM, Taylor SF, Polk TA, and Vesia M
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- Humans, Male, Female, Adult, Young Adult, Motor Cortex physiology, Transcranial Magnetic Stimulation methods, Evoked Potentials, Motor physiology, Parietal Lobe physiology, Neuronal Plasticity physiology
- Abstract
Objective: Repeated spaced sessions of repetitive transcranial magnetic stimulation (TMS) to the human primary motor cortex can lead to dose-dependent increases in motor cortical excitability. However, this has yet to be demonstrated in a defined cortical circuit. We aimed to examine the effects of repeated spaced cortical paired associative stimulation (cPAS) on excitability in the motor cortex., Methods: cPAS was delivered to the primary motor cortex (M1) and posterior parietal cortex (PPC) with two coils. In the multi-dose condition, three sessions of cPAS were delivered 50-min apart. The single-dose condition had one session of cPAS, followed by two sessions of a control cPAS protocol. Motor-evoked potentials were evaluated before and up to 40 min after each cPAS session as a measure of cortical excitability., Results: Compared to a single dose of cPAS, motor cortical excitability significantly increased after multi-dose cPAS. Increasing the number of cPAS sessions resulted in a cumulative, dose-dependent effect on excitability in the motor cortex, with each successive cPAS session leading to notable increases in potentiation., Conclusion: Repeated spaced cPAS sessions summate to increase motor cortical excitability induced by single cPAS., Significance: Repeated spaced cPAS could potentially restore abilities lost due to disorders like stroke., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
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- 2024
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5. Enhancing Protein Content in Wild-Type Saccharomyces cerevisiae via Random Mutagenesis and Optimized Fermentation Conditions.
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Do SH, Lee TG, and Kim SK
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- Molasses, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Mutation, Zea mays microbiology, Zea mays metabolism, Batch Cell Culture Techniques, Dietary Proteins, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Fermentation, Mutagenesis
- Abstract
Single-cell protein (SCP) derived from microorganisms is widely recognized as a viable alternative protein source for the future. Nevertheless, the commercialization of yeast-based SCP is hampered by its relatively low protein content. Therefore, this study aimed to enhance the protein content of Saccharomyces cerevisiae via random mutagenesis. To achieve this, S. cerevisiae KCCM 51811, which exhibited the highest protein concentration among 20 edible S. cerevisiae strains, was selected as a chassis strain. Subsequently, a KCCM 51811 mutant library was constructed (through UV irradiation) and screened to isolate mutants exhibiting high protein content and/or concentration. Among the 174 mutant strains studied, the #126 mutant exhibited a remarkable 43% and 36% higher protein content and concentration, respectively, compared to the parental strain. Finally, the #126 mutant was cultured in a fed-batch system using molasses and corn-steep liquor, resulting in a protein concentration of 21.6 g/l in 100 h, which was 18% higher than that produced by the parental strain. These findings underscore the potential of our approach for the cost-effective production of food-grade SCP.
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- 2024
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6. Preparation of fragmented polyethylene nanoplastics using a focused ultrasonic system and assessment of their cytotoxic effects on human cells.
- Author
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Hwangbo S, Kim IY, Ko K, Park K, Hong J, Kang G, Wi JS, Kim J, and Lee TG
- Abstract
With the growing prevalence of plastic use, the environmental release of plastic waste is escalating, and fragmented nanoscale plastic particles are emerging as significant environmental threats. This study aimed to evaluate the cytotoxic effects of fragmented polyethylene nanoplastics (PE NPs) manufactured using a focused ultrasonic system. The ultrasonic irradiation process generated fragmented PE NPs with a geometric mean diameter of 85.14 ± 5.37 nm and a size range of 25-350 nm. To assess cytotoxicity, we conducted a series of tests on various human cell lines, including stomach, blood, colon, lung, skin, liver, and brain-derived cells. The testing involved MTS-based cell viability assays to evaluate direct impacts on cell viability, lactate dehydrogenase (LDH) leakage assays to measure membrane damage, and ELISA to quantify TNF-α release as an indicator of inflammation. Although PE-NPs did not immediately induce apoptosis, significant LDH leakage and elevated TNF-α levels were observed across all cell lines, indicating membrane damage and inflammatory responses. Additionally, flow cytometry and TEM analyses revealed the intracellular accumulation of PE-NPs, further supporting their cytotoxic potential. These results demonstrate that fragmented PE-NPs can disrupt cellular membranes and induce inflammatory responses through accumulation within cells. The findings suggest that these NPs pose potential hazards to cell viability and underscore the need for further research into their environmental and health impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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7. Impact of Rhg1 copy number variation on a soybean cyst nematode resistance transcriptional network.
- Author
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Chaiprom U, Miraeiz E, Lee TG, Drnevich J, and Hudson M
- Abstract
Soybean yield loss due to soybean cyst nematode (SCN) infestation has a negative impact on the U.S. economy. Most SCN-resistant soybeans carry a common resistance locus (Rhg1), conferred by copy number variation of a 31.2-kb segment at the Rhg1 locus. To identify the effects of Rhg1 copy number on the plant prior to SCN infection, we investigated genome-wide expression profiles in isogenic Fayette plants carrying different copy numbers at the Rhg1 locus (9-11 copies), that confer different levels of resistance to SCN. We found that even small differences in copy number lead to large changes in expression of downstream defense genes. The co-expression network constructed from differentially expressed genes (DEGs) outside the Rhg1 locus revealed complex effects of Rhg1 copy number on transcriptional regulation involving signal transduction and ethylene-mediated signaling pathways. Moreover, we report a variation in expression levels of phytoalexin biosynthesis-related genes that is correlated with copy number, and the activation of different NBS-LRR gene sets, indicating a broad effect of copy number on defense responses. Using qRT-PCR time series during SCN infection, we validated the SCN responses of DEGs detected in the copy number comparison and showed a stable upregulation of genes related to phytoalexin biosynthesis in resistant Fayette lines during the early stages of the incompatible interaction between soybeans and SCN, before syncytium formation. These results suggest additional genes that could enhance Rhg1-mediated SCN resistance., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
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- 2024
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8. Long-Term Culture of Human Pluripotent Stem Cells in Xeno-Free Condition Using Functional Polymer Films.
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Cho Y, Lee H, Jeong W, Jung KB, Lee SY, Park S, Yeun J, Kwon O, Son JG, Lee TG, Son MY, and Im SG
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- Humans, Human Embryonic Stem Cells cytology, Human Embryonic Stem Cells metabolism, Laminin chemistry, Laminin pharmacology, Cell Proliferation drug effects, Cell Adhesion drug effects, Proteoglycans chemistry, Proteoglycans pharmacology, Cell Line, Collagen chemistry, Cell Differentiation drug effects, Drug Combinations, Cell Culture Techniques methods, Polymers chemistry, Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism
- Abstract
Human pluripotent stem cells (hPSCs), encompassing human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold immense potential in regenerative medicine, offering new opportunities for personalized cell therapies. However, their clinical translation is hindered by the inevitable reliance on xenogeneic components in culture environments. This study addresses this challenge by engineering a fully synthetic, xeno-free culture substrate, whose surface composition is tailored systematically for xeno-free culture of hPSCs. A functional polymer surface, pGC2 (poly(glycidyl methacrylate-grafting-guanidine-co-carboxylic acrylate)), offers excellent cell-adhesive properties as well as non-cytotoxicity, enabling robust hESCs and hiPSCs growth while presenting cost-competitiveness and scalability over Matrigel. This investigation includes comprehensive evaluations of pGC2 across diverse experimental conditions, demonstrating its wide adaptability with various pluripotent stem cell lines, culture media, and substrates. Crucially, pGC2 supports long-term hESCs and hiPSCs expansion, up to ten passages without compromising their stemness and pluripotency. Notably, this study is the first to confirm an identical proteomic profile after ten passages of xeno-free cultivation of hiPSCs on a polymeric substrate compared to Matrigel. The innovative substrate bridges the gap between laboratory research and clinical translation, offering a new promising avenue for advancing stem cell-based therapies., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)
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- 2024
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9. ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases.
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Elbedwehy AM, Wu J, Na HK, Baek A, Jung H, Kwon IH, Lee SW, Kim JH, and Lee TG
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- Animals, Humans, Cattle, Cell Line, Porosity, Drug Delivery Systems, Drug Carriers chemistry, Mice, Polyethylene Glycols chemistry, Mice, Inbred C57BL, Apoptosis drug effects, Retinal Diseases drug therapy, Silicon Dioxide chemistry, Reactive Oxygen Species metabolism, Nanoparticles chemistry, Retinal Neovascularization drug therapy
- Abstract
Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to -25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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10. Effects of arginine intake during weight training on blood variables.
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Kim YC, Lee TG, and Kim JS
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This experiment studied the effect of arginine intake on blood pressure and blood variables during weight training in 20 men in their 20s. The resistance exercise program was performed 3 times a week at 60% of one repetition maximum for 8 weeks. The arginine intake group consumed 1,000 mg of arginine 2 tablets per day before weight training for 8 weeks. The placebo group was instructed to consume two of placebo with water, the same as the arginine intake group. After 8 weeks, the day after the end of the resistance exercise program, systolic pressure, diastolic pressure, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, muscle mass, and maximum muscle strength were measured. In changes in systolic blood pressure, the arginine intake group was 118.20±2.40 mmHg, showed a statistically significant decrease compared to the placebo group. Triglyceride in the arginine intake group was 112.62±2.40 mg/dL, showing a statistically significant decrease compared to the placebo group. Based on these results, arginine intake during resistance exercise is judged to have a positive effect on lowering blood pressure, and is also believed to reduce triglycerides, a blood lipid variable, so it is thought to function as a supplement during exercise., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 Korean Society of Exercise Rehabilitation.)
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- 2024
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11. First Trial of a Novel Caseous Lymphadenitis Inactivated Vaccine in South Korea: Experimental Evaluation across Various Animal Models.
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Park GS, Lee S, Jeong MA, Lee SY, Cho DG, Cho W, Kim SC, Kim HJ, Lee TG, Jeong CG, Kim WI, Oh Y, Cho HS, Seo BJ, and Kim C
- Abstract
Caseous lymphadenitis (CLA) is a chronic and subclinical bacterial disease of ruminants caused by Corynebacterium pseudotuberculosis ( C. pseudotuberculosis ) infection. Until 2014, there were no reports of CLA outbreaks in South Korea; however, the prevalence of CLA cases has steadily increased. In this study, we used recently obtained field isolates to develop the first inactivated CLA vaccine in South Korea and evaluated it in various animal models. The inactivated vaccine was evaluated for virulence and effectiveness. Mice were tested for virulence and immunization challenges, and guinea pigs and Korean Native Black Goats (KNBGs) evaluated various vaccine concentrations to determine the optimal dose and effectiveness. In the case of KNBGs, clinical symptoms were not observed after vaccination. In addition, CLA-specific IgG was detected at a significantly ( p < 0.05) high level and was maintained. In histopathological evaluations, inflammation was predominantly observed in the prefemoral lymph nodes in the non-vaccinated+CHAL group. The genetic diversity of C. pseudotuberculosis , which has become widespread in South Korea, is less than 0.5% our vaccine is expected to prevent infection by a wide range of strains effectively. In summary, our CLA vaccine can potentially prevent CLA and foster the growth of South Korea's domestic KNBG industry.
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- 2024
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12. Improving efficacy of repetitive transcranial magnetic stimulation for treatment of Parkinson disease gait disorders.
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Panda R, Deluisi JA, Lee TG, Davis S, Muñoz-Orozco I, Albin RL, and Vesia M
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Parkinson disease (PD) is a neurodegenerative disorder that causes motor and cognitive deficits, presenting complex challenges for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a type of neuromodulation that can produce plastic changes in neural activity. rTMS has been trialed as a therapy to treat motor and non-motor symptoms in persons with Parkinson disease (PwP), particularly treatment-refractory postural instability and gait difficulties such as Freezing of Gait (FoG), but clinical outcomes have been variable. We suggest improving rTMS neuromodulation therapy for balance and gait abnormalities in PwP by targeting brain regions in cognitive-motor control networks. rTMS studies in PwP often targeted motor targets such as the primary motor cortex (M1) or supplementary motor area (SMA), overlooking network interactions involved in posture-gait control disorders. We propose a shift in focus toward alternative stimulation targets in basal ganglia-cortex-cerebellum networks involved in posture-gait control, emphasizing the dorsolateral prefrontal cortex (dlPFC), cerebellum (CB), and posterior parietal cortex (PPC) as potential targets. rTMS might also be more effective if administered during behavioral tasks designed to activate posture-gait control networks during stimulation. Optimizing stimulation parameters such as dosage and frequency as used clinically for the treatment of depression may also be useful. A network-level perspective suggests new directions for exploring optimal rTMS targets and parameters to maximize neural plasticity to treat postural instabilities and gait difficulties in PwP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Panda, Deluisi, Lee, Davis, Muñoz-Orozco, Albin and Vesia.)
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- 2024
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13. Evidence for a Causal Dissociation of the McGurk Effect and Congruent Audiovisual Speech Perception via TMS to the Left pSTS.
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Ahn E, Majumdar A, Lee TG, and Brang D
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- Humans, Male, Female, Young Adult, Adult, Reaction Time physiology, Photic Stimulation, Acoustic Stimulation, Illusions physiology, Transcranial Magnetic Stimulation, Speech Perception physiology, Temporal Lobe physiology, Visual Perception physiology
- Abstract
Congruent visual speech improves speech perception accuracy, particularly in noisy environments. Conversely, mismatched visual speech can alter what is heard, leading to an illusory percept that differs from the auditory and visual components, known as the McGurk effect. While prior transcranial magnetic stimulation (TMS) and neuroimaging studies have identified the left posterior superior temporal sulcus (pSTS) as a causal region involved in the generation of the McGurk effect, it remains unclear whether this region is critical only for this illusion or also for the more general benefits of congruent visual speech (e.g., increased accuracy and faster reaction times). Indeed, recent correlative research suggests that the benefits of congruent visual speech and the McGurk effect rely on largely independent mechanisms. To better understand how these different features of audiovisual integration are causally generated by the left pSTS, we used single-pulse TMS to temporarily disrupt processing within this region while subjects were presented with either congruent or incongruent (McGurk) audiovisual combinations. Consistent with past research, we observed that TMS to the left pSTS reduced the strength of the McGurk effect. Importantly, however, left pSTS stimulation had no effect on the positive benefits of congruent audiovisual speech (increased accuracy and faster reaction times), demonstrating a causal dissociation between the two processes. Our results are consistent with models proposing that the pSTS is but one of multiple critical areas supporting audiovisual speech interactions. Moreover, these data add to a growing body of evidence suggesting that the McGurk effect is an imperfect surrogate measure for more general and ecologically valid audiovisual speech behaviors.
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- 2024
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14. Metabolic engineering of Caldicellulosiruptor bescii for hydrogen production.
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Cha M, Kim JK, Lee WH, Song H, Lee TG, Kim SK, and Kim SJ
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- Biomass, Hydrogen, Metabolic Engineering, Clostridiales
- Abstract
Hydrogen is an alternative fuel for transportation vehicles because it is clean, sustainable, and highly flammable. However, the production of hydrogen from lignocellulosic biomass by microorganisms presents challenges. This microbial process involves multiple complex steps, including thermal, chemical, and mechanical treatment of biomass to remove hemicellulose and lignin, as well as enzymatic hydrolysis to solubilize the plant cell walls. These steps not only incur costs but also result in the production of toxic hydrolysates, which inhibit microbial growth. A hyper-thermophilic bacterium of Caldicellulosiruptor bescii can produce hydrogen by decomposing and fermenting plant biomass without the need for conventional pretreatment. It is considered as a consolidated bioprocessing (CBP) microorganism. This review summarizes the basic scientific knowledge and hydrogen-producing capacity of C. bescii. Its genetic system and metabolic engineering strategies to improve hydrogen production are also discussed. KEY POINTS: • Hydrogen is an alternative and eco-friendly fuel. • Caldicellulosiruptor bescii produces hydrogen with a high yield in nature. • Metabolic engineering can make C. bescii to improve hydrogen production., (© 2024. The Author(s).)
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- 2024
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15. People are more error-prone after committing an error.
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Adkins TJ, Zhang H, and Lee TG
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- Humans, Male, Female, Adult, Young Adult, Psychomotor Performance physiology, Computer Simulation, Reaction Time physiology, Cognition physiology
- Abstract
Humans tend to slow down after making an error. A longstanding account of this post-error slowing is that people are simply more cautious. However, accuracy typically does not improve following an error, leading some researchers to suggest that an initial 'orienting' response may initially impair performance immediately following error. Unfortunately, characterizing the nature of this error-based impairment remains a challenge in standard tasks that use free response times. By exerting control over the timing of responses, we reveal the time course of stimulus-response processing. Participants are less accurate after an error even when given ample time to make a response. A computational model of response preparation rules out the possibility that errors lead to slower cognitive processing. Instead, we find that the efficacy of cognitive processing in producing an intended response is impaired following errors. Following an error, participants commit more slips of action that tend to be a repetition of the previous mistake. Rather than a strategic shift along a single speed-accuracy tradeoff function, post-error slowing observed in free response time tasks may be an adaptive response to impaired cognitive processing that reflects an altered relationship between the speed and accuracy of responses., (© 2024. The Author(s).)
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- 2024
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16. Role of Chalcogenides in Sensitive Therapeutic Drug Monitoring Using Laser Desorption and Ionization.
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Joh S, Yoo J, Lee SM, Lee E, Na HK, Son JG, Kim J, Jeong MS, Lee SG, and Lee TG
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- Humans, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Chalcogens chemistry, Drug Monitoring methods, Anticonvulsants chemistry
- Abstract
This study investigates the applicability of six transition metal dichalcogenides to efficient therapeutic drug monitoring of ten antiepileptic drugs using laser desorption/ionization-mass spectrometry. We found that molybdenum ditelluride and tungsten ditelluride are suitable for the sensitive quantification of therapeutic drugs. The contribution of tellurium to the enhanced efficiency of laser desorption ionization was validated through theoretical calculations utilizing an integrated model that incorporates transition-metal dichalcogenides and antiepileptic drugs. The results of our theoretical calculations suggest that the relatively low surface electron density for the tellurium-containing transition metal dichalcogenides induces stronger Coulombic interactions, which results in enhanced laser desorption and ionization efficiency. To demonstrate applicability, up to 120 patient samples were analyzed to determine drug concentrations, and the results were compared with those of immunoassay and liquid chromatography-tandem mass spectrometry. Agreements among these methods were statistically evaluated using the Passing-Bablok regression and Bland-Altman analysis. Furthermore, our method has been shown to be applicable to the simultaneous detection and multiplexed quantification of antiepileptic drugs.
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- 2024
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17. Genome sequence data of the contemporary fresh-market tomatoes.
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Kim J and Lee TG
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- High-Throughput Nucleotide Sequencing, Solanum lycopersicum genetics, Genome, Plant genetics, Whole Genome Sequencing
- Abstract
Objective: The fresh-market tomato (Solanum lycopersicum) is bred for direct human consumption. It is selected for specific traits to meet market demands and production systems, and unique genetic variations underlying fresh-market tomato yields have been recently identified. However, DNA sequence variant-trait associations are not yet fully examined even for major traits. To provide a rich genome sequence resource for various genetics and breeding goals for fresh-market tomato traits, we report whole genome sequence data of a pool of contemporary U.S. fresh-market tomatoes., Data Description: Eighty-one tomatoes were nominated by academic tomato breeding programs in the U.S. Of the 81 tomatoes, 68 were contemporary fresh-market tomatoes, whereas the remaining 13 were relevant fresh-market tomato breeding and germplasm accessions. Whole genome sequencing (WGS) of the 81 tomatoes was conducted using the Illumina next-generation sequencing technology. The polymerase chain reaction (PCR)-free, paired-end sequencing libraries were sequenced on an average depth per sequenced base of 24 × for each tomato. This data note enhances visibility and potential for use of the more diverse, freely accessible whole genome sequence data of contemporary fresh-market tomatoes., (© 2024. The Author(s).)
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- 2024
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18. Communicative competence of generative artificial intelligence in responding to patient queries about colorectal cancer surgery.
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Jo MH, Kim MJ, Oh HK, Choi MJ, Shin HR, Lee TG, Ahn HM, Kim DW, and Kang SB
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- Humans, Male, Female, Middle Aged, Surveys and Questionnaires, Colorectal Surgery, Colorectal Neoplasms surgery, Artificial Intelligence, Communication
- Abstract
Purpose: To examine the ability of generative artificial intelligence (GAI) to answer patients' questions regarding colorectal cancer (CRC)., Methods: Ten clinically relevant questions about CRC were selected from top-rated hospitals' websites and patient surveys and presented to three GAI tools (Chatbot Generative Pre-Trained Transformer [GPT-4], Google Bard, and CLOVA X). Their responses were compared with answers from the CRC information book. Response evaluation was performed by two groups, each consisting of five healthcare professionals (HCP) and patients. Each question was scored on a 1-5 Likert scale based on four evaluation criteria (maximum score, 20 points/question)., Results: In an analysis including only HCPs, the information book scored 11.8 ± 1.2, GPT-4 scored 13.5 ± 1.1, Google Bard scored 11.5 ± 0.7, and CLOVA X scored 12.2 ± 1.4 (P = 0.001). The score of GPT-4 was significantly higher than those of the information book (P = 0.020) and Google Bard (P = 0.001). In an analysis including only patients, the information book scored 14.1 ± 1.4, GPT-4 scored 15.2 ± 1.8, Google Bard scored 15.5 ± 1.8, and CLOVA X scored 14.4 ± 1.8, without significant differences (P = 0.234). When both groups of evaluators were included, the information book scored 13.0 ± 0.9, GPT-4 scored 14.4 ± 1.2, Google Bard scored 13.5 ± 1.0, and CLOVA X scored 13.3 ± 1.5 (P = 0.070)., Conclusion: The three GAIs demonstrated similar or better communicative competence than the information book regarding questions related to CRC surgery in Korean. If high-quality medical information provided by GAI is supervised properly by HCPs and published as an information book, it could be helpful for patients to obtain accurate information and make informed decisions., (© 2024. The Author(s).)
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- 2024
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19. Effect of prophylactic abdominal drainage on postoperative pain in laparoscopic hemicolectomy for colon cancer: a single-center observational study in Korea.
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Hwang SS, Oh HK, Shin HR, Lee TG, Choi MJ, Jo MH, Ahn HM, Park H, Sim HH, Ji E, Singhi AN, Kim DW, and Kang SB
- Abstract
Purpose: This study aimed to evaluate the effect of prophylactic abdominal drainage (AD) in laparoscopic hemicolectomy, focusing on assessing postoperative pain outcomes., Methods: Patients were categorized into two groups: those with and without AD (AD group vs. no-AD group). A numerical rating scale (NRS) was used to assess postoperative pain on each postoperative day (POD). Further, the inverse probability of treatment weighting (IPTW) method was used to reduce intergroup bias., Results: In total, 204 patients who underwent laparoscopic hemicolectomies by a single surgeon between June 2013 and September 2022 at a single institution were retrospectively reviewed. After adjusting for IPTW, NRS scores on POD 2 were significantly lower in the no-AD group (3.2 ± 0.8 vs. 3.4 ± 0.8, p = 0.043). Further examination of postoperative outcomes showed no statistically significant differences in complications between the AD (17.3%) and no-AD (12.4%) groups ( p = 0.170). The postoperative length of hospital stay was 7.3 ± 2.8 days in the AD group and 6.9 ± 3.0 days in the no-AD group, with no significant difference ( p = 0.298). Time to first flatus was 3.0 ± 0.9 days in the AD group and 2.7 ± 0.9 days in the no-AD group, with no significant difference ( p = 0.078). Regarding readmission within 1 month, there were four cases each in the AD (2.3%) and no-AD (1.7%) groups, with no significant difference ( p = 0.733)., Conclusion: Laparoscopic hemicolectomy without AD resulted in no significant differences in postoperative clinical outcomes, except for postoperative pain. This finding suggests that prophylactic AD may exacerbate postoperative pain.
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- 2024
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20. Cranial-first approach for laparoscopic extended right hemicolectomy.
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Kang KM, Oh HK, Ahn HM, Lee TG, Shin HR, Choi MJ, Kim DW, and Kang SB
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Complete mesocolic excision and central vascular ligation with D3 lymphadenectomy are important surgical principles for improving oncological outcomes in colon cancer. The cranial-first approach is a colonic mobilization-first approach to radical right hemicolectomy, which has several advantages, including early feasibility assessment, safe dissection from surrounding organs, preestablished inferior margin of lymph node dissection, and revelation of the tangible anatomy of the tributaries of the gastrocolic trunk. This video demonstrates the cranial-first approach to radical right hemicolectomy in a 66-year-old man with locally advanced cecal cancer.
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- 2024
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21. Comparative analysis of different surgical approaches for recurrent inguinal hernia: a single-center observational study.
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Choi MJ, Lee KS, Oh HK, Ahn SH, Ahn HM, Shin HR, Lee TG, Jo MH, Kim DW, and Kang SB
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Purpose: Managing recurrent inguinal hernias is complex, and choosing the right surgical approach (laparoscopic vs. open) is vital for patient outcomes. This study compared the outcomes of using the same vs. different surgical approaches for initial and subsequent hernia repairs., Methods: We retrospectively analyzed patients who underwent recurrent inguinal hernia repair at Seoul National University Bundang Hospital between January 2014 and May 2023. Patients were divided into the "concordant" and "discordant" groups, comprising patients who underwent same and different approaches in both surgeries, respectively. Preoperative baseline characteristics, index surgery data, postoperative outcomes, and recurrence rates were analyzed and compared., Results: In total, 131 patients were enrolled; the concordant and discordant groups comprised 31 (open, n = 19; laparoscopic, n = 12) and 100 patients (open to laparoscopic, n = 68; laparoscopic to open, n = 32), respectively. No significant differences were observed in the mean operation time (50.5 ± 21.7 minutes vs. 50.2 ± 20.0 minutes, P = 0.979), complication rates (6.5% vs. 14.0%, P = 0.356), or 36-month cumulative recurrence rates (9.8% vs. 9.8%; P = 0.865). The mean postoperative hospital stay was significantly shorter in the discordant than in the concordant group (1.8 ± 0.7 vs. 1.4 ± 0.6, P = 0.003)., Conclusion: Most recurrent inguinal hernia repairs were performed using the discordant surgical approach. Overall, concordance in the surgical approach did not significantly affect postoperative outcomes. Therefore, the selection of the surgical approach based on the patient's condition and surgeon's preference may be advisable., Competing Interests: Conflicts of Interest: Duck-Woo Kim, serving as the Editor-in-Chief of Annals of Surgical Treatment and Research, did not participate in the review process of this article. No other potential conflicts of interest pertinent to this article were reported., (Copyright © 2024, the Korean Surgical Society.)
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- 2024
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22. Totally Extraperitoneal Approach for Recurrent Lateral Pelvic Lymph Nodes After Rectal Cancer Surgery.
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Lee TG, Ahn HM, Shin HR, Choi MJ, Jo MH, Oh HK, Kim DW, and Kang SB
- Subjects
- Humans, Middle Aged, Lymphatic Metastasis, Neoplasm Recurrence, Local surgery, Proctectomy methods, Lymph Node Excision methods, Lymph Nodes pathology, Lymph Nodes surgery, Pelvis surgery, Rectal Neoplasms surgery, Rectal Neoplasms pathology
- Published
- 2024
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23. Whole genome sequence data of 516 F 2 plants of tomato ( Solanum lycopersicum ).
- Author
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Lee TG
- Abstract
The large-fruited fresh-market tomato cultivated in the U.S. represents a unique fruit market class of contemporary (modern) tomatoes for direct consumption. The genomes of F
2 plants from crosses between inbred contemporary U.S. large-fruited fresh-market tomatoes were sequenced. 516 F2 individual plants randomly selected from five different biparental segregating populations were used for DNA extraction. The polymerase chain reaction (PCR)-free, paired-end (2 × 150 bp) sequencing libraries (350 bp DNA fragment length) were prepared, and sequenced on average 5 Gb for each plant using the Illumina next-generation sequencing technologies [1,2]. Raw Illumina reads with adapter contamination and/or uncertain nucleotides constitute (Ns, >10 % of either read; Q-score 5 or lower, >50 % of either read) were removed. This data article will contribute to improving our knowledge of the genetic recombination and variation in tomato., (© 2024 The Author(s).)- Published
- 2024
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24. Rapid Surface Reconstruction of In 2 S 3 Photoanode via Flame Treatment for Enhanced Photoelectrochemical Performance.
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Jeong YJ, Tan R, Nam S, Lee JH, Kim SK, Lee TG, Shin SS, Zheng X, and Cho IS
- Abstract
Surface reconstruction, reorganizing the surface atoms or structure, is a promising strategy to manipulate materials' electrical, electrochemical, and surface catalytic properties. Herein, a rapid surface reconstruction of indium sulfide (In
2 S3 ) is demonstrated via a high-temperature flame treatment to improve its charge collection properties. The flame process selectively transforms the In2 S3 surface into a diffusionless In2 O3 layer with high crystallinity. Additionally, it controllably generates bulk sulfur vacancies within a few seconds, leading to surface-reconstructed In2 S3 (sr-In2 S3 ). When using those sr-In2 S3 as photoanode for photoelectrochemical water splitting devices, these dual functions of surface In2 O3 /bulk In2 S3 reduce the charge recombination in the surface and bulk region, thus improving photocurrent density and stability. With optimized surface reconstruction, the sr-In2 S3 photoanode demonstrates a significant photocurrent density of 8.5 mA cm-2 at 1.23 V versus a reversible hydrogen electrode (RHE), marking a 2.5-fold increase compared to pristine In2 S3 (3.5 mA cm-2 ). More importantly, the sr-In2 S3 photoanode exhibits an impressive photocurrent density of 7.3 mA cm-2 at 0.6 V versus RHE for iodide oxidation reaction. A practical and scalable surface reconstruction is also showcased via flame treatment. This work provides new insights for surface reconstruction engineering in sulfide-based semiconductors, making a breakthrough in developing efficient solar-fuel energy devices., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)- Published
- 2024
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25. Fatal progression of the leptomeningeal carcinomatosis from primary rectal adenocarcinoma: A case report.
- Author
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Lee TG and Hwang HJ
- Subjects
- Humans, Fatal Outcome, Male, Middle Aged, Magnetic Resonance Imaging, Meningeal Carcinomatosis secondary, Rectal Neoplasms pathology, Adenocarcinoma pathology, Adenocarcinoma secondary, Disease Progression
- Abstract
Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare with regard to this study.
- Published
- 2024
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26. Using machine learning and partial dependence to evaluate robustness of best linear unbiased prediction (BLUP) for phenotypic values.
- Author
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Bhandari P and Lee TG
- Subjects
- Genotype, Linear Models, Phenotype, Machine Learning, Models, Genetic
- Abstract
Best linear unbiased prediction (BLUP) is widely used in plant research to address experimental variation. For phenotypic values, BLUP accuracy is largely dependent on properly controlled experimental repetition and how variable components are outlined in the model. Thus, determining BLUP robustness implies the need to evaluate contributions from each repetition. Here, we assessed the robustness of BLUP values for simulated or empirical phenotypic datasets, where the BLUP value and each experimental repetition served as dependent and independent (feature) variables, respectively. Our technique incorporated machine learning and partial dependence. First, we compared the feature importance estimated with the neural networks. Second, we compared estimated average marginal effects of individual repetitions, calculated with a partial dependence analysis. We showed that contributions of experimental repetitions are unequal in a phenotypic dataset, suggesting that the calculated BLUP value is likely to be influenced by some repetitions more than others (such as failing to detect simulated true positive associations). To resolve disproportionate sources, variable components in the BLUP model must be further outlined., (© 2024. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)
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- 2024
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27. Microstructural Evolution, Hardness and Wear Resistance of WC-Co-Ni Composite Coatings Fabricated by Laser Cladding.
- Author
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Kim G, Kim YC, Cho JE, Yim CH, Yun DS, Lee TG, Park NK, Chung RH, and Hong DG
- Abstract
This study investigated how process parameters of laser cladding affect the microstructure and mechanical properties of WC-12Co composite coating for use as a protective layer of continuous caster rolls. WC-Co powders, WC-Ni powders, and Ni-Cr alloy powder with various wear resistance characteristics were evaluated in order to determine their applicability for use as cladding materials for continuous caster roll coating. The cladding process was conducted with various parameters, including laser powers, cladding speeds, and powder feeding rates, then the phases, microstructure, and micro-hardness of the cladding layer were analyzed in each specimen. Results indicate that, to increase the hardness of the cladding layer in WC-Co composite coating, the dilution of the cladding layer by dissolution of Fe from the substrate should be minimized, and the formation of the Fe-Co alloy phase should be prevented. The mechanical properties and wear resistance of each powder with the same process parameters were compared and analyzed. The microstructure and mechanical properties of the laser cladding layer depend not only on the process parameters, but also on the powder characteristics, such as WC particle size and the type of binder material. Additionally, depending on the degree of thermal decomposition of WC particles and evolution of W distribution within the cladding layer, the hardness of each powder can differ significantly, and the wear mechanism can change.
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- 2024
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28. Downregulation of TRIB3 enhances the sensitivity of lung cancer cells to amino acid deprivation by suppressing AKT activation.
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Ahn SH, Jang SK, Kim MJ, Kim G, Park KS, Hong J, Lee TG, Kim CH, Park IC, and Jin HO
- Abstract
Tribbles pseudokinase 3 (TRIB3), a member of the mammalian Tribbles family, is implicated in multiple biological processes. This study aimed to investigate the biological functions of TRIB3 in lung cancer and its effect on amino acid-deprived lung cancer cells. TRIB3 mRNA expression was elevated in lung cancer tissues and cell lines compared to normal lung tissues and cells. TRIB3 knockdown markedly reduced the viability and proliferation of H1299 lung cancer cells. Deprivation of amino acids, particularly arginine, glutamine, lysine, or methionine, strongly increased TRIB3 expression via ATF4 activation in H1299 lung cancer cells. Knockdown of TRIB3 led to transcriptional downregulation of ATF4 and reduced AKT activation induced by amino acid deprivation, ultimately increasing the sensitivity of H1299 lung cancer cells to amino acid deprivation. Additionally, TRIB3 knockdown enhanced the sensitivity of H1299 cells to V-9302, a competitive antagonist of transmembrane glutamine flux. These results suggest that TRIB3 is a pro-survival regulator of cell viability in amino acid-deficient tumor microenvironments and a promising therapeutic target for lung cancer treatment., Competing Interests: None., (AJCR Copyright © 2024.)
- Published
- 2024
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29. Serosal Tear After Diagnostic and Subsequent Therapeutic Colonoscopy: A Rare Complication.
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Lee TG, Kim DW, Ahn HM, Shin HR, Choi MJ, Jo MH, Oh HK, and Kang SB
- Subjects
- Humans, Colonoscopy adverse effects
- Published
- 2024
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30. Public effect of the 2022 Colorectal Cancer Awareness Campaign delivered through a metaverse platform.
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Lee TG, Song GH, Ahn HM, Oh HK, Byun M, Han EC, Kim S, Kim CW, Kim HJ, Hong S, Song KH, Kim CW, and Cho YB
- Abstract
Purpose: The Korean Society of Coloproctology has been conducting Colorectal Cancer Awareness Campaign, also known as the Gold Ribbon Campaign, every September since 2007. The 2022 campaign was held through a metaverse platform targeting the younger age group under the slogan of raising awareness of early-onset colorectal cancer (CRC). This study aimed to analyze the impact of the 2022 campaign on a metaverse platform., Methods: Anonymized survey data were collected from participants in the metaverse campaign from September 1 to 15, 2022. The satisfaction score of the participants was evaluated by sex, age group, and previous campaign participation status., Results: During the campaign, 2,770 people visited the metaverse. Among them, 455 people participated in the survey (response rate, 16.4%). Approximately 95% of the participants reported being satisfied with the information provided by the campaign, understood the necessity of undergoing screening for and prevention of early-onset CRC, and were familiar with the structure of the metaverse. The satisfaction score for campaign information tended to decrease as the participants' age increased. When the participants' overall level of satisfaction with the metaverse platform was assessed, teenagers scored particularly lower than the other age groups. The satisfaction scores for CRC information provided in the metaverse, as well as the scores for recognizing the seriousness and necessity of screening for early-onset CRC, indicated a high positive tendency (P<0.001)., Conclusion: Most of the 2022 Gold Ribbon Campaign participants were satisfied with the metaverse platform. Medical society should pay attention to increasing participation in and satisfaction with future public campaigns.
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- 2024
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31. Visualization Materials Using Silicon-Based Optical Nanodisks (ViSiON) for Enhanced NIR Imaging in Ophthalmology.
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Ki J, Lee H, Lee TG, Lee SW, Wi JS, and Na HK
- Subjects
- Animals, Chick Embryo, Ophthalmology methods, Phantoms, Imaging, Spectroscopy, Near-Infrared methods, Retina diagnostic imaging, Contrast Media chemistry, Nanostructures chemistry, Silicon chemistry, Tomography, Optical Coherence methods
- Abstract
ViSiON (visualization materials composed of silicon-based optical nanodisks) is presented, which offers a unique optical combination of near-infrared (NIR) optical properties and biodegradability. Initially, numerical simulations are conducted to calculate the total extinction and scattering effects of ViSiON by the diameter-to-thickness ratio, predicting precise control over its scattering properties in the NIR region. A top-down patterning technique is employed to synthesize ViSiON with accurate diameter and thickness control. ViSiON with a 50 nm thickness exhibits scattering properties over 400 times higher than that of 30 nm, rendering it suitable as a contrast agent for optical coherence tomography (OCT), especially in ophthalmic applications. Furthermore, ViSiON possesses inherent biodegradability in media, with ≈95% degradation occurring after 48 h, and the degradation rate can be finely tuned based on the quantity of protein coating applied to the surface. Subsequently, the OCT imaging capability is validated even within vessels smaller than 300 µm, simulating retinal vasculature using a retinal phantom. Then, using an ex ovo chick embryo model, it is demonstrated that ViSiON enhances the strength of protein membranes by 6.17 times, thereby presenting the potential for ViSiON as an OCT imaging probe capable of diagnosing retinal diseases., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)
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- 2024
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32. Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats.
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Han HY, Kim BK, Rho J, Park SM, Choi MS, Kim S, Heo MB, Yang YS, Oh JH, Lee TG, and Yoon S
- Subjects
- Rats, Male, Female, Animals, Rats, Sprague-Dawley, Drug Delivery Systems, Nanoparticles chemistry, Cerium toxicity, Cerium chemistry, Metal Nanoparticles toxicity, Metal Nanoparticles chemistry
- Abstract
Cerium oxide nanoparticles (CeO
2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions., (© 2024. The Author(s).)- Published
- 2024
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33. Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer.
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Kim H, Choi SY, Heo TY, Kim KR, Lee J, Yoo MY, Lee TG, and Han JH
- Abstract
Background: There are limited data on the use of glucose transport protein 1 (GLUT-1) expression as a biomarker for predicting lymph node metastasis in patients with colorectal cancer. GLUT-1 and GLUT-3, hexokinase (HK)-II, and hypoxia-induced factor (HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT)., Aim: To evaluate GLUT-1, GLUT-3, HK-II, and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT., Methods: This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012. Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist, and the expressions of GLUT-1, GLUT-3, HK-II, and HIF-1 were determined using immunohistochemical staining. We analyzed the correlations among their expressions, various clinicopathological factors, and the maximum standardized uptake value (SUVmax) of PET/CT., Results: GLUT-1 was found at the center or periphery of the tumors in 109 (64.5%) of the 169 patients. GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes, regardless of the biopsy site (tumor center, P < 0.001 and P = 0.012; tumor periphery, P = 0.030 and P = 0.010, respectively). GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT, respectively, for the detection of lymph node metastasis, regardless of the biopsy site. GLUT3, HK-II, and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes., Conclusion: GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes. Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare regarding the publication of this work., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
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34. Lateral Prefrontal Stimulation of Active Cortex With Theta Burst Transcranial Magnetic Stimulation Affects Subsequent Engagement of the Frontoparietal Network.
- Author
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Taylor SF, Gu P, Simmonite M, Lasagna C, Tso IF, Lee TG, Vesia M, and Hernandez-Garcia L
- Subjects
- Humans, Female, Male, Cerebral Cortex, Magnetic Resonance Imaging, Memory, Short-Term physiology, Transcranial Magnetic Stimulation methods, Prefrontal Cortex physiology
- Abstract
Background: A critical unanswered question about therapeutic transcranial magnetic stimulation is what patients should do during treatment to optimize its effectiveness. Here, we address this lack of knowledge in healthy participants, testing the hypotheses that stimulating the left dorsolateral prefrontal cortex (dlPFC) while participants perform a working memory task will provide stronger effects on subsequent activation, perfusion, connectivity, and performance than stimulating resting dlPFC., Methods: After a baseline functional magnetic resonance imaging session to localize dlPFC activation and the associated frontoparietal network (FPN) engaged by an n-back task, healthy participants (N = 40, 67.5% female) underwent 3 counterbalanced sessions, separated by several weeks, during which they received intermittent theta burst stimulation (iTBS) followed by magnetic resonance imaging scans as follows: 1) iTBS to the dlPFC while resting passively (passive), 2) iTBS to the dlPFC while performing the n-back task (active), and 3) iTBS to a vertex site, while not engaged in the n-back task and resting passively (control)., Results: We found no difference in n-back performance between the 3 conditions. However, FPN activation was reduced while performing the n-back task in the active condition relative to the passive and control conditions. There was no differential activity in the FPN on comparing passive with control conditions, i.e., there was no effect of the site of stimulation. We found no effects of state or site of stimulation on perfusion or connectivity with the dlPFC., Conclusions: In this study, the state of the brain while receiving iTBS affected FPN activation, possibly reflecting greater efficiency of FPN network activation when participants were stimulated while engaging the FPN., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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35. Modified laparoscopic Sugarbaker technique for parastomal hernia repair using overlapping composite meshes - A video vignette.
- Author
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Lee TG, Oh HK, Ahn H, Shin HR, Kim DW, and Kang SB
- Subjects
- Humans, Herniorrhaphy methods, Surgical Mesh, Laparoscopy methods, Hernia, Ventral etiology, Hernia, Ventral surgery, Surgical Stomas adverse effects, Incisional Hernia etiology, Incisional Hernia surgery
- Published
- 2024
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- View/download PDF
36. Monitoring lipid alterations in Drosophila heads in an amyotrophic lateral sclerosis model with time-of-flight secondary ion mass spectrometry.
- Author
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Le MUT, Park JH, Son JG, Shon HK, Joh S, Chung CG, Cho JH, Pirkl A, Lee SB, and Lee TG
- Subjects
- Animals, Drosophila, Spectrometry, Mass, Secondary Ion, Lipids, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis metabolism
- Abstract
Lipid alterations in the brain are well-documented in disease and aging, but our understanding of their pathogenic implications remains incomplete. Recent technological advances in assessing lipid profiles have enabled us to intricately examine the spatiotemporal variations in lipid compositions within the complex brain characterized by diverse cell types and intricate neural networks. In this study, we coupled time-of-flight secondary ion mass spectrometry (ToF-SIMS) to an amyotrophic lateral sclerosis (ALS) Drosophila model, for the first time, to elucidate changes in the lipid landscape and investigate their potential role in the disease process, serving as a methodological and analytical complement to our prior approach that utilized matrix-assisted laser desorption/ionization mass spectrometry. The expansion of G
4 C2 repeats in the C9orf72 gene is the most prevalent genetic factor in ALS. Our findings indicate that expressing these repeats in fly brains elevates the levels of fatty acids, diacylglycerols, and ceramides during the early stages (day 5) of disease progression, preceding motor dysfunction. Using RNAi-based genetic screening targeting lipid regulators, we found that reducing fatty acid transport protein 1 (FATP1) and Acyl-CoA-binding protein (ACBP) alleviates the retinal degeneration caused by G4 C2 repeat expression and also markedly restores the G4 C2 -dependent alterations in lipid profiles. Significantly, the expression of FATP1 and ACBP is upregulated in G4 C2 -expressing flies, suggesting their contribution to lipid dysregulation. Collectively, our novel use of ToF-SIMS with the ALS Drosophila model, alongside methodological and analytical improvements, successfully identifies crucial lipids and related genetic factors in ALS pathogenesis.- Published
- 2024
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37. Novel Organoid Culture System for Improved Safety Assessment of Nanomaterials.
- Author
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Baek A, Kwon IH, Lee DH, Choi WH, Lee SW, Yoo J, Heo MB, and Lee TG
- Subjects
- Extracellular Matrix, Organoids, Nanostructures
- Abstract
Over the past few decades, the increased application of nanomaterials has raised questions regarding their safety and possible toxic effects. Organoids have been suggested as promising tools, offering efficient assays for nanomaterial-induced toxicity evaluation. However, organoid systems have some limitations, such as size heterogeneity and poor penetration of nanoparticles because of the extracellular matrix, which is necessary for organoid culture. Here, we developed a novel system for the improved safety assessment of nanomaterials by establishing a 3D floating organoid paradigm. In addition to overcoming the limitations of two-dimensional systems including the lack of in vitro - in vivo cross-talk, our method provides multiple benefits as compared with conventional organoid systems that rely on an extracellular matrix for culture. Organoids cultured using our method exhibited relatively uniform sizing and structural integrity and were more conducive to the internalization of nanoparticles. Our floating culture system will accelerate the research and development of safe nanomaterials.
- Published
- 2024
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- View/download PDF
38. Genome characterization of a Korean isolate of porcine epidemic diarrhea virus.
- Author
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Kim D-M, Moon S-H, Kim S-C, Lee TG, Cho H-S, and Tark D
- Abstract
Porcine epidemic diarrhea (PED) outbreaks occur annually in the Republic of Korea. The complete genome sequence of the PED virus isolate CKK1-1 obtained from an infected pig was determined. The genome is 28,037 nt long, excluding the poly(A) tail, and contains seven open reading frames flanked by two untranslated regions., Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
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39. Hydrophobic surface induced pro-metastatic cancer cells for in vitro extravasation models.
- Author
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Lee M, Kim S, Lee SY, Son JG, Park J, Park S, Yeun J, Lee TG, Im SG, and Jeon JS
- Abstract
In vitro vascularized cancer models utilizing microfluidics have emerged as a promising tool for mechanism study and drug screening. However, the lack of consideration and preparation methods for cancer cellular sources that are capable of adequately replicating the metastatic features of circulating tumor cells contributed to low relevancy with in vivo experimental results. Here, we show that the properties of cancer cellular sources have a considerable impact on the validity of the in vitro metastasis model. Notably, with a hydrophobic surface, we can create highly metastatic spheroids equipped with aggressive invasion, endothelium adhesion capabilities, and activated metabolic features. Combining these metastatic spheroids with the well-constructed microfluidic-based extravasation model, we validate that these metastatic spheroids exhibited a distinct extravasation response to epidermal growth factor (EGF) and normal human lung fibroblasts compared to the 2D cultured cancer cells, which is consistent with the previously reported results of in vivo experiments. Furthermore, the applicability of the developed model as a therapeutic screening platform for cancer extravasation is validated through profiling and inhibition of cytokines. We believe this model incorporating hydrophobic surface-cultured 3D cancer cells provides reliable experimental data in a clear and concise manner, bridging the gap between the conventional in vitro models and in vivo experiments., Competing Interests: None., (© 2023 The Authors.)
- Published
- 2024
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40. Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa.
- Author
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Brissenden JA, Scerbak T, Albin RL, and Lee TG
- Subjects
- Male, Humans, Female, Aged, Hypokinesia, Motivation, Movement, Dopamine pharmacology, Antiparkinson Agents therapeutic use, Antiparkinson Agents pharmacology, Levodopa pharmacology, Levodopa therapeutic use, Parkinson Disease drug therapy
- Abstract
Background: Impaired movement vigor (bradykinesia) is a cardinal feature of Parkinson's disease (PD) and hypothesized to result from abnormal motivational processes-impaired motivation-vigor coupling. Dopamine replacement therapy (DRT) improves bradykinesia, but the response to DRT is multifaceted, comprising a short-duration response (SDR) and a long-duration response (LDR) only manifesting with chronic treatment. Prior experiments assessing motivation-vigor coupling in PD used chronically treated subjects, obscuring the roles of the SDR and LDR., Methods: To disambiguate the SDR and LDR, 11 de novo PD subjects (6 male [M]:5 female [F]; mean age, 67) were studied before treatment, after an acute levodopa (l-dopa) dose, and in both the practical "off" (LDR) and "on" (LDR + SDR) states after chronic stable treatment. At each visit, subjects were characterized with a standard battery including the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and an incentivized joystick task to assess motor performance in response to varying rewards., Results: l-Dopa induced a robust SDR and LDR, with further improvement in the combined SDR + LDR state. At baseline, after acute treatment (SDR), and after LDR induction, subjects did not exhibit the normal increase in movement speed with increasing reward. Only in the combined SDR + LDR state was there restoration of motivation-vigor coupling., Conclusions: Although consistent with prior results in chronically treated PD subjects, the significant improvement in motor performance observed with the SDR and LDR suggests that bradykinesia is not solely secondary to deficient modulation of motivational processes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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- 2024
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41. Transcriptome analysis of skeletal muscle in dermatomyositis, polymyositis, and dysferlinopathy, using a bioinformatics approach.
- Author
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Jeong HN, Lee TG, Park HJ, Yang Y, Oh SH, Kang SW, and Choi YC
- Abstract
Background: Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies. Dysferlinopathy, caused by a dysferlin gene mutation, usually presents in late adolescence with muscle weakness, degenerative muscle changes are often accompanied by inflammatory infiltrates, often resulting in a misdiagnosis as polymyositis., Objective: To identify differential biological pathways and hub genes related to polymyositis, dermatomyositis and dysferlinopathy using bioinformatics analysis for understanding the pathomechanisms and providing guidance for therapy development., Methods: We analyzed intramuscular ribonucleic acid (RNA) sequencing data from seven dermatomyositis, eight polymyositis, eight dysferlinopathy and five control subjects. Differentially expressed genes (DEGs) were identified by using DESeq2. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein-protein interaction (PPI) network was constructed, and clarified the gene cluster using the molecular complex detection tool (MCODE) analysis to identify hub genes., Results: A total of 1,048, 179 and 3,807 DEGs were detected in DM, PM and dysferlinopathy, respectively. Enrichment analyses revealed that upregulated DEGs were involved in type 1 interferon (IFN1) signaling pathway in DM, antigen processing and presentation of peptide antigen in PM, and cellular response to stimuli in dysferlinopathy. The PPI network and MCODE cluster identified 23 genes related to type 1 interferon signaling pathway in DM, 4 genes ( PDIA3, HLA-C, B2M, and TAP1 ) related to MHC class 1 formation and quality control in PM, and 7 genes ( HSPA9, RPTOR, MTOR, LAMTOR1, LAMTOR5, ATP6V0D1, and ATP6V0B ) related to cellular response to stress in dysferliniopathy., Conclusion: Overexpression of genes related to the IFN1 signaling pathway and major histocompatibility complex (MHC) class I formation was identified in DM and PM, respectively. In dysferlinopathy, overexpression of HSPA9 and the mTORC1 signaling pathway genes was detected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jeong, Lee, Park, Yang, Oh, Kang and Choi.)
- Published
- 2023
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42. Dual-Function Janus Nanozymes for Performance Evaluation and Application in a Surrogate Virus Neutralization Test with Vaccinated Samples.
- Author
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Kwak SH, Jeong DG, Shon HK, Kim DH, Lee TG, Wi JS, and Na HK
- Subjects
- Neutralization Tests, Gold, Kinetics, SARS-CoV-2, Biological Assay, Middle East Respiratory Syndrome Coronavirus
- Abstract
The need exists for biosensing technologies capable of sensitively and accurately detecting various biomarkers. In response, the development of nanozymes is actively underway; they have advantages in stability, cost, performance, and functionalization over natural enzymes commonly used for signal amplification in sensing technologies. However, the performance of nanozymes is interdependent with factors such as shape, size, and surface functional moiety, making it challenging to perform quantitative performance comparisons based on the nanozyme material. In this study, we propose a physical synthetic approach to fabricate double-layered bimetallic nanozymes with identical shapes, sizes, and surfaces but different material compositions. These Janus nanozymes consist of a nanozymatic layer responsible for catalytic activity and a gold layer responsible for quantification and efficient surface modification. Based on their identical physicochemical properties, the synthesized double-layered bimetallic nanozymes allow, for the first time, a quantitative comparison of nanozymatic activities in terms of various kinetic parameters. We compared several candidates and found that the Ir-Au nanozyme exhibited the best performance. Subsequently, we applied this nanozyme to detect neutralizing antibodies against SARS-CoV-2 based on a surrogate virus neutralization test. The results demonstrated a limit of detection as low as 2 pg/mL and selectivity specifically toward MERS-CoV. The performance of this assay was further validated using vaccinated samples, demonstrating the potential of our approach as a cost-effective, rapid, and sensitive diagnostic tool for neutralizing antibody detection against viruses such as SARS-CoV-2.
- Published
- 2023
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43. Development of Maximum Residual Stress Prediction Technique for Shot-Peened Specimen Using Rayleigh Wave Dispersion Data Based on Convolutional Neural Network.
- Author
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Choi YW, Lee TG, Yeom YT, Kwon SD, Kim HH, Lee KY, Kim HJ, and Song SJ
- Abstract
Shot peening is a surface treatment process that improves the fatigue life of a material and suppresses cracks by generating residual stress on the surface. The injected small shots create a compressive residual stress layer on the material's surface. Maximum compressive residual stress occurs at a certain depth, and tensile residual stress gradually occurs as the depth increases. This process is primarily used for nickel-based superalloy steel materials in certain environments, such as the aerospace industry and nuclear power fields. To prevent such a severe accident due to the high-temperature and high-pressure environment, evaluating the residual stress of shot-peened materials is essential in evaluating the soundness of the material. Representative methods for evaluating residual stress include perforation strain gauge analysis, X-ray diffraction (XRD), and ultrasonic testing. Among them, ultrasonic testing is a representative, non-destructive evaluation method, and residual stress can be estimated using a Rayleigh wave. Therefore, in this study, the maximum compressive residual stress value of the peened Inconel 718 specimen was predicted using a prediction convolutional neural network (CNN) based on the relationship between Rayleigh wave dispersion and stress distribution on the specimen. By analyzing the residual stress distribution in the depth direction generated in the model from various studies in the literature, 173 residual stress distributions were generated using the Gaussian function and factorial design approach. The distribution generated using the relationship was converted into 173 Rayleigh wave dispersion data to be used as a database for the CNN model. The CNN model was learned through this database, and performance was verified using validation data. The adopted Rayleigh wave dispersion and convolutional neural network procedures demonstrate the ability to predict the maximum compressive residual stress in the peened specimen.
- Published
- 2023
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44. Impact on clinical outcomes of renin-angiotensin system inhibitors against doxorubicin-related toxicity in patients with breast cancer and hypertension: A nationwide cohort study in South Korea.
- Author
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Hwang HJ and Lee TG
- Subjects
- Humans, Female, Antihypertensive Agents therapeutic use, Angiotensin-Converting Enzyme Inhibitors adverse effects, Renin-Angiotensin System, Cohort Studies, Doxorubicin adverse effects, Enzyme Inhibitors pharmacology, Angiotensin Receptor Antagonists adverse effects, Breast Neoplasms complications, Breast Neoplasms drug therapy, Breast Neoplasms chemically induced, Hypertension chemically induced, Hypertension drug therapy, Heart Failure
- Abstract
Background: Although doxorubicin (DOX) is a commonly used potent chemotherapeutic agent in patients with breast cancer, its cardiotoxic effect is a concern, particularly in patients with hypertension. Antihypertensive renin-angiotensin system (RAS) inhibitors may potentially play a role in preventing overt heart failure (HF) due to DOX toxicity. This study aimed to evaluate whether the use of RAS inhibitors improves clinical outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy., Methods: A total of 54,344 female patients who were first diagnosed with breast cancer and initiated into DOX therapy between 2008 and 2015 were recruited from a nationwide Korean cohort. Patients were divided into two groups: with and without hypertension (HT, n = 10,789; non-HT, n = 43,555), and the RAS inhibitor group (n = 1,728) was sub-classified from the HT group. Two propensity score-matched cohorts were constructed to compare the clinical outcomes between non-HT and HT groups and between non-HT and RAS inhibitor groups. The primary outcome was the composite of HF and death., Results: After propensity score matching, the HT group had a higher risk for HF (adjusted hazard ratio [HR] = 1.30, 95% confidence intervals [95% CI] = 1.09-1.55) compared to the non-HT group, but there was no significant difference in primary outcome between the two groups. The RAS inhibitor group had a lower risk for primary outcome (adjusted HR = 0.78, 95% CI = 0.65-0.94) and death (adjusted HR = 0.81, 95% CI = 0.66-0.99) compared to the non-HT group., Conclusions: Hypertension is a risk factor for HF in patients with breast cancer undergoing DOX chemotherapy. However, the RAS inhibitors used to treat hypertension may contribute to decreased mortality and improved clinical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hwang, Lee. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
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45. A meta-analytic investigation of problem gambling and self-harm: A causal inference perspective.
- Author
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Edson TC, Slabczynski JM, Lee TG, McAuliffe WHB, and Gray HM
- Subjects
- Humans, Cross-Sectional Studies, Suicide, Attempted, Suicidal Ideation, Gambling epidemiology, Self-Injurious Behavior epidemiology
- Abstract
Objective: Problem gambling may be an underappreciated treatment target for reducing self-harm. Multivariate studies examining the relationship between problem gambling and self-harm have returned inconsistent results, perhaps due to insufficient power or differences in study quality., Method: We conducted a series of meta-analyses examining the effect of problem gambling on self-harm outcomes of varying severity. We assessed the sensitivity of results to study characteristics, publication bias, and influential cases. To highlight threats to causal inference, we evaluated each study for residual confounding bias., Results: In total, two types of meta-analyses were adequately powered: those assessing (a) the effect of problem gambling (binary) on suicide ideation and (b) problem gambling (binary) on suicide attempt ( k = 14 unique studies between the two meta-analyses). For both meta-analyses, we found a positive, statistically significant average effect of problem gambling on the respective self-harm outcome. We did not detect any influential studies among these two meta-analyses, nor residual confounding. However, these findings are limited by the overall quality of included literature. PET-PEESE analysis detected substantial potential publication bias in the main results, with both meta-analytic effects being reduced to statistical nonsignificance. All included studies also used a cross-sectional design for their analysis of interest, thus simultaneity bias cannot be ruled out., Conclusion: While these findings suggest there is an appreciable relationship between problem gambling and at least two forms of self-harm (suicide ideation and attempts), well-designed longitudinal research is needed to make more firm conclusions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
- Published
- 2023
- Full Text
- View/download PDF
46. The behavioral and neural effects of parietal theta burst stimulation on the grasp network are stronger during a grasping task than at rest.
- Author
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Goldenkoff ER, Deluisi JA, Destiny DP, Lee TG, Michon KJ, Brissenden JA, Taylor SF, Polk TA, and Vesia M
- Abstract
Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Goldenkoff, Deluisi, Destiny, Lee, Michon, Brissenden, Taylor, Polk and Vesia.)
- Published
- 2023
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47. Background free in vivo 29 Si MR imaging with hyperpolarized PEGylated silicon nanoparticles.
- Author
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Yang SH, Kim J, Lee TG, Park M, Son HY, Joo CG, Shim JH, Lee Y, and Huh YM
- Abstract
This study demonstrated the potential of 50 nm PEGylated Si NPs for high-resolution in vivo
29 Si MR imaging, emphasizing their biocompatibility and water dispersibility. The acquisition of in vivo Si MR images using the lowest reported dose after subcutaneous and intraperitoneal administration opens new avenues for future29 Si MR studies.- Published
- 2023
- Full Text
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48. Time-sequential fibroblast-to-myofibroblast transition in elastin-variable 3D hydrogel environments by collagen networks.
- Author
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Do NT, Lee SY, Lee YS, Shin C, Kim D, Lee TG, Son JG, and Kim SH
- Abstract
Background: Fibrosis plays an important role in both normal physiological and pathological phenomena as fibroblasts differentiate to myofibroblasts. The activation of fibroblasts is determined through interactions with the surrounding extracellular matrix (ECM). However, how this fibroblast-to-myofibroblast transition (FMT) is regulated and affected by elastin concentration in a three-dimensional (3D) microenvironment has not been investigated., Methods: We developed an insoluble elastin-gradient 3D hydrogel system for long-lasting cell culture and studied the molecular mechanisms of the FMT in embedded cells by nanoflow LC-MS/MS analysis along with validation through real-time PCR and immunofluorescence staining., Results: By optimizing pH and temperature, four 3D hydrogels containing fibroblasts were successfully fabricated having elastin concentrations of 0, 20, 50, and 80% in collagen. At the low elastin level (20%), fibroblast proliferation was significantly increased compared to others, and in particular, the FMT was clearly observed in this condition. Moreover, through mass spectrometry of the hydrogel environment, it was confirmed that differentiation proceeded in two stages. In the early stage, calcium-dependent proteins including calmodulin and S100A4 were highly associated. On the other hand, in the late stage after several passages of cells, distinct markers of myofibroblasts were presented such as morphological changes, increased production of ECM, and increased α-SMA expression. We also demonstrated that the low level of elastin concentration induced some cancer-associated fibroblast (CAF) markers, including PDGFR-β, and fibrosis-related disease markers, including THY-1., Conclusion: Using our developed 3D elastin-gradient hydrogel system, we evaluated the effect of different elastin concentrations on the FMT. The FMT was induced even at a low concentration of elastin with increasing CAF level via calcium signaling. With this system, we were able to analyze varying protein expressions in the overall FMT process over several cellular passages. Our results suggest that the elastin-gradient system employing nonlinear optics imaging provides a good platform to study activated fibroblasts interacting with the microenvironment, where the ECM plays a pivotal role., (© 2023. The Korean Society for Biomaterials.)
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- 2023
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49. The combination of osimertinib with Raf inhibitor overcomes osimertinib resistance induced by KRAS amplification in EGFR-mutated lung cancer cells.
- Author
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Lee TG, Kang HM, Kim SY, Kim HR, and Kim CH
- Subjects
- Humans, Animals, Mice, Drug Resistance, Neoplasm genetics, Cell Line, Tumor, Aniline Compounds pharmacology, ErbB Receptors genetics, Protein Kinase Inhibitors pharmacology, Mutation, Proto-Oncogene Proteins p21(ras) genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Osimertinib is a third-generation epidermal growth factor receptor (EGFR)
1 tyrosine kinase inhibitor (TKI) approved for the treatment of EGFR-positive patients exhibiting a T790 M resistance mutation after treatment with an earlier generation of EGFR TKIs. However, resistance to osimertinib inevitably develops despite its efficacy, and the resistance mechanisms are complex and not fully understood. We established cell lines with acquired resistance to osimertinib from gefitinib- or erlotinib-resistant NSCLC cells using a dose-escalation method, and found that they had upregulated levels of phosphorylated ERK1/2. Targeted next-generation sequencing of 143 genes was performed, and interestingly, amplification of KRAS was observed in osimertinib-resistant cells. Transfection of siRNA against the KRAS gene notably reduced the activation of ERK1/2 and AKT and significantly enhanced the induction of apoptosis by osimertinib treatment in osimertinib-resistant cells. LY3009120, a RAF inhibitor, showed a significant synergistic effect with osimertinib on apoptotic cell death in osimertinib-resistant cells. Combined treatment with osimertinib and LY3009120 also demonstrated remarkable synergistic anti-tumor activity in mouse xenografts of these cells. This could be a potential new treatment option for KRAS amplification-induced osimertinib failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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50. Clinical Link between the BARD Score at Diagnosis and Mortality during Follow-Up in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
- Author
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Lee TG, Park PG, Park YB, Huh JH, and Lee SW
- Abstract
This study investigated whether the BARD score at diagnosis could predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study included 236 immunosuppressive drug-naïve patients without chronic liver diseases such as viral hepatitis, non-alcoholic fatty liver disease (NAFLD), and advanced liver diseases and their clinical data at diagnosis, such as age, sex, and the Birmingham Vasculitis Activity Score (BVAS). The BARD score was calculated by the sum of aspartate transaminase (AST)/alanine transaminase (ALT) ratio ≥ 0.8 (+2 points), body mass index (BMI) ≥ 28 kg/m
2 (+1 point), and the presence of type 2 diabetes mellitus (T2DM) (+1 point). All-cause mortality was investigated as a poor outcome of AAV. The median age of AAV patients was 60.0 years, and 34.7% were men. Among AAV patients, 7, 50, and 187 scored 1, 1, and 2 points owing to having a BMI ≥ 28 kg/m2 , T2DM, and an AST/ALT ratio ≥ 0.8, respectively. Patients with a BARD score ≥ 2 and those with a BARD score ≥ 3 exhibited significantly lower cumulative patient survival rates than those without ( p = 0.038 and p = 0.003, respectively). In the multivariable Cox analysis, among the two cut-offs of the BARD scores, only a BARD score ≥ 3 (HR 2.866), along with age (HR 1.061), male sex (HR 2.327), and BVAS (HR 1.100), was independently associated with all-cause mortality during follow-up. In conclusion, this study was the first to demonstrate that the BARD score ≥ 3 at AAV diagnosis could predict all-cause mortality during follow-up in AAV patients.- Published
- 2023
- Full Text
- View/download PDF
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