Publications by authors named "Se Hyun Kim"

271 Publications

Ensemble evaluation of the potential risk areas of yellow-legged hornet distribution.

Environ Monit Assess 2021 Aug 26;193(9):601. Epub 2021 Aug 26.

Department of Smart Agriculture Systems, Chungnam National University, Daejoen, 34134, Korea.

Invasion of alien species facilitated by climate change and human assistant is one of global threats that cause irreversible damages on the local flora and fauna. One of these issued species, Vespa velutina nigrithorax du Buysson, 1905 (Hymenoptera:Vespidae), is a significant threat to entomofauna, including honeybees, in the introduced regions. This wasp is still expanding its habitats, prioritizing the development of a reliable species distribution model based on recently updated occurrence data. Therefore, the aim of this study was to evaluate the potential areas that are climatically exposed to V. v. nigrithorax invasion globally and in South Korea, where the wasp has caused severe damage to local ecosystems and apiculture after its recent introduction. We developed a new global scale ensemble model based on CLIMEX and Maxent models and applied it to South Korea using field survey data. As a result, risky areas were predicted to be temperate and subtropical climate regions, including the eastern USA, western Europe, Far East Asia, and small areas in South America and Australia. In particular, South Korea has a high potential risk throughout the country. We expect that this study would provide fundamental data for monitoring the environmental risks caused by V. v. nigrithorax using advanced species distribution modeling.
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http://dx.doi.org/10.1007/s10661-021-09406-2DOI Listing
August 2021

A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer.

Cancer Res Treat 2021 Aug 13. Epub 2021 Aug 13.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Purpose: We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.

Materials And Methods: This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.

Results: A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of 4 prior lines of chemotherapy (4.5 lines when including endocrine therapy), and 66 (64.7%) patients were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 (35.3%) patients were Luminal A, 28 (27.5%) were Luminal B, 18 (17.7%) were HER2-positive, and 20 (19.6%) had triple-negative disease. Fifty (49.0%) patients were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% CI, 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p<0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.

Conclusion: This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.
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http://dx.doi.org/10.4143/crt.2021.394DOI Listing
August 2021

Predictive protein markers for depression severity in mood disorders: A preliminary trans-diagnostic approach study.

J Psychiatr Res 2021 Oct 24;142:63-72. Epub 2021 Jul 24.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea. Electronic address:

Depression is a common symptom of many mental disorders, especially major depressive disorder (MDD) and bipolar disorder (BD). Previous studies have reported that these diseases share common pathophysiological pathways; therefore, this study elucidated whether the plasma levels of protein markers related to common depressive symptoms differed between patients with BD and those with MDD. Plasma samples of 71 patients with mood disorders and clinical manifestations were analyzed in this study. After depleting the abundant proteins, liquid chromatography-tandem mass spectrometry and label-free quantification were performed. Five proteins, viz., cholesteryl ester transfer protein (CETP), apolipoprotein D (APOD), mannan-binding lectin serine protease 2 (MASP2), Ig lambda chain V-II region BO (IGLV2-8) and Ig kappa chain V-III region NG9 (IGKV3-20) were negatively associated with the total scores of the Hamilton depression rating scale (HAM-D), after adjusting for the covariates. CETP and APOD also showed significant negative correlations with the anhedonia/retardation and guilt/agitation scores of the HAM-D. Four proteins, namely, Ig kappa chain V-II region TEW (IGKC; IGKV2D-28), Ig lambda variable 5-45 (IGLV5-45), complement factor H (CFH) and attractin (ATRN), showed significant associations with anhedonia/retardation after adjusting for covariates. Proteins that significantly correlated with the symptoms could predict the remission state of depression (area under the curve [AUC], 0.83) and anhedonia/retardation (AUC, 0.80). Bioinformatics analysis revealed that complement activation, immune response, and lipid metabolism were significantly enriched pathways. Although our study design was cross-sectional and no controls were included, protein markers identified in this preliminary study will be further investigated in our subsequent longitudinal study.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.041DOI Listing
October 2021

A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients.

Cancer Res Treat 2021 Jul 13. Epub 2021 Jul 13.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Purpose: We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic.

Materials And Methods: In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time.

Results: The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88.

Conclusion: The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.
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http://dx.doi.org/10.4143/crt.2021.483DOI Listing
July 2021

Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non-Small Cell Lung Cancer Patients treated with immune checkpoint inhibitors.

Cancer Res Treat 2021 Jul 7. Epub 2021 Jul 7.

Department of Pathology; Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non-small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.

Materials And Methods: This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. PD-L1 protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString® nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.

Results: Eleven (36.7%) patients showed a durable clinical benefit (DCB), whereas nineteen (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044, 0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (Area under the curve [AUC]=0.794), followed by TMB (AUC=0.679) and PD-L1 (AUC=0.622). TMB and ES showed the highest AUC (0.8373) among other combinations (AUC, TMB and PD-L1=0.7775; AUC, PD-L1 and ES=0.7632) and was similar to that of all biomarkers used together (0.8325).

Conclusion: The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.
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http://dx.doi.org/10.4143/crt.2021.583DOI Listing
July 2021

Systematic Review of the Neural Effect of Electroconvulsive Therapy in Patients with Schizophrenia: Hippocampus and Insula as the Key Regions of Modulation.

Psychiatry Investig 2021 Jun 24;18(6):486-499. Epub 2021 Jun 24.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: Electroconvulsive therapy (ECT) has been the most potent treatment option for treatment-resistant schizophrenia (TRS). However, the underlying neural mechanisms of ECT in schizophrenia remain largely unclear. This paper examines studies that investigated structural and functional changes after ECT in patients with schizophrenia.

Methods: We carried out a systematic review with following terms: 'ECT', 'schizophrenia', and the terms of various neuroimaging modalities.

Results: Among the 325 records available from the initial search in May 2020, 17 studies were included. Cerebral blood flow in the frontal, temporal, and striatal structures was shown to be modulated (n=3), although the results were divergent. Magnetic resonance spectroscopy (MRS) studies suggested that the ratio of N-acetyl-aspartate/creatinine was increased in the left prefrontal cortex (PFC; n=2) and left thalamus (n=1). The hippocampus and insula (n=6, respectively) were the most common regions of structural/functional modulation, which also showed symptom associations. Functional connectivity of the default mode network (DMN; n=5), PFC (n=4), and thalamostriatal system (n=2) were also commonly modulated.

Conclusion: Despite proven effectiveness, there has been a dearth of studies investigating the neurobiological mechanisms underlying ECT. There is preliminary evidence of structural and functional modulation of the hippocampus and insula, functional changes in the DMN, PFC, and thalamostriatal system after ECT in patients with schizophrenia. We discuss the rationale and implications of these findings and the potential mechanism of action of ECT. More studies evaluating the mechanisms of ECT are needed, which could provide a unique window into what leads to treatment response in the otherwise refractory TRS population.
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http://dx.doi.org/10.30773/pi.2020.0438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256139PMC
June 2021

Prognostic implications of regression of metastatic axillary lymph nodes after neoadjuvant chemotherapy in patients with breast cancer.

Sci Rep 2021 Jun 9;11(1):12128. Epub 2021 Jun 9.

Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, 13620, Gyeonggi, Republic of Korea.

Prognostic implications of therapeutic response of metastatic lymph nodes (LNs) to neoadjuvant chemotherapy (NAC) remain unclear in patients with breast cancer. We aimed to evaluate the prognostic value of axillary LN regression after NAC in locally-advanced breast cancer patients. Therapeutic response of the LNs was evaluated in 563 breast cancer patients and classified into four grades according to the regression pattern. Initial pathologic N stage was estimated from the sum of the metastatic LNs and those with complete regression. In survival analyses, LN regression grade, pathologic N stage after NAC, and presumed initial pathologic N stage stratified clinical outcome of the patients in the whole group, in both ER-positive and ER-negative subgroups, and in those with residual breast disease. On multivariate analysis, LN regression grade and presumed initial pathologic N stage were revealed as independent prognostic factors. The number of completely-responsive LNs and the ratio of non-responsive LNs also revealed a prognostic value. In conclusion, regression grade of axillary LNs and presumed initial pathologic N stage have prognostic values in breast cancer patients who receive NAC. Thus, regression of axillary LNs should be evaluated and included in pathologic reporting of post-NAC resection specimens.
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http://dx.doi.org/10.1038/s41598-021-91643-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190075PMC
June 2021

Novel and Highly Potent ATR Inhibitor M4344 Kills Cancer Cells With Replication Stress, and Enhances the Chemotherapeutic Activity of Widely Used DNA Damaging Agents.

Mol Cancer Ther 2021 Aug 27;20(8):1431-1441. Epub 2021 May 27.

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.

Although several ATR inhibitors are in development, there are unresolved questions regarding their differential potency, molecular signatures of patients with cancer for predicting activity, and most effective therapeutic combinations. Here, we elucidate how to improve ATR-based chemotherapy with the newly developed ATR inhibitor, M4344 using and models. The potency of M4344 was compared with the clinically developed ATR inhibitors BAY1895344, berzosertib, and ceralasertib. The anticancer activity of M4344 was investigated as monotherapy and combination with clinical DNA damaging agents in multiple cancer cell lines, patient-derived tumor organoids, and mouse xenograft models. We also elucidated the anticancer mechanisms and potential biomarkers for M4344. We demonstrate that M4344 is highly potent among the clinically developed ATR inhibitors. Replication stress (RepStress) and neuroendocrine (NE) gene expression signatures are significantly associated with a response to M4344 treatment. M4344 kills cancer cells by inducing cellular catastrophe and DNA damage. M4344 is highly synergistic with a broad range of DNA-targeting anticancer agents. It significantly synergizes with topotecan and irinotecan in patient-derived tumor organoids and xenograft models. Taken together, M4344 is a promising and highly potent ATR inhibitor. It enhances the activity of clinical DNA damaging agents commonly used in cancer treatment including topoisomerase inhibitors, gemcitabine, cisplatin, and talazoparib. RepStress and NE gene expression signatures can be exploited as predictive markers for M4344.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-1026DOI Listing
August 2021

Highly chemoselective deoxygenation of N-heterocyclic -oxides under transition metal-free conditions.

Org Biomol Chem 2021 Apr;19(16):3735-3742

Department of Advanced Materials Chemistry, Dongguk University Gyeongju Campus, Gyeongju 38066, Republic of Korea.

Because their site-selective C-H functionalizations are now considered one of the most useful tools for synthesizing various N-heterocyclic compounds, the highly chemoselective deoxygenation of densely functionalized N-heterocyclic N-oxides has received much attention from the synthetic chemistry community. Here, we provide a protocol for the highly chemoselective deoxygenation of various functionalized N-oxides under visible light-mediated photoredox conditions with Na2-eosin Y as an organophotocatalyst. Mechanistic studies imply that the excited state of the organophotocatalyst is reductively quenched by Hantzsch esters. This operationally simple technique tolerates a wide range of functional groups and allows high-yield, multigram-scale deoxygenation.
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http://dx.doi.org/10.1039/d1ob00260kDOI Listing
April 2021

The Antipsychotic Drug Clozapine Suppresses the RGS4 Polyubiquitylation and Proteasomal Degradation Mediated by the Arg/N-Degron Pathway.

Neurotherapeutics 2021 Apr 21. Epub 2021 Apr 21.

Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, 03080, Korea.

Although diverse antipsychotic drugs have been developed for the treatment of schizophrenia, most of their mechanisms of action remain elusive. Regulator of G-protein signaling 4 (RGS4) has been reported to be linked, both genetically and functionally, with schizophrenia and is a physiological substrate of the arginylation branch of the N-degron pathway (Arg/N-degron pathway). Here, we show that the atypical antipsychotic drug clozapine significantly inhibits proteasomal degradation of RGS4 proteins without affecting their transcriptional expression. In addition, the levels of Arg- and Phe-GFP (artificial substrates of the Arg/N-degron pathway) were significantly elevated by clozapine treatment. In silico computational model suggested that clozapine may interact with active sites of N-recognin E3 ubiquitin ligases. Accordingly, treatment with clozapine resulted in reduced polyubiquitylation of RGS4 and Arg-GFP in the test tube and in cultured cells. Clozapine attenuated the activation of downstream effectors of G protein-coupled receptor signaling, such as MEK1 and ERK1, in HEK293 and SH-SY5Y cells. Furthermore, intraperitoneal injection of clozapine into rats significantly stabilized the endogenous RGS4 protein in the prefrontal cortex. Overall, these results reveal an additional therapeutic mechanism of action of clozapine: this drug posttranslationally inhibits the degradation of Arg/N-degron substrates, including RGS4. These findings imply that modulation of protein post-translational modifications, in particular the Arg/N-degron pathway, may be a novel molecular therapeutic strategy against schizophrenia.
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http://dx.doi.org/10.1007/s13311-021-01039-0DOI Listing
April 2021

High-Efficiency Electrospray Deposition Method for Nonconductive Substrates: Applications of Superhydrophobic Coatings.

ACS Appl Mater Interfaces 2021 Apr 7;13(15):18227-18236. Epub 2021 Apr 7.

Department of Electronic Materials and Devices Engineering, Soonchunhyang University, 22, Soonchunhyang-ro, Asan-City, Chungnam 31538, South Korea.

When highly insulating materials are used as substrates for electronic devices, manufacturing yields become worse, and electronic components are often damaged due to undissipated electrostatic charges on such substrates. In the case of electrospray deposition, the problem of undissipated charges is particularly vexing. If charges accumulated on the substrate are not properly compensated, a repulsive force is generated against the incoming charged droplets, which negatively affects the uniformity and deposition rate of the coating layer. In order to overcome this limitation, we demonstrated a new electrospray method, which can significantly increase the deposition efficiency even in the presence of accumulated charges on nonconductive substrates. A highly reliable superhydrophobic layer was uniformly deposited on highly insulating substrates, including printed circuit board (PCB), polyester (PET), and polyimide (PI) substrates.
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http://dx.doi.org/10.1021/acsami.0c22867DOI Listing
April 2021

Programmed death-ligand 1 expression level as a predictor of EGFR tyrosine kinase inhibitor efficacy in lung adenocarcinoma.

Transl Lung Cancer Res 2021 Feb;10(2):699-711

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

Background: The main objective of this study was to investigate the impact of programmed death-ligand 1 (PD-L1) expression on the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in patients with advanced non-small cell lung cancer (NSCLC).

Methods: This study analyzed 108 patients with NSCLC who had received EGFR-TKI as first-line systemic treatment at Seoul National University Bundang Hospital and Seoul National University Hospital between December 2012 and October 2018. The National Cancer Center Research Institute (NCCRI) and The Cancer Genome Atlas (TCGA) datasets were analyzed to investigate the mechanisms underlying EGFR-TKI-resistance in tumors with high PD-L1 expression.

Results: Among the 108 patients, 55, 37, and 16 had negative (PD-L1 Tumor proportion score <1%), weak (1-49%), and strong (≥50%) PD-L1 expression, respectively. Patients with strong PD-L1 expression had significantly shorter median progression-free survival (PFS; 7.07 months) than patients with weak (14.73 months, P<0.001) or negative (12.70 months, P=0.001) PD-L1 expression. After adjustment for covariates by Cox regression, PD-L1 expression remained a significant indicator of adverse prognosis. In EGFR-TKI-refractory patients, the frequency of T790M mutation and the PFS following treatment with third-generation EGFR-TKI and PD-1 antibody were similar in the three groups. TCGA and NCCRI database analysis showed that high PD-L1 expression in EGFR-mutated NSCLCs correlated with IL-6/JAK/STAT3 signaling and high mutation frequency.

Conclusions: Strong PD-L1 expression in tumors might be a surrogate indicator of poor response to first-line EGFR-TKIs in NSCLC patients with sensitizing EGFR mutations, and may reflect a resistance mechanism involving JAK-STAT signaling.
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http://dx.doi.org/10.21037/tlcr-20-893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947423PMC
February 2021

Effect of liraglutide 3.0mg treatment on weight reduction in obese antipsychotic-treated patients.

Psychiatry Res 2021 05 23;299:113830. Epub 2021 Feb 23.

Department of Psychiatry, Nowon Eulji Hospital, Eulji University College of Medicine, Seoul, South Korea; Institute of Clinical Psychopharmacology, Dongguk University College of Medicine, Goyang, Gyeonggi-do, South Korea. Electronic address:

Background: Patients treated with antipsychotics experience significant weight gain and accompanying metabolic disorders. We investigated the efficacy of liraglutide 3.0 mg in reducing the weight of antipsychotic-treated obese patients.

Method: We retrospectively reviewed 16 obese patients with schizophrenia or bipolar disorder who were treated with 3.0 mg of liraglutide each. During the 16 weeks of treatment, changes in body weight and Clinical Global Impression-Severity scale (CGI-S) were analyzed. The participants were divided into responders (lost at least 5% of body weight) and non-responders for analysis.

Results: Treatment with liraglutide 3.0 mg significantly decreased body weight (estimated marginal mean, 93.2 kg at baseline and 88.9 kg at 16 weeks; p < 0.001) as well as waist circumference, BMI and plasma glucose levels. Six of 16 patients (37.5%) complained of a modest degree of nausea. Six of the 12 subjects (50%) completing 16 weeks of treatment were responders. There were no significant differences in baseline characteristics between responders and non-responders. There was no worsening of CGI-S scores.

Conclusion: Liraglutide 3.0 mg significantly decreased body weight in obese patients treated with antipsychotics without altering the status of psychiatric diseases. A randomized controlled study is required to corroborate the results of this study.
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http://dx.doi.org/10.1016/j.psychres.2021.113830DOI Listing
May 2021

A single-arm feasibility study of gradual dose de-escalation of antiemetic dexamethasone for older patients receiving chemotherapy.

J Geriatr Oncol 2021 07 26;12(6):922-929. Epub 2021 Feb 26.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

Objectives: To investigate whether discontinuation of prophylactic dexamethasone by gradual dose de-escalation is practicable in older patients with cancer undergoing moderately emetogenic chemotherapy.

Materials And Methods: This single-arm, feasibility study prospectively enrolled 40 patients (≥70 years old) with colorectal cancer, who were scheduled to undergo adjuvant FOLFOX chemotherapy, and ten patients ≤60 years old to serve as a control group for pharmacokinetic study. All patients received an antiemetic regimen consisting of intravenous dexamethasone 8 mg and palonosetron at day 1 of the first cycle and underwent phone interviews using symptom questionnaires at day 7 of each cycle. Dexamethasone was tapered off through gradual de-escalation by 2 mg per cycle, when complete response (CR; no emesis and no rescue therapy) was achieved. Primary endpoint was the proportion of patients who discontinued dexamethasone completely.

Results: The median age of the patient was 74 years, and 50% were male. Of the 40 patients, 36 completed twelve cycles of chemotherapy, and 73% (N = 29) were able to discontinue dexamethasone completely. The mean (±SD) dose of dexamethasone per cycle was 3.0 mg (±2.4 mg), which was reduced to 37.5% of the initial dose level. The severity of patient-reported nausea did not significantly change over chemotherapy cycle. Geriatric assessment revealed no decline in any domain and fasting blood glucose and hemoglobin A1c levels were not elevated after twelve cycles of chemotherapy, compared to the baseline.

Conclusion: Gradual dose de-escalation and discontinuation of prophylactic dexamethasone is feasible without compromising its antiemetic effect in older patients undergoing chemotherapy.
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http://dx.doi.org/10.1016/j.jgo.2021.02.018DOI Listing
July 2021

Vapor phase polymerization for electronically conductive nanopaper based on bacterial cellulose/poly(3,4-ethylenedioxythiophene).

Carbohydr Polym 2021 Apr 16;257:117658. Epub 2021 Jan 16.

Department of Plant & Environmental New Resources and Biotechnology and Institute of Life Science and Resources, Kyung Hee University, 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 446-701, South Korea. Electronic address:

Eco-friendly conductive polymer nanocomposites have garnered attention as an effective alternative for conventional conductive nanocomposites. Here, we report the fabrication and optimization of flexible, self-standing, and conductive bacterial cellulose/poly(3,4-ethylene dioxythiophene) (BC/PEDOT) nanocomposites using the vapor phase polymerization (VPP) method. Eco-friendly bacterial cellulose (BC) is used as a flexible matrix, and the highly conductive PEDOT polymer is introduced into the BC matrix to achieve electronic conductivity. We demonstrate that vapor phase polymerized BC/PEDOT composites exhibit more than 10 times lower sheet resistance (18 Ω/square) compared to solution polymerized BC/PEDOT (188 Ω/square). The resultant BC/PEDOT fabricated could be bent up to 100 times and completely rolled up without a notable decrease in electronic performance. Moreover, bent BC/PEDOT films enable operation of a green light-emitting diode (LED) light, indicating the flexibility and stability of conductive BC/PEDOT films. Overall, this study suggests a strategy for the development of eco-friendly, flexible, and conductive nanocomposite films.
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http://dx.doi.org/10.1016/j.carbpol.2021.117658DOI Listing
April 2021

Real-World Clinical Outcomes and Prognostic Factors for Patients with Advanced Angiosarcoma who Received Systemic Treatment.

Cancer Res Treat 2021 Feb 1. Epub 2021 Feb 1.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Purpose: Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated.

Materials And Methods: We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions.

Results: Among the patients evaluated, 51 patients were male (68%) and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression free survival (mPFS) of 4.0 months (95% confidence interval [CI] 3.0-6.1), and a median overall survival (mOS) of 10.2 months (95% CI 7.0-14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 vs. 3.2 months, respectively, p=0.014) with a tendency for prolonged mOS (13.8 vs. 11.6 months, respectively, p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI 1.8-4.3) and a mOS of 5.4 months (95% CI 3.5-NA).

Conclusion: Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.
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http://dx.doi.org/10.4143/crt.2020.1337DOI Listing
February 2021

Clinical pattern of failure after a durable response to immune check inhibitors in non-small cell lung cancer patients.

Sci Rep 2021 01 28;11(1):2514. Epub 2021 Jan 28.

Department of Internal Medicine, Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 beon-gil, Bundang-Gu, Seongnam, Gyeonggi-do, 13620, Republic of Korea.

Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5-21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months [95% CI, 10.6-NR] vs. 8.8 months [95% CI, 5.7-NR], P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups (P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.
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http://dx.doi.org/10.1038/s41598-021-81666-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844257PMC
January 2021

Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study.

Cancers (Basel) 2021 Jan 18;13(2). Epub 2021 Jan 18.

Division of Medical Oncology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea.

Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4-47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3-5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.
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http://dx.doi.org/10.3390/cancers13020331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829741PMC
January 2021

Tumor LAG-3 and NY-ESO-1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer.

Thorac Cancer 2021 03 17;12(5):619-630. Epub 2021 Jan 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.

Background: Immune checkpoint inhibitors (ICIs) are an established treatment for non-small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested NY-ESO-1 and LAG-3 to be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of their expression in NSCLC.

Methods: We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti-PD-1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum-based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY-ESO-1, LAG-3, and PD-L1 expression, whose ability to predict progression-free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values.

Results: NY-ESO-1 or LAG-3 expression was detected in all tumor samples from patients with high PD-L1 expression and was significantly associated with favorable outcomes, unlike PD-L1 expression. Patients with both NY-ESO-1- and LAG-3-expressing tumors had a high DCB rate and those with triple-positive PD-L1, LAG-3, and NY-ESO expression had a superior median OS and PFS than those with triple-negative expression. Furthermore, LAG-3 and NY-ESO-1 co-expression was an independent predictor of both PFS and OS, while LAG-3 displayed a good NPV.

Conclusions: Patients with NSCLC who co-express NY-ESO-1 or LAG-3 with PD-L1 exhibit greater DCBs and improved long-term survival following anti-PD-1 therapy. Moreover, NY-ESO-1 and LAG-3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.
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http://dx.doi.org/10.1111/1759-7714.13834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919166PMC
March 2021

Strategy for Selective Printing of Gate Insulators Customized for Practical Application in Organic Integrated Devices.

ACS Appl Mater Interfaces 2021 Jan 28;13(1):1043-1056. Epub 2020 Dec 28.

Department of Advanced Organic Materials Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea.

Direct drawing techniques have contributed to the ease of patterning soft electronic materials, which are the building blocks of analog and digital integrated circuits. In parallel with the printing of semiconductors and electrodes, selective deposition of gate insulators (GI) is an equally important factor in simplifying the fabrication of integrated devices, such as NAND and NOR gates, and memory devices. This study demonstrates the fabrication of six types of printed GI layers (high/low- polymer and organic-inorganic hybrid material), which are utilized as GIs in organic field-effect transistors (OFETs), using the electrostatic-force-assisted dispensing printing technique. The selective printing of GIs on the gate electrodes enables us to develop practical integrated devices that go beyond unit OFET devices, exhibiting robust switching performances, non-destructive operations, and high gain values. Moreover, the flexible integrated devices fabricated using this technique exhibit excellent operational behavior. Therefore, this facile fabrication technique can pave a new path for the production of practical integrated device arrays for next-generation devices.
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http://dx.doi.org/10.1021/acsami.0c18477DOI Listing
January 2021

Effectiveness of antipsychotic drugs in schizophrenia: a 10-year retrospective study in a Korean tertiary hospital.

NPJ Schizophr 2020 Nov 19;6(1):32. Epub 2020 Nov 19.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

Extensive research has been carried out on the comparative effectiveness of antipsychotic medications. Most studies, however, have been performed in Western countries. The purpose of this study was to compare the effectiveness, indicated by time to any-cause discontinuation, of antipsychotic drugs in a large number of patients with schizophrenia in South Korea. We identified 1458 patients with schizophrenia or schizophreniform disorder who were treated with antipsychotic medications using a clinical data warehouse at the Seoul National University Hospital between March 2005 and February 2014. Kaplan-Meier survival analyses were used to estimate the time to discontinuation of antipsychotic drugs. We compared the survival curves of different antipsychotics using log-rank tests. Overall, the median time to discontinuation for any cause was 133 days (95% CI, 126-147). The longest time to discontinuation was observed for clozapine, followed by aripiprazole, paliperidone, olanzapine, amisulpride, risperidone, quetiapine, ziprasidone, and haloperidol. Specifically, clozapine was significantly different from all other antipsychotic drugs (all p < 0.001). Aripiprazole also had a significantly longer time to discontinuation than amisulpride (p = 0.001), risperidone (p < 0.001), quetiapine (p < 0.001), ziprasidone (p < 0.001), and haloperidol (p < 0.001). In Asian patients with schizophrenia, clozapine was the most effective antipsychotic in terms of time to discontinuation, followed by aripiprazole. This study extends the findings of previous effectiveness studies from Western populations and suggests the need to develop guidelines for the pharmacotherapy of schizophrenia tailored to Asian individuals.
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http://dx.doi.org/10.1038/s41537-020-00122-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677553PMC
November 2020

Phase II study of durvalumab and tremelimumab in pulmonary sarcomatoid carcinoma: KCSG-LU16-07.

Thorac Cancer 2020 12 7;11(12):3482-3489. Epub 2020 Oct 7.

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Pulmonary sarcomatoid carcinoma (PSC) is rare with a poor outcome and is resistant to conventional cytotoxic chemotherapy. The efficacy and safety of durvalumab and tremelimumab for treating recurrent or metastatic PSCs were assessed by a nonrandomized, open-label, phase II study.

Methods: A total of 18 patients with recurrent or metastatic PSC received 1500 mg of durvalumab and 75 mg of tremelimumab every four weeks, followed by 750 mg of durvalumab every two weeks until the disease progressed, or an unacceptable toxicity level was reached. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. Genomic profiling of PSC by next-generation sequencing (NGS) and determination of peripheral blood lymphocyte subsets using flow cytometry were performed for exploratory analysis.

Results: A total of 15 out of 18 patients were evaluated for the analysis of the primary endpoint. At the data cutoff point, the ORR of 26.7% (95% confidence interval [CI]: 7.8-55.1) was achieved with the median follow-up duration of 12.0 months (range, 8.4-16.1). Median PFS and OS were 5.9 months (95% CI: 1.1-11.9) and 15.4 months (95% CI: 11.1-not reached), respectively. Treatment-related adverse events (AEs) of any grade were reported in 16 patients; the most common AEs were pruritus (n = 5), pneumonitis (n = 4), and rash (n = 4). Treatment was discontinued in two patients due to AEs of grade ≥ 3.

Conclusions: Durvalumab and tremelimumab demonstrated clinical benefit with a prolonged survival and manageable toxicity profile in patients with recurrent or metastatic PSC.
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http://dx.doi.org/10.1111/1759-7714.13684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705626PMC
December 2020

Pneumocystis jirovecii pneumonia in diffuse large B-cell Lymphoma treated with R-CHOP.

Mycoses 2021 Jan 28;64(1):60-65. Epub 2020 Oct 28.

Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: The aim of this study was to estimate the incidence of and risk factors for Pneumocystis pneumonia (PCP) infection in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP).

Methods: The medical records of 739 DLBCL patients who received R-CHOP between May 2004 and January 2019 were retrospectively evaluated. Patients were divided into two groups: those who received primary PCP prophylaxis (prophylaxis group) and those who did not (control group). The incidence rate of PCP in each group was calculated, and risk factors for PCP were evaluated in the control group.

Results: Baseline characteristics were significantly different between the two groups. Compared to the 602 patients who did not receive prophylaxis, the prophylaxis group (n = 137) had poor prognostic factors of older age, high lactate dehydrogenase (LDH) levels, advanced Ann Arbour stage, and high International Prognostic Index (IPI) risk scores. None of the patients receiving PCP prophylaxis developed PCP, while the incidence of PCP in the control group was 8.1% (definite cases 5.5% and probable cases 2.7%). Out of the 49 patients who developed PCP, 10 patients (20.4%) were admitted to the intensive care unit, and the PCP-related death rate was 16.3% (8/49).

Conclusion: This study showed that PCP prophylaxis is highly effective against PCP infection and may help guide prevention of PCP during R-CHOP treatment in DLBCL patients.
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http://dx.doi.org/10.1111/myc.13184DOI Listing
January 2021

PI3K p110α Blockade Enhances Anti-Tumor Efficacy of Abemaciclib in Human Colorectal Cancer Cells.

Cancers (Basel) 2020 Sep 3;12(9). Epub 2020 Sep 3.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.

Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of mutation status but showed greater efficacy in the mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer.
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http://dx.doi.org/10.3390/cancers12092500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564416PMC
September 2020

Identifying germline APOBEC3B deletion and immune phenotype in Korean patients with operable breast cancer.

Breast Cancer Res Treat 2020 Oct 26;183(3):697-704. Epub 2020 Jul 26.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea.

Background: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) is implicated in anti-viral immune response and cancer mutagenesis. Germline APOBEC3B deletion is associated with increased susceptibility to breast cancer. We aimed to evaluate the association between germline APOBEC3B deletion and clinical phenotypes of breast cancer in Korean patients with operable breast cancer.

Methods: Mononuclear blood cell DNA of 103 patients with operable breast cancer was collected at Seoul National University Bundang Hospital in 2009. The DNA was sequenced to analyze APOBEC3B deletion status. Further, tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor cells were measured using immunohistochemistry.

Results: Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3B), one-one copy deletion (A3B), and no deletion (A3B), respectively. For other cancer susceptibility gene alterations, 9 (8.7%) patients were identified as pathogenic variants: RAD51D (n = 1), GJB2 (n = 1), BRCA1 (n = 1), BRCA2 (n = 2), ATM (n = 1), USH2A (n = 1), RET (n = 1), BARD1 (n = 1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer, such as age, family history of cancer, and bilateral breast cancer. Further, according to follow-up observations, APOBEC3B deletion was not predictive of disease-free survival. In ER+ subtype, a trend toward better survival was observed in patients with A3B genotype as compared to patients with A3B and A3B genotype (log-rank, P = 0.25). In patients with sufficient tumor samples for the assessment of TIL (n = 63) and PD-L1 (n = 71), the A3B genotype was significantly associated with high TILs (> 10%) than other tumor genotypes (6/7 patients in A3B vs. 13/24 in A3B vs. 15/32 in A3B: Fisher's exact test, P = 0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients > 1% PD-L1 in A3B vs. 4/26 in A3B vs. 8/38 in A3B: P = 0.901).

Conclusion: We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3B genotype and high TILs suggests that patients carrying this genotype could be potential candidates for immunotherapy.
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http://dx.doi.org/10.1007/s10549-020-05811-2DOI Listing
October 2020

PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer.

Sci Rep 2020 07 23;10(1):12308. Epub 2020 Jul 23.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173 Beon-gil Bundang-gu, Seongnam, 13620, Republic of Korea.

PIK3CA mutations are frequently observed in various human cancers including gastric cancer (GC). This study was conducted to investigate the anti-tumor effects of alpelisib, a PI3K p110α-specific inhibitor, using preclinical models of GC. In addition, the combined effects of alpelisib and paclitaxel on GC were evaluated. Among the SNU1, SNU16, SNU484, SNU601, SNU638, SNU668, AGS, and MKN1 GC cells, three PIK3CA-mutant cells were predominantly sensitive to alpelisib. Alpelisib monotherapy decreased AKT and S6K1 phosphorylation and induced G/G phase arrest regardless of PIK3CA mutational status. The alpelisib and paclitaxel combination demonstrated synergistic anti-proliferative effects, preferentially on PIK3CA-mutant cells, resulting in increased DNA damage response and apoptosis. In addition, alpelisib and paclitaxel combination potentiated anti-migratory activity in PIK3CA-mutant cells. Alpelisib partially reversed epithelial-mesenchymal transition markers in PIK3CA-mutant cells. In a xenograft model of MKN1 cells, the alpelisib and paclitaxel combination significantly enhanced anti-tumor activity by decreasing Ki-67 expression and increasing apoptosis. Moreover, this combination tended to prolong the survival of tumor-bearing mice. Our data suggest promising anti-tumor efficacy of alpelisib alone or in combination with paclitaxel in PIK3CA-mutant GC cells.
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http://dx.doi.org/10.1038/s41598-020-68998-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378194PMC
July 2020

Direct Patterned Zinc-Tin-Oxide for Solution-Processed Thin-Film Transistors and Complementary Inverter through Electrohydrodynamic Jet Printing.

Nanomaterials (Basel) 2020 Jul 3;10(7). Epub 2020 Jul 3.

School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea.

The solution-processed deposition of metal-oxide semiconducting materials enables the fabrication of large-area and low-cost electronic devices by using printing technologies. Additionally, the simple patterning process of these types of materials become an important issue, as it can simplify the cost and process of fabricating electronics such as thin-film transistors (TFTs). In this study, using the electrohydrodynamic (EHD) jet printing technique, we fabricated directly patterned zinc-tin-oxide (ZTO) semiconductors as the active layers of TFTs. The straight lines of ZTO semiconductors were successfully drawn using a highly soluble and homogeneous solution that comprises zinc acrylate and tin-chloride precursors. Besides, we found the optimum condition for the fabrication of ZTO oxide layers by analyzing the thermal effect in processing. Using the optimized condition, the resulting devices exhibited satisfactory TFT characteristics with conventional electrodes and conducting materials. Furthermore, these metal-oxide TFTs were successfully applied to complementary inverter with conventional p-type organic semiconductor-based TFT, showing high quality of voltage transfer characteristics. Thus, these printed ZTO TFT results demonstrated that solution processable metal-oxide transistors are promising for the realization of a more sustainable and printable next-generation industrial technology.
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http://dx.doi.org/10.3390/nano10071304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407936PMC
July 2020

Direct Printing of Asymmetric Electrodes for Improving Charge Injection/Extraction in Organic Electronics.

ACS Appl Mater Interfaces 2020 Jul 14;12(30):33999-34010. Epub 2020 Jul 14.

Department of Advanced Organic Materials Engineering, Yeungnam University, Gyeongsan 38541, Korea.

Engineering the energy levels of organic conducting materials can be useful for developing high-performance organic field-effect transistors (OFETs), whose electrodes must be well controlled to facilitate easy charge carrier transport from the source to drain through an active channel. However, symmetric source and drain electrodes that have the same energy levels are inevitably unfavorable for either charge injection or charge extraction. In this study, asymmetric source and drain electrodes are simply prepared using the electrohydrodynamic (EHD)-jet printing technique after the careful work function engineering of organic conducting material composites. Two types of additives effectively tune the energy levels of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate-based composites. These solutions are alternately patterned using the EHD-jet printing process, where the use of an electric field makes fine jet control that enables to directly print asymmetric electrodes. The asymmetric combination of EHD-printed electrodes helps in obtaining advanced charge transport properties in p-type and n-type OFETs, as well as their organic complementary inverters. This strategy is believed to provide useful guidelines for the facile patterning of asymmetric electrodes, enabling the desirable properties of charge injection and extraction to be achieved in organic electronic devices.
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http://dx.doi.org/10.1021/acsami.0c08683DOI Listing
July 2020

Facile Photo-cross-linking System for Polymeric Gate Dielectric Materials toward Solution-Processed Organic Field-Effect Transistors: Role of a Cross-linker in Various Polymer Types.

ACS Appl Mater Interfaces 2020 Jul 25;12(27):30600-30615. Epub 2020 Jun 25.

Department of Advanced Organic Materials Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea.

Energy-efficient solution-processed organic field-effect transistors (OFETs) are highly sought after in the low-cost printing industry as well as for the manufacture of flexible and other next-generation devices. The fabrication of such electronic devices requires high-functioning insulating materials that are chemically and mechanically robust to avoid lowering insulating properties during the device fabrication process or utilization of devices. In this study, we report a facile, fluorinated, UV-assisted cross-linker series using a fluorophenyl azide (FPA), which reacts with the C-H groups of a conventional polymer. This demonstrates the application of the cross-linked films in OFET gate dielectrics. The effects of the cross-linkable chemical structure of the FPA series on the cross-linking chemistry, photopatternability, and dielectric properties of the resulting films are investigated for low/high- or amorphous/crystalline polymeric gate dielectric materials. The characteristics of insulating layers and behavior of OFETs containing these cross-linked gate dielectrics (for example, leakage current density (), hysteresis, and charge trap density) depend on the polymer type. Furthermore, an organic-based complementary inverter and various printable OFETs with excellent electrical characteristics are successfully fabricated. Thus, these reported cross-linkers that enable the solution process and patterning of well-developed conventional polymer dielectric materials are promising for the realization of a more sustainable next-generation industrial technology for flexible and printable devices.
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http://dx.doi.org/10.1021/acsami.0c04356DOI Listing
July 2020

Ultra-Low Power Electrochromic Heat Shutters Through Tailoring Diffusion-Controlled Behaviors.

ACS Appl Mater Interfaces 2020 Jul 24;12(27):30635-30642. Epub 2020 Jun 24.

Department of Chemical Engineering, University of Seoul, Seoul 02504, Republic of Korea.

In this study, we propose low power consumption, all-in-one type electrochromic devices (ECDs) for effective heat shutters. Considering diffusion-controlled device operation, polymeric viologens (poly-viologens) are synthesized to lower the diffusivity of EC chromophores and to minimize self-bleaching. In comparison with devices based on mono-viologens corresponding to the monomer of poly-viologens, poly-viologen-containing ECDs exhibit advantages of lower coloration voltage (ca, -0.55 V) and higher coloration/bleaching cyclic stability (>1500 cycles). In particular, poly-viologen ECDs show remarkably reduced self-bleaching as designed, resulting in extremely low power consumption (∼8.3 μW/cm) to maintain the colored state. Moreover, we successfully demonstrate solar heat shutters that suppress the increment of indoor temperature by taking the advantage of low-power operation and near-IR absorption of the colored poly-viologen-based ECDs. Overall, these results imply that the control of the diffusivity of EC chromophores is an effective methodology for achieving single-layered, low-power electrochemical heat shutters that can save indoor cooling energy when applied as smart windows for buildings or vehicles.
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http://dx.doi.org/10.1021/acsami.0c05918DOI Listing
July 2020
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