Publications by authors named "Eun Jung Lee"

599 Publications

Deep learning-based histopathological segmentation for whole slide images of colorectal cancer in a compressed domain.

Sci Rep 2021 Nov 18;11(1):22520. Epub 2021 Nov 18.

Department of Hospital Pathology, The Catholic University of Korea, College of Medicine, Uijeongbu St. Mary's Hospital, Seoul, South Korea.

Automatic pattern recognition using deep learning techniques has become increasingly important. Unfortunately, due to limited system memory, general preprocessing methods for high-resolution images in the spatial domain can lose important data information such as high-frequency information and the region of interest. To overcome these limitations, we propose an image segmentation approach in the compressed domain based on principal component analysis (PCA) and discrete wavelet transform (DWT). After inference for each tile using neural networks, a whole prediction image was reconstructed by wavelet weighted ensemble (WWE) based on inverse discrete wavelet transform (IDWT). The training and validation were performed using 351 colorectal biopsy specimens, which were pathologically confirmed by two pathologists. For 39 test datasets, the average Dice score, the pixel accuracy, and the Jaccard score were 0.804 ± 0.125, 0.957 ± 0.025, and 0.690 ± 0.174, respectively. We can train the networks for the high-resolution image with the large region of interest compared to the result in the low-resolution and the small region of interest in the spatial domain. The average Dice score, pixel accuracy, and Jaccard score are significantly increased by 2.7%, 0.9%, and 2.7%, respectively. We believe that our approach has great potential for accurate diagnosis.
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http://dx.doi.org/10.1038/s41598-021-01905-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602325PMC
November 2021

Transformation of electrospun Keratin/PVA nanofiber membranes into multilayered 3D Scaffolds: Physiochemical studies and corneal implant applications.

Int J Pharm 2021 Oct 26;610:121228. Epub 2021 Oct 26.

Carbon Composite Energy Nanomaterials Research Center, Woosuk University, Wanju 55338, Republic of Korea; Woosuk Institute of Smart Convergence Life Care (WSCLC), Woosuk University, Wanju 55338, Republic of Korea. Electronic address:

In this study, we engineered an electrospun keratin/polyvinyl alcohol (PVA) nanofiber membrane with a three-dimensional (3D) fiber network. Both keratin and PVA are known as biocompatible materials, and the 3D assembly of these two led to a transparent membrane with superior mechanical properties. The as-prepared three-dimensionally assembled keratin/PVA nanofiber (3D keratin/PVA NFs) membrane was characterized by state-of-the-art techniques and used as a corneal implant in rabbit eyes. The transparency, mechanical properties, and biocompatibility of the electrospun keratin/PVA NFs were highly enhanced after 3D modification which is mainly attributed to its unique three-dimensional morphology. The performance of 3D keratin/PVA NFs membrane was compared with horse amniotic membrane (AM), and the results obtained from the clinical and histological evaluations showed that it could be considered as an alternative material to the AM. Furthermore, this study provides an emerging approach for converting a two-dimensional electrospun nanofiber membrane to three-dimensional fiber networks that resemble the structure of the extracellular matrix (ECM).
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http://dx.doi.org/10.1016/j.ijpharm.2021.121228DOI Listing
October 2021

Comparative Topographical Analysis of Choroidal Microvascular Dropout Between Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

Invest Ophthalmol Vis Sci 2021 10;62(13):27

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

Purpose: To identify the presence of choroidal microvascular dropout (MvD) in nonarteritic anterior ischemic optic neuropathy (NAION) eyes and to characterize the topographical distribution for the mechanistic interpretation of MvD development.

Methods: We performed optical coherence tomography angiography on 47 open-angle glaucoma (OAG) and 19 NAION eyes with β-zone peripapillary atrophy (βPPA). We recorded the presence of MvD and compared between the peripapillary topographical measures of MvD, retinal nerve fiber layer (RNFL) defect, and βPPA in angular width and location.

Results: MvD was present in both diseases, marginally more frequently in NAION eyes (19/19, 100.0%) than in OAG eyes (38/47, 80.6%, P = 0.050), without a discernable difference in appearance. NAION eyes also showed wider MvD and RNFL defects compared to OAG eyes (both P < 0.001). In topographical measurements, the distribution of MvD showed a strong correspondence to superimposition areas of βPPA and RNFL defects, more distinctly than to RNFL defects (all P < 0.001). The outline of superimposition area also remarkably resembled the MvD area.

Conclusions: MvD was present in both the OAG and NAION groups. The βPPA-RNFL defect superimposition area topographically and morphologically matched MvD. Further investigations are needed to elucidate the role of RNFL defects in the pathogenesis of MvD and the clinical significance.
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http://dx.doi.org/10.1167/iovs.62.13.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556563PMC
October 2021

Dosimetric parameters associated with the long-term oncological outcomes of Gamma Knife surgery for sellar and parasellar tumors in pediatric patients.

J Neurosurg Pediatr 2021 Oct 22:1-9. Epub 2021 Oct 22.

1Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul.

Objective: The authors aimed to investigate the dosimetric parameter and the minimally required dose associated with long-term control of sellar and parasellar tumors after Gamma Knife surgery (GKS) in children.

Methods: A retrospective analysis was performed on pediatric patients younger than 19 years of age who were diagnosed with sellar and parasellar tumors and received GKS at the authors' institution from 1998 to 2019. Cox proportional hazards regression analyses were used to investigate the dosimetric parameters associated with treatment outcome. The Kaplan-Meier method was used to analyze tumor control rates after GKS.

Results: Overall, 37 patients with 40 sellar and parasellar tumors, including 22 craniopharyngiomas and 12 pituitary adenomas, had a mean follow-up of 85.8 months. The gross target volume was 0.05 cm3 to 15.28 cm3, and the mean marginal dose was 15.8 Gy (range 9.6-30.0 Gy). Ten patients experienced treatment failure at a mean of 28.0 ± 26.7 months. The actuarial 5- and 10-year tumor control rates were 79.0% and 69.8%, respectively. D98% was an independent predictive factor of tumor control (HR 0.846 [95% CI 0.749-0.956], p = 0.007), with a cutoff value of 11.5 Gy for the entire cohort and 10 Gy for the craniopharyngioma group. Visual deterioration occurred in 2 patients with the maximum point dose of 10.1 Gy and 10.6 Gy to the optic apparatus.

Conclusions: In pediatric patients, D98% was a reliable index of the minimum required dose for long-term control of sellar and parasellar tumors after GKS. The optimal D98% value for each tumor diagnosis needs to be elucidated in the future.
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http://dx.doi.org/10.3171/2021.7.PEDS21312DOI Listing
October 2021

Particulate Matter Promotes Melanin Production through Endoplasmic Reticulum Stress‒Mediated IRE1α Signaling.

J Invest Dermatol 2021 Oct 19. Epub 2021 Oct 19.

Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Particulate matter (PM) is believed to be related to cardiovascular and respiratory diseases. The skin is also known to be affected by PM exposure as a result of skin barrier dysfunction, cutaneous inflammation, and apoptotic cell death. Epidemiological studies have suggested that PM is related to pigment spots. Recently, diesel exhaust particles are reported to cause a tanning response mediated by oxidative stress. However, the direct effects of PM on melanogenesis and the related mechanisms have not yet been clarified. Our study showed that PM can increase melanin production in melanocyte, mouse skin, and human skin models. RNA-sequencing analyses of melanocytes revealed that the expressions of unfolded protein response molecules were increased after PM exposure. In particular, IRE1α signaling pathway, which was consistently upregulated, was related to PM-triggered melanogenesis. In addition, PM-induced melanogenesis was abrogated by an IRE1α inhibitor. Therefore, our findings corroborate previous findings in melanocytes and in mouse and human models and also illuminate the involvement of the IRE1α pathway as a mechanism of PM-induced melanogenesis.
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http://dx.doi.org/10.1016/j.jid.2021.08.444DOI Listing
October 2021

Association between septal deviation and OSA diagnoses: a nationwide 9-year follow-up cohort study.

J Clin Sleep Med 2021 10;17(10):2099-2106

Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Jeonbuk National University, Jeonju, Republic of Korea.

Study Objectives: Obstructive sleep apnea (OSA) is a multilevel problematic disease. Major septal deviation (SD) can lead to severe nasal congestion, which, in turn, can lead to sleep apnea. Although SD seems to be related to OSA, very few studies have quantitatively examined this relationship. In this study, we investigate this using a 9-year large-scale cohort study.

Methods: The SD group was selected out of 1 million individuals randomly extracted by the National Health Insurance Service. The non-SD group was obtained through propensity score matching considering several variables. The primary end point was OSA diagnosis.

Results: The study (SD) group included 11,238 individuals and the non-SD group (control group) included 22,476 persons. The overall hazard ratio for OSA in the SD group was 4.39 (95% confidence interval [CI]: 3.56-5.42). In subgroup analysis, the hazard ratio for OSA of male individuals was 3.77 (95% CI: 2.83-5.03), high economic status was 1.27 (95% CI: 1.05-1.56), metropolitan area was 1.31 (95% CI: 1.07-1.62), young age was 0.79 (95% CI: 0.64-0.98), hypertension was 1.00 (95% CI: 0.37-2.7), and diabetes mellitus was 2.44 (95% CI: 1.15-5.21). In the SD group, the hazard ratio for OSA after septoplasty was 0.71 (95% CI: 0.54-0.94).

Conclusions: From long-term follow-up, the prevalence of OSA was 4.39 times higher in the SD group compared with the control group. This phenomenon was more pronounced with increasing body mass index and decreased significantly after septoplasty.

Citation: Yeom SW, Chung SK, Lee EJ, et al. Association between septal deviation and OSA diagnoses: a nationwide 9-year follow-up cohort study. . 2021;17(10):2099-2106.
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http://dx.doi.org/10.5664/jcsm.9352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494085PMC
October 2021

A new minisatellite VNTR marker, Pscp1, discovered for the identification of opium poppy.

Forensic Sci Int Genet 2021 11 20;55:102581. Epub 2021 Aug 20.

Forensic DNA Division, National Forensic Service, Wonju 26460, Republic of Korea. Electronic address:

Opium poppy, a member of the Papaveraceae family, is an ancient herbaceous plant and well-known medical resource in the pharmaceutical industry. However, opium poppies are grown worldwide for producing illicit drugs, significantly increasing the incidence of narcotic drug abuse. Since the narcotic poppy has not yet been genetically investigated, we characterized a novel variable number tandem repeat (VNTR) marker of forensically important poppy species based on the genetic analysis of 164 samples collected from two locations spanning the Jeolla province and Jeju island of South Korea. Comparing analysis of the chloroplast (cp) genome sequences for four representative species of Papaver (Papaver somniferum, Papaver somniferum subs. setigerum, Papaver orientale, and Papaver rhoeas) revealed a unique region with 1-3 repeats for 16 nucleotide motifs in the genome inverted repeat A (IRA, positions 128,651 to 128,698) region. For 16 nucleotide motifs, 3 repeats were found in P. somniferum, and 2 repeats were found in P. somniferum subs. setigerum. Therefore, 10 known and the 133 unknown, seized Papaver species were compared to determine whether the species could be identified via variations in the repeat units. The sizes of a novel VNTR ranged from 181 to 252 bp between the species. Phylogenetic analysis confirmed that a novel VNTR, which we named Pscp1, could clearly distinguish between the narcotic and non-narcotic types of Papaver species based on the patterns of sequence variation. Interestingly, we found that Pscp1 could also distinguish between P. somniferum and P. somniferum subs. setigerum. The regions of eight non-narcotic species displayed similar patterns and also differences were found due to the nucleotide substitution and deletion events. The structural differences of Pscp1 were observed within the two narcotic species or between the narcotic and non-narcotic species, suggesting that these variations may act as a genetic marker. We, therefore, developed a new Pscp1 PCR-capillary electrophoresis (CE) method that can reliably identify the narcotic type of Papaver species. Taken together, our findings suggest that the newly developed Pscp1 can be used as an identification marker of opium poppy, and establish that the Pscp1 genotyping method by PCR-CE is an effective primary screening tool that can also contribute to species discrimination in the field of forensic diagnosis and applications.
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http://dx.doi.org/10.1016/j.fsigen.2021.102581DOI Listing
November 2021

Caspase-cleavable peptide-doxorubicin conjugate in combination with CD47-antagonizing nanocage therapeutics for immune-mediated elimination of colorectal cancer.

Biomaterials 2021 10 28;277:121105. Epub 2021 Aug 28.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Here we report a novel combination of a caspase-cleavable peptide-doxorubicin conjugate (MPD-1) with CD47-antagonizing nanocage therapeutics for the treatment of microsatellite-stable (MSS) colorectal cancer (CRC). MPD-1 (i) upregulated markers of immunogenic cell death (ICD) in tumor, and increased co-stimulatory markers on dendritic cells (DCs), (ii) enhanced CD8 T cell infiltration and antigen presenting cell (APC) activation, and (iii) showed negligible off-target immune-related toxicity compared to free dox. Then, the CD47 antagonist FS nanocage, a SIRPα-expressing ferritin nanocage, was co-administered with MPD-1 that resulted in 95.2% (p < 0.001) tumor growth inhibition in an established CRC model. T cell-mediated elimination of tumors was also confirmed by the tumor-specific activation of T cells detected by IFNγ and tumor-free mice were observed (95%) that bared a memory response when re-challenged. The strategically developed MPD-1 is an ideal adjuvant to immunotherapy and the combination with FS nanocage triggers potent immunity against MSS CRC. In summary, we present an approach to initiate and stimulate immune-mediated eradication of cancer cells using synergistic immunogenic agents targeting the MSS CRC.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121105DOI Listing
October 2021

Cathepsin L, a Target of Hypoxia-Inducible Factor-1-α, Is Involved in Melanosome Degradation in Melanocytes.

Int J Mol Sci 2021 Aug 10;22(16). Epub 2021 Aug 10.

Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.

Hypoxic conditions induce the activation of hypoxia-inducible factor-1α (HIF-1α) to restore the supply of oxygen to tissues and cells. Activated HIF-1α translocates into the nucleus and binds to hypoxia response elements to promote the transcription of target genes. Cathepsin L (CTSL) is a lysosomal protease that degrades cellular proteins via the endolysosomal pathway. In this study, we attempted to determine if CTSL is a hypoxia responsive target gene of HIF-1α, and decipher its role in melanocytes in association with the autophagic pathway. The results of our luciferase reporter assay showed that the expression of CTSL is transcriptionally activated through the binding of HIF1-α at its promoter. Under autophagy-inducing starvation conditions, HIF-1α and CTSL expression is highly upregulated in melan-a cells. The mature form of CTSL is closely involved in melanosome degradation through lysosomal activity upon autophagosome-lysosome fusion. The inhibition of conversion of pro-CTSL to mature CTSL leads to the accumulation of gp100 and tyrosinase in addition to microtubule-associated protein 1 light chain 3 (LC3) II, due to decreased lysosomal activity in the autophagic pathway. In conclusion, we have identified that CTSL, a novel target of HIF-1α, participates in melanosome degradation in melanocytes through lysosomal activity during autophagosome-lysosome fusion.
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http://dx.doi.org/10.3390/ijms22168596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395286PMC
August 2021

Influence of MXene Particles with a Stacked-Lamellar Structure on Osteogenic Differentiation of Human Mesenchymal Stem Cells.

Materials (Basel) 2021 Aug 9;14(16). Epub 2021 Aug 9.

Department of Nano-Biomedical Science, BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea.

MXenes with a two-dimensional (2D) structure have attracted attention as potential biomedical materials. In this study, TiC MXene particles with 2D-lamellar structures were intercalated and their potential as a biomaterial was evaluated using human mesenchymal stem cells. Intercalated MXene was characterized in terms of microstructure, phase composition, and size. Cell proliferation experiments with MXene particles confirmed that concentrations >50 μg/mL were cytotoxic, while concentrations <20 μg/mL promoted osteogenic differentiation. Moreover, MXene effectively facilitated the early and late osteogenic gene expression.
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http://dx.doi.org/10.3390/ma14164453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401813PMC
August 2021

Influenza and anosmia: Important prediction factors for severity and death of COVID-19.

J Infect 2021 Nov 19;83(5):e10-e13. Epub 2021 Aug 19.

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Jeonbuk National University, Jeonju-si 54907, Republic of Korea; Department of Medical Informatics, College of Medicine, Jeonbuk National University, Jeonju-si 54907, Republic of Korea; Research Institute of Clinical Medicine of Jeonbuk National University - Biomedical, Research Institute of Jeonbuk National University Hospital, Jeonju-si 54907, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373587PMC
November 2021

Association of gastroesophageal reflux disease with increased risk of chronic otitis media with effusion in adults: A nationwide population-based cohort study.

Medicine (Baltimore) 2021 Aug;100(33):e26940

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Jeonbuk National University, Jeonju, Republic of Korea.

Abstract: This study aimed to evaluate the risk of developing chronic otitis media with effusion (OME) in individuals with gastroesophageal reflux disease (GERD).A retrospective propensity score-matched cohort study was performed using data from the Korea National Health Insurance Service. The GERD group (n = 3532) included certain individuals who had been diagnosed with GERD between January 2002 and December 2005. A comparison control group (n = 14,128) was calculated by 1:4 propensity score matching considering age, sex, and comorbidities and year of enrollment. Each patient was monitored until 2013. Survival analysis, the Log-rank test, and Cox proportional hazard regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of chronic OME for each group.Among the 17,660 individuals included in the study population (53.2% men), the overall incidence of chronic OME during the 11-year follow-up was 1.84-fold higher in the GERD group than in the non-GERD group (1.8 vs 3.0 per 1000 person-year; adjusted HR 1.84; 95% confidence interval [CI], 1.46-2.31). Moreover, the adjusted HRs of developing chronic OME (allergic rhinitis, 1.69 [95% CI, 1.37-2.10]; asthma, 1.29 [95% CI, 1.02-1.64]; chronic rhinosinusitis, 1.61 [95% CI, 1.26-2.05]) were greater in study population with comorbidities.From long-term follow-up, the prevalence of chronic OME in adults was 1.84 times higher in the GERD group compared with the non-GERD group. Specifically, it found that allergic rhinitis, asthma, or chronic rhinosinusitis showed increase the risk of developing chronic OME than those without these conditions.
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http://dx.doi.org/10.1097/MD.0000000000026940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376319PMC
August 2021

Impact of coronavirus disease 2019 on respiratory surveillance and explanation of high detection rate of human rhinovirus during the pandemic in the Republic of Korea.

Influenza Other Respir Viruses 2021 11 18;15(6):721-731. Epub 2021 Aug 18.

Division of Emerging Infectious Diseases, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea.

Background: After the detection of the first case of coronavirus disease 2019 (COVID-19) in South Korea on January 20, 2019, it has triggered three major outbreaks. To decrease the disease burden of COVID-19, social distancing and active mask wearing were encouraged, reducing the number of patients with influenza-like illness and altering the detection rate of influenza and respiratory viruses in the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). We examined the changes in respiratory viruses due to COVID-19 in South Korea and virological causes of the high detection rate of human rhinovirus (hRV) in 2020.

Methods: We collected 52 684 oropharyngeal or nasopharyngeal swab samples from patients with influenza-like illness in cooperation with KINRESS from 2016 to 2020. Influenza virus and other respiratory viruses were confirmed using real-time RT-PCR. The weekly detection rate was used to compare virus detection patterns.

Results: Non-enveloped virus (hRV, human bocavirus, and human adenovirus) detection rates during the COVID-19 pandemic were maintained. The detection rate of hRV significantly increased in 2020 compared with that in 2019 and was negatively correlated with number of COVID-19-confirmed cases in 2020. The distribution of strains and genetic characteristics in hRV did not differ between 2019 and 2020.

Conclusions: The COVID-19 pandemic impacted the respiratory virus detection rate. The extremely low detection rate of enveloped viruses resulted from efforts to prevent the spread of COVID-19 in South Korea. The high detection rate of hRV may be related to resistance against environmental conditions as a non-enveloped virus and the long period of viral shedding from patients.
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http://dx.doi.org/10.1111/irv.12894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446939PMC
November 2021

Association of gastroesophageal reflux disease with increased risk of chronic otitis media with effusion in adults: A nationwide population-based cohort study.

Medicine (Baltimore) 2021 Jul;100(29):e26727

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Jeonbuk National University, Jeonju, Republic of Korea.

Abstract: This study aimed to evaluate the risk of developing chronic otitis media with effusion (OME) in individuals with gastroesophageal reflux disease (GERD).A retrospective propensity score-matched cohort study was performed using data from the Korea National Health Insurance Service. The GERD group (n = 3532) included certain individuals who had been diagnosed with GERD between January 2002 and December 2005. A comparison control group (n = 14,128) was calculated by 1:4 Propensity Score (PS) matching considering age, sex, and comorbidities and year of enrolment. Each patient was monitored until 2013. Survival analysis, the log-rank test, and Cox proportional hazard regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of chronic OME for each group.Among the 17,660 individuals included in the study population (53.2% male), the overall incidence of chronic OME during the 11-year follow-up was 1.84-fold higher in the GERD group than in the non-GERD group (1.8 vs 3.0 per 1000 person-year; adjusted HR 1.84; 95% confidence interval [CI], 1.46-2.31). Moreover, the adjusted HRs of developing chronic OME (allergic rhinitis, 1.69 [95% CI, 1.37-2.10]; asthma, 1.29 [95% CI, 1.02-1.64]; chronic rhinosinusitis, 1.61 [95% CI, 1.26-2.05]) were greater in study population with comorbidities.From long-term follow-up, the prevalence of chronic OME in adults was 1.84 times higher in the GERD group compared with the non-GERD group. Specifically, it found that allergic rhinitis, asthma, or chronic rhinosinusitis showed increase the risk of developing chronic OME than those without these conditions.
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http://dx.doi.org/10.1097/MD.0000000000026727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294894PMC
July 2021

Nanocages displaying SIRP gamma clusters combined with prophagocytic stimulus of phagocytes potentiate anti-tumor immunity.

Cancer Gene Ther 2021 09 4;28(9):960-970. Epub 2021 Aug 4.

KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.

Antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), play a crucial role in bridging innate and adaptive immunity; thereby, innate immune checkpoint blockade-based therapy is an attractive approach for the induction of sustainable tumor-specific immunity. The interaction between the cluster of differentiation 47 (CD47) on tumor and signal-regulatory protein alpha (SIRPα) on phagocytic cells inhibits the phagocytic function of APCs, acting as a "don't eat me" signal. Accordingly, CD47 blockade is known to increase tumor cell phagocytosis, eliciting tumor-specific CD8 T-cell immunity. Here, we introduced a nature-derived nanocage to deliver SIRPγ for blocking of antiphagocytic signaling through binding to CD47 and combined it with prophagocytic stimuli using a metabolic reprogramming reagent for APCs (CpG-oligodeoxynucleotides). Upon delivering the clustered SIRPγ variant, the nanocage showed enhanced CD47 binding profiles on tumor cells, thereby promoting active engulfment by phagocytes. Moreover, combination with CpG potentiated the prophagocytic ability, leading to the establishment of antitumorigenic surroundings. This combination treatment could competently inhibit tumor growth by invigorating APCs and CD8 T-cells in TMEs in B16F10 orthotopic tumor models, known to be resistant to CD47-targeting therapeutics. Collectively, enhanced delivery of an innate immune checkpoint antagonist with metabolic modulation stimuli of immune cells could be a promising strategy for arousing immune responses against cancer.
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http://dx.doi.org/10.1038/s41417-021-00372-yDOI Listing
September 2021

Development of an inside-out augmented reality technique for neurosurgical navigation.

Neurosurg Focus 2021 08;51(2):E21

3Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: With the advancement of 3D modeling techniques and visualization devices, augmented reality (AR)-based navigation (AR navigation) is being developed actively. The authors developed a pilot model of their newly developed inside-out tracking AR navigation system.

Methods: The inside-out AR navigation technique was developed based on the visual inertial odometry (VIO) algorithm. The Quick Response (QR) marker was created and used for the image feature-detection algorithm. Inside-out AR navigation works through the steps of visualization device recognition, marker recognition, AR implementation, and registration within the running environment. A virtual 3D patient model for AR rendering and a 3D-printed patient model for validating registration accuracy were created. Inside-out tracking was used for the registration. The registration accuracy was validated by using intuitive, visualization, and quantitative methods for identifying coordinates by matching errors. Fine-tuning and opacity-adjustment functions were developed.

Results: ARKit-based inside-out AR navigation was developed. The fiducial marker of the AR model and those of the 3D-printed patient model were correctly overlapped at all locations without errors. The tumor and anatomical structures of AR navigation and the tumors and structures placed in the intracranial space of the 3D-printed patient model precisely overlapped. The registration accuracy was quantified using coordinates, and the average moving errors of the x-axis and y-axis were 0.52 ± 0.35 and 0.05 ± 0.16 mm, respectively. The gradients from the x-axis and y-axis were 0.35° and 1.02°, respectively. Application of the fine-tuning and opacity-adjustment functions was proven by the videos.

Conclusions: The authors developed a novel inside-out tracking-based AR navigation system and validated its registration accuracy. This technical system could be applied in the novel navigation system for patient-specific neurosurgery.
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http://dx.doi.org/10.3171/2021.5.FOCUS21184DOI Listing
August 2021

Clinical Features and Treatment Outcomes of Cerebral Arteriovenous Malformation Associated With Moyamoya Disease.

World Neurosurg 2021 Oct 28;154:e633-e640. Epub 2021 Jul 28.

Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Republic of Korea. Electronic address:

Background: Cerebral arteriovenous malformation (AVM) can rarely occur in conjunction with moyamoya disease (MMD). There is still no consensus on how to treat AVM when accompanied by MMD. In this study, we assessed the clinical features and suggested appropriate management when AVM was combined with MMD.

Methods: From August 1994 to December 2020, 7 out of 4004 patients with MMD were found to have AVM. The Karnofsky Performance Scale (KPS) was used to evaluate the clinical outcomes of AVM and MMD. KPS greater than 80 was classified as a good outcome. In addition, the radiologic outcomes of the patients were evaluated.

Results: The incidence of AVM with MMD was 1.7 per 1000 persons. Five patients underwent bypass surgery for MMD, and 5 patients underwent Gamma Knife surgery (GKS) for concurrent AVM. Postoperative perfusion magnetic resonance imaging and brain single photon emission computerized tomography showed improved cerebral hemodynamics in 4 out of 7 territories. Postoperative cerebral angiography showed good revascularization in 4 out of 8 territories. After GKS, 4 patients showed complete obliteration, and 1 patient showed a significantly decreased AVM size. Six patients showed favorable clinical outcomes (KPS 80-100), and 1 patient with delayed GKS for AVM had a poor outcome (KPS 20) due to AVM rupture.

Conclusions: In this study, AVM tended to occur where the angiographic stage of MMD was higher. When AVM is combined with MMD, MMD bypass surgery is recommended based on symptoms and cerebral perfusion status. For AVM, less invasive but effective treatments, such as GKS, should be implemented as soon as possible.
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http://dx.doi.org/10.1016/j.wneu.2021.07.100DOI Listing
October 2021

Single- and hypofractionated stereotactic radiosurgery for large (> 2 cm) brain metastases: a systematic review.

J Neurooncol 2021 Aug 15;154(1):25-34. Epub 2021 Jul 15.

Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Purpose: Since frameless stereotactic radiosurgery (SRS) techniques have been recently introduced, hypofractionated SRS (HF-SRS) for large brain metastases (BMs) is gradually increasing. To verify the efficacy and safety of HF-SRS for large BMs, we aimed to perform a systematic review and compared them with SF-SRS.

Methods: We systematically searched the studies regarding SF-SRS or HF-SRS for large (> 2 cm) BM from databases including PubMed, Embase, and the Cochrane Library on July 31, 2018. Biologically effective dose with the α/β ratio of 10 (BED), 1-year local control (LC), and radiation necrosis (RN) were compared between the two groups, with the studies being weighted by the sample size.

Results: The 15 studies with 1049 BMs that described 1-year LC and RN were included. HF-SRS tended to be performed in larger tumors; however, higher mean BED (50.1 Gy versus 40.4 Gy, p < 0.0001) was delivered in the HF-SRS group, which led to significantly improved 1-year LC (81.6 versus 69.0%, p < 0.0001) and 1-year overall survival (55.1 versus 47.2%, p < 0.0001) in the HF-SRS group compared to the SF-SRS group. In contrast, the incidence of radiation toxicity was significantly decreased in the HF-SRS group compared to the SF-SRS group (8.0 versus 15.6%, p < 0.0001).

Conclusion: HF-SRS results in better LC of large BMs while simultaneously reducing RN compared to SF-SRS. Thus, HF-SRS should be considered a priority for SF-SRS in patients with large BMs who are not suitable to undergo surgical resection.
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http://dx.doi.org/10.1007/s11060-021-03805-8DOI Listing
August 2021

Electroacupuncture for post-thoracotomy pain: A systematic review and meta-analysis.

PLoS One 2021 7;16(7):e0254093. Epub 2021 Jul 7.

Department of Korean Rehabilitation Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea.

Background: Thoracotomy is an invasive surgical procedure that produces intense postoperative pain. Electroacupuncture has been used to induce analgesia in various situations, including after surgery. The aim of the following systematic review and meta-analysis was to evaluate the effect of electroacupuncture on post-thoracotomy pain.

Methods: The studies for the systematic review were searched using the following 9 databases: PubMed, Cochrane Library, EMBASE, MEDLINE Complete, Google Scholar, China National Knowledge Infrastructure (CNKI), Korean Medical Database (KMBASE), Koreanstudies Information Service System (KISS), and OASIS, without language restriction. Randomized controlled trials (RCTs) that met the inclusion criteria were selected. The quality assessment was performed using the Cochrane risk-of-bias tool, and RevMan 5.3 was used for meta-analysis. The review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42019142157.

Results: Eleven randomized controlled trials were included in the systematic review. The meta-analysis was performed for two outcome measures: pain score 24 hours after surgery and total dose of opioid analgesics. A subgroup analysis was performed according to the control group: sham acupuncture and conventional analgesia group. Pain score 24 hours after surgery of electroacupuncture group showed a standard mean difference of -0.98 (95% CI: -1.62 to -0.35) compared to sham acupuncture. The standard mean difference was -0.94 (95% CI: -1.33 to -0.55) compared to conventional analgesia. The total dose of opioid analgesics of electroacupuncture group showed a standard mean difference values of -0.95 (95% CI: -1.42 to -0.47) compared to sham acupuncture. The standard mean difference was -1.96 (95% CI: -2.82 to -1.10) compared to conventional analgesia.

Conclusion: Current evidence suggests that electroacupuncture might provide useful pain relieving effect on post-thoracotomy patients. However, due to low quality and high heterogeneity of existing data, further rigorously designed studies should be performed to confirm the safety and efficacy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254093PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263274PMC
November 2021

High-Efficient Production of Adipose-Derived Stem Cell (ADSC) Secretome Through Maturation Process and Its Non-scarring Wound Healing Applications.

Front Bioeng Biotechnol 2021 16;9:681501. Epub 2021 Jun 16.

School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, South Korea.

Recently, the stem cell-derived secretome, which is the set of proteins expressed by stem cells and secreted into the extracellular space, has been demonstrated as a critical contributor for tissue repair. In this study, we have produced two sets of high concentration secretomes from adipose-derived mesenchymal stem cells (ADSCs) that contain bovine serum or free of exogenous molecules. Through proteomic analysis, we elucidated that proteins related to extracellular matrix organization and growth factor-related proteins are highly secreted by ADSCs. Additionally, the application of ADSC secretome to full skin defect showed accelerated wound closure, enhanced angiogenic response, and complete regeneration of epithelial gaps. Furthermore, the ADSC secretome was capable of reducing scar formation. Finally, we show high-dose injection of ADSC secretome intraperitoneal or transdermal delivery demonstrated no detectable pathological conditions in various tissues/organs, which supports the notion that ADSC secretome can be safely utilized for tissue repair and regeneration.
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http://dx.doi.org/10.3389/fbioe.2021.681501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242583PMC
June 2021

Nano-Topographical Control of Ti-Nb-Zr Alloy Surfaces for Enhanced Osteoblastic Response.

Nanomaterials (Basel) 2021 Jun 7;11(6). Epub 2021 Jun 7.

Department of Biomedical-Chemical Engineering, Catholic University of Korea, Bucheon 14662, Korea.

Nano-scale surface roughening of metallic bio-implants plays an important role in the clinical success of hard tissue reconstruction and replacement. In this study, the nano-topographical features of titanium-niobium-zirconium (TNZ) alloy surfaces were controlled by using the target-ion induced plasma sputtering (TIPS) technique to improve the in vitro osteoblastic response. The TIPS technique is a novel strategy for etching the surface of metallic bio-implants using bombardment of target metal cations, which were accelerated by an extremely high negative bias voltage applied to the substrates. The nano-topography of the TNZ surfaces was successfully controlled by modulating experimental variables (such as the ion etching energy and the type of substrate or target materials) of TIPS. As a result, various nanopatterns (size: 10-210 nm) were fabricated on the surface of the TNZ alloys. Compared with the control group, experimental groups with nanopattern widths of ≥130 nm (130 and 210 nm groups) exhibited superior cell adhesion, proliferation, and differentiation. Our findings demonstrate that TIPS is a promising technology that can impart excellent biological functions to the surface of metallic bio-implants.
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http://dx.doi.org/10.3390/nano11061507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229642PMC
June 2021

Hydroxycoumarin Scopoletin Inhibits Bone Loss through Enhancing Induction of Bone Turnover Markers in a Mouse Model of Type 2 Diabetes.

Biomedicines 2021 Jun 7;9(6). Epub 2021 Jun 7.

Department of Food and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Korea.

Diabetes induces bone deterioration, which leads to increased risk of fracture, osteopenia, and osteoporosis. Thus, diabetes-associated bone fragility has been recognized as a diabetic complication. However, the pathophysiological effects of hyperglycemia on bone turnover remain unclear. Literature evidence demonstrates that anti-diabetic medications increase the risk of fractures in individuals with type 2 diabetes. Scopoletin is a naturally occurring hydroxycoumarin potentially exhibiting anti-inflammatory and antioxidant activities and ameliorating insulin resistance as an anti-diabetic agent. However, little is known regarding the effects of scopoletin on the impairment of bone remodeling that is caused by diabetes. The aim of this study was to identify that scopoletin was capable of inhibiting the impairment of bone remodeling and turnover in a mouse model of type 2 diabetes. Submicromolar scopoletin accelerated the formation TRAP-positive multinucleated osteoclasts (40.0 vs. 105.1%) and actin ring structures impaired by 33 mM glucose. Further, 1-20 μM scopoletin enhanced bone resorption and the induction of matrix-degrading enzymes in diabetic osteoclasts. The oral administration of 10 mg/kg scopoletin elevated serum RANKL/OPG ratio and osteocalcin level reduced in db/db mice along with an increase in BMD by ~6-14%; however, it was not effective in lowering blood glucose and hemoglobin glycation. In addition, the supplementation of scopoletin elevated the formation of trabecular bones and collagen fibers in femoral epiphysis and metaphysis with a thicker epiphyseal plate and cortical bones. Furthermore, 1-20 μM scopoletin enhanced ALP activity (4.39 vs. 7.02 nmol -nitrophenyl phosphate/min/mg protein) and deposits of mineralized bone nodules in cultured osteoblasts reduced by 33 mM glucose. The treatment of diabetic osteoblasts with scopoletin stimulated the cellular induction of BMP-2 and osteopontin and Runx2 transcription. Accordingly, the administration of scopoletin protected mice from type 2 diabetes-associated bone loss through boosting bone remodeling via the robust induction of bone turnover markers of both osteoclasts and osteoblasts. These findings suggest that scopoletin could be a potential osteoprotective agent for the treatment of diabetes-associated bone loss and fractures.
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http://dx.doi.org/10.3390/biomedicines9060648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227109PMC
June 2021

Middle meningeal artery embolization for postoperative supratentorial chronic subdural hematoma occurring after posterior fossa neurosurgery.

J Cerebrovasc Endovasc Neurosurg 2021 Jun 18;23(2):152-158. Epub 2021 Jun 18.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.

Chronic subdural hematoma (CSDH) after posterior fossa surgery is rare but may occur. A 70-year-old man with trigeminal neuralgia underwent microvascular decompression. The patient took several medications for trigeminal neuralgia and tremor for a long time. The patient tended to bleed easily and did not stop well, but the bleeding was thoroughly controlled intraoperatively. A month later, he presented with left side weakness, and brain computed tomography showed huge amount of CSDH in the right cerebral convex with midline shifting. Although CSDH was completely drained via burr hole trephination, the brain was not fully expanded, and the CSDH recurred a month later. CSDH was evacuated, but there was still considerable subdural space and remained small CSDH in another superficial subdural space. We considered that the patient was at high risk of recurrence of CSDH and performed middle meningeal artery (MMA) embolization. Afterward, he did not suffer a recurrence. Here, we reviewed the risk factors of CSDH recurrence and the usefulness of MMA embolization in the treatment of CSDH, and we recommend upfront MMA embolization as an effective adjuvant to treat CSDH in patients at a high risk of recurrence of CSDH.
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http://dx.doi.org/10.7461/jcen.2021.E2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256020PMC
June 2021

Gyejibokryeong-Hwan improves recovery of injured muscles in mouse model of muscle contusion.

J Tradit Chin Med 2021 Jun;41(3):406-413

Department of Korean Medicine Rehabilitation, College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea.

Objective: To investigate the effects of Gyejibokryeong-Hwan (Guizhifuling-wan, GBH) on muscle injury in a mouse model of muscle contusion.

Methods: C57/BL6 mouse biceps femoris muscles were injured using the drop-mass method and injured animals were treated orally with GBH (50, 100, or 500 mg/kg) once a day for 7 d. Open field and treadmill running tests were performed to assess functional recovery from muscle injury. The production of pro-inflammatory cytokines was examined by enzyme-linked immunosorbent assay and Western blotting analysis. Expression of the muscle regeneration biomarkers, myoblast determination (MyoD), myogenic factor 5 (Myf5), and smooth muscle actin (α-SMA), in the biceps femoris muscle was investigated at the protein and mRNA level by Western blotting and real time-PCR, respectively. Histological analysis was performed using hematoxylin and eosin staining. Finally, myosin heavy chain production was investigated in differentiated C2C12 myoblasts in the presence of GBH.

Results: GBH treatment markedly improved locomotion and running behavior. GBH significantly inhibited the secretion of monocyte chemoattractant protein-1 into the bloodstream in muscle-contused animals. The levels of MyoD, Myf5, and α-SMA protein and mRNA were significantly up-regulated by GBH in injured muscle tissue. Histological studies suggested that GBH facilitated recovery from muscle damage. However, GBH did not induce the production of myosin heavy chain in vitro.

Conclusion: Overall, the present study suggested that GBH improves the recovery of the injured muscles in the mouse model of muscle contusion.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2021.03.008DOI Listing
June 2021

Enhanced Effect of Polyethyleneimine-Modified Graphene Oxide and Simvastatin on Osteogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells.

Biomedicines 2021 May 2;9(5). Epub 2021 May 2.

Department of Nano-biomedical Science, BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea.

Statin derivatives traditionally have been used for the treatment of hyperlipidemia, but recent studies have shown their ability to regulate bone metabolism and promote bone growth. In this study, simvastatin (Sim), a new therapeutic candidate for bone regeneration, was combined with graphene oxide (GO), which has recently attracted much interest as a drug delivery method, to produce a compound substance effective for bone regeneration. To create a stable and homogenous complex with Sim, GO was modified with polyethylenimine, and the effect of modification was analyzed using Fourier transform infrared spectroscopy, zeta potential, and cytotoxicity testing. More specifically, the osteogenic differentiation potential expected by the combination of the two effective materials for osteogenic differentiation, GO and Sim, was evaluated in mesenchymal stem cells. Compared with control groups with GO and Sim used separately, the GO/Sim complex showed excellent osteogenic differentiation properties, with especially enhanced effects in the complex containing < 1 μM Sim.
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http://dx.doi.org/10.3390/biomedicines9050501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147488PMC
May 2021

Ahmed implant coated with poly(2-methacryloyloxyethyl phosphorylcholine) inhibits foreign body reactions in rabbit eyes.

PLoS One 2021 28;16(5):e0252467. Epub 2021 May 28.

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

Purpose: Wound healing after Ahmed glaucoma valve (AGV) implantation often entails fibrosis as a foreign body reaction to the silicone plate. Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) forms an antifouling surface that inhibits fibrosis during wound healing. In this study, we aimed to compare the effects of the implantation of AGV coated with PMPC (wPMPC) versus AGV without PMPC (woPMPC) in rabbits.

Methods: Six New Zealand White rabbit does underwent AGV implantation in both eyes. For each rabbit, one eye was randomly selected for implantation of AGV wPMPC and a conventional AGV (woPMPC) was implanted in the contralateral eye. Gross conjunctival vascularity was compared between the two groups at the first, second, and fourth weeks after surgery. The eyes were enucleated in four weeks and subjected to staining with hematoxylin and eosin and Masson's trichrome stain. The fibrosis and inflammation status among the eye samples were compared by measuring the thickness of the fibrotic walls and counting the number of chronic inflammatory cells around the AGV. Counting of inflammatory cells and measuring fibrotic wall thickness were done in a blinded method to eliminate observer bias. Statistical analysis was performed using the Mann-Whitney U test.

Results: Gross and histological examinations revealed no toxic effects of PMPC. There were no apparent differences in overall conjunctival vascularity between the two groups at weeks 1, 2, and 4 after surgery. The average inflammatory cell counts were 14.3 ± 5.8 per slide and 27.3 ± 8.6 per slide in the wPMPC and woPMPC groups, respectively (p = 0.037). The average thicknesses of the fibrotic wall were 57.9 ± 11.3 μm and 81.5 ± 21.3 μm in the wPMPC and woPMPC groups, respectively (p = 0.025).

Conclusion: Compared to the woPMPC group, the number of inflammatory cells and fibrosis were significantly decreased in the wPMPC group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252467PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162657PMC
October 2021

Treatment Planning Factors Associated with Long-Term Outcomes of Gamma Knife Surgery in Patients with Trigeminal Neuralgia.

World Neurosurg 2021 07 11;151:e899-e910. Epub 2021 May 11.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea; GammaKnife Radiosurgery Center, Seoul National University Hospital, Seoul, Republic of Korea; Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objective: Gamma Knife surgery (GKS) is an established treatment option for trigeminal neuralgia (TN). However, the long-term efficacy of GKS for patients with TN has not been well studied. The aim of the study is to evaluate the sequential course of pain control after GKS and analyze the factors associated with the long-term analgesic effect, focusing on radiation dosimetry and neurovascular conflict (NVC) factors.

Methods: We analyzed 83 patients undergoing GKS for TN in our institution between 2005 and 2013 with a follow-up duration >7 years. Tolerable pain with increased medication, persistent-intractable pain, and recurrence were classified as poor outcomes, and any other outcome was classified as a favorable outcome. The dosimetry factors and locational relationship between NVC and the target were analyzed in terms of their correlation with a favorable outcome.

Results: Adequate pain relief was achieved in 93% of patients a month and a half after GKS, but the pain recurred in 41.5% of patients on average 36 months after treatment. A larger V (P = 0.002) and higher homogeneity index (P = 0.027) were significantly associated with the long-term favorable outcomes. About 40% of patients had multiple NVC sites, and insufficient inclusion of the NVC in the target was significantly correlated with long-term poor outcomes (P = 0.002).

Conclusions: Targeting the center of the trigeminal nerve in the area of NVC with GKS is associated with favorable long-term pain control.
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http://dx.doi.org/10.1016/j.wneu.2021.05.008DOI Listing
July 2021

Prognostic Prediction Based on Dynamic Contrast-Enhanced MRI and Dynamic Susceptibility Contrast-Enhanced MRI Parameters from Non-Enhancing, T2-High-Signal-Intensity Lesions in Patients with Glioblastoma.

Korean J Radiol 2021 08 4;22(8):1369-1378. Epub 2021 May 4.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: Few attempts have been made to investigate the prognostic value of dynamic contrast-enhanced (DCE) MRI or dynamic susceptibility contrast (DSC) MRI of non-enhancing, T2-high-signal-intensity (T2-HSI) lesions of glioblastoma multiforme (GBM) in newly diagnosed patients. This study aimed to investigate the prognostic values of DCE MRI and DSC MRI parameters from non-enhancing, T2-HSI lesions of GBM.

Materials And Methods: A total of 76 patients with GBM who underwent preoperative DCE MRI and DSC MRI and standard treatment were retrospectively included. Six months after surgery, the patients were categorized into early progression (n = 15) and non-early progression (n = 61) groups. We extracted and analyzed the permeability and perfusion parameters of both modalities for the non-enhancing, T2-HSI lesions of the tumors. The optimal percentiles of the respective parameters obtained from cumulative histograms were determined using receiver operating characteristic (ROC) curve and univariable Cox regression analyses. The results were compared using multivariable Cox proportional hazards regression analysis of progression-free survival.

Results: The 95th percentile value (PV) of Ktrans, mean Ktrans, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, = 0.005; AUC = 0.684, = 0.021; and AUC = 0.670, = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of Ktrans and the mean Ktrans were significant predictors of early progression (hazard ratio [HR] = 1.06, = 0.009; HR = 1.25, = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of Ktrans was the sole significant independent predictor of early progression (HR = 1.062, < 0.009).

Conclusion: The 95th PV of Ktrans from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.
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http://dx.doi.org/10.3348/kjr.2020.1272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316772PMC
August 2021

Application of T1 Map Information Based on Synthetic MRI for Dynamic Contrast-Enhanced Imaging: A Comparison Study with the Fixed Baseline T1 Value Method.

Korean J Radiol 2021 08 4;22(8):1352-1368. Epub 2021 May 4.

Department of Radiology, Human Medical Imaging & Intervention Center, Seoul, Korea.

Objective: For an accurate dynamic contrast-enhanced (DCE) MRI analysis, exact baseline T1 mapping is critical. The purpose of this study was to compare the pharmacokinetic parameters of DCE MRI using synthetic MRI with those using fixed baseline T1 values.

Materials And Methods: This retrospective study included 102 patients who underwent both DCE and synthetic brain MRI. Two methods were set for the baseline T1: one using the fixed value and the other using the T1 map from synthetic MRI. The volume transfer constant (K), volume of the vascular plasma space (v), and the volume of the extravascular extracellular space (v) were compared between the two methods. The interclass correlation coefficients and the Bland-Altman method were used to assess the reliability.

Results: In normal-appearing frontal white matter (WM), the mean values of K, v, and v were significantly higher in the fixed value method than in the T1 map method. In the normal-appearing occipital WM, the mean values of v and v were significantly higher in the fixed value method. In the putamen and head of the caudate nucleus, the mean values of K, v, and v were significantly lower in the fixed value method. In addition, the T1 map method showed comparable interobserver agreements with the fixed baseline T1 value method.

Conclusion: The T1 map method using synthetic MRI may be useful for reflecting individual differences and reliable measurements in clinical applications of DCE MRI.
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http://dx.doi.org/10.3348/kjr.2020.1201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316777PMC
August 2021

Marliolide Derivative Induces Melanosome Degradation via Nrf2/p62-Mediated Autophagy.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

STEMORE Co. Ltd., Incheon 21983, Korea.

Nuclear factor erythroid 2-related factor 2 (Nrf2), which is linked to autophagy regulation and melanogenesis regulation, is activated by marliolide. In this study, we investigated the effect of a marliolide derivative on melanosome degradation through the autophagy pathway. The effect of the marliolide derivative on melanosome degradation was investigated in α-melanocyte stimulating hormone (α-MSH)-treated melanocytes, melanosome-incorporated keratinocyte, and ultraviolet (UV)B-exposed HRM-2 mice (melanin-possessing hairless mice). The marliolide derivative, 5-methyl-3-tetradecylidene-dihydro-furan-2-one (DMF02), decreased melanin pigmentation by melanosome degradation in α-MSH-treated melanocytes and melanosome-incorporated keratinocytes, evidenced by premelanosome protein (PMEL) expression, but did not affect melanogenesis-associated proteins. The UVB-induced hyperpigmentation in HRM-2 mice was also reduced by a topical application of DMF02. DMF02 activated Nrf2 and induced autophagy in vivo, evidenced by decreased PMEL in microtubule-associated proteins 1A/1B light chain 3B (LC3)-II-expressed areas. DMF02 also induced melanosome degradation via autophagy in vitro, and DMF02-induced melanosome degradation was recovered by chloroquine (CQ), which is a lysosomal inhibitor. In addition, Nrf2 silencing by siRNA attenuated the DMF02-induced melanosome degradation via the suppression of p62. DMF02 induced melanosome degradation in melanocytes and keratinocytes by regulating autophagy via Nrf2-p62 activation. Therefore, Nrf2 activator could be a promising therapeutic agent for reducing hyperpigmentation.
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http://dx.doi.org/10.3390/ijms22083995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070456PMC
April 2021
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