Publications by authors named "Dong Hoon Shin"

533 Publications

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

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease.

Parkinsonism Relat Disord 2021 Mar 17;85:84-90. Epub 2021 Mar 17.

Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Republic of Korea. Electronic address:

Objectives: Despite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).

Methods: In this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the "pROC" package of R (version 1.16.2).

Results: The area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912-1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.

Conclusions: Our deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.
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http://dx.doi.org/10.1016/j.parkreldis.2021.03.004DOI Listing
March 2021

Comorbidity index for predicting mortality at 6 months after reperfusion therapy.

Sci Rep 2021 Mar 16;11(1):5963. Epub 2021 Mar 16.

Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 03722, Korea.

The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p < 0.001). Six out of the 19 comorbidities were included for developing the reperfusion comorbidity index on the basis of the odds ratios in the multivariate logistic regression analysis. This index showed good prediction of 6-month mortality in the retrospective cohort (area under the curve [AUC], 0.747; 95% CI, 0.704-0.790) and in 333 patients in the prospective cohort (AUC, 0.784; 95% CI, 0.709-0.859). Consideration of comorbidities might be helpful for the prediction of the 6-month mortality in patients with acute ischemic stroke who receive reperfusion therapy.
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http://dx.doi.org/10.1038/s41598-021-85390-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966783PMC
March 2021

Effectiveness of Albumin-bilirubin Score as a Predictor of Post-hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

Korean J Gastroenterol 2021 03;77(3):115-122

Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, Korea.

Backgrounds/aims: Post-hepatectomy liver failure (PHLF) is a major concern for patients with hepatocellular carcinoma (HCC) who have undergone liver resection. The albumin-bilirubin (ALBI) score is a novel model for assessing liver function. We aimed to investigate the effectiveness of the ALBI score as a predictor of PHLF in HCC patients who have undergone hepatectomy in South Korea.

Methods: Between January 2014 and November 2018, HCC patients who underwent hepatectomy and indocyanine retention rate at 15 min (ICG-R15) test were enrolled in this study.

Results: A total of 101 patients diagnosed with HCC underwent hepatectomy. Thirty-two patients (31.7%) experienced PHLF. The ALBI score (OR 2.83; 95% CI 1.22-6.55; p=0.015), ICG-R15 (OR 1.07; 95% CI 1.02-1.12; p=0.007) and ALBI grade (OR 2,86; 95% CI 1.08-7.58; p=0.035) were identified as independent predictors of PHLF by multivariable analysis. The area under the receiver operating characteristic curve of the ALBI score and ICG-R15 were 0.676 (95% CI 0.566-0.785) and 0.632 (95% CI 0.513-0.752), respectively. The optimal cutoff value of the ALBI score in predicting PHLF was -2.62, with a sensitivity of 75.0% and a specificity of 56.5%.

Conclusions: The ALBI score is an effective predictor of PHLF in patients with HCC, and its predictive ability is comparable to that of ICG-R15.
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http://dx.doi.org/10.4166/kjg.2020.148DOI Listing
March 2021

Optimal ICG dosage of preoperative colonoscopic tattooing for fluorescence-guided laparoscopic colorectal surgery.

Surg Endosc 2021 Feb 26. Epub 2021 Feb 26.

Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.

Background: Indocyanine green (ICG) is a multifunctional dye used in tumor localization, tissue perfusion, and lymph node (LN) mapping during fluorescence-guided laparoscopic colorectal surgery.

Purpose: This study aimed to establish the optimal protocol for preoperative endoscopic submucosal ICG injection to perform fluorescence lymph node mapping (FLNM), along with undisturbed fluorescent tumor localization and ICG angiography during a single surgery.

Methods: Colorectal cancer patients (n = 192) were enrolled from May 2017 to December 2019. Colonoscopic submucosal ICG injection was performed 12 to 18 h before surgery. ICG injection protocols were modified based on the total injected ICG (mg) and tattooing site number. The concentrations of ICG were gradually decreased from the standard dose (2.5 mg/ml) to the minimum dose (0.2 mg/ml). Successful FLNM (FLNM-s) was defined as distinct fluorescent LNs observed under NIR camera. The patient's age, sex, body mass index (BMI), stage, cancer location, obstruction, and laboratory findings were compared between the FLNM-s and failed FLNM (FLNM-f) groups to identify clinical and pathological factors that affect FLNM.

Results: In the ICG dose section of 0.5 to 1 mg, the success rate was highest within all functions including FLNM, fluorescent tumor localization, and ICG angiography. FLNM-s was related to ICG dose (0.5-1 mg), multiple submucosal injections, location of cancer, camera light source, and lower BMI. In the multivariate analysis, camera light source, non-obesity, and multiple injections were independent factors for FLNM-s). The mean total number of harvested LNs was significantly higher in the FLNM-s group than that in the FLNM-f group (p < 0.001). The number of metastatic lymph nodes was comparable between the two groups (p = 0.859).

Conclusions: Preoperative, endoscopic submucosal ICG injection with dose range 0.5 to 1 mg would be optimal protocol for multifunctional ICG applications during fluorescence-guided laparoscopic colorectal surgery.
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http://dx.doi.org/10.1007/s00464-021-08382-5DOI Listing
February 2021

Semiconductor-less vertical transistor with I/I of 10.

Nat Commun 2021 Feb 12;12(1):1000. Epub 2021 Feb 12.

Department of Physics, Konkuk University, Seoul, Republic of Korea.

Semiconductors have long been perceived as a prerequisite for solid-state transistors. Although switching principles for nanometer-scale devices have emerged based on the deployment of two-dimensional (2D) van der Waals heterostructures, tunneling and ballistic currents through short channels are difficult to control, and semiconducting channel materials remain indispensable for practical switching. In this study, we report a semiconductor-less solid-state electronic device that exhibits an industry-applicable switching of the ballistic current. This device modulates the field emission barrier height across the graphene-hexagonal boron nitride interface with I/I of 10 obtained from the transfer curves and adjustable intrinsic gain up to 4, and exhibits unprecedented current stability in temperature range of 15-400 K. The vertical device operation can be optimized with the capacitive coupling in the device geometry. The semiconductor-less switching resolves the long-standing issue of temperature-dependent device performance, thereby extending the potential of 2D van der Waals devices to applications in extreme environments.
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http://dx.doi.org/10.1038/s41467-021-21138-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881104PMC
February 2021

Increased risk of herpes zoster in gynecological cancer patients receiving radiotherapy combined with chemotherapy: a need for paying attention to vaccines.

J Gynecol Oncol 2021 Mar 8;32(2):e35. Epub 2021 Feb 8.

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

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http://dx.doi.org/10.3802/jgo.2021.32.e35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930444PMC
March 2021

The longitudinal associations between trajectory of and quantity of alcohol consumption and subsequent changes in blood pressure levels among non-hypertensive adults.

Br J Nutr 2021 Jan 14:1-26. Epub 2021 Jan 14.

Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.

Given the dynamic characteristic of an individual's drinking behaviors, comprehensive consideration of alcohol consumption variation using repeated measures may improve insight into the nature of its association with blood pressure (BP) change. We examined the association between longitudinal alcohol consumption (trajectory and quantity) and changes in BP and pulse pressure (PP) among Korean aged ≥40 years living in rural areas. Totally, 1682 hypertension-free participants who completed all three health examinations (median, 5.3 years) were included. All three visits were used to determine the cumulative trajectory of and quantity of alcohol consumption and the latest two visits and the last visit were used for the recent trajectory and the most recent quantity of alcohol consumption, respectively. Changes in BP and PP from the baseline to the 3rd visit were used as outcome. In men, ≥30 ml/d cumulative average alcohol consumption was associated with the greatest increase in systolic BP (SBP) in both baseline outcome-unadjusted (2.9 mmHg, p-value = 0.032) and -adjusted models (3.6 mmHg, p-value = 0.001) and the given association for the most recent alcohol consumption was observed in the baseline outcome-adjusted model (3.9 mmHg, p-value = 0.003). For PP, similar associations were observed only in the baseline outcome-adjusted model. No meaningful associations in diastolic BP in men and any BP or PP in women existed. The quantity of alcohol consumption than the trajectory may be significantly related to raised SBP and a possible short-term influence of the most recent alcohol consumption may exist when baseline SBP adjusted in men.
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http://dx.doi.org/10.1017/S0007114521000088DOI Listing
January 2021

Phylogenetic Positioning of a Strongyloides stercoralis Isolate Recovered from a Korean Patient and Comparison with Other Asian Isolates.

Korean J Parasitol 2020 Dec 29;58(6):689-694. Epub 2020 Dec 29.

Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University, Yangsan 50612, Korea.

Strongyloidiasis is caused by Strongyloides stercoralis and is one of the most neglected tropical diseases in tropical and subtropical regions. Although several strongyloidiasis cases have been reported in Korea, genetic analysis of Korean isolates is still incomplete. In this study, a parasite was isolated from a 61-year-old man diagnosed with strongyloidiasis during the treatment of lymphoma on his retroperitoneal lymph node. Diffuse symmetric wall thickening from the ascending to descending colon and a nematode-infected intestine was observed following microscopic examination. Genomic DNA was isolated from a patient tissue block, and S. stercoralis was identified by PCR and sequencing (18S rDNA). In order to determine phylogenetic location of a Korean isolate (named KS1), we analyzed cox1 gene (500-bp) and compared it with that from 47 previous S. stercoralis isolates (28 human isolates and 19 canid isolates) from Asian countries. Our results showed that phylogenetic tree could clearly be divided into 5 different groups according to hosts and regions. KS1 was most closely related with the Chinese isolates in terms of genetic distance.
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http://dx.doi.org/10.3347/kjp.2020.58.6.689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806424PMC
December 2020

Metagonimus yokogawai Ancient DNA Recovered from 16th- to 17th-Century Korean Mummy Feces of the Joseon Dynasty.

J Parasitol 2020 11;106(6):802-808

Laboratory of Bioanthropology, Paleopathology and History of Diseases, Seoul National University College of Medicine, Seoul, South Korea.

Metagonimiasis is foodborne intestinal parasitism occurring by the definitive hosts' ingestion of raw or undercooked fish, mostly commonly sweetfish. Most Metagonimus infection is caused by Metagonimus yokogawai but also rarely by Metagonimus takahashii as well as Metagonimus miyatai. Despite recent molecular work on Metagonimus spp., there are still insufficient data to reveal the genetic characteristics of ancient M. yokogawai in a wide geo-historical scope. In this study, we were successful in the analysis of M. yokogawai ancient DNA (aDNA) using coprolite samples retrieved from 16th- to 17th-century Korean mummies. In BLAST and phylogenetic analyses, M. yokogawai 28S rDNA of Korean mummies were clustered along with the 28S rDNA taxa of M. takahashii and M. miyatai in GenBank. Conversely, the cytochrome c oxidase subunit I (COI) of M. yokogawai aDNA from Korean mummies was distinctly clustered apart from M. takahashii and M. miyatai sequences. This study is the first report of its kind to identify M. yokogawai aDNA retrieved from the archaeological specimens and confirms the usefulness of COI in molecular diagnosis of M. yokogawai. Considering the rarity of reports on the genetics of genus Metagonimus spp., our study will be fundamental for the future study of M. yokogawai paleogenetics.
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http://dx.doi.org/10.1645/20-42DOI Listing
November 2020

Identification of the CFAP410 Pathogenic Variants in a Korean Patient with Autosomal Recessive Retinitis Pigmentosa and Skeletal Anomalies.

Korean J Ophthalmol 2020 12 3;34(6):500-502. Epub 2020 Dec 3.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3341/kjo.2020.0087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738230PMC
December 2020

A call for antimicrobial stewardship in patients with COVID-19: a nationwide cohort study in Korea.

Clin Microbiol Infect 2021 Apr 31;27(4):653-655. Epub 2020 Oct 31.

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

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http://dx.doi.org/10.1016/j.cmi.2020.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604125PMC
April 2021

Unilateral synchronous papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma: a case report with KRAS and PIK3CA mutations.

Diagn Pathol 2020 Oct 6;15(1):123. Epub 2020 Oct 6.

Department of Urology, School of Medicine, Pusan National University, Yangsan, Korea.

Background: The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS).

Case Presentation: A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for 1 week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G > T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G > A/p.E542K in exon 10).

Conclusions: We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.
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http://dx.doi.org/10.1186/s13000-020-01042-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539524PMC
October 2020

Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis.

Sci Rep 2020 09 30;10(1):16078. Epub 2020 Sep 30.

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

To investigate associations of the duration of voriconazole treatment and radiological response with relapse of invasive pulmonary aspergillosis (IPA) in immunocompromised patients, we explored the risk factors for IPA relapse after successful initial treatment. All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography. Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2-17.5; P = 0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Longer duration of therapy should be considered for those at higher risk of relapse.
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http://dx.doi.org/10.1038/s41598-020-73098-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527978PMC
September 2020

Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8 T cell responses.

Cell Mol Immunol 2020 Aug 31. Epub 2020 Aug 31.

Biomedicine Production Branch, Program for Immunotherapy Research, Goyang, 10408, Republic of Korea.

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy. However, the adverse side effects associated with agonist antibodies have hindered their clinical development. Here, we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs. We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1CD8 T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8 T cells, which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction. However, repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes (TDLNs) of mice due to recruitment and accumulation of macrophages via the CD8 T cell-IFN-γ axis. This was accompanied by excessive lymph node swelling, which impaired the sequential activation of CD8 T cells. Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing, which should be considered during the clinical development of immunomodulating therapy.
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http://dx.doi.org/10.1038/s41423-020-00533-3DOI Listing
August 2020

Midkine Is a Potential Therapeutic Target of Tumorigenesis, Angiogenesis, and Metastasis in Non-Small Cell Lung Cancer.

Cancers (Basel) 2020 Aug 24;12(9). Epub 2020 Aug 24.

Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 10408, Korea.

Hypoxia-inducible factors (HIFs) induced by reduced O availability activate the transcription of target genes encoding proteins that play important roles in communication between cancer and stromal cells. Cancer cells were incubated under hypoxic conditions: H1299, A549 (NSCLC); Hep3B, HepG2 (HCC); HCT116, CT26 (Colon cancer); MCF-7, MDAMB231 (Breast cancer); MKN1, MKN5 (Gastric cancer); U87MG, SHSY5Y (Brain cancer); and SKOV3, SNU840 (Ovary cancer). All cells expressed HIF-1α and HIF-2α mRNA and proteins. However, cell proliferation of NSCLC, breast, gastric, and brain cancer cells under hypoxia was more dependent on HIF-1α except for HCC cells where it was more dependent on HIF-2α. Among HIF-1α dependent cells H1299 was the most affected in terms of cell proliferation by HIF-1α knockdown. To examine which cytokines are secreted in NSCLC cells by HIF-1α to communicate with stromal cells, we performed a cytokine-profiling array with H1299. We screened the top 14 cytokines which were dependent on the HIF-1α expression pattern. Among them, midkine (MDK) expression was affected the most in response to HIF-1α. MDK is a heparin-binding growth factor that promotes angiogenesis and carcinogenesis. Indeed, MDK significantly increased HUVEV endothelial cell migration and neo- vascularization in chick chorioallantoic membrane assay (CAM) assay via paracrine signaling. In addition, MDK secreted from NSCLC cells interacted with Notch2 which activated the Notch signaling pathway and induced EMT, upregulated NF-κB, and increased cancer promotion. However, in response to MDK knock down, siRNA or the MDK inhibitor, iMDK treatment not only decreased MDK-induced migration and angiogenesis of endothelial cells but also abrogated the progression and metastasis of NSCLC cells in in vitro and in vivo orthotopic and spontaneous lung metastasis models. Consequently, iMDK treatment significantly increased mice survival rates compared with the control or MDK expression group. MDK plays a very important role in the progression and metastasis of NSCLC cells. Moreover, the MDK targeting strategy provides a potential therapeutic target for the treatment of MDK-expressing lung cancers.
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http://dx.doi.org/10.3390/cancers12092402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563676PMC
August 2020

Calcium silicate-based root canal sealers: a literature review.

Restor Dent Endod 2020 Aug 9;45(3):e35. Epub 2020 Jun 9.

Department of Conservative Dentistry, College of Dentistry, Dankook University, Cheonan, Korea.

Epoxy resin-based sealers are currently widely used, and several studies have considered AH Plus to be the gold-standard sealer. However, it still has limitations, including possible mutagenicity, cytotoxicity, inflammatory response, and hydrophobicity. Drawing upon the advantages of mineral trioxide aggregate, calcium silicate-based sealers were introduced with high levels of biocompatibility and hydrophilicity. Because of the hydrophilic environment in root canals, water resorption and solubility of root canal sealers are important factors contributing to their stability. Sealers displaying lower microleakage and stronger push-out bond strength are also needed to endure the dynamic tooth environment. Although the physical properties of calcium silicate-based sealers meet International Organization for Standardization recommendations, and they have consistently reported to be biocompatible, they have not overcome conventional resin-based sealers in actual practice. Therefore, further studies aiming to improve the physical properties of calcium silicate-based sealers are needed.
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http://dx.doi.org/10.5395/rde.2020.45.e35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431927PMC
August 2020

Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation.

Proc Natl Acad Sci U S A 2020 08 4;117(33):19982-19993. Epub 2020 Aug 4.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 120-749 Seoul, Republic of Korea;

The underlying mechanism of necroptosis in relation to cancer is still unclear. Here, MYC, a potent oncogene, is an antinecroptotic factor that directly suppresses the formation of the RIPK1-RIPK3 complex. Gene set enrichment analyses reveal that the MYC pathway is the most prominently down-regulated signaling pathway during necroptosis. Depletion or deletion of MYC promotes the RIPK1-RIPK3 interaction, thereby stabilizing the RIPK1 and RIPK3 proteins and facilitating necroptosis. Interestingly, MYC binds to RIPK3 in the cytoplasm and inhibits the interaction between RIPK1 and RIPK3 in vitro. Furthermore, MYC-nick, a truncated form that is mainly localized in the cytoplasm, prevented TNF-induced necroptosis. Finally, down-regulation of MYC enhances necroptosis in leukemia cells and suppresses tumor growth in a xenograft model upon treatment with birinapant and emricasan. MYC-mediated suppression of necroptosis is a mechanism of necroptosis resistance in cancer, and approaches targeting MYC to induce necroptosis represent an attractive therapeutic strategy for cancer.
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http://dx.doi.org/10.1073/pnas.2000979117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443878PMC
August 2020

Vasodilatory Effect of Extract in Rat Mesenteric Arteries.

Molecules 2020 Jul 10;25(14). Epub 2020 Jul 10.

Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University, 50 Yeonseiro, Seodaemun-gu, Seoul 03722, Korea.

is a well-known medicinal mushroom that is widely used in Asian countries. In several experimental models, extracts were reported to have various biological effects, including anti-inflammatory, anti-cancer, hepatoprotective, anti-diabetic, neuroprotective, and anti-angiogenic activity. In the present study, several bioactive compounds, including palmitic acid ethyl ester and linoleic acid, were identified in . The intermediate-conductance calcium-activated potassium channel (IK) plays an important role in the regulation of the vascular smooth muscle cells' (VSMCs) contraction and relaxation. The activation of the IK channel causes the hyperpolarization and relaxation of VSMCs. To examine whether extract causes vasodilation in the mesenteric arteries of rats, we measured the isometric tension using a wire myograph. After the arteries were pre-contracted with U46619 (a thromboxane analogue, 1 µM), extract was administered. The extract induced vasodilation in a dose-dependent manner, which was independent of the endothelium. To further investigate the mechanism, we used the non-selective K channel blocker tetraethylammonium (TEA). TEA significantly abolished extract-induced vasodilation. Thus, we tested three different types of K channel blockers: iberiotoxin (BK channel blocker), apamin (SK channel blocker), and charybdotoxin (IK channel blocker). Charybdotoxin significantly inhibited extract-induced relaxation, while there was no effect from apamin and iberiotoxin. Membrane potential was measured using the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC(3)) in the primary isolated vascular smooth muscle cells (VSMCs). We found that the extract induced hyperpolarization of VSMCs, which is associated with a reduced phosphorylation level of 20 KDa myosin light chain (MLC).
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http://dx.doi.org/10.3390/molecules25143160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397296PMC
July 2020

Clinical manifestations of cuticular drusen in Korean patients.

Sci Rep 2020 07 10;10(1):11469. Epub 2020 Jul 10.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

Cuticular drusen show some similarities to and differences from soft drusen in age-related macular degeneration (AMD) and might thus be a unique AMD subtype. Previous studies on cuticular drusen were performed mainly in white ethnic groups, but AMD shows ethnic differences. We investigated clinical manifestations of cuticular drusen in Korean patients to evaluate possible ethnic differences. Clinical records of Korean patients with cuticular drusen were retrospectively reviewed. Fundus distribution pattern, imaging features, and presence of large drusen, drusenoid pigment epithelial detachment (PED), and macular complications, including geographic atrophy (GA), choroidal neovascularization (CNV), and acquired vitelliform lesion (AVL), were assessed via multimodal imaging in 162 eyes with cuticular drusen (n = 81 patients; 67 females; mean age: 66.6 ± 9.1 years). Diffuse distribution was found in 61.7% and peripapillary involvement in 75.3% of eyes. Large drusen, drusenoid PED, GA, CNV, and AVL were observed in 59.3%, 26.5%, 18.5%, 3.7%, and 1.2% of eyes, respectively. The macular complication prevalence was similar between patients ≤ 60 and those > 60 years old. In Korean patients, cuticular drusen were less frequently associated with macular complications than in white patients, and the proportion of macular complications differed significantly, with AVL representing an uncommon complication.
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http://dx.doi.org/10.1038/s41598-020-68493-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351725PMC
July 2020

Bicarbonate permeation through anion channels: its role in health and disease.

Pflugers Arch 2020 08 4;472(8):1003-1018. Epub 2020 Jul 4.

Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, 03722, South Korea.

Many anion channels, frequently referred as Cl channels, are permeable to different anions in addition to Cl. As the second-most abundant anion in the human body, HCO permeation via anion channels has many important physiological roles. In addition to its classical role as an intracellular pH regulator, HCO also controls the activity and stability of dissolved proteins in bodily fluids such as saliva, pancreatic juice, intestinal fluid, and airway surface liquid. Moreover, HCO permeation through these channels affects membrane potentials that are the driving forces for transmembrane transport of solutes and water in epithelia and affect neuronal excitability in nervous tissue. Consequently, aberrant HCO transport via anion channels causes a number of human diseases in respiratory, gastrointestinal, genitourinary, and neuronal systems. Notably, recent studies have shown that the HCO permeabilities of several anion channels are not fixed and can be altered by cellular stimuli, findings which may have both physiological and pathophysiological significance. In this review, we summarize recent progress in understanding the molecular mechanisms and the physiological roles of HCO permeation through anion channels. We hope that the present discussions can stimulate further research into this very important topic, which will provide the basis for human disorders associated with aberrant HCO transport.
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http://dx.doi.org/10.1007/s00424-020-02425-xDOI Listing
August 2020

Remote heteroepitaxy of GaN microrod heterostructures for deformable light-emitting diodes and wafer recycle.

Sci Adv 2020 Jun 3;6(23):eaaz5180. Epub 2020 Jun 3.

Department of Nanotechnology and Advanced Materials Engineering, Sejong University, Seoul 05006, Republic of Korea.

There have been rapidly increasing demands for flexible lighting apparatus, and micrometer-scale light-emitting diodes (LEDs) are regarded as one of the promising lighting sources for deformable device applications. Herein, we demonstrate a method of creating a deformable LED, based on remote heteroepitaxy of GaN microrod (MR) - junction arrays on -AlO wafer across graphene. The use of graphene allows the transfer of MR LED arrays onto a copper plate, and spatially separate MR arrays offer ideal device geometry suitable for deformable LED in various shapes without serious device performance degradation. Moreover, remote heteroepitaxy also allows the wafer to be reused, allowing reproducible production of MR LEDs using a single substrate without noticeable device degradation. The remote heteroepitaxial relation is determined by high-resolution scanning transmission electron microscopy, and the density functional theory simulations clarify how the remote heteroepitaxy is made possible through graphene.
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http://dx.doi.org/10.1126/sciadv.aaz5180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269673PMC
June 2020

Risk factors for and clinical outcomes of carbapenem non-susceptible gram negative bacilli bacteremia in patients with acute myelogenous leukemia.

BMC Infect Dis 2020 Jun 9;20(1):404. Epub 2020 Jun 9.

Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro 101, Jongro-gu, Seoul, 03080, Republic of Korea.

Background: Carbapenem is frequently used when gram negative bacilli (GNB) bacteremia is detected especially in neutropenic patients. Consequently, appropriate treatment could be delayed in GNB bacteremia cases involving organisms which are not susceptible to carbapenem (carba-NS), resulting in a poor clinical outcomes. Here, we explored risk factors for carba-NS GNB bacteremia and its clinical outcomes in patients with acute myelogenous leukemia (AML) that underwent chemotherapy.

Methods: We reviewed all GNB bacteremia cases that occurred during induction or consolidation chemotherapy, over a 15-year period, in a tertiary-care hospital.

Results: Among 489 GNB bacteremia cases from 324 patients, 45 (9.2%) were carba-NS and 444 (90.8%) were carbapenem susceptible GNB. Independent risk factors for carba-NS GNB bacteremia were: carbapenem use at bacteremia onset (adjusted odds ratio [aOR]: 91.2; 95% confidence interval [95%CI]: 29.3-284.1; P < 0.001); isolation of carbapenem-resistant Acinetobacter baumannii (aOR: 19.4, 95%CI: 3.4-112.5; P = 0.001) in the prior year; and days from chemotherapy to GNB bacteremia (aOR: 1.1 per day, 95%CI: 1.1-1.2; P < 0.001). Carba-NS bacteremia was independently associated with in-hospital mortality (aOR: 6.6, 95%CI: 3.0-14.8; P < 0.001).

Conslusion: Carba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors.
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http://dx.doi.org/10.1186/s12879-020-05131-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282079PMC
June 2020

Sex-specific associations of habitual intake of soy protein and isoflavones with risk of type 2 diabetes.

Clin Nutr 2021 Jan 4;40(1):127-136. Epub 2020 May 4.

Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, South Korea; Institute for Health and Society, Hanyang University, Seoul, South Korea.

Background & Aims: A possible mechanism by which intake of soy isoflavones leads to an improvement in glucose metabolism has been suggested. However, epidemiological evidence of a link between dietary soy isoflavone and type 2 diabetes is not convincing. This study aimed to evaluate the prospective associations between intake of dietary soy protein and isoflavones (total isoflavones, daidzein and genistein) and risk of type 2 diabetes in a community-based cohort of Korean adults aged ≥ 40 years, the Korean Multi-Rural Communities Cohort (MRCohort).

Methods: A total of 8269 participants who did not have type 2 diabetes were enrolled. Dietary intake was calculated using a food frequency questionnaire.

Results: Over 50,063 person-years of follow-up, 531 participants developed type 2 diabetes. Significant dose-response inverse associations were observed between dietary soy protein and isoflavones (quartiles) and type 2 diabetes in women (incidence rate ratio, IRR = 0.63, 95% CI = 0.45-0.87, P for trend = 0.0078 for soy protein; IRR = 0.62, 95% CI = 0.45-0.86, P for trend = 0.0031 for total isoflavones for the highest quartile compared with the lowest quartile). Similar significant linear trends were found for both daidzein and genistein. However, there were no significant associations with soy protein and isoflavones in men. The sex-specific differences in associations between soy protein and isoflavones intakes and type 2 diabetes risk were statistically significant (all P for interaction < 0.05).

Conclusions: Habitual intake of soy protein and isoflavones may be inversely associated with type 2 diabetes in women, but not in men. Dietary soy components may play different roles in the development of type 2 diabetes in men and women.
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http://dx.doi.org/10.1016/j.clnu.2020.04.035DOI Listing
January 2021

Transformation and Evaporation of Surface Adsorbents on a Graphene "Hot Plate".

ACS Appl Mater Interfaces 2020 Jun 27;12(23):26313-26319. Epub 2020 May 27.

Department of Physics, Ewha Womans University, 03760 Seoul, Korea.

Dynamic surface modification of suspended graphene at high temperatures was directly observed with in situ scanning transmission electron microscopy (STEM) measurements. The suspended graphene devices were prepared on a SiN membrane substrate with a hole so that STEM observations could be conducted during Joule heating. Current-voltage characteristics of suspended graphene devices inside the STEM chamber were measured while monitoring and controlling the temperature of graphene by estimating the electrical power of the devices. During the in situ STEM observation at high temperatures, residual hydrocarbon adsorbents that had remained on graphene effectively evaporated creating large, atomically clean graphene areas. At other places, dynamic changes in the shape, position, and orientation of adsorbents could be directly observed. The temperature of the suspended graphene sample was estimated to reach up to 2000 K during the experiment, making graphene an efficient high-temperature micrometer-sized electron-transparent hot plate for future experiments in microscopes.
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http://dx.doi.org/10.1021/acsami.0c02056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291352PMC
June 2020

Real-time effect of electron beam on MoS field-effect transistors.

Nanotechnology 2020 Nov 23;31(45):455202. Epub 2020 Apr 23.

School of Electrical Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.

Irradiation of MoS field-effect transistors (FETs) fabricated on Si/SiO substrates with electron beams (e-beams) below 30 keV creates electron-hole pairs (EHP) in the SiO, which increase the interface trap density (N ) and change the current path in the channel, resulting in performance changes. In situ measurements of the electrical characteristics of the FET performed using a nano-probe system mounted inside a scanning electron microscope show that e-beam irradiation enables both multilayer and monolayer MoS channels act as conductors. The e-beams mostly penetrate the channel owing to their large kinetic energy, while the EHPs formed in the SiO layer can contribute to the conductance by flowing into the MoS channel or inducing the gate bias effect. The analysis of the device parameters in the initial state and the vent-evacuation state after e-beam irradiation can clarify the effect of the interplay between the e-beam-induced EHPs and ambient adsorbates on the carrier behavior, which depends on the thickness of the MoS layer. DC and low frequency noise analysis reveals that the e-beam-induced EHPs increase N from 10-10 to 10 cm eV in both monolayer and multilayer devices, while the interfacial Coulomb scattering parameter α increases by three times in the monolayer and decreases to one-tenth of its original value in the multilayer. In other words, an MoS layer with a thickness of ∼30 nm is less sensitive to adsorbates by surface screening. Thus, the carrier mobility in the monolayer device decreases from 45.7 to 40 cm V s, while in the 30 nm-thick multilayer device, it increases from 4.9 to 5.6 cm V s. This is further evidenced by simulations of the distribution of interface traps and channel carriers in the MoS FET before and after e-beam irradiation, demonstrating that Coulomb scattering decreases as the effective channel moves away from the interface.
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http://dx.doi.org/10.1088/1361-6528/ab8c78DOI Listing
November 2020

Dietary iodine, seaweed consumption, and incidence risk of metabolic syndrome among postmenopausal women: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).

Eur J Nutr 2021 Feb 24;60(1):135-146. Epub 2020 Mar 24.

Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, South Korea.

Purpose: Despite a beneficial role of iodine and seaweed consumption against metabolic syndrome (MetS), which is high in postmenopausal women, few studies investigated such associations in a prospective study. This study aimed to investigate the association of dietary iodine and seaweed consumption with the incidence of MetS and its components in postmenopausal women.

Methods: A total of 2588 postmenopausal women aged ≥ 40 years were recruited between 2005 and 2011 in the Multi-Rural Communities Cohort (MRCohort). A validated semiquantitative food frequency questionnaire was used to collect dietary intake data. MetS was defined as three of five components [abdominal obesity, elevated blood pressure, glucose, triglyceride, and low-high density lipoprotein cholesterol (HDL-C)] and the incidence of MetS was checked every 2-4 years. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator.

Results: During the mean follow-up period (3.4 ± 2.1 years), MetS occurred in 481 participants. The median cumulative average iodine intake was 108.9 µg/day (interquartile range, 60.8-190.2 µg/day). In multivariable analyses, average iodine and seaweed consumption were inversely associated with MetS (IRR = 0.61, 95% CI 0.47-0.78 in the highest quartile of iodine intake, P for trend = 0.0018; IRR = 0.52, 95% CI 0.39-0.69 in the highest quartile of seaweed consumption, P for trend = 0.0004). Among MetS components, blood glucose (> 100 mg/dL), blood pressure (≥ 130/85 mmHg), and lipid profiles (triglyceride, ≥ 150 mg/dL and HDL-C, < 50 mg/dL) were significantly inversely associated with dietary iodine and seaweed consumption, but there was no clear association for waist circumference (≥ 85 cm).

Conclusion: Dietary iodine and seaweed consumption may be inversely associated with MetS incidence and its individual abnormalities in postmenopausal women.
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http://dx.doi.org/10.1007/s00394-020-02225-0DOI Listing
February 2021

Validation of the T category for distal cholangiocarcinoma: Measuring the depth of invasion is complex but correlates with survival.

Ann Diagn Pathol 2020 Jun 3;46:151489. Epub 2020 Mar 3.

Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea. Electronic address:

According to the current 8th edition of the American Joint Committee of Cancer (AJCC), the T category of distal cholangiocarcinomas is classified based on the depth of invasion (DOI) (T1, < 5 mm; T2, between 5 and 12 mm; T3, > 12 mm). In consideration of the discrepancies between previous studies about the prognostic significance, we aimed to validate the current AJCC T staging system of distal cholangiocarcinomas. DOI was measured using three different methods: DOI1, DOI2, and DOI3. DOI1 was defined and stratified according to the AJCC 8th edition. DOI2 was measured as the distance from an imaginary curved line approximated along the distorted mucosal surface to the deepest invasive tumor cells. DOI3 was defined as the total tumor thickness. DOI2 and DOI3 were also divided into three categories using the same cut-off points as in the AJCC 8th edition. We compared these three DOI methods to the AJCC 7th edition as well. In contrast with the AJCC 7th edition, all three groups showed a correlation with patients' overall survival. Above all, the DOI2 group demonstrated the best significance in multivariate analysis. However, when the C indices were compared between these groups, differential significance proved to be negligible (DOI1 vs DOI2, p = 0.915; DOI2 vs DOI3, p = 0.057). Therefore, the measurement of DOI does not need to be rigorously and stringently performed. In conclusion, we showed that the current T classification system better correlates with the overall survival of patients with distal cholangiocarcinomas than the previous system.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151489DOI Listing
June 2020

Improving the Clinical Outcome in Stroke Patients Receiving Thrombolytic or Endovascular Treatment in Korea: from the SECRET Study.

J Clin Med 2020 Mar 6;9(3). Epub 2020 Mar 6.

Department of Neurology, Yonsei University College of Medicine, Seoul 03722, Korea.

We investigated whether there was an annual change in outcomes in patients who received the thrombolytic therapy or endovascular treatment (EVT) in Korea. This analysis was performed using data from a nationwide multicenter registry for exploring the selection criteria of patients who would benefit from reperfusion therapies in Korea. We compared the annual changes in the modified Rankin scale (mRS) at discharge and after 90 days and the achievement of successful recanalization from 2012 to 2017. We also investigated the determinants of favorable functional outcomes. Among 1230 included patients, the improvement of functional outcome at discharge after reperfusion therapy was noted as the calendar year increased ( < 0.001). The proportion of patients who were discharged to home significantly increased (from 45.6% in 2012 to 58.5% in 2017) ( < 0.001). The successful recanalization rate increased over time from 78.6% in 2012 to 85.1% in 2017 ( = 0.006). Time from door to initiation of reperfusion therapy decreased over the years ( < 0.05). These secular trends of improvements were also observed in 1203 patients with available mRS data at 90 days ( < 0.05). Functional outcome was associated with the calendar year, age, initial stroke severity, diabetes, preadmission disability, intervals from door to reperfusion therapy, and achievement of successful recanalization. This study demonstrated the secular trends of improvement in functional outcome and successful recanalization rate in patients who received reperfusion therapy in Korea.
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http://dx.doi.org/10.3390/jcm9030717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141338PMC
March 2020

IRE1α kinase-mediated unconventional protein secretion rescues misfolded CFTR and pendrin.

Sci Adv 2020 02 19;6(8):eaax9914. Epub 2020 Feb 19.

Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.

The most prevalent pathogenic mutations in the (Δ) and /pendrin (), which cause cystic fibrosis and congenital hearing loss, respectively, evoke protein misfolding and subsequent defects in their cell surface trafficking. Here, we report that activation of the IRE1α kinase pathway can rescue the cell surface expression of ΔF508-CFTR and p.H723R-pendrin through a Golgi-independent unconventional protein secretion (UPS) route. In mammalian cells, inhibition of IRE1α kinase, but not inhibition of IRE1α endonuclease and the downstream effector XBP1, inhibited CFTR UPS. Treatment with the IRE1α kinase activator, (E)-2-(2-chlorostyryl)-3,5,6-trimethyl-pyrazine (CSTMP), rescued cell surface expression and functional activity of ΔF508-CFTR and p.H723R-pendrin. Treatment with a nontoxic dose of CSTMP to ΔF508-CFTR mice restored CFTR surface expression and CFTR-mediated anion transport in the mouse colon. These findings suggest that UPS activation via IRE1α kinase is a strategy to treat diseases caused by defective cell surface trafficking of membrane proteins, including ΔF508-CFTR and p.H723R-pendrin.
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http://dx.doi.org/10.1126/sciadv.aax9914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030921PMC
February 2020