Publications by authors named "Joo Young Kim"

402 Publications

Standalone real-time health monitoring patch based on a stretchable organic optoelectronic system.

Sci Adv 2021 Jun 4;7(23). Epub 2021 Jun 4.

Organic Material Lab., Samsung Advanced Institute of Technology (SAIT), Samsung Electronics, Suwon 16678, Korea.

Skin-like health care patches (SHPs) are next-generation health care gadgets that will enable seamless monitoring of biological signals in daily life. Skin-conformable sensors and a stretchable display are critical for the development of standalone SHPs that provide real-time information while alleviating privacy concerns related to wireless data transmission. However, the production of stretchable wearable displays with sufficient pixels to display this information remains challenging. Here, we report a standalone organic SHP that provides real-time heart rate information. The 15-μm-thick SHP comprises a stretchable organic light-emitting diode display and stretchable organic photoplethysmography (PPG) heart rate sensor on all-elastomer substrate and operates stably under 30% strain using a combination of stress relief layers and deformable micro-cracked interconnects that reduce the mechanical stress on the active optoelectronic components. This approach provides a rational strategy for high-resolution stretchable displays, enabling the production of ideal platforms for next-generation wearable health care electronics.
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http://dx.doi.org/10.1126/sciadv.abg9180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177712PMC
June 2021

Behavioral variation according to feeding organ diversification in glossiphoniid leeches (Phylum: Annelida).

Sci Rep 2021 May 25;11(1):10940. Epub 2021 May 25.

Department of Biological Sciences and Biotechnology, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.

Adaptive radiation is a phenomenon in which various organs are diversified morphologically or functionally as animals adapt to environmental inputs. Leeches exhibit a variety of ingestion behaviors and morphologically diverse ingestion organs. In this study, we investigated the correlation between behavioral pattern and feeding organ structure of leech species. Among them, we found that Alboglossiphonia sp. swallows prey whole using its proboscis, whereas other leeches exhibit typical fluid-sucking behavior. To address whether the different feeding behaviors are intrinsic, we investigated the behavioral patterns and muscle arrangements in the earlier developmental stage of glossiphoniid leeches. Juvenile Glossiphoniidae including the Alboglossiphonia sp. exhibit the fluid ingestion behavior and have the proboscis with the compartmentalized muscle layers. This study provides the characteristics of leeches with specific ingestion behaviors, and a comparison of structural differences that serves as the first evidence of the proboscis diversification.
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http://dx.doi.org/10.1038/s41598-021-90421-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149456PMC
May 2021

Low PDCD4 Expression Is Associated With Poor Prognosis of Colorectal Carcinoma.

Appl Immunohistochem Mol Morphol 2021 May 24. Epub 2021 May 24.

Department of Pathology, Nowon Eulji Medical Center, Eulji University Department of Pathology, Uijeongbu Eulji University Medical Center, Eulji University, Gyeonggi-do Department of Pathology, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Korea.

Programmed cell death 4 (PDCD4) is a tumor suppressor gene that inhibits tumor progression, invasion, and metastasis. Decreased PDCD4 expression is associated with poor prognosis in various types of cancers. We evaluated PDCD4 expression and its clinicopathologic correlation, including patient survival, in 289 surgically resected colorectal cancers. Low nuclear PDCD4 expression was identified in 177 (61.2%) cases and was associated with large tumor size, high pT classification, and the presence of lymphovascular and perineural invasion. The 5-year survival rate of patients with low nuclear PDCD4 expression was significantly lower than that of patients with high expression (72.2% vs. 93.3%, P<0.001). American Joint Committee on Cancer stage II and III colorectal cancer patients with low nuclear PDCD4 expression (76.9% and 67.2%, respectively) showed significantly worse overall survival than those with high expression (100% and 92.9%, P=0.002 and 0.032, respectively). Low nuclear PDCD4 expression was an independent poor prognostic factor in colorectal cancer patients (hazard ratio=3.556; 95% confidence interval, 1.739-7.271; P=0.001). Our study suggests that low PDCD4 expression is associated with aggressive behavior and can be used as a prognostic indicator of colorectal cancer patients.
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http://dx.doi.org/10.1097/PAI.0000000000000948DOI Listing
May 2021

Minimally Invasive Spine Surgery versus Open Posterior Instrumentation Surgery for Unstable Thoracolumbar Burst Fracture.

Asian Spine J 2021 May 20. Epub 2021 May 20.

Department of Orthopedic Surgery, Sung-Ae Hospital, Seoul, Korea.

Study Design: Retrospective study.

Purpose: To compare the clinical and radiological results of minimally invasive spine surgery (MISS) and open posterior instrumentation surgery for the treatment of unstable burst fractures.

Overview Of Literature: MISS has exhibited postoperative outcomes similar to those obtained using open posterior instrumentation in various spine diseases. There remains no consensus regarding the use of MISS in the treatment of unstable burst fracture.

Methods: We enrolled 40 patients who underwent either MISS (M group, 20 patients) or open posterior instrumentation surgery (O group, 20 patients) for the treatment of traumatic unstable burst fractures. Clinical outcomes were evaluated based on postoperative back pain, operation time, blood loss, hospital stay duration, and perioperative complications. For radiologic evaluation, preoperative magnetic resonance imaging and plain radiography were performed before and after the surgery to evaluate the changes in the kyphotic angle and fracture union.

Results: The change in the kyphotic angle was -8.2°±5.8° in the M group and -8.0°±7.8° in the O group. No significant difference was noted in terms of the change in the kyphotic angle (p=0.94, t-test) after 12 months of surgery. The Visual Analog Scale score was 1.5±0.7 points in the M group, while it was 5.2±1.4 points in the O group. In the M group, back pain has significantly decreased (p<0.01, t-test). The estimated blood loss was 195.5 mL in the M group and 1,077.5 mL in the O group; the operation time was significantly decreased in the O group from 290.7 to 120.7 minutes in the M group (p<0.05, t-test) (p=0.36, t-test). The average duration of hospital stay was 36.0 days in the M group and 41.9 days in the O group (p=0.36, t-test).

Conclusions: For the treatment of unstable burst fractures, MISS showed significant differences in terms of postoperative back pain, operation time, and blood loss as compared to open posterior instrumentation surgery.
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http://dx.doi.org/10.31616/asj.2020.0572DOI Listing
May 2021

A 12-week, randomized, double-blind, placebo-controlled study assessing the efficacy of EGHB010, a standardized extract of and , in patients with early age-related macular degeneration.

Ann Transl Med 2021 Apr;9(7):541

Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: EGHB010, a standardized extract of and , inhibits choroidal neovascularization. The aim of this study is to evaluate the efficacy and safety of EGHB010 on early age-related macular degeneration (AMD) progression inhibition.

Methods: The study was designed as a randomized, double-blind, single-center, placebo-controlled study. Subjects were 50 years of age or older, and early AMD satisfied the criteria of more than 15 small (<63 µm) drusen, less than 20 intermediate (≥63, <125 µm) drusen, or pigment abnormalities. For 12 weeks, the treatment group received EGHB010 and the control received the placebo. The main outcomes were changes in macular pigment optical density (MPOD), central macular thickness (CMT), and central choroidal thickness (CCT). Subgroup analysis was performed on subjects with MPOD <0.75 at baseline.

Results: Forty-eight subjects out of 94 were assigned to the treatment group, and 46 to the control group. At 12 weeks, mean MPOD of the treatment group increased by 0.04±0.27 (P=0.2730), and that of the control group decreased by 0.03±0.21 (P=0.7240), but there was no significant difference between the two groups (P=0.1234). There were no significant differences between the two groups in mean CMT and CCT (P=0.6718 and 0.6608, respectively). In subgroup analysis, there were 39 subjects with MPOD <0.75 in the treatment group and 36 in the control. Mean MPOD of the treatment group significantly increased by 0.09±0.25 (P=0.0218), and there was a significant difference in mean MPOD at 12 weeks between the two groups (P=0.0248). Adverse reactions were similar in both groups, and no subjects had serious adverse events.

Conclusions: EGHB010 is expected to increase MPOD when administered to subjects with MPOD <0.75. EGHB010 is worth considering as a substance that inhibits the progression of early AMD.
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http://dx.doi.org/10.21037/atm-20-4701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105837PMC
April 2021

Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker.

J Cell Mol Med 2021 Jun 3;25(11):5177-5190. Epub 2021 May 3.

Kidney Research Institute, Seoul National University, Seoul, Korea.

Identification of a urinary metabolite biomarker with diagnostic or prognostic significance for early immunoglobulin A nephropathy (IgAN) is needed. We performed nuclear magnetic resonance-based metabolomic profiling and identified 26 metabolites in urine samples. We collected urine samples from 201, 77, 47, 36 and 136 patients with IgAN, patients with membranous nephropathy, patients with minimal change disease, patients with lupus nephritis and healthy controls, respectively. We determined whether a metabolite level is associated with the prognosis of IgAN through Cox regression and continuous net reclassification improvement (cNRI). Finally, in vitro experiments with human kidney tubular epithelial cells (hTECs) were performed for experimental validation. As the results, the urinary glycine level was higher in the IgAN group than the control groups. A higher urinary glycine level was associated with lower risk of eGFR 30% decline in IgAN patients. The addition of glycine to a predictive model including clinicopathologic information significantly improved the predictive power for the prognosis of IgAN [cNRI 0.72 (0.28-0.82)]. In hTECs, the addition of glycine ameliorated inflammatory signals induced by tumour necrosis factor-α. Our study demonstrates that urinary glycine may have diagnostic and prognostic value for IgAN and indicates that urinary glycine is a protective biomarker for IgAN.
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http://dx.doi.org/10.1111/jcmm.16520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178259PMC
June 2021

Plasma Membrane Localized GCaMP-MS4A12 by Orai1 Co-Expression Shows Thapsigargin- and Ca-Dependent Fluorescence Increases.

Mol Cells 2021 Apr;44(4):223-232

Department of Pharmacology and Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03080, Korea.

Uniquely expressed in the colon, MS4A12 exhibits store-operated Ca entry (SOCE) activity. However, compared to MS4A1 (CD20), a Ca channel and ideal target for successful leukaemia immunotherapy, MS4A12 has rarely been studied. In this study, we investigated the involvement of MS4A12 in Ca influx and expression changes in MS4A12 in human colonic malignancy. Fluorescence of GCaMP-fused MS4A12 (GCaMP-M12) was evaluated to analyse MS4A12 activity in Ca influx. Plasma membrane expression of GCaMP-M12 was achieved by homo- or hetero-complex formation with no-tagged MS4A12 (nt-M12) or Orai1, respectively. GCaMP-M12 fluorescence in plasma membrane increased only after thapsigargin-induced depletion of endoplasmic reticulum Ca stores, and this fluorescence was inhibited by typical SOCE inhibitors and siRNA for Orai1. Furthermore, GCaMP-MS4A12 and Orai1 co-transfection elicited greater plasma membrane fluorescence than GCaMP-M12 co-transfected with nt-M12. Interestingly, the fluorescence of GCaMP-M12 was decreased by STIM1 over-expression, while increased by siRNA for STIM1 in the presence of thapsigargin and extracellular Ca. Moreover, immunoprecipitation assay revealed that Orai1 co-expression decreased protein interactions between MS4A12 and STIM1. In human colon tissue, MS4A12 was expressed in the apical region of the colonic epithelium, although its expression was dramatically decreased in colon cancer tissues. In conclusion, we propose that MS4A12 contributes to SOCE through complex formation with Orai1, but does not cooperate with STIM1. Additionally, we discovered that MS4A12 is expressed in the apical membrane of the colonic epithelium and that its expression is decreased with cancer progression.
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http://dx.doi.org/10.14348/molcells.2021.2031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112172PMC
April 2021

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size.

Gut 2021 Apr 13. Epub 2021 Apr 13.

Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Objective: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown.

Design: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS).

Results: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%).

Conclusions: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.
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http://dx.doi.org/10.1136/gutjnl-2020-322595DOI Listing
April 2021

IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Department of Biomedical Sciences, Seoul National University College of Medicine, Chongno-gu, 03080 Seoul, Korea;

Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient () BMT to understand why myeloid IDO limits the severity of GVHD. Hosts with BM exhibited increased lethality, with enhanced proinflammatory and reduced regulatory T cell responses compared with wild type (WT) allo-BMT controls. Despite the comparable expression of the myeloid-derived suppressor cell (MDSC) mediators, arginase-1, inducible nitric oxide synthase, and interleukin 10, Gr-1CD11b cells from allo-BMT or in vitro BM culture showed compromised immune-suppressive functions and were skewed toward the Ly6CLy6G subset, compared with the WT counterparts. Importantly, Gr-1CD11b cells exhibited elevated levels of reactive oxygen species (ROS) and neutrophil numbers. These characteristics were rescued by human IDO1 with intact heme-binding and catalytic activities and were recapitulated by the treatment of WT cells with the IDO1 inhibitor L1-methyl tryptophan. ROS scavenging by -acetylcysteine reverted the Gr-1CD11b composition and function to an MDSC state, as well as improved the survival of GVHD hosts with BM. In summary, myeloid-derived IDO1 enhances GVHD survival by regulating ROS levels and limiting the ability of Gr-1CD11b MDSCs to differentiate into proinflammatory neutrophils. Our findings provide a mechanistic insight into the immune-regulatory roles of the metabolic enzyme IDO1.
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http://dx.doi.org/10.1073/pnas.2011170118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958359PMC
March 2021

Molecular Orientation Control of Liquid Crystal Organic Semiconductor for High-Performance Organic Field-Effect Transistors.

ACS Appl Mater Interfaces 2021 Mar 25;13(9):11125-11133. Epub 2021 Feb 25.

Material Research Center, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Samsung-ro 130, Yongtong-gu, Suwon-si, Gyeonggi-do 16678, Republic of Korea.

The control of molecular orientation and ordering of liquid crystal (LC) organic semiconductor (OSC) for high-performance and thermally stable organic thin-film transistors is investigated. A liquid crystalline molecule, 2-(4-dodecyl thiophenyl)[1]dibenzothiopheno[6,5-:6',5'-]-thieno[3,2-]thiophene (C12-Th-DBTTT) is synthesized, showing the highly ordered smectic X (SmX) phase, demonstrating molecular reorganization via thermal annealing. The resulting thermally evaporated polycrystalline film and solution-sheared thin film show high charge carrier mobilities of 9.08 and 27.34 cm V s, respectively. Atomic force microscopy and grazing-incidence X-ray diffraction analyses prove that the random SmA-like structure (smectic monolayer) is reorganized to the highly ordered SmA-like structure (smectic bilayer) of C12-Ph-DBTTT at the crystal-SmX transition temperature region. Because of the strong intermolecular interactions between rigid DBTTT cores, the thin film devices of C12-Th-DBTTT show excellent thermal stability up to 300 °C, indicating that LC characterization of conventional OSC materials can obtain high electrical performance as well as superior thermal durability.
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http://dx.doi.org/10.1021/acsami.0c22393DOI Listing
March 2021

Role of Sevoflurane on Natural Killer Group 2, Member D-Mediated Immune Response in Non-Small-Cell Lung Cancer: An In Vitro Study.

Med Sci Monit 2020 Nov 3;26:e926395. Epub 2020 Nov 3.

Department of Anesthesia and Pain Medicine, Pusan National University, School of Medicine, Busan, South Korea.

BACKGROUND The purpose of this study was to investigate the effects of sevoflurane on cancer immunosurveillance and metastasis in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS NCI-H23 cells, a human NSCLC cell line, were incubated with or without sevoflurane at the concentrations of 0, 12.5, 25, 50, 100, and 200 μM for 6 h. Cell viability, the expression of natural killer group 2, member D ligands (NKG2D ligands: UL16-binding proteins 1-3 [ULBP1-3] and major histocompatibility complex class I chain-related molecules A/B [MICA/B]), the expression of matrix metalloproteinases (MMPs), NK cell-mediated cytotoxicity, and cancer cell migration were measured. RESULTS At 12.5, 25, 50, and 100 μM, sevoflurane increased the expression of NKG2D ligands (ULBP2-3 and MICA, ULBP1-3, ULBP1-3, and ULBP1, respectively). Sevoflurane decreased the expression of NKG2D ligands at 200 μM (MICA/B). NK cell-mediated lysis of NCI-H23 cells at 200 μM sevoflurane was significantly reduced compared with the control (P=0.025; target cell: effect cell=1: 10). Sevoflurane increased the expression of MMP-1, -2, and -9 and increased cell migration in NCI-H23 cells at 50, 100, and 200 μM (P=0.001, 0.035, and 0.039, respectively, compared with the control after 18 h of wound formation). CONCLUSIONS Sevoflurane could suppress NKG2D-mediated NK cell cytotoxicity and increased expression of MMPs and migration in NCI-H23 cells. Further research is needed to determine the effects of sevoflurane on cancer immunosurveillance and metastasis in NSCLC.
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http://dx.doi.org/10.12659/MSM.926395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648410PMC
November 2020

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years.

Cancer Res Treat 2021 Apr 28;53(2):378-388. Epub 2020 Oct 28.

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

Purpose: Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years.

Materials And Methods: A search of medical records from seven centers was performed between January 2005 and December 2016.

Results: Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01).

Conclusion: Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.
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http://dx.doi.org/10.4143/crt.2020.756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053862PMC
April 2021

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years.

Cancer Res Treat 2021 Apr 28;53(2):378-388. Epub 2020 Oct 28.

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

Purpose: Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years.

Materials And Methods: A search of medical records from seven centers was performed between January 2005 and December 2016.

Results: Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01).

Conclusion: Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.
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http://dx.doi.org/10.4143/crt.2020.756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053862PMC
April 2021

Melatonin Exerts Anticancer Effects in Human Tongue Squamous Cell Carcinoma Cells by Promoting Autophagy.

Anticancer Res 2020 Nov;40(11):6295-6303

Department of Pharmacology, College of Korean Medicine, Pusan National University, Yangsan, Republic of Korea

Background/aim: The global prevalence of head and neck squamous cell carcinoma (HNSCC) remains high, and its prognosis poor. We investigated the anticancer effects of melatonin in human tongue squamous cell carcinoma cells (SCC-25) and its mechanisms of action.

Materials And Methods: MTT assay was used to determine cell viability. To assess the effects of melatonin on SCC-25 cell metastasis, we conducted cell formation, wound healing, transwell migration and invasion assay. Western blot analysis was performed to measure the levels of autophage marker proteins.

Results: We found that melatonin treatment significantly reduced the viability and colony formation ability of SCC-25 cells, impairing cell migration and invasion. Western blotting assay revealed that melatonin increased the levels of autophagy markers, such as LC-3B and Beclin-1. Consequently, melatonin induces autophage in SCC-25 cells.

Conclusion: Melatonin may be a promising anticancer agent for the treatment of human tongue squamous cell carcinoma.
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http://dx.doi.org/10.21873/anticanres.14650DOI Listing
November 2020

Isoproterenol-induced hypertrophy of neonatal cardiac myocytes and H9c2 cell is dependent on TRPC3-regulated Ca1.2 expression.

Cell Calcium 2020 12 6;92:102305. Epub 2020 Oct 6.

Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea. Electronic address:

Ca1.2 and transient receptor potential canonical channel 3 (TRPC3) are two proteins known to have important roles in pathological cardiac hypertrophy; however, such roles still remain unclear. A better understanding of these roles is important for furthering the clinical understanding of heart failure. We previously reported that Trpc3-knockout (KO) mice are resistant to pathologic hypertrophy and that their Ca1.2 protein expression is reduced. In this study, we aimed to examine the relationship between these two proteins and characterize their role in neonatal cardiomyocytes. We measured Ca1.2 expression in the hearts of wild-type (WT) and Trpc3 mice, and examined the effects of Trpc3 knockdown and overexpression in the rat cell line H9c2. We also compared the hypertrophic responses of neonatal cardiomyocytes cultured from Trpc3 mice to a representative hypertrophy-causing drug, isoproterenol (ISO), and measured the activity of nuclear factor of activated T cells 3 (NFAT3) in neonatal cardiomyocytes (NCMCs). We inhibited the L-type current with nifedipine, and measured the intracellular calcium concentration using Fura-2 with 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced Ba influx. When using the Trpc3-mediated Ca influx, both intracellular calcium concentration and calcium influx were reduced in Trpc3-KO myocytes. Not only was the expression of Ca1.2 greatly reduced in Trpc3-KO cardiac lysate, but the size of the Ca1.2 currents in NCMCs was also greatly reduced. When NCMCs were treated with Trpc3 siRNA, it was confirmed that the expression of Ca1.2 and the intracellular nuclear transfer activity of NFAT decreased. In H9c2 cells, the ISO activated- and verapamil inhibited- Ca influxes were dramatically attenuated by Trpc3 siRNA treatment. In addition, it was confirmed that both the expression of Ca1.2 and the size of H9c2 cells were regulated according to the expression and activation level of TRPC3. We found that after stimulation with ISO, cell hypertrophy occurred in WT myocytes, while the increase in size of Trpc3-KO myocytes was greatly reduced. These results suggest that not only the cell hypertrophy process in neonatal cardiac myocytes and H9c2 cells were regulated according to the expression level of Ca1.2, but also that the expression level of Ca1.2 was regulated by TRPC3 through the activation of NFAT.
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http://dx.doi.org/10.1016/j.ceca.2020.102305DOI Listing
December 2020

Treatment outcome and long-term follow-up of central nervous system germ cell tumor using upfront chemotherapy with subsequent photon or proton radiation therapy: a single tertiary center experience of 127 patients.

BMC Cancer 2020 Oct 9;20(1):979. Epub 2020 Oct 9.

Departments of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of brain tumors, which are more common in Asian countries. There have been different therapeutic strategies in treating germinoma and non-germinomatous germ cell tumors (NGGCT), depending on prognosis. Moreover, long-term follow up should be emphasized due to higher late complication rates. Here, we investigated long-term outcomes and complication profiles of 127 CNS GCT patients who received uniform upfront chemotherapy.

Methods: We retrospectively evaluated outcomes of CNS GCT patients treated in Seoul National University Children's Hospital from August 2004 to April 2019. Patients were classified as low risk (LR) or high risk (HR) based on pathologic diagnosis and tumor markers. Most patients received upfront systemic chemotherapy with carboplatin, cyclophosphamide, etoposide, and/or bleomycin, followed by either proton or photon radiation therapy according to patients' choice.

Results: The median age at diagnosis was 11.9 (range, 3.8-25.1) years, and 54.3% of patients were LR. Photon and proton radiation therapy were administered to 73.2 and 25.2% of patients, respectively. In both LR and HR groups, there were no significant differences in survival between photon and proton radiation therapy. The 10-year relapse incidences were 9.3 and 5.6% in the LR and HR groups, respectively. All recurrences, except one, were local relapse. Six secondary malignancies occurred; the 10-year incidences of secondary malignancy were 2.2 and 7.6% in the LR and HR groups, respectively. The 10-year overall survival rates were 98.3 ± 1.7 and 91.8 ± 3.9% in the LR and HR groups, respectively. In a subgroup analysis of HR group, pathologically diagnosed NGGCT patients (n = 20) showed worse 10-year EFS (65.9 ± 11.9%, p < 0.001) and OS (77.9 ± 9.8%, p = 0.024) rates compared to other HR patients who were not pathologically diagnosed or were confirmed as germinoma with elevated tumor markers. All mortalities were related to disease progression or secondary malignancy.

Conclusion: The strategy of treating CNS GCTs with upfront chemotherapy according to risk groups resulted in good clinical outcomes and acceptable relapse incidence. However, further modification in the definition of the HR group is needed to reduce long-term complications.
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http://dx.doi.org/10.1186/s12885-020-07484-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547441PMC
October 2020

Erythema induratum of Bazin in a 10-year-old boy.

Pediatr Dermatol 2021 Jan 1;38(1):290-291. Epub 2020 Oct 1.

Department of Dermatology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea.

Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle-aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10-year-old Korean boy.
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http://dx.doi.org/10.1111/pde.14374DOI Listing
January 2021

In-Depth Investigation of the Correlation between Organic Semiconductor Orientation and Energy-Level Alignment Using In Situ Photoelectron Spectroscopy.

ACS Appl Mater Interfaces 2020 Nov 27;12(45):50628-50637. Epub 2020 Oct 27.

Organic Material Laboratory, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Suwon 16678, Korea.

Organic semiconductors (OSCs) are of interest for replacing traditional Si-based semiconductors as their flexibility and transparency enable new applications. The properties of OSC materials greatly depend on their orientation and molecular arrangement, which are strongly dependent on the underlying substrate material. Hence, in this study, in situ ultraviolet photoelectron spectroscopy (UPS) is used to elucidate the effect of the substrate on OSC orientation. Two types of OSCs, namely those with shape anisotropy (pentacene, dinaphtho[2,3-b:2',3'-f]thieno[3,2-]thiophene, and dibenzothiopheno[6,5-b:6',5'-f]thieno[3,2-]thiophene) and those with shape isotropy (,'-di(1-naphthyl)-,'-diphenyl-(1,1'-biphenyl)-4,4'-diamine, tris(4-carbazoyl-9-ylphenyl)amine, and [6,6]-phenyl C71 butyric acid methyl ester), are deposited on different electrode materials. The differences in the UPS spectra of these materials are observed directly. In general, the orientation of anisotropic OSC molecules significantly depends on the substrate properties, while that of the isotropic ones do not. All the anisotropic OSC molecules grown on poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) electrodes show a greater degree of molecular ordering than those grown on Au and multiwalled carbon nanotube/PEDOT:PSS electrodes. The molecular arrangements within the OSC/electrode structures are reflected in the energy-level shifts in the corresponding UPS spectra and hence in the electronic configurations. The results of this study should aid the design and synthesis of OSC materials with configurations suitable for organic electronic devices.
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http://dx.doi.org/10.1021/acsami.0c09602DOI Listing
November 2020

Prognostic factors of cytomegalovirus retinitis after hematopoietic stem cell transplantation.

PLoS One 2020 2;15(9):e0238257. Epub 2020 Sep 2.

Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: To identify the visual prognostic factors in patients with cytomegalovirus (CMV) retinitis after hematopoietic stem cell transplantation (HSCT).

Methods: This retrospective cohort study included 4241 patients who underwent HSCT from April 1, 2010 to March 31, 2019 at Seoul St. Mary's Hospital. Of them, 1063 patients presented CMV viremia, and 67 patients (93 eyes) were diagnosed with CMV retinitis. We enrolled 66 patients (91 eyes). The main outcomes included the initial best-corrected visual acuity (BCVA), BCVA at the diagnosis of retinitis and last visit, involved retinal zone, peak CMV DNA levels in the peripheral blood and aqueous humor, time between HSCT and the diagnosis of retinitis, time between the diagnosis of viremia and retinitis, complications, recurrence, survival, and so on.

Results: The mean BCVA (logarithm of the minimum angle of resolution) values before HSCT, at the time of retinitis diagnosis, and at the last visit were 0.041 ± 0.076, 0.262 ± 0.529, and 0.309 ± 0.547, respectively. Multiple regression analysis revealed that the involved zone (P = 0.001), time between HSCT and retinitis diagnosis (P = 0.019), and survival status (P = 0.001) were associated with the final visual acuity.

Conclusions: The final visual prognosis was worse in patients with greater invasion of the central retinal zone, those with a longer interval between HSCT and the diagnosis of retinitis, and those who died. Prompt diagnosis of CMV retinitis through periodic fundus examinations of patients with CMV viremia can prevent severe vision loss. Once CMV viremia is confirmed, we recommend fundus examinations to be immediately performed and repeated every 2 weeks for at least 2 months, even if the CMV DNA titer in the peripheral blood becomes negative.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238257PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467317PMC
October 2020

VGLL4 with low YAP expression is associated with favorable prognosis in colorectal cancer.

APMIS 2020 Oct 14;128(10):543-551. Epub 2020 Sep 14.

Department of Pathology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea.

The Hippo pathway is a tumor suppressive pathway regulating Yes-associated protein-TEA domain-containing sequence-specific transcription factor (YAP-TEAD) complex. VGLL (Vestigial-like) proteins are transcriptional cofactors competing with YAP for TEAD binding and interfering oncogenic activity of YAP-TEAD complex. We evaluated the expression of VGLL4, YAP, and TEAD4 and assessed their correlations with clinicopathologic factors and prognostic effects in 295 colorectal cancers. VGLL4 was positive in 164 (55.6%) cases and correlated with small tumor size, low pT classification, and absence of lymph node metastasis. YAP and TEAD4 were highly expressed in 138 (46.8%) cases and 144 (48.8%) cases, respectively, and high expressions were associated with presence of lymphovascular invasion and lymph node metastasis, or distant metastasis. VGLL4 expression was significantly correlated with low YAP expression (p < 0.001) and had significantly better overall survival than negative expression (p < 0.001). High YAP (HR, 2.108; 95% confidence interval, 1.239-3.584; p = 0.006) and TEAD4 (1.724; 1.021-2.912; p = 0.042) expressions were associated with poor overall survivals. The combined VGLL4 YAP expression showed the best overall survival than other groups (p < 0.001). VGLL4 expression (0.381; 0.212-0.683; p = 0.001) and combined VGLL4 YAP expression (0.227; 0.108-0.475; p < 0.001) were independent good prognostic factors in colorectal cancers. The expressions of VGLL4, YAP, and TEAD4 can be used as prognostic markers in colorectal cancer patients.
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http://dx.doi.org/10.1111/apm.13070DOI Listing
October 2020

Chromogranin A Expression in Rectal Neuroendocrine Tumors Is Associated With More Aggressive Clinical Behavior and a Poorer Prognosis.

Am J Surg Pathol 2020 11;44(11):1496-1505

Departments of Pathology.

Although rectal neuroendocrine tumors (NETs) with an L-cell phenotype and small size are generally less clinically serious, the new 2019 World Health Organization (WHO) classification system has categorized all of these lesions as malignant. Identifying biomarkers of rectal NETs is thus important for stratifying their clinical behavior. Chromogranin A protein expression was assessed in 538 endoscopically or surgically resected rectal NETs and compared with clinicopathologic factors to identify its clinical and prognostic significance. All of the rectal NETs analyzed (100%) were synaptophysin positive, but chromogranin A labeling was only detected in 111 cases (20.6%). Chromogranin A expression in the rectal NETs was more commonly associated with older age (50 y and older; P=0.013), male sex (P=0.002), radical resection (P=0.003), large tumor size (≥1 cm; P=0.038), muscularis propria invasion (P=0.002), lymphovascular (P=0.014) and perineural (P<0.001) invasion, an involved resection margin (P=0.028), and lymph node metastasis (P=0.003). Patients with chromogranin A expression had higher plasma chromogranin A levels (P=0.023) than those without chromogranin A expression during follow-up. The 10-year disease-free survival rate in rectal NET patients with chromogranin A expression (91.5%) was significantly shorter than the negative cases (99.7%) by both univariate (hazard ratio=14.438; 95% confidence interval: 2.911-71.598; P<0.001) and multivariate (hazard ratio=12.099; 95% confidence interval, 2.044-71.608; P=0.006) analyses. In summary, rectal NETs that are positive for chromogranin A are less common than those with synaptophysin expression and show more aggressive clinical behavior. Chromogranin A is therefore a prognostic indicator of higher recurrence risk in patients with endoscopically or surgically resected rectal NETs.
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http://dx.doi.org/10.1097/PAS.0000000000001526DOI Listing
November 2020

Characterization of overwintering sites of Haemaphysalis longicornis (Acari: Ixodidae) and tick infection rate with severe fever with thrombocytopenia syndrome virus from eight provinces in South Korea.

Ticks Tick Borne Dis 2020 09 13;11(5):101490. Epub 2020 Jun 13.

Department of Life Sciences, Gachon University, Gyeonggi-do, South Korea. Electronic address:

Haemaphysalis longicornis (Acari: Ixodidae) is an important vector of pathogens causing tick-borne diseases such as severe fever with thrombocytopenia syndrome (SFTS) in eastern Asia. Although an understanding of the overwintering ecology of ticks is fundamental to management of this vector, its winter biology remains unclear. Therefore, we conducted a field survey from eight provinces in South Korea to characterize overwintering sites of H. longicornis and investigate their SFTS virus infection rates. First, we conducted flagging which consists of horizontal sweeping of a 1 m cloth back-and-forth to collect ticks that may exhibit questing behaviors in four different landscapes: grassland, shrub, coniferous forest, and deciduous forest. From 640 sweeps of flagging (where each sweep covered 3.8 m), we collected five unfed ixodid ticks. However, H. longicornis was not found. After the flagging, to locate overwintering ticks, we inspected a total of 679 samples consisting of three different structures: ground (leaf litter, soil surface, and topsoil layer), rocks, and dead trees. From the samples inspected, 85 unfed overwintering ixodid ticks were found. Haemaphysalis longicornis was the dominant species (88 %), and mostly nymphs were collected (94 %). This species was collected from ground samples, especially from the topsoil layer. Most H. longicornis were found in herbaceous landscapes such as grassland (46 %) and shrub (52 %). SFTS virus was found in 3 out of 38 pools of unfed nymphs (minimal infection rate: 4 %). Our results can serve as baseline information for the development of vector management programs.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101490DOI Listing
September 2020

Choosing Wisely: The Korean Perspective and Launch of the 'Right Decision in Cancer Care' Initiative.

Cancer Res Treat 2020 Jul 2;52(3):655-660. Epub 2020 Jun 2.

Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Korea.

Government healthcare expenditure is rising in Korea, and the costs incurred by patients in Korea exceed those incurred by patients in other Organization for Economic Co-operation and Development countries. Despite the increasing health expenditure, patient demand for services is increasing as well, so it is now becoming recognized that cancer care needs to be balanced. The most important measure in cancer care optimization is to provide high-quality care while keeping costs sustainable. The Korean Cancer Association considers the current situation of cancer therapy in Korea the foremost issue, which has led to the implementation of the nationwide 'Right Decisions in Cancer Care' initiative. This initiative is based on the concepts of medical professionalism in that it should be led by physicians working in the field of oncology, that education should be offered to patients and clinicians, and that it should influence healthcare policy. In this article, we introduce the nationwide 'Right Decision in Cancer Care' initiative and highlight the five initial items on its agenda. The agenda is open to expansion and update as the medical environment evolves and additional clinical evidence becomes available.
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http://dx.doi.org/10.4143/crt.2020.221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373865PMC
July 2020

Metformin induces caspase-dependent and caspase-independent apoptosis in human bladder cancer T24 cells.

Anticancer Drugs 2020 08;31(7):655-662

Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu, South Korea.

Bladder cancer (BC) is the sixth most common cancer in men. Moreover, chemotherapy for BC leads to various side effects. Metformin is known to induce apoptosis in vitro in many types of cancer. Furthermore, it has feasibility as a drug repositioning used for the treatment of cancer. The molecular mechanism of metformin mediating apoptosis in BC is still unclear. In this study, we showed that metformin stimulated the caspase-dependent apoptotic signaling pathway in T24 cells, a human BC cell line. Moreover, the induced apoptosis was partially inhibited by a general caspase inhibitor, z-VAD-fmk, which suggested that metformin-induced apoptosis in T24 cells is partially caspase-independent. Notably, we observed the nuclear translocation of apoptosis-inducing factors (AIFs) in metformin-promoted apoptosis, which is a typical characteristic of the caspase-independent apoptotic pathway. In addition, we found that metformin-mediated apoptosis occurred via degradation of the cellular FADD-like interleukin-1β-converting enzyme inhibitory protein (c-FLIP) by facilitating ubiquitin/proteasome-mediated c-FLIPL degradation. Furthermore, treatment with the reactive oxygen species scavenger N-acetylcysteine, failed to suppress metformin-induced apoptosis and c-FLIPL protein degradation in metformin-treated T24 cells. In conclusion, these results indicate that metformin-induced apoptosis was mediated through AIF-promoted caspase-independent pathways as well as caspase-dependent pathways in T24 cells. As such, metformin could be used as a possible apoptotic agent for the treatment of BC.
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http://dx.doi.org/10.1097/CAD.0000000000000966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365670PMC
August 2020

Metformin induces caspase-dependent and caspase-independent apoptosis in human bladder cancer T24 cells.

Anticancer Drugs 2020 08;31(7):655-662

Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu, South Korea.

Bladder cancer (BC) is the sixth most common cancer in men. Moreover, chemotherapy for BC leads to various side effects. Metformin is known to induce apoptosis in vitro in many types of cancer. Furthermore, it has feasibility as a drug repositioning used for the treatment of cancer. The molecular mechanism of metformin mediating apoptosis in BC is still unclear. In this study, we showed that metformin stimulated the caspase-dependent apoptotic signaling pathway in T24 cells, a human BC cell line. Moreover, the induced apoptosis was partially inhibited by a general caspase inhibitor, z-VAD-fmk, which suggested that metformin-induced apoptosis in T24 cells is partially caspase-independent. Notably, we observed the nuclear translocation of apoptosis-inducing factors (AIFs) in metformin-promoted apoptosis, which is a typical characteristic of the caspase-independent apoptotic pathway. In addition, we found that metformin-mediated apoptosis occurred via degradation of the cellular FADD-like interleukin-1β-converting enzyme inhibitory protein (c-FLIP) by facilitating ubiquitin/proteasome-mediated c-FLIPL degradation. Furthermore, treatment with the reactive oxygen species scavenger N-acetylcysteine, failed to suppress metformin-induced apoptosis and c-FLIPL protein degradation in metformin-treated T24 cells. In conclusion, these results indicate that metformin-induced apoptosis was mediated through AIF-promoted caspase-independent pathways as well as caspase-dependent pathways in T24 cells. As such, metformin could be used as a possible apoptotic agent for the treatment of BC.
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http://dx.doi.org/10.1097/CAD.0000000000000966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365670PMC
August 2020

Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan-Korea collaborative study.

J Hepatobiliary Pancreat Sci 2020 Sep 2;27(9):581-597. Epub 2020 Jul 2.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location.

Methods: IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated.

Results: Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P < 0.001). There were significant differences in 5-year cumulative survival rates (75.2% vs 50.9%; P < 0.0001) and 5-year cumulative disease-free survival rates (64.1% vs 35.3%; P < 0.0001) between the two groups.

Conclusion: Type 1 and Type 2 IPNBs differ in their clinicopathological features and prognosis. This classification may help to further understand IPNB.
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http://dx.doi.org/10.1002/jhbp.785DOI Listing
September 2020

Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid-enhanced MRI: A Multicenter Study.

Radiology 2020 08 2;296(2):335-345. Epub 2020 Jun 2.

From the Department of Radiology, Seoul National University Hospital, Seoul, Korea (I.J., J.M.L.); Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea (S.Y.K.); Department of Radiology, Samsung Medical Center, Seoul, Korea (T.W.K., Y.K.K.); Department of Radiology, Korea University Anam Hospital, Seoul, Korea (B.J.P.); Department of Radiology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (Y.J.L.); Department of Radiology, Seoul St. Mary's Hospital, Seoul, Korea (J.I.C.); Department of Radiology, Korea University Guro Hospital, Seoul, Korea (C.H.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Korea (H.S.P.); Department of Pathology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea (K.L., H.K.); Department of Pathology, Asan Medical Center, Seoul, Korea (E.Y., H.J.K.); Department of Pathology, Samsung Medical Center, Seoul, Korea (S.Y.H.); Department of Pathology, Korea University Anam Hospital, Seoul, Korea (J.Y.K.); Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (S.A.); Department of Pathology, Seoul St. Mary's Hospital, Seoul, Korea (E.S.J.); Department of Pathology, Korea University Guro Hospital, Seoul, Korea (B.H.K.); and Department of Pathology, Konkuk University Hospital, Seoul, Korea (H.S.H.).

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; = .01) and MRI features including well-defined margin (odds ratio, 5.5; = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; < .001), and restricted diffusion (odds ratio, 1.9; = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 See also the editorial by Motosugi in this issue.
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http://dx.doi.org/10.1148/radiol.2020192275DOI Listing
August 2020

Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid-enhanced MRI: A Multicenter Study.

Radiology 2020 08 2;296(2):335-345. Epub 2020 Jun 2.

From the Department of Radiology, Seoul National University Hospital, Seoul, Korea (I.J., J.M.L.); Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea (S.Y.K.); Department of Radiology, Samsung Medical Center, Seoul, Korea (T.W.K., Y.K.K.); Department of Radiology, Korea University Anam Hospital, Seoul, Korea (B.J.P.); Department of Radiology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (Y.J.L.); Department of Radiology, Seoul St. Mary's Hospital, Seoul, Korea (J.I.C.); Department of Radiology, Korea University Guro Hospital, Seoul, Korea (C.H.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Korea (H.S.P.); Department of Pathology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea (K.L., H.K.); Department of Pathology, Asan Medical Center, Seoul, Korea (E.Y., H.J.K.); Department of Pathology, Samsung Medical Center, Seoul, Korea (S.Y.H.); Department of Pathology, Korea University Anam Hospital, Seoul, Korea (J.Y.K.); Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (S.A.); Department of Pathology, Seoul St. Mary's Hospital, Seoul, Korea (E.S.J.); Department of Pathology, Korea University Guro Hospital, Seoul, Korea (B.H.K.); and Department of Pathology, Konkuk University Hospital, Seoul, Korea (H.S.H.).

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; = .01) and MRI features including well-defined margin (odds ratio, 5.5; = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; < .001), and restricted diffusion (odds ratio, 1.9; = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 See also the editorial by Motosugi in this issue.
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http://dx.doi.org/10.1148/radiol.2020192275DOI Listing
August 2020

Unsupervised automatic seizure detection for focal-onset seizures recorded with behind-the-ear EEG using an anomaly-detecting generative adversarial network.

Comput Methods Programs Biomed 2020 Sep 23;193:105472. Epub 2020 Mar 23.

Department of Biomedical Engineering, Hanyang University, Seoul, South Korea. Electronic address:

Background And Objective: Epilepsy is a neurological disorder of the brain, which involves recurrent seizures. An encephalogram (EEG) is a gold standard method in the detection and analysis of epileptic seizures. However, the standard EEG recording system is too obstructive to be used in daily life. Behind-the-ear EEG is an alternative approach to record EEG conveniently. Previous researchers applied machine learning to automatically detect seizures with EEG, but the epileptic EEG waveform contains subtle changes that are difficult to be identified. Furthermore, the extremely small proportion of ictal events in the long-term monitoring may cause the imbalance problem and, consequently, poor prediction performance in supervised learning approaches. In this study, we present an automatic seizure detection algorithm with a generative adversarial network (GAN) trained by unsupervised learning and evaluated it with behind-the-ear EEG.

Methods: We recorded behind-the-ear EEGs from 12 patients who have various types of epilepsy. Data were reviewed separately by two epileptologists, who determined the onsets and ends of seizures. First, we conducted unsupervised learning with the normal records for the GAN to learn the representation of normal states. Second, we performed automatic seizure detection with the trained GAN as an anomaly detector. Last, we combined the Gram matrix with other anomaly losses to improve detection performance.

Results: The proposed approach achieved detection performance with an area under the receiver operating curve of 0.939 and sensitivity of 96.3% with a false alarm rate of 0.14 per hour in the test dataset. In addition, we confirmed distinguishability with the distribution of the anomaly scores in terms of EEG frequency bands.

Conclusions: It is expected that the proposed anomaly detection via GAN with the behind-the-ear EEG can be effectively used for long-term seizure monitoring in daily life.
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http://dx.doi.org/10.1016/j.cmpb.2020.105472DOI Listing
September 2020

Effect of addition of bevacizumab to chemoradiotherapy in newly diagnosed stage IVB cervical cancer: a single institution experience in Korea.

Int J Gynecol Cancer 2020 06 9;30(6):764-771. Epub 2020 Apr 9.

Proton Therapy Center, National Cancer Center, Goyang-si, Gyeonggi-do, the Republic of Korea

Objective: The aim of this study was to compare the clinical outcomes of chemoradiotherapy with or without bevacizumab in patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer.

Methods: 41 patients with stage IVB cervical cancer who underwent chemoradiotherapy between August 2015 and December 2017 were retrospectively analyzed. This study included 11 patients who received bevacizumab before or after radiotherapy (group A) and 30 patients who received conventional chemoradiotherapy without bevacizumab (group B). We excluded the following patients: those with dual primary cancers; those whose pathologic diagnosis was neither squamous cell carcinoma nor adenocarcinoma; those who did not undergo radiotherapy; or those from whom follow-up data could not be collected. We analyzed the treatment responses, toxicities, progression-free survival, and overall survival rates.

Results: A total of 41 patients were included in the analysis. The median follow-up was 19 months (range 3-108). The response rates at 3 months after treatment were 90.9% in group A and 83.3% in group B (p=0.54). After completing all treatments, the complete response rates were 81.8% in group A and 47% in group B (p=0.04). Grade ≥3 gastrointestinal toxicities, including bleeding, fistula, perforation, and obstruction, were more frequent in group A (54.5%) than in group B (6.7%) (p=0.003). The 12 month progression-free survival and overall survival rates were similar in both arms (12 month progression-free survival: 45.5% vs 46.7%, respectively, p=0.22; 12 month overall survival: 81.8% vs 72.9%, respectively, p=0.57). Patients with node-only metastasis had better 12 month progression-free survival in group B than in group A (59.1% vs 42.9%, respectively, p=0.04). However, the responses to both treatments did not differ in patients with organ metastasis.

Conclusions: Bevacizumab for stage IVB cervical cancer is associated with higher complete response rates. However, patients treated with bevacizumab experienced more bowel toxicities. Bevacizumab did not improve progression-free survival among patients with node-only metastasis.
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http://dx.doi.org/10.1136/ijgc-2020-001200DOI Listing
June 2020