Publications by authors named "Tae Hyun Kim"

673 Publications

Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid-secretory phases.

Exp Ther Med 2021 Jun 20;21(6):660. Epub 2021 Apr 20.

Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea.

Successful embryo implantation is the first step for establishing natural pregnancy and is dependent on the crosstalk between the embryo and a receptive endometrium. However, the molecular signaling events for successful embryo implantation are not entirely understood. To identify differentially expressed transcripts [long-noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs] and competing endogenous RNA (ceRNA) networks associated with endometrial receptivity, the current study analyzed gene expression profiles between proliferative and mid-secretory endometria in fertile women. A total of 247 lncRNAs, 67 miRNAs and 2,154 mRNAs were identified as differentially expressed between proliferative and mid-secretory endometria. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these differentially expressed genes were significantly enriched for 'cell adhesion molecules.' Additionally, 98 common mRNAs were significantly involved in tryptophan metabolism, metabolic pathways and FoxO signaling. From the differentially expressed lncRNA/miRNA/mRNA ceRNA network, hub RNAs that formed three axes were identified: The DLX6-AS1/miR-141 or miR-200a/OLFM1 axis, the WDFY3-AS2/miR-135a or miR-183/STC1 axis, and the LINC00240/miR-182/NDRG1 axis. These may serve important roles in the regulation of endometrial receptivity. The hub network of the current study may be developed as a candidate marker for endometrial receptivity.
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http://dx.doi.org/10.3892/etm.2021.10092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097233PMC
June 2021

Label-Free Assay of Protein Kinase A Activity and Inhibition Using a Peptide-Based Electrochemical Sensor.

Biomedicines 2021 Apr 13;9(4). Epub 2021 Apr 13.

Department of ICT Environmental Health System, Graduate School, Soonchunhyang University, Asan 31538, Korea.

We propose a simple label-free electrochemical biosensor for monitoring protein kinase activity and inhibition using a peptide-modified electrode. The biosensor employs cys-kemptide (CLRRASLG) as a substrate peptide which was immobilized on the surface of a gold electrode via the self-assembly of the thiol terminals in cysteine (C) residues. The interaction between protein kinase A (PKA) and adenosine 5'-triphosphate (ATP) on the cys-kemptide immobilized electrode can cause the transfer of ATP terminal phosphates to the peptide substrates at serine (S) residues, which alters the surface charge of the electrode, thus enabling monitoring of the PKA activity via measuring the interfacial electron transfer resistance with electrochemical impedance spectroscopy. The proposed sensor showed reliable, sensitive, and selective detection of PKA activity with a wide dynamic range of 0.1-100 U/mL and a detection limit of 56 mU/mL. The sensor also exhibited high selectivity, rendering it possible to screen PKA inhibitors. Moreover, the sensor can be employed to evaluate the activity and inhibition of PKA in real samples.
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http://dx.doi.org/10.3390/biomedicines9040423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069798PMC
April 2021

Inhibition of AKT/GSK3β/CREB Pathway Improves the Responsiveness to AMPA Receptor Antagonists by Regulating GRIA1 Surface Expression in Chronic Epilepsy Rats.

Biomedicines 2021 Apr 14;9(4). Epub 2021 Apr 14.

Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, Korea.

α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) has been reported as one of the targets for treatment of epilepsy. Although maladaptive regulation of surface expression of glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) subunit is relevant to the responsiveness to AMPAR antagonists (perampanel and GYKI 52466) in LiCl-pilocarpine-induced chronic epilepsy rats, the underlying mechanisms of refractory seizures to AMPAR antagonists have yet been unclear. In the present study, we found that both AMPAR antagonists restored the up-regulations of GRIA1 surface expression and Src family-mediated glycogen synthase kinase 3β (GSK3β)-Ca/cAMP response element-binding protein (CREB) phosphorylations to control levels in responders (whose seizure activities were responsive to AMPAR) but not non-responders (whose seizure activities were uncontrolled by AMPAR antagonists). In addition, 3-chloroacetyl indole (3CAI, an AKT inhibitor) co-treatment attenuated spontaneous seizure activities in non-responders, accompanied by reductions in AKT/GSK3β/CREB phosphorylations and GRIA1 surface expression. Although AMPAR antagonists reduced GRIA2 tyrosine (Y) phosphorylations in responders, they did not affect GRIA2 surface expression and protein interacting with C kinase 1 (PICK1) protein level in both responders and non-responders. Therefore, our findings suggest that dysregulation of AKT/GSK3β/CREB-mediated GRIA1 surface expression may be responsible for refractory seizures in non-responders, and that this pathway may be a potential target to improve the responsiveness to AMPAR antagonists.
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http://dx.doi.org/10.3390/biomedicines9040425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103519PMC
April 2021

BMI, weight change, and incidence of disability among Korean adults: A nationwide retrospective cohort study.

Disabil Health J 2021 Apr 1:101104. Epub 2021 Apr 1.

College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, South Korea. Electronic address:

Background: Little is known about the risk of acquired disability diagnosed by a physician in relation to baseline BMI and weight change, particularly in the Asian population.

Objective: This study assessed the association of baseline BMI and weight change with incidence of disability.

Methods: This study included 331,900 individuals aged ≥40 years who participated in two health-screening programs since 2002 or 2003 and who were followed up until 2013. This study measured the baseline BMI and weight change for two years and estimated the adjusted hazard ratio (aHR) of the risk of acquired disability diagnosed by a physician using a Cox proportional hazards model.

Results: This study identified 1758 incident disability cases during an average follow-up period of 10.7 ± 1.3 years from baseline (9.1 ± 1.4 years from the follow-up health screening). Baseline underweight (BMI<18.5 kg/m) was associated with an increased risk of acquired disability compared with those with normal BMI (aHR, 1.44; 95% confidence interval [CI], 1.14-1.83). The risk of acquired disability was higher in individuals with weight loss of 5-10% (aHR, 1.21; 95% CI, 1.04-1.40), weight loss of ≥10% (aHR, 1.61; 95% CI, 1.27-2.04), weight gain of 5-10% (aHR, 1.30; 95% CI, 1.12-1.52), or weight gain of ≥10% (aHR, 1.35; 95% CI, 1.09-1.75) compared to those with weight change of <5%.

Conclusion: This study demonstrated that baseline underweight and weight changes (both loss and gain) are associated with an increased risk of acquired disability.
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http://dx.doi.org/10.1016/j.dhjo.2021.101104DOI Listing
April 2021

Relationship between workers' return to work, job retention and income in industrial accidents in Korea: a longitudinal study.

BMJ Open 2021 Apr 9;11(4):e039948. Epub 2021 Apr 9.

Graduate School of Public Health, Yonsei University, Seoul, South Korea

Objective: This study aims to compare workers' income before and after an occupational injury, with regard to return to work and job retention, over a period of 5 years.

Design: This study was designed as a longitudinal study.

Setting: The Panel Study of Workers' Compensation Insurance (PSWCI) survey targeted workers involved in industrial accidents for which medical care was terminated in the year 2012.

Participants: The panel study was conducted on a final sample of 2000 workers who were selected proportionally by region (nine regions) after priority assignment by disability rating (six levels). A total of 1458 workers were finally included in this study.

Methods: This study used data from the first to fifth PSWCI. To identify the effect on income after occupational injury considering return to work and job retention, we used the generalised estimating equation.

Results: In regard to workers' return to work, the OR that income after an occupational injury would be higher than that before an occupational injury was 3.17 (2.41-4.17) for those who returned to original work and 2.32 (1.81-2.97) for those re-employed as compared with who did not return to work and 1.27 (1.07-1.15) for those who retained their job as compared with those who did not. The ORs were 2.91 (2.26-3.75) for those who were re-employed and retained jobs and 2.96 (2.15-4.08) for those who returned to original work and did not retain jobs as compared with those who did not return to work and did not retain jobs.

Conclusions: It is important for accident victims to retain their jobs to maintain their economic status.
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http://dx.doi.org/10.1136/bmjopen-2020-039948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043011PMC
April 2021

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006).

J Breast Cancer 2021 Apr 25;24(2):164-174. Epub 2021 Mar 25.

Department of Surgery, Pusan National University Hospital, Busan, Korea.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels.

Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3-4, 5-6, and 7-8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate.

Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8-96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively ( = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively ( = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity.

Conclusion: Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Trial Registration: ClinicalTrials.gov Identifier: NCT01069211.
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http://dx.doi.org/10.4048/jbc.2021.24.e17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090806PMC
April 2021

Evaluation of Patient No-Shows in a Tertiary Hospital: Focusing on Modes of Appointment-Making and Type of Appointment.

Int J Environ Res Public Health 2021 03 22;18(6). Epub 2021 Mar 22.

Department of Healthcare Management, Graduate School of Public Health, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

No-show appointments waste resources and decrease the sustainability of care. This study is an attempt to evaluate patient no-shows based on modes of appointment-making and types of appointments. We collected hospital information system data and appointment data including characteristics of patients, service providers, and clinical visits over a three-month period (1 September 2018 to 30 November 2018), at a large tertiary hospital in Seoul, Korea. We used multivariate logistic regression analyses to identify the factors associated with no-shows (Model 1). We further assessed no-shows by including the interaction term ("modes of appointment-making" X "type of appointment") (Model 2). Among 1,252,127 appointments, the no-show rate was 6.12%. Among the modes of appointment-making, follow-up and online/telephone appointment were associated with higher odds of no-show compared to walk-in. Appointments for treatment and surgery had higher odds ratios of no-show compared to consultations. Tests for the interaction between the modes of appointment-making and type of appointment showed that follow-up for examination and online/telephone appointments for treatment and surgery had much higher odds ratios of no-shows. Other significant factors of no-shows include age, type of insurance, time of visit, lead time (time between scheduling and the appointment), type of visits, doctor's position, and major diagnosis. Our results suggest that future approaches for predicting and addressing no-show should also consider and analyze the impact of modes of appointment-making and type of appointment on the model of prediction.
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http://dx.doi.org/10.3390/ijerph18063288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005203PMC
March 2021

"The Power of Ethical Leadership": The Influence of Corporate Social Responsibility on Creativity, the Mediating Function of Psychological Safety, and the Moderating Role of Ethical Leadership.

Int J Environ Res Public Health 2021 03 14;18(6). Epub 2021 Mar 14.

College of Business, Korea Advanced Institute of Science and Technology, Seoul 02455, Korea.

A body of existing literature delves into how corporate social responsibility (CSR) affects employees' cognition, emotion, and behavior within an organization. These previous studies, however, pay relatively little attention to the influence of CSR on levels of creativity in employees. Considering that creativity is closely related to innovative capability, which is critical for a firm to survive, the relationship between CSR and employees' creativity and its elaborate underlying processes need further investigation. Based on a group creativity model, we argue that CSR may increase levels of creativity in employees through mediation of enhanced levels of psychological safety in employees. In addition, existing works on CSR have relatively underexplored the contextual role of leadership in translating CSR practices into employees' attitudes, perceptions, and behaviors. Using three-wave time-lagged survey data from 311 employees in South Korea, we found that CSR enhances employees' creativity via mediation of psychological safety. Additionally, ethical leadership positively moderates the relationship between CSR and psychological safety. Our findings suggest that psychological safety in employees functions as an important underlying mechanism to describe the CSR-employee creativity link. Furthermore, this paper emphasizes the importance of the moderating role of ethical leadership in the process of CSR activities.
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http://dx.doi.org/10.3390/ijerph18062968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998312PMC
March 2021

Preclinical evaluation of radiation therapy of -associated mammary tumors using a mouse model.

Int J Biol Sci 2021 31;17(3):689-701. Epub 2021 Jan 31.

Research Institute, National Cancer Center, Goyang, 10408, Korea.

Although germline mutations in highly predispose women towards breast and ovarian cancer, few substantial improvements in preventing or treating such cancers have been made. Importantly, BRCA1 function is closely associated with DNA damage repair, which is required for genetic stability. Here, we examined the efficacy of radiotherapy, assessing the accumulation of genetic instabilities, in the treatment of -associated breast cancer using a -mutant mouse model. Treatment of -mutant tumor-engrafted mice with X-rays reduced tumor progression by 27.9% compared with untreated controls. A correlation analysis of irradiation responses and biomarker profiles in tumors at baseline identified differences between responders and non-responders at the protein level (pERα, pCHK2, p53, and EpCAM) and at the SOX2 target expression level. We further demonstrated that combined treatment of -mutant mammary tumors with irradiation and AZD2281, which inhibits PARP, significantly reduced tumor progression and extended survival. Our findings enhance the understanding of DNA damage and biomarker responses in -associated mammary tumors and provide preclinical evidence that radiotherapy with synthetic DNA damage is a potential strategy for the therapeutic management of -associated breast cancer.
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http://dx.doi.org/10.7150/ijbs.53667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975707PMC
January 2021

Multi-Institutional Retrospective Study of Radiotherapy for Hepatocellular Carcinoma in the Caudate Lobe.

Front Oncol 2021 26;11:646473. Epub 2021 Feb 26.

Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea.

No studies evaluating the clinical outcomes of radiotherapy (RT) for hepatocellular carcinoma (HCC) in the caudate lobe have been available to date. The purpose of this study was to evaluate the effectiveness and safety of RT for HCC in the caudate lobe. Seventy patients with HCC in the caudate lobe treated with RT from a multi-institutional database were included in this study. The median equivalent dose in 2 Gy (EQD2) was 80.0 Gy (range, 31.3-99.3), and freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were evaluated. The median time of follow-up was 47.9 months (range, 3.4-127), and the 5-year FFLP, PFS, and OS rates were 80.6% [95% confidence interval (CI), 70.8-91.8], 13.8% (95% CI, 7.5-25.4), and 51.3% (95% CI, 39.9-66.1), respectively. In the multivariate analysis, the radiation dose was significantly associated with the FFLP rate [hazard ratio (HR), 0.57 per 10 Gy increase, = 0.001], and the status of FFLP was significantly associated with OS (HR, 2.694, = 0.014). The overall rate of ≥grade 3 adverse events was 5.7% (4 of 70), and RT-related mortality was not observed. RT for HCC in the caudate lobe showed promising FFLP and OS rates with safe toxicity profiles. These findings suggest that RT may be a promising treatment option for HCC in the caudate lobe.
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http://dx.doi.org/10.3389/fonc.2021.646473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952981PMC
February 2021

Chip-Scale Ultra-Low Field Atomic Magnetometer Based on Coherent Population Trapping.

Sensors (Basel) 2021 Feb 22;21(4). Epub 2021 Feb 22.

Time and Frequency Group, Korea Research Institute of Standards and Science, Daejeon 34113, Korea.

We report a chip-scale atomic magnetometer based on coherent population trapping, which can operate near zero magnetic field. By exploiting the asymmetric population among magnetic sublevels in the hyperfine ground state of cesium, we observe that the resonance signal acquires sensitivity to magnetic field in spite of degeneracy. A dispersive signal for magnetic field discrimination is obtained near-zero-field as well as for finite fields (tens of micro-tesla) in a chip-scale device of 0.94 cm volume. This shows that it can be readily used in low magnetic field environments, which have been inaccessible so far in miniaturized atomic magnetometers based on coherent population trapping. The measured noise floor of 300 pT/Hz at the zero-field condition is comparable to that of the conventional finite-field measurement obtained under the same conditions. This work suggests a way to implement integrated atomic magnetometers with a wide operating range.
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http://dx.doi.org/10.3390/s21041517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926612PMC
February 2021

PrP Aptamer Conjugated-Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells.

Int J Mol Sci 2021 Feb 17;22(4). Epub 2021 Feb 17.

Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Korea.

Anticancer drugs, such as fluorouracil (5-FU), oxaliplatin, and doxorubicin (Dox) are commonly used to treat colorectal cancer (CRC); however, owing to their low response rate and adverse effects, the development of efficient drug delivery systems (DDSs) is required. The cellular prion protein PrP, which is a cell surface glycoprotein, has been demonstrated to be overexpressed in CRC, however, there has been no research on the development of PrP-targeting DDSs for targeted drug delivery to CRC. In this study, PrP aptamer (Apt)-conjugated gold nanoparticles (AuNPs) were synthesized for targeted delivery of Dox to CRC. Thiol-terminated PrP-Apt was conjugated to AuNPs, followed by hybridization of its complementary DNA for drug loading. Finally, Dox was loaded onto the AuNPs to synthesize PrP-Apt-functionalized doxorubicin-oligomer-AuNPs (PrP-Apt DOA). The PrP-Apt DOA were spherical nanoparticles with an average diameter of 20 nm. Treatment of CRC cells with PrP-Apt DOA induced reactive oxygen species generation by decreasing catalase and superoxide dismutase activities. In addition, treatment with PrP-Apt DOA inhibited mitochondrial functions by decreasing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, complex 4 activity, and oxygen consumption rates. Compared to free Dox, PrP-Apt DOA decreased proliferation and increased apoptosis of CRC cells to a greater degree. In this study, we demonstrated that PrP-Apt DOA targeting could effectively deliver Dox to CRC cells. PrP-Apt DOA can be used as a treatment for CRC, and have the potential to replace existing anticancer drugs, such as 5-FU, oxaliplatin, and Dox.
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http://dx.doi.org/10.3390/ijms22041976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922473PMC
February 2021

LONP1 Regulates Mitochondrial Accumulations of HMGB1 and Caspase-3 in CA1 and PV Neurons Following Status Epilepticus.

Int J Mol Sci 2021 Feb 25;22(5). Epub 2021 Feb 25.

Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym Unversity, Chuncheon 24252, Korea.

Lon protease 1 (LONP1) is a highly conserved serine peptidase that plays an important role in the protein quality control system in mammalian mitochondria. LONP1 catalyzes the degradation of oxidized, dysfunctional, and misfolded matrix proteins inside mitochondria and regulates mitochondrial gene expression and genome integrity. Therefore, LONP1 is up-regulated and suppresses cell death in response to oxidative stress, heat shock, and nutrient starvation. On the other hand, translocation of high mobility group box 1 (HMGB1) and active caspase-3 into mitochondria is involved in apoptosis of parvalbumin (PV) cells (one of the GABAergic interneurons) and necrosis of CA1 neurons in the rat hippocampus, respectively, following status epilepticus (SE). In the present study, we investigated whether LONP1 may improve neuronal viability to prevent or ameliorate translocation of active caspase-3 and HMGB1 in mitochondria within PV and CA1 neurons. Following SE, LONP1 expression was up-regulated in mitochondria of PV and CA1 neurons. LONP1 knockdown deteriorated SE-induced neuronal death with mitochondrial accumulation of active caspase-3 and HMGB1 in PV cells and CA1 neurons, respectively. LONP1 knockdown did not affect the aberrant mitochondrial machinery induced by SE. Therefore, our findings suggest, for the first time, that LONP1 may contribute to the alleviation of mitochondrial overloads of active caspase-3 and HMGB1, and the maintenance of neuronal viability against SE.
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http://dx.doi.org/10.3390/ijms22052275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956547PMC
February 2021

RF Transceiver for the Multi-Mode Radar Applications.

Sensors (Basel) 2021 Feb 24;21(5). Epub 2021 Feb 24.

School of Electronic and Information Engineering, Korea Aerospace University, Goyang 10540, Korea.

In this work, a multi-mode radar transceiver supporting pulse, FMCW and CW modes was designed as an integrated circuit. The radars mainly detect the targets move by using the Doppler frequency which is significantly affected by flicker noise of the receiver from several Hz to several kHz. Due to this flicker noise, the long-range detection performance of the radars is greatly reduced, and the accuracy of range to the target and velocity is also deteriorated. Therefore, we propose a transmitter that suppresses LO leakage in consideration of long-range detection, target distance, velocity, and noise figure. We also propose a receiver structure that suppresses DC offset due to image signal and LO leakage. The design was conducted with TSMC 65 nm CMOS process, and the designed and fabricated circuit consumes a current of 265 mA at 1.2 V supply voltage. The proposed transmitter confirms the LO leakage suppression of 37 dB at 24 GHz. The proposed receiver improves the noise figure by about 20 dB at 100 Hz by applying a double conversion architecture and an image rejection, and it illustrates a DC rejection of 30 dB. Afterwards, the operation of the pulse, FMCW, and CW modes of the designed radar in integrated circuit was confirmed through experiment using a test PCB.
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http://dx.doi.org/10.3390/s21051563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956796PMC
February 2021

Uncertain Clinical Effect of Polymyxin B Hemoperfusion in Patients with Septic Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

Shock 2021 Feb 17. Epub 2021 Feb 17.

Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Division of Nephrology, Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, South Korea Department of Nursing, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Abstract: Polymyxin B hemoperfusion (PMX-HP) may improve the clinical outcomes of patients with sepsis and gram-negative bacteremia by reducing endotoxin levels. However, the recent studies with the variable degree of renal support have shown that the improvement of survival rate by PMX-HP remains unclear in such patients. Therefore, we investigated whether the addition of PMX-HP to continuous renal replacement therapy (CRRT) could improve the survival rate than CRRT alone. This study included 231 patients with sepsis undergoing CRRT alone or PMX-HP with CRRT. Primary outcomes were 28-day and 90-day all-cause mortality. Urine output, ventilator support, and Sequential Organ Failure Assessment (SOFA) score were not significantly different between the two groups. Crude 28-day and 90-day mortality rates were higher in the PMX-HP with CRRT group than in the CRRT alone group. To correct for disease severity, propensity score (PS) matching was performed with acute respiratory distress syndrome, mechanical ventilation support, extracorporeal membrane oxygenation, infection source (abdomen), age, inotropic score, SOFA score, C-reactive protein, and procalcitonin levels. Sixty-six PS-matched pairs revealed significantly higher 28-day and 90-day mortality rates in the PMX-HP with CRRT group than in the CRRT alone group. Considering the mortality rates after PS matching, the additional use of PMX-HP does not improve the clinical outcomes of patients with sepsis and acute kidney injury requiring CRRT.
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http://dx.doi.org/10.1097/SHK.0000000000001752DOI Listing
February 2021

Efficacy of Local Therapy for Oligometastatic Hepatocellular Carcinoma: A Propensity Score Matched Analysis.

J Hepatocell Carcinoma 2021 11;8:35-44. Epub 2021 Feb 11.

Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: With respect to various solid cancers, patients with oligometastasis may benefit from local therapy. However, this approach is not widely accepted for hepatocellular carcinoma. This study investigated the efficacy of local therapy for oligometastatic lesions in patients with hepatocellular carcinoma.

Patients And Methods: The study included 69 hepatocellular carcinoma patients presenting with oligometastasis to the lung. Characteristics of the patients and treatment options for metastatic lesions were reviewed, and a survival analysis was performed. After propensity score matching, overall survival and progression-free survival were calculated from the time of pulmonary metastasis detection. Factors predicting prognosis were analyzed using a multivariate Cox regression analysis.

Results: After propensity score matching, 58 patients with Child-Pugh grade A disease were selected. Among them, 22 patients were treated with systemic therapy alone while 36 patients received local therapy or a combination of local and systemic therapies for metastatic lesions. Survival rates were higher in patients receiving local therapy than in those receiving systemic therapy (2-year overall survival rate, 66.6 vs 31.2%, p<0.001; 2-year progression-free survival rate, 47.0 vs 10.6%, p=0.005). In the multivariate Cox regression analysis, alpha-fetoprotein levels less than 400 ng/mL and the use of local therapy for metastatic lesions were found to be significant favorable prognostic factors.

Conclusion: Local therapy for metastatic lesions improved the oncologic outcomes of patients with hepatocellular carcinoma with pulmonary oligometastasis.
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http://dx.doi.org/10.2147/JHC.S290197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886258PMC
February 2021

Porous Clay Heterostructure with Alginate Encapsulation for Toluene Removal.

Nanomaterials (Basel) 2021 Feb 3;11(2). Epub 2021 Feb 3.

Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Korea.

A volatile organic compound adsorbent based on a porous clay heterostructure (PCH) with alginate biopolymer was successfully prepared. From N adsorption-desorption analysis, the specific surface area, pore volume, and pore size of bentonite were dramatically increased after introducing the porous structure. Following complexation with alginate (Alg-PCH), the pore volume and pore size were not significantly affected by pore structure. The thermal stability of Alg-PCH shows enhanced thermal stability compared to alginate and alginate beads. The morphology layered structure of Alg-PCH was carried out by transmission electron microscopy (TEM), suggesting the disorder and re-order of the -axis layer stacking by porous structure and complexation with alginate, respectively, which was well-matched with X-ray diffraction results. To optimize the preparation of Alg-PCH, various reaction conditions (alginate, CaCl concentration, bead size, and weight ratio between alginate and PCH) were utilized. According to the toluene adsorption-desorption experiments, the preparation conditions for Alg-PCH were selected as a 2 mm extrusion tip, 0.5% of alginate, and 2% of CaCl solution with a 1:50 alginate:PCH weight ratio. Additionally, it shows 61.63 mg/g adsorption capacity with around 49% desorption efficacy under atmospheric temperature and pressure.
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http://dx.doi.org/10.3390/nano11020388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913573PMC
February 2021

Apoptosis inhibitor of macrophage (AIM) contributes to IL-10-induced anti-inflammatory response through inhibition of inflammasome activation.

Cell Death Dis 2021 01 4;12(1):19. Epub 2021 Jan 4.

Department of Physiology, College of Medicine, Ewha Womans University, Seoul, 07804, Korea.

Apoptosis inhibitor of macrophage (AIM) modulates the signaling in inflammatory responses, including infection, cancer, or other immune diseases. Recent studies suggest that like interleukin-10 (IL-10), AIM is involved in alternatively activated (M2) macrophage polarization. We aimed to understand whether and how AIM is involved in IL-10-induced inhibition of inflammasome activation and resolution of inflammation. First, we demonstrated that IL-10 induced increases in mRNA and protein expression of AIM in murine bone marrow-derived macrophages (BMDM). In addition, genetic and pharmacologic inhibition of STAT3 (signal transducer and activator of transcription 3) reduced IL-10-induced AIM expression. We also found that IL-10-induced STAT3 activity enhanced the AIM promoter activity by directly binding the promoter of the AIM gene. Additionally, reduction of LPS/adenosine triphosphate (ATP)-induced IL-1β production and caspase-1 activation by IL-10 was reversed in BMDM from AIM mice. Treatment of BMDM from both wild type (WT) and IL-10 mice with recombinant AIM showed the inhibitory effects on IL-1β and IL-18 production and caspase-1 activation. Endogenous and exogenous AIM inhibited apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) speck formation. In LPS-induced acute peritonitis, inhibition of IL-1β and IL-18 production in peritoneal lavage fluid (PLF) and serum, reduction of caspase-1 activation in peritoneal macrophages, and reduction of numbers of neutrophils and peritoneal macrophages in PLF by administration of IL-10 were not evident in AIM mice. Our in vitro and in vivo data reveal a novel role of AIM in the inhibition of inflammasome-mediated caspase-1 activation and IL-1β and IL-18 production.
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http://dx.doi.org/10.1038/s41419-020-03332-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791024PMC
January 2021

PLPP/CIN-mediated NF2-serine 10 dephosphorylation regulates F-actin stability and Mdm2 degradation in an activity-dependent manner.

Cell Death Dis 2021 01 4;12(1):37. Epub 2021 Jan 4.

Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.

Neurofibromin 2 (NF2, also known as merlin) is a tumor suppressor protein encoded by the neurofibromatosis type 2 gene NF2. NF2 is also an actin-binding protein that functions in an intrinsic signaling network critical for actin dynamics. Although protein kinase A (PKA)-mediated NF2-serin (S) 10 phosphorylation stabilizes filamentous actin (F-actin), the underlying mechanisms of NF2-S10 dephosphorylation and the role of NF2 in seizures have been elusive. Here, we demonstrate that pyridoxal-5'-phosphate phosphatase/chronophin (PLPP/CIN) dephosphorylated NF2-S10 site as well as cofilin-S3 site. In addition, NF2-S10 dephosphorylation reversely regulated murine double minute-2 (Mdm2) and postsynaptic density 95 (PSD95) degradations in an activity-dependent manner, which increased seizure intensity and its progression in response to kainic acid (KA). In addition, NF2 knockdown facilitated seizure intensity and its progress through F-actin instability independent of cofilin-mediated actin dynamics. Therefore, we suggest that PLPP/CIN may be a potential therapeutic target for epileptogenesis and NF2-associated diseases.
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http://dx.doi.org/10.1038/s41419-020-03325-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791067PMC
January 2021

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

Breast Cancer Res Treat 2021 Apr 4;186(2):453-462. Epub 2021 Jan 4.

Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Purpose: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC).

Methods: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149).

Results: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development.

Conclusions: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.
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http://dx.doi.org/10.1007/s10549-020-06043-0DOI Listing
April 2021

Homogeneous Incorporation of Gallium into Layered Double Hydroxide Lattice for Potential Radiodiagnostics: Proof-of-Concept.

Nanomaterials (Basel) 2020 Dec 26;11(1). Epub 2020 Dec 26.

Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Korea.

Trivalent gallium ion was successfully incorporated into chemically well-defined MgAl-layered double hydroxide (LDH) frameworks through postsynthetic hydrothermal treatment. Quantitative analysis with inductively coupled plasma-mass spectroscopy exhibited that Ga was first incorporated into LDH through partial dissolution-precipitation at the edge of LDH particle and homogeneously distributed throughout the particle by substitution of Ga for Al in LDH frame works. The powder X-ray diffraction patterns showed that the Ga incorporation did not affect the crystal structure without evolution of unexpected impurities. The morphology and surface property of LDH evaluated by scanning electron microscopy and light scattering showed the preservation of physicochemical properties throughout 24 h of hydrothermal reaction. The distribution of incorporated Ga was visualized with energy dispersive spectroscopy-assisted transmission electron microscopy, suggesting the homogeneous location of Ga in an LDH particle. The X-ray absorption near-edge structure and extended X-ray absorption fine structure suggested that the Ga moiety was immobilized in LDH from 0.5 h and readily crystallized upon reaction time.
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http://dx.doi.org/10.3390/nano11010044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824364PMC
December 2020

Cross-Linked Mixed-Matrix Membranes Using Functionalized UiO-66-NH into PEG/PPG-PDMS-Based Rubbery Polymer for Efficient CO Separation.

ACS Appl Mater Interfaces 2020 Dec 18;12(52):57916-57931. Epub 2020 Dec 18.

Organic Material Synthesis Laboratory, Department of Chemistry, Incheon National University, Incheon 22012, Korea.

Mixed-matrix membranes (MMMs) with an ideal polymer-filler interface and high gas separation performance are very challenging to fabricate because of incompatibility between the fillers and the polymer matrix. This work provides a simple technique to prepare a series of cross-linked MMMs (xMMM@) by covalently attaching UiO-66-NB metal-organic frameworks (MOFs) within the PEG/PPG-PDMS copolymer matrix via ring-opening metathesis polymerization and in situ membrane casting. The norbornene-modified MOF (UiO-66-NB) is successfully copolymerized and dispersed homogeneously into a PEG/PPG-PDMS matrix because of very fast polymer formation and strong covalent interaction between MOFs and the rubbery polymer. A significant improvement in gas permeability is achieved in membranes up to a 5 wt % MOF loading compared to the pristine polymer membrane without affecting selectivity. The CO/N separation performance of xMMM@1, xMMM@3, and xMMM@5 with 1, 3, and 5 wt % MOF loading, respectively, surpassed Robeson's 2008 upper bound. In addition, the best performing membrane, xMMM@3 (P = 585 Barrer and CO/N ∼53), approaches the 2019 upper bound, indicating that the cross-linked MMMs (xMMM@) are very promising for CO separation from flue gas. The experimental results of our study were evaluated and are supported by theoretical data obtained using the Maxwell model for MMMs. Moreover, the developed MMMs, xMMM@s, displayed outstanding antiplasticization performance at pressures of up to 25 atm and very stable antiaging performance for up to 11 months with good temperature switching behaviors.
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http://dx.doi.org/10.1021/acsami.0c18415DOI Listing
December 2020

Simplified Diagnosis of Critical Illness Polyneuropathy in Patients with Prolonged Mechanical Ventilation: A Prospective Observational Cohort Study.

J Clin Med 2020 Dec 13;9(12). Epub 2020 Dec 13.

Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Background: Although early identification of critical illness polyneuropathy (CIP) is necessary, the established diagnostic criteria have several limitations in the intensive care unit (ICU) setting. The purpose of this study was to define simplified diagnostic criteria of CIP that best predict clinical outcomes.

Methods: This prospective, single-center study included 41 ICU patients with prolonged mechanical ventilation (≥21 days). We applied three different sets of diagnostic criteria (combining the results of the Medical Research Council (MRC) sum score and nerve conduction studies (NCS)) for CIP in order to identify the criteria with the best predictive power for clinical outcomes.

Results: The simplified diagnosis of CIP meeting the criteria, i.e., that the MRC sum score < 48 and amplitudes of the tibial and sural nerve < 80% of the lower limit of normal, showed the strongest association with 0 ventilator-free days at day 60 (odds ratio, 6.222; = 0.029).

Conclusions: The diagnostic criteria combining the MRC sum score and the tibial and the sural NCS were identified as the simplified criteria of CIP that best predicted the clinical outcomes. The implementation of these simplified criteria may allow for early identification of CIP in the ICU, thereby contributing to prompt interventions for patients with a poor prognosis.
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http://dx.doi.org/10.3390/jcm9124029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764577PMC
December 2020

Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer.

Sci Rep 2020 12 10;10(1):21712. Epub 2020 Dec 10.

Center for Proton Therapy, National Cancer Center, Goyang, 10408, Republic of Korea.

To evaluate the clinical efficacy and feasibility of proton beam radiotherapy (PBT) using the simultaneous integrated boost (SIB) technique in locally advanced pancreatic cancer (LAPC), 81 LAPC patients receiving PBT using SIB technique were analyzed. The prescribed doses to planning target volume (PTV)1 and PTV2 were 45 or 50 GyE and 30 GyE in 10 fractions, respectively. Of 81 patients, 18 patients received PBT without upfront and maintenance chemotherapy (group I), 44 received PBT followed by maintenance chemotherapy (group II), and 19 received PBT after upfront chemotherapy followed by maintenance chemotherapy (n = 16) (group III). The median follow-up time was 19.6 months (range 2.3-57.6 months), and the median overall survival (OS) times of all patients and of those in groups I, II, and III were 19.3 months (95% confidence interval [CI] 16.8-21.7 months), 15.3 months (95% CI 12.9-17.7 months), 18.3 months (95% CI 15.9-20.7 months), and 26.1 months (95% CI 17.8-34.3 months), respectively (p = 0.043). Acute and late grade ≥ 3 toxicities related to PBT were not observed. PBT with the SIB technique showed promising OS for LAPC patients with a safe toxicity profile, and intensive combinations of PBT and chemotherapy could improve OS in these patients.
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http://dx.doi.org/10.1038/s41598-020-78875-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729854PMC
December 2020

Visual outcomes of proton beam therapy for choroidal melanoma at a single institute in the Republic of Korea.

PLoS One 2020 2;15(12):e0242966. Epub 2020 Dec 2.

Proton Therapy Center, Research Institute and Hospital, National Cancer center, Gyeonggi-do, Korea.

We evaluate the ocular effects of proton beam therapy (PBT) in a single institution, in Korea, and identify factors contributing to decreasing visual acuity (VA) after PBT. A total of 40 patients who received PBT for choroidal melanoma (2009‒2016) were reviewed. Dose fractionation was 60‒70 cobalt gray equivalents (CGEs) over five fractions. Complete ophthalmic examinations including funduscopy and ultrasonography were performed at baseline and at 3, 6, and 12 months after PBT, then annually thereafter. Only patients with at least 12 months follow-up were included. During the follow-up, consecutive best-corrected visual acuity (BCVA) changes were determined, and univariate and multivariate logistic regression analyses were performed to identify predictors for VA loss. The median follow-up duration was 32 months (range: 12‒82 months). The final BCVA of nine patients was > 20/40. The main cause of vision loss was intraocular bleeding, such as neovascular glaucoma or retinal hemorrhage. Vision loss was correlated with the tumor size, tumor distance to the optic disc or fovea, maculae receiving 30 CGEs, optic discs receiving 30 CGEs, and retinas receiving 30 CGEs. Approximately one-third of PBT-treated choroidal melanoma patients with good pretreatment BCVA maintained their VA. The patients who finally lost vision (VA < count fingers) usually experienced rapid declines in VA from 6‒12 months after PBT. Tumor size, tumor distance to the optic disc or fovea, volume of the macula, and optic discs or retinas receiving 30 CGEs affected the final VA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242966PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710050PMC
January 2021

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes.

Yonsei Med J 2020 Dec;61(12):1004-1012

Department of Cardiology, Peking University Shougang Hospital, Shijingshan District, Beijig, China.

Purpose: Dissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.

Materials And Methods: A total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).

Results: The cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, =0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, =0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.

Conclusion: The presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277).
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http://dx.doi.org/10.3349/ymj.2020.61.12.1004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700881PMC
December 2020

Crosslinked Pore-Filling Anion Exchange Membrane Using the Cylindrical Centrifugal Force for Anion Exchange Membrane Fuel Cell System.

Polymers (Basel) 2020 Nov 23;12(11). Epub 2020 Nov 23.

Department of Materials Engineering and Convergence Technology, Engineering Research Institute, Gyeongsang National University, Jinju 52828, Korea.

In this study, novel crosslinked pore-filling membranes were fabricated by using a centrifugal force from the cylindrical centrifugal machine. For preparing these crosslinked pore-filling membranes, the poly(phenylene oxide) containing long side chains to improve the water management (hydrophilic), porous polyethylene support (hydrophobic) and crosslinker based on the diamine were used. The resulting membranes showed a uniform thickness, flexible and transparent because it is well filled. Among them, PF-XAc-PPO70_25 showed good mechanical properties (56.1 MPa of tensile strength and 781.0 MPa of Young's modulus) and dimensional stability due to the support. In addition, it has a high hydroxide conductivity (87.1 mS/cm at 80 °C) and low area specific resistance (0.040 Ω·cm), at the same time showing stable alkaline stability. These data outperformed the commercial FAA-3-50 membrane sold by Fumatech in Germany. Based on the optimized properties, membrane electrode assembly using XAc-PPO70_25 revealed excellent cell performance (maximum power density: 239 mW/cm at 0.49 V) than those of commercial FAA-3-50 Fumatech anion exchange membrane (maximum power density: 212 mW/cm at 0.54 V) under the operating condition of 60 °C and 100% RH as well. It was expected that PF-XAc-PPO70_25 could be an excellent candidate based on the results superior to those of commercial membranes in these essential characteristics of fuel cells.
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http://dx.doi.org/10.3390/polym12112758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700159PMC
November 2020

Poly(-Terphenylene-Methyl Piperidinium)-Based Anion Exchange Membranes: The Effect of Backbone Structure in AEMFC Application.

Membranes (Basel) 2020 Nov 5;10(11). Epub 2020 Nov 5.

Organic Material Synthesis Laboratory, Department of Chemistry, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Korea.

A series of poly(-terphenylene-methyl piperidinium)-based anion exchange membranes devoid of benzylic sites or aryl ether bonds, that are vulnerable to degradation by hydroxide ions, are synthesized and investigated for their application as novel anion exchange membranes. The copolymers are composed of both linear -terphenyl units and kink-structured -terphenyl units. The -connectivity in terphenyl units permits the polymer backbones to fold back, maximizing the interactions among the hydrocarbon polymer chains and enhancing the peripheral formation of ion aggregates, due to the free volume generated by the kink structure. The effects of the copolymer composition between -terphenyl and -terphenyl on the morphology and the electrochemical and physicochemical properties of the corresponding polymer membranes are investigated.
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http://dx.doi.org/10.3390/membranes10110329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694387PMC
November 2020

Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701).

Cancers (Basel) 2020 Nov 4;12(11). Epub 2020 Nov 4.

Department of Radiation Oncology, Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan 54538, Korea.

The purpose of the current in silico planning study is to compare radiation doses of whole-breast irradiation (WBI) and whole-breast plus regional lymph node irradiation (WBI+RNI) administered to the regional lymph nodes (RLN) in pN1 breast cancer. Twenty-four participating institutions were asked to create plans of WBI and WBI+RNI for two dummy cases. To compare target coverage between the participants, an isodose line equal to 90% of the prescribed dose was converted to an isodose contour (contour) The relative nodal dose (RND) was obtained using the ratio of RLN dose to the target dose. The Fleiss's kappa values which represent inter-observer agreement of contour were over 0.68. For RNI, 6 institutions included axillary lymph node (ALN), supraclavicular lymph node (SCN), and internal mammary lymph node (IMN), while 18 hospitals included only ALN and SCN. The median RND between the WBI and WBI+RNI were as follows: 0.64 vs. 1.05 (ALN level I), 0.27 vs. 1.08 (ALN level II), 0.02 vs. 1.12 (ALN level III), 0.01 vs. 1.12 (SCN), and 0.54 vs. 0.82 (IMN). In all nodal regions, the RND was significantly lower in WBI than in WBI+RNI ( < 0.01). In this study, we could identify the nodal dose difference between WBI and WBI+RNI.
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http://dx.doi.org/10.3390/cancers12113261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694237PMC
November 2020

Smoking Cessation, Weight Change, Diabetes, and Hypertension in Korean Adults.

Am J Prev Med 2021 02 3;60(2):205-212. Epub 2020 Nov 3.

Department of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, South Korea. Electronic address:

Introduction: This study investigates the association of smoking cessation and postcessation weight gain with the development of type 2 diabetes mellitus and hypertension.

Methods: A total of 96,524 individuals without diabetes mellitus and hypertension aged ≥20 years between 2006 and 2008 were included, with follow-up until December 31, 2015. Smoking status and weight changes were monitored for 2 years. Hazard ratios and 95% CIs were calculated for the respective risks of the 2 conditions. Analyses were completed in 2020.

Results: Compared with current smokers, the adjusted hazard ratios for the risk of type 2 diabetes and hypertension were 0.90 (95% CI=0.85, 0.96) and 1.00 (95% CI=0.95, 1.05) in recent quitters, 0.89 (95% CI=0.84, 0.95) and 0.92 (95% CI=0.88, 0.97) in long-term quitters, and 0.82 (95% CI=0.78, 0.86) and 0.92 (95% CI=0.89, 0.95) in never smokers. Compared with current smokers, the adjusted hazard ratios for the risk of type 2 diabetes and hypertension were 0.86 (95% CI=0.80, 0.93) and 0.98 (95% CI=0.92, 1.04) in recent quitters with no weight gain, 0.94 (95% CI=0.87, 1.03) and 1.00 (95% CI=0.94, 1.07) in those with 0.1-5 kg weight gain, 0.93 (95% CI=0.73, 1.19) and 1.14 (95% CI=0.96, 1.36) in those with 5.1-10 kg weight gain, and 1.49 (95% CI=0.84, 2.62) and 1.10 (95% CI=0.68, 1.77) in those with a weight gain of >10 kg.

Conclusions: Smoking cessation with no subsequent weight gain is associated with a reduced risk of developing type 2 diabetes. However, weight gain after smoking cessation attenuates the reduced risk of type 2 diabetes. The association between recent quitting and incident hypertension was nonsignificant, whereas long-term quitters had reduced risk of developing hypertension and type 2 diabetes.
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http://dx.doi.org/10.1016/j.amepre.2020.08.024DOI Listing
February 2021