Publications by authors named "Hyunjin Kim"

188 Publications

A Sensing Device with the Optical Temperature Sensors-Based Quad-RX Module and a Security Module.

Sensors (Basel) 2021 Feb 25;21(5). Epub 2021 Feb 25.

IMR, Gwangju 61008, Korea.

In this paper, we present a sensing device with the optical temperature sensors-based quad receiver (Quad-RX) module and a security module. In addition, in order to prevent cyberattacks on critical national infrastructures and key facilities, we implemented symmetric-key and secure hash algorithm-based hardware security modules in the key elements of the sensing device. A preliminary test was conducted prior to a field trial to verify the performance of the developed sensing device. The accuracy and stability of the sensing device were then verified for 1 month in a field test at facilities for energy storage systems and photovoltaic converters in sewage treatment plants.
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http://dx.doi.org/10.3390/s21051620DOI Listing
February 2021

Association of High-density Lipoprotein Cholesterol Variability and the Risk of Developing Parkinson's Disease.

Neurology 2021 Feb 3. Epub 2021 Feb 3.

Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea

Objectives: We aimed to investigate the longitudinal association between high-density lipoprotein cholesterol (HDL-C) level, HDL-C variability, and the risk of developing Parkinson's disease.

Methods: We conducted a nationwide, population-based cohort study. We included 382,391 subjects aged ≥ 65 years who underwent at least three health examinations provided by the Korean National Health Insurance System from 2008 to 2013 and followed up until 2017. Individuals with a history of PD and missing values were excluded (n = 1,987). We assessed HDL-C variability using three indices, including variability independent of the mean (VIM). A multivariate-adjusted Cox proportional hazards regression analysis was performed.

Results: Among the 380,404 participants, 2733 individuals were newly diagnosed with PD during a median follow-up period of 5 years. The lowest quartile (Q1) group of baseline HDL-C and mean HDL-C was associated with increased PD incidence as compared with the highest quartile (Q4) group [adjusted hazard ratio (aHR), 1.20; 95% CI, 1.08-1.34 and aHR, 1.16; 95% CI, 1.04-1.30, respectively]. The Q4 group of HDL-C variability (VIM) associated with increased PD incidence compared to the Q1 group (aHR, 1.19; 95% CI, 1.06-1.33). The group with the Q1 of baseline HDL-C and with the Q4 of HDL-C variability had the highest risk of PD incidence (aHR, 1.6; 95% CI, 1.31-1.96).

Conclusions: Lower HDL-C level and greater HDL-C variability were associated with a higher incidence of PD.
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http://dx.doi.org/10.1212/WNL.0000000000011553DOI Listing
February 2021

Correlation-driven topological phases in magic-angle twisted bilayer graphene.

Nature 2021 Jan 18;589(7843):536-541. Epub 2021 Jan 18.

T. J. Watson Laboratory of Applied Physics, California Institute of Technology, Pasadena, CA, USA.

Magic-angle twisted bilayer graphene (MATBG) exhibits a range of correlated phenomena that originate from strong electron-electron interactions. These interactions make the Fermi surface highly susceptible to reconstruction when ±1, ±2 and ±3 electrons occupy each moiré unit cell, and lead to the formation of various correlated phases. Although some phases have been shown to have a non-zero Chern number, the local microscopic properties and topological character of many other phases have not yet been determined. Here we introduce a set of techniques that use scanning tunnelling microscopy to map the topological phases that emerge in MATBG in a finite magnetic field. By following the evolution of the local density of states at the Fermi level with electrostatic doping and magnetic field, we create a local Landau fan diagram that enables us to assign Chern numbers directly to all observed phases. We uncover the existence of six topological phases that arise from integer fillings in finite fields and that originate from a cascade of symmetry-breaking transitions driven by correlations. These topological phases can form only for a small range of twist angles around the magic angle, which further differentiates them from the Landau levels observed near charge neutrality. Moreover, we observe that even the charge-neutrality Landau spectrum taken at low fields is considerably modified by interactions, exhibits prominent electron-hole asymmetry, and features an unexpectedly large splitting between zero Landau levels (about 3 to 5 millielectronvolts). Our results show how strong electronic interactions affect the MATBG band structure and lead to correlation-enabled topological phases.
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http://dx.doi.org/10.1038/s41586-020-03159-7DOI Listing
January 2021

Invasive Micropapillary Carcinoma of the Uterine Cervix.

Case Rep Oncol 2020 Sep-Dec;13(3):1446-1453. Epub 2020 Dec 9.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

We herein present a case of uterine cervical invasive micropapillary carcinoma (IMPC) in a 35-year-old woman. She had neither specific symptoms nor any previous gynecological history. A cervical punch biopsy revealed a high-grade squamous intraepithelial lesion and concurrent intestinal-type mucinous carcinoma. Based on the preoperative diagnosis of endocervical adenocarcinoma, she underwent radical hysterectomy with bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection. Grossly, there was an ovoid, slightly elevated mass with surface nodularity in the lower endocervix, measuring 10 × 8 mm. Histologically, the tumor consisted predominantly of tufts of tumor cells arranged in micropapillary structures devoid of fibrovascular cores and surrounded by clear, empty, lacunar spaces between tumor cell nests and stroma. The IMPC component comprised 90% of the entire tumor volume. The greatest dimension and stromal invasion depth of the IMPC were 8 and 3 mm, respectively (FIGO stage IA2). Immunostaining revealed that mucin 1 (MUC1) surrounded each micropapillary structure, indicating the reverse epithelial polarity of the glandular cells. MUC1 was localized predominantly in the stroma-facing surface of the cell clusters, accentuating the outlines of the micropapillary structures by forming a distinct, characteristic band on this surface. In addition, targeted sequencing analysis of the IMPC revealed a missense mutation (c.1633G>A). In summary, we present the clinicopathological characteristics of cervical IMPC. We demonstrate for the first time that IMPC of the uterine cervix harbors a pathogenic missense mutation in . Further investigations using larger cohorts of patients are necessary to confirm these findings.
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http://dx.doi.org/10.1159/000510744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772833PMC
December 2020

Placental Site Plaque of the Uterine Cervix Misinterpreted as Low-Grade Squamous Intraepithelial Lesion in Liquid-Based Cervicovaginal Cytology: Usefulness of Inhibin-α Immunocytochemistry.

Case Rep Oncol 2020 Sep-Dec;13(3):1415-1420. Epub 2020 Nov 30.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Cytological features of placental site plaques in liquid-based cervicovaginal preparations have been seldom documented in the literature. We present a rare case of endocervical placental site plaque misinterpreted as a low-grade squamous intraepithelial lesion in a liquid-based cytological preparation. A 32-year-old woman with polycystic ovarian syndrome gave birth 7 months previously. After delivery, she was diagnosed with cervical low-grade squamous intraepithelial lesion during routine cytological examination. Cytologically, many atypical cells showed large hyperchromatic nuclei with irregular membranes. The perinuclear cytoplasmic clearing closely resembled koilocytosis. Histologically, the endocervix showed typical histological features of a placental site plaque. Immunohistochemically, the trophoblasts were positive for p63, CD10, and inhibin-α but negative for p16. Based on genotyping, both the cytological and biopsied specimens tested negative for human papillomavirus. We re-examined the liquid-based preparation cytology slides thoroughly and concluded that the atypical cells initially misinterpreted as low-grade squamous intraepithelial lesion were actually trophoblasts. Immunocytochemical staining revealed uniform cytoplasmic inhibin-α expression in the trophoblasts. In summary, we demonstrated that endocervical placental site plaques can mimic low-grade squamous intraepithelial lesions in liquid-based cytological preparations. Immunocytochemical staining results and negative results on human papillomavirus genotyping further support that atypical cells resembling koilocytes are trophoblasts obtained from the placental site plaque.
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http://dx.doi.org/10.1159/000510310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772827PMC
November 2020

PD-L1 expression in paired biopsies and surgical specimens in gastric adenocarcinoma: A digital image analysis study.

Pathol Res Pract 2021 Feb 2;218:153338. Epub 2021 Jan 2.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Center of Companion Diagnostics, Samsung Medical Center, Seoul, Republic of Korea; Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea. Electronic address:

Programmed death-ligand 1 (PD-L1) expression in biopsies of gastric carcinoma may predict the results in corresponding surgical specimens. We compared PD-L1 immunohistochemistry (IHC) 22C3 pharmDx expression in paired biopsy and resection specimens. We also characterized the validity of a new PD-L1 assay using digital image analysis. PD-L1 IHC with 22C3 pharmDx and clone 73-10 was performed in 224 gastric cancer tissues (112 biopsies and paired surgical tissues) and the specimens were analyzed with the Leica Aperio Imagescope. For statistical analyses, the area under the receiver operating characteristic curve and R package were used. With 22C3 pharmDx, a PD-L1 combined positive score of ≥1 was found in 36 biopsied (32.14 %) and 53 surgical (47.32 %) samples. PD-L1 expression results were concordant in 71 cases (63.4 %) and discordant in 41 (36.6 %). The overall discordance rate was 36.61 % (95 % confidence interval 2.101-8.983) and the κ value was 0.254 with fair agreement. The sensitivity and specificity of biopsy PD-L1 to predict the results of the surgical specimen was 62 % and 73 %, respectively. The correlation of 22C3 pharmDx and clone 73-10 was high (correlation coefficient = 0.88). When only tumor cell staining was compared, this correlation was increased (correlation coefficient = 0.95). Our results indicated moderate association of PD-L1 expression between gastric biopsies and corresponding resected tumors. Results of PD-L1 assay with 73-10 are comparable to 22C3 pharmDx results.
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http://dx.doi.org/10.1016/j.prp.2020.153338DOI Listing
February 2021

Olmutinib in T790M-positive non-small cell lung cancer after failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy: A global, phase 2 study.

Cancer 2021 Jan 12. Epub 2021 Jan 12.

Hanmi Pharmaceutical Company, Ltd, Seoul, Republic of Korea.

Background: In this open-label, international phase 2 study, the authors assessed the efficacy and safety of olmutinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had a confirmed T790M mutation and disease progression on previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.

Methods: Patients aged ≥20 years received once-daily oral olmutinib 800 mg continuously in 21-day cycles. The primary endpoint was the objective response rate (patients who had a confirmed best overall response of a complete or partial response), assessed by central review. Secondary endpoints included the disease control rate, the duration of objective response, progression-free survival, and overall survival. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).

Results: Overall, 162 patients (median age, 63 years; women, >60%) were enrolled from 68 sites in 9 countries. At the time of database cutoff, 23.5% of enrolled patients remained on treatment. The median treatment duration was 6.5 months (range, 0.03-21.68 months). Overall, 46.3% of patients (95% CI, 38.4%-54.3%) had a confirmed objective response (all partial responses). The best overall response (the objective response rate regardless of confirmation) was 51.9% (84 patients; 95% CI, 43.9%-59.8%). The confirmed disease control rate for all patients was 86.4% (95% CI, 80.2%-91.3%). The median duration of objective response was 12.7 months (95% CI, 8.3-15.4 months). Estimated median progression-free survival was 9.4 months (95% CI, 6.9-12.3 months), and estimated median overall survival was 19.7 months (95% CI, 15.1 months to not reached). All patients experienced treatment-emergent adverse events, and 71.6% of patients had grade ≥3 treatment-emergent adverse events.

Conclusions: Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M-positive non-small cell lung cancer who received previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
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http://dx.doi.org/10.1002/cncr.33385DOI Listing
January 2021

A Quenched Annexin V-Fluorophore for the Real-Time Fluorescence Imaging of Apoptotic Processes In Vitro and In Vivo.

Adv Sci (Weinh) 2020 Dec 28;7(24):2002988. Epub 2020 Oct 28.

Research Institute National Cancer Center 323 Ilsan-ro Goyang Gyeonggi 10408 Republic of Korea.

Annexin-based probes have long been used to study apoptotic cell death, which is of key importance to many areas of biological research, drug discovery, and clinical applications. Although apoptosis is a dynamic biological event with cell-to-cell variations, current annexin-based probes are impractical for monitoring apoptosis in real-time. Herein, a quenched annexin V-near-infrared fluorophore conjugate (Q-annexin V) is reported as the first OFF-ON annexin protein-based molecular sensor for real-time near-infrared fluorescence imaging of apoptosis. Q-annexin V is non-fluorescent in the extracellular region, due to photoinduced electron transfer interactions between the conjugated dye and amino acid quenchers (tryptophan and tyrosine). The probe becomes highly fluorescent when bound to phosphatidylserines on the outer layer of cell membranes during apoptosis, thereby enabling apoptosis to be monitored in real-time in 2D and 3D cell structures. In particular, Q-annexin V shows superior utility for in vivo apoptosis fluorescence imaging in animal models of cisplatin-induced acute kidney injury and cancer immune therapy, compared to the conventional polarity-sensitive pSIVA-IANBD or annexin V-Alexa647 conjugates.
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http://dx.doi.org/10.1002/advs.202002988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7740095PMC
December 2020

Ubiquinone-BODIPY nanoparticles for tumor redox-responsive fluorescence imaging and photodynamic activity.

J Mater Chem B 2021 01;9(3):824-831

Department of Chemistry and Research Institute of Basic Sciences, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea.

Successful applications of photodynamic therapy (PDT) in cancer treatment require the development of effective photosensitizers with controllable singlet oxygen generation. Here we report a ubiquinone-BODIPY photosensitizer that self-assembles into nanoparticles (PS-Q-NPs) and undergoes selective activation and deaggregation within the highly reductive intracellular environment of tumor cells. PS-Q-NPs are highly stable in aqueous buffer solution, and exhibit minimal fluorescence and photosensitization due to a rapid non-radiative relaxation process. Upon endocytosis by cancer cells, reduction of the ubiquinone moiety by intracellular glutathione (GSH) triggers the conversion of the aggregated hydrophobic precursor into the active hydrophilic carboxylate derivative PS-A. The conversion results in enhanced fluorescence and therapeutic singlet oxygen generation, portending to its application as an activatable photosensitizer for fluorescence imaging-guided photodynamic cancer therapy.
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http://dx.doi.org/10.1039/d0tb02529aDOI Listing
January 2021

Deep Learning-Based Method to Differentiate Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis.

Front Neurol 2020 30;11:599042. Epub 2020 Nov 30.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Differentiating neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) is crucial in the field of diagnostics because, despite their similarities, the treatments for these two diseases are substantially different, and disease-modifying treatments for MS can worsen NMOSD. As brain magnetic resonance imaging (MRI) is an important tool to distinguish the two diseases, extensive research has been conducted to identify the defining characteristics of MRI images corresponding to these two diseases. However, the application of such research in clinical practice is still limited. In this study, we investigate the applicability of a deep learning-based algorithm for differentiating NMOSD from MS. In this study, we included 338 participants (213 patients with MS, 125 patients with NMOSD) who visited the Asan medical center between February 2009 and February 2020. A 3D convolutional neural network, which is a deep learning-based algorithm, was trained using fluid-attenuated inversion recovery images and clinical information of the participants. The performance of the final model in differentiating NMOSD from MS was evaluated and compared with that of two neurologists. The deep learning-based model exhibited an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.75-0.89). It differentiated NMOSD from MS with an accuracy of 71.1% (sensitivity = 87.8%, specificity = 61.6%), which is comparable to that exhibited by the neurologists. The intra-rater reliability of the two neurologists was moderate (κ = 0.47, 0.50), which was in contrast with the consistent classification of the deep learning-based model. The proposed model was verified to be capable of differentiating NMOSD from MS with accuracy comparable to that of neurologists, exhibiting the advantage of consistent classification. As a result, it can aid differential diagnosis between two important central nervous system inflammatory diseases in clinical practice.
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http://dx.doi.org/10.3389/fneur.2020.599042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734316PMC
November 2020

Unboxed: US Young Adult Tobacco Users' Responses to a New Heated Tobacco Product.

Int J Environ Res Public Health 2020 11 3;17(21). Epub 2020 Nov 3.

Center for Tobacco Control Research and Education, University of California, San Francisco, CA 94143, USA.

The heated tobacco product (HTP) IQOS was authorized for sale in the US in 2019. We investigated how young adults with experience using multiple tobacco products reacted to, perceived, and developed interest in IQOS, informing policies that might prevent HTPs from becoming ubiquitous. We used a novel qualitative method in which 33 young adult tobacco users in California (fall 2019) "unboxed" an IQOS device, tobacco sticks, and marketing materials and narrated their impressions and opinions. We conducted content and thematic analyses of participants' reactions, sensory experiences, and interest. Multiple attributes influenced appeal for participants, including sleek electronic design, novel technology, perceived harmfulness, complexity, and high cost. The "no smoke" claim and heating technology suggested that smoking IQOS was safer than smoking cigarettes. Public health programs should closely monitor HTP marketing and uptake, particularly as "reduced exposure" claims were authorized in July 2020. Evidence-based regulations (e.g., requiring plain packaging for tobacco sticks), actions addressing IQOS' unique attributes (e.g., regulating device packaging to reduce high-tech appeal), and public education might help to counter the appeal generated by potentially misleading IQOS marketing tactics.
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http://dx.doi.org/10.3390/ijerph17218108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662359PMC
November 2020

Dissemination of Verona Integron-encoded Metallo-β-lactamase among clinical and environmental Enterobacteriaceae isolates in Ontario, Canada.

Sci Rep 2020 10 29;10(1):18580. Epub 2020 Oct 29.

Public Health Ontario Laboratory, Toronto, ON, Canada.

Surveillance data from Southern Ontario show that a majority of Verona Integron-encoded Metallo-β-lactamase (VIM)-producing Enterobacteriaceae are locally acquired. To better understand the local epidemiology, we analysed clinical and environmental bla-positive Enterobacteriaceae from the area. Clinical samples were collected within the Toronto Invasive Bacterial Diseases Network (2010-2016); environmental water samples were collected in 2015. We gathered patient information on place of residence and hospital admissions prior to the diagnosis. Patients with and without plausible source of acquisition were compared regarding risk exposures. Microbiological isolates underwent whole-genome sequencing (WGS); bla carrying plasmids were characterized. We identified 15 patients, thereof 11 with bla-positive Enterobacter hormaechei within two genetic clusters based on WGS. Whereas no obvious epidemiologic link was identified among cluster I patients, those in cluster II were connected to a hospital outbreak. Except for patients with probable acquisition abroad, we did not identify any further risk exposures. Two bla-positive E. hormaechei from environmental waters matched with the clinical clusters; plasmid sequencing suggested a common ancestor plasmid for the two clusters. These data show that both clonal spread and horizontal gene transfer are drivers of the dissemination of bla-carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.
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http://dx.doi.org/10.1038/s41598-020-75247-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596063PMC
October 2020

Atypical Mesonephric Hyperplasia of the Uterus Harbors Pathogenic Mutation of Kirsten Rat Sarcoma 2 Viral Oncogene Homolog () and Gain of Chromosome 1q.

Cancer Genomics Proteomics 2020 Nov-Dec;17(6):813-826

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Background/aim: Mesonephric carcinoma (MNC) is a rare but notable entity of the female genital tract. While many researchers have acknowledged and studied MNC, much remains unknown on the characteristics of mesonephric remnant (MNR) or hyperplasia (MNH). There has not been any study examining the molecular features of MNR and MNH so far. The aim of this study was to investigate the clinicopathological and molecular characteristics of ten uterine mesonephric lesions, including two MNRs without atypia, four MNHs without atypia, and three MNHs with atypia.

Materials And Methods: We reviewed the electronic medical records and all available slides of ten cases from multiple institutions. Targeted sequencing and array comparative genomic hybridization were performed.

Results: Three atypical MNHs displayed nuclear enlargement, mild-to-moderate nuclear pleomorphism, and nuclear membrane irregularity, and harbored pathogenic Kirsten rat sarcoma 2 viral oncogene homolograt sarcoma 2 viral oncogene homolog (KRAS) mutation. Two of those that co-existed with MNC harbored the same sequence alterations as each of their adjacent MNC. One of the three atypical MNHs harbored chromosome 1q gain.

Conclusion: Atypical MNH is a potential premalignant lesion in which KRAS mutation and chromosome 1q gain play an important role in the early stage of mesonephric carcinogenesis.
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http://dx.doi.org/10.21873/cgp.20235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675654PMC
June 2020

-Inspired Intelligent Hydrochromic Adhesive Film.

ACS Appl Mater Interfaces 2020 Nov 20;12(44):49982-49991. Epub 2020 Oct 20.

Department of Chemistry, Kookmin University, 77 Jeongneung-ro, Seongbuk-gu, Seoul 02707, Republic of Korea.

-inspired hydrochromic nano/microstructured films have received much attention for its promising smart hydrochromic applications owing to their simple and low-cost but energy-effective strategy. A new type of water-switchable glazing film patterned with various nano/micro air-hole inverse opal arrays is introduced by selectively removing nano/microsphere polystyrene arrays embedded in the surface of polydimethylsiloxane (PDMS) films. Using the significant contrast ratio of the bleaching and the scattering states, we have optimized the switching properties of Mie scattered patterns. As a result, we obtained a single inverse opal layer-embedded PDMS adhesive film with hexagonally close-packed 1 μm air-hole arrays as an optimum scattered film. The differences of diffusive transmittance and optical haze values between the dry and the wet states of the best scattered film reached 44.93% (Δ = 59.11-14.18%) and 54.88% (Δ = 69.42-14.54%), respectively. In addition, using the best-optimized inverse opal layer-embedded PDMS film, we fabricated a perfectly imitated structure for camouflage application and an intelligent hydrochromic window device. The dynamic water modulation of the scattered opaque and nonscattered transparent state of the inverse opal-patterned PDMS adhesive film can provide an advanced platform structure in the area of hydrochromic technology for smart windows, camouflage, and clear umbrellas for rainy days.
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http://dx.doi.org/10.1021/acsami.0c13185DOI Listing
November 2020

Bicine promotes rapid formation of β-sheet-rich amyloid-β fibrils.

PLoS One 2020 13;15(10):e0240608. Epub 2020 Oct 13.

Department of Pharmacy, Yonsei University, Incheon, Republic of Korea.

Fibrillar aggregates of amyloid-β (Aβ) are the main component of plaques lining the cerebrovasculature in cerebral amyloid angiopathy. As the predominant Aβ isoform in vascular deposits, Aβ40 is a valuable target in cerebral amyloid angiopathy research. However, the slow process of Aβ40 aggregation in vitro is a bottleneck in the search for Aβ-targeting molecules. In this study, we sought a method to accelerate the aggregation of Aβ40 in vitro, to improve experimental screening procedures. We evaluated the aggregating ability of bicine, a biological buffer, using various in vitro methods. Our data suggest that bicine promotes the aggregation of Aβ40 with high speed and reproducibility, yielding a mixture of aggregates with significant β-sheet-rich fibril formation and toxicity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240608PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553346PMC
December 2020

Anti-CASPR2-Antibody-Positive Isaacs' Syndrome Presenting with Myokymia, Neuropathic Pain, and Hyperhidrosis.

J Clin Neurol 2020 Oct;16(4):699-701

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3988/jcn.2020.16.4.699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542001PMC
October 2020

Protective effect of a novel clinical-grade small molecule necrosis inhibitor against oxidative stress and inflammation during islet transplantation.

Am J Transplant 2020 Sep 25. Epub 2020 Sep 25.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Inhibition of mitochondrial reactive oxygen species (ROS) and subsequent damage-associated molecular patterns (DAMPs)-induced inflammatory responses could be a novel target in clinical islet transplantation. We investigated the protective effects of NecroX-7, a novel clinical-grade necrosis inhibitor that specifically targets mitochondrial ROS, against primary islet graft failure. Islets from heterozygote human islet amyloid polypeptide transgenic (hIAPP ) mice and nonhuman primates (NHPs) were isolated or cultured with or without NecroX-7 in serum-deprived medium. Supplementation with NecroX-7 during hIAPP mouse islet isolation markedly increased islet viability and adenosine triphosphate content, and attenuated ROS, transcription of c-Jun N-terminal kinases, high mobility group box 1, interleukin-1beta (IL-1 ), IL-6, and tumor necrosis factor-alpha. Supplementation of NecroX-7 during serum-deprived culture also protected hIAPP mouse and NHP islets against impaired viability, serum deprivation-induced ROS, proinflammatory response, and accumulation of toxic IAPP oligomer. Supplementation with NecroX-7 during isolation or serum-deprived culture of hIAPP mouse and NHP islets also improved posttransplant glycemia in the recipient streptozotocin-induced diabetic hIAPP mice and BALB/c-nu/nu mice, respectively. In conclusion, pretransplant administration of NecroX-7 during islet isolation and serum-deprived culture suppressed mitochondrial ROS injury, generation of DAMPs-induced proinflammatory responses, and accumulation of toxic IAPP oligomers ex vivo, and improved posttransplant glycemia in vivo.
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http://dx.doi.org/10.1111/ajt.16323DOI Listing
September 2020

Clinicopathological Characteristics of Pleomorphic High-Grade Squamous Intraepithelial Lesion of the Uterine Cervix: A Single-Institutional Series of 31 Cases.

Diagnostics (Basel) 2020 Aug 15;10(8). Epub 2020 Aug 15.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

We investigated the clinicopathological characteristics of 31 cases of pleomorphic high-grade squamous intraepithelial lesions (PHSIL) of the uterine cervix. We reviewed electronic medical records and all available slides to collect clinical and pathological information. PHSILs were histologically characterized by significant nuclear enlargement, marked pleomorphism, hyperchromasia, increased mitotic activity, and frequent atypical mitoses. In the majority of cases (24/31; 77.4%), this striking nuclear atypia involved both the surface epithelium and the endocervical glands. In the remaining seven cases, pleomorphic cells were observed in the surface epithelium only. PHSILs involving both the surface epithelium and glands showed higher mitotic counts and Ki-67 labelling indices than the surface-only PHSILs. Invasive squamous cell carcinoma was present in only one case (3.2%), and none developed recurrent disease. Our observations of striking nuclear atypia in cases of HSIL did not indicate increased aggressiveness. Further investigations are required for confirmation of our data in larger cohorts.
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http://dx.doi.org/10.3390/diagnostics10080595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459519PMC
August 2020

A recombinant human immunoglobulin with coherent avidity to hepatitis B virus surface antigens of various viral genotypes and clinical mutants.

PLoS One 2020 13;15(8):e0236704. Epub 2020 Aug 13.

Mogam Institute for Biomedical Research, Youngin, Korea.

The hepatitis B virus (HBV) envelope is composed of a lipid bilayer and three glycoproteins, referred to as the large (L), middle (M), and small (S) hepatitis B virus surface antigens (HBsAg). S protein constitutes the major portion of the viral envelope and an even greater proportion of subviral particles (SVP) that circulate in the blood. Recombinant S proteins are currently used as a preventive vaccine, while plasma fractions isolated from vaccinated people, referred to as hepatitis B immune globulin (HBIG), are used for short-term prophylaxis. Here, we characterized a recombinant human IgG1 type anti-S antibody named Lenvervimab regarding its binding property to a variety of cloned S antigens. Immunochemical data showed an overall consistent avidity of the antibody to S antigens of most viral genotypes distributed worldwide. Further, antibody binding was not affected by the mutations in the antigenic 'a' determinant found in many clinical variants, including the immune escape mutant G145R. In addition, mutations in the S gene sequence that confer drug resistance to the viral polymerase did not interfere with the antibody binding. These results support for a preventive use of the antibody against HBV infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236704PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425877PMC
October 2020

Comparison of MOG and AQP4 antibody seroprevalence in Korean adults with inflammatory demyelinating CNS diseases.

Mult Scler 2020 Aug 11:1352458520948213. Epub 2020 Aug 11.

Department of Neurology, National Cancer Center, Goyang, Korea/Division of Clinical Research, National Cancer Center, Goyang, Korea.

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.
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http://dx.doi.org/10.1177/1352458520948213DOI Listing
August 2020

Quenched cetuximab conjugate for fast fluorescence imaging of EGFR-positive lung cancers.

Biomater Sci 2021 Jan 6;9(2):456-462. Epub 2020 Aug 6.

Research Institute, National Cancer Center, 323 Ilsanro, Goyang, Gyeonggi-do 10408, Republic of Korea.

Cetuximab-dye conjugates have shown great potential for image-guided surgery of epidermal growth factor receptor (EGFR)-positive cancers in clinical trials. However, their long circulation half-life and prolonged generation of high background signals require the injection of antibody conjugates several days prior to imaging, which limits the clinical applications. Herein, we developed a cetuximab-ATTO655 conjugate (i.e., Q-Cetuximab) for fast and real-time fluorescence imaging of EGFR-positive lung cancers. The fluorescence intensity of Q-Cetuximab was quenched to just 6.9% of that of the unconjugated dye when only 2.14 ATTO655 dyes were conjugated to cetuximab. In vitro real-time cell imaging showed that EGFR-positive A549 cells emitted strong fluorescence at 10 min after Q-Cetuximab treatment in the absence of the washing step, implying target-specific activation of quenched Q-Cetuximab fluorescence upon binding with EGFR-positive cancer cells. When mice with orthotropic A549 tumors received intravenous injection of Q-Cetuximab, scattered microsized tumors in the lungs could be clearly identified from near-infrared fluorescence imaging with a tumor-to-background ratio of 4.28 at 8 h post-injection. For comparison, the cetuximab-Alexa647 conjugate (i.e., ON-Cetuximab), which does not show fluorescence quenching, was synthesized as an always-on type of probe. The ON-Cetuximab-treated mice expressed strong fluorescence throughout their body at 8 h post-injection; therefore, lung tumor sites could not be discriminated using fluorescence imaging. These results confirm the benefits of Q-Cetuximab for image-guided precision surgery of EGFR-positive lung cancers.
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http://dx.doi.org/10.1039/d0bm01148gDOI Listing
January 2021

Selective Class I HDAC Inhibitors Based on Aryl Ketone Zinc Binding Induce HIV-1 Protein for Clearance.

ACS Med Chem Lett 2020 Jul 22;11(7):1476-1483. Epub 2020 Jun 22.

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.

HIV persistence in latently infected, resting CD4 T cells is broadly considered a barrier to eradicate HIV. Activation of the provirus using latency-reversing agents (LRAs) followed by immune-mediated clearance to purge reservoirs has been touted as a promising therapeutic approach. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) control the acetylation level of lysine residues in histones to regulate the gene transcription. Several clinical HDAC inhibitors had been examined as LRAs, which induced HIV activation in vitro and in vivo. Here we report the discovery of a series of selective and potent class I HDAC inhibitors based on aryl ketones as a zinc binding group, which reversed HIV latency using a Jurkat model of HIV latency in 2C4 cells. The SAR led to the discovery of a highly selective class I HDAC inhibitor with excellent potency. HDACi induces the HIV P24 protein in patient latent CD4 T cells.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357218PMC
July 2020

Superconductivity in metallic twisted bilayer graphene stabilized by WSe.

Nature 2020 07 15;583(7816):379-384. Epub 2020 Jul 15.

T. J. Watson Laboratory of Applied Physics, California Institute of Technology, Pasadena, CA, USA.

Magic-angle twisted bilayer graphene (TBG), with rotational misalignment close to 1.1 degrees, features isolated flat electronic bands that host a rich phase diagram of correlated insulating, superconducting, ferromagnetic and topological phases. Correlated insulators and superconductivity have been previously observed only for angles within 0.1 degree of the magic angle and occur in adjacent or overlapping electron-density ranges; nevertheless, the origins of these states and the relation between them remain unclear, owing to their sensitivity to microscopic details. Beyond twist angle and strain, the dependence of the TBG phase diagram on the alignment and thickness of the insulating hexagonal boron nitride (hBN) used to encapsulate the graphene sheets indicates the importance of the microscopic dielectric environment. Here we show that adding an insulating tungsten diselenide (WSe) monolayer between the hBN and the TBG stabilizes superconductivity at twist angles much smaller than the magic angle. For the smallest twist angle of 0.79 degrees, superconductivity is still observed despite the TBG exhibiting metallic behaviour across the whole range of electron densities. Finite-magnetic-field measurements further reveal weak antilocalization signatures as well as breaking of fourfold spin-valley symmetry, consistent with spin-orbit coupling induced in the TBG via its proximity to WSe. Our results constrain theoretical explanations for the emergence of superconductivity in TBG and open up avenues towards engineering quantum phases in moiré systems.
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http://dx.doi.org/10.1038/s41586-020-2473-8DOI Listing
July 2020

What shear wave elastography parameter best differentiates breast cancer and predicts its histologic aggressiveness?

Ultrasonography 2020 Jun 15. Epub 2020 Jun 15.

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

Purpose: This study aimed to identify useful shear wave elastography (SWE) parameters for differentiating breast cancer and predicting associated immunohistochemical factors and subtypes.

Methods: From November 2018 to February 2019, a total of 211 breast lesions from 190 patients who underwent conventional breast ultrasonography and SWE were included. The Breast Imaging, Reporting and Data System categories and qualitative and quantitative SWE parameters for each lesion were obtained. Pathologic results including immunohistochemical factors were evaluated. The diagnostic performance of each parameter and its correlation with histological characteristics, immunohistochemical factors, and subtypes of breast cancer were analyzed using analysis of variance, the independent t test, the Fisher exact test, logistic regression analysis, and the DeLong method.

Results: Among 211 breast lesions, 82 were malignant, and 129 were benign. Of the SWE parameters, Emax showed the highest area under the curve (AUC) for differentiating malignant from benign lesions (AUC, 0.891; cut-off>50.85). Poor tumor differentiation and progesterone receptor-negativity were correlated with higher SDmean and Emax (P<0.05). Ki-67-positive breast cancer showed higher SDmean and a heterogeneous color distribution (P<0.05). Ki-67 and cytokeratin 5/6-positive breast cancers showed higher Emax/Efat ratios (P<0.05). Luminal B, human epidermal growth factor receptor 2-enriched, and triple-negative (non-basal) subtypes showed somewhat higher SDmean values than the luminal A and triple-negative (basal) subtypes (P=0.028).

Conclusion: Emax is a reliable parameter for differentiating malignancies from benign breast lesions. In addition, high stiffness and SDmean values in tumors measured on SWE could be used to predict poorly differentiated, progesterone receptor-negative, or Ki-67-positive breast cancer.
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http://dx.doi.org/10.14366/usg.20007DOI Listing
June 2020

Clinical Outcome of Minor Salivary Gland Cancers in the Oral Cavity: A Comparative Analysis With Squamous Cell Carcinomas of the Oral Cavity.

Front Oncol 2020 3;10:881. Epub 2020 Jun 3.

Department of Otorhinolaryngology - Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Salivary gland cancer (SGC) in the oral cavity is not common and has been less studied in comparison with oral squamous cell carcinoma (SCC). This study aimed to identify the clinical characteristics and outcomes of SGC in the oral cavity compared with oral SCC. The medical charts of the patients with SGC ( = 68) arising from minor salivary glands and SCC ( = 750) in the oral cavity between 1995 and 2017 were reviewed retrospectively. The clinical and pathological factors and treatment outcomes were compared to identify clinical differences between oral SGC and SCC in total cases and in tumor size and subsite (propensity score)-matched pairs ( = 68 in each group). In addition, pattern of local invasion was pathologically assessed in a subset of SGC and SCC tumors. Patients with SGC in the oral cavity showed >90% survival at 5 years. Most common pathologies of SGC were mucoepidermoid carcinoma (39.7%) and adenoid cystic carcinoma (35.3%), where high-grade tumors (including adenoid cystic carcinomas having solid components, grade 2 or 3) represented only 36.8%. Compared with oral SCC, surgery for SGC had narrow surgical safety margin. However, local control was very successful in SGC even with <5 mm or positive resection margin through surgery plus adjuvant radiation treatments or surgery alone for small low-grade tumors. Pathologic analysis revealed that the frequency of oral SGC with infiltrative tumor border was significantly lower than that of oral SCC (46.4 vs. 87.2%, < 0.001). SGC in the oral cavity represents relatively good prognosis and has a locally less aggressive pathology compared with oral SCC. Adjuvant radiation can be very effective to control minimal residual disease in oral SGC. Our study proposed that a different treatment strategy for oral SGC would be reasonable in comparison with oral SCC.
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http://dx.doi.org/10.3389/fonc.2020.00881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283496PMC
June 2020

Clinical and imaging features of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cysteine-sparing NOTCH3 mutations.

PLoS One 2020 18;15(6):e0234797. Epub 2020 Jun 18.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Characteristics of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and cysteine-sparing NOTCH3 mutations are relatively unknown. This study compared clinical and imaging characteristics between patients with CADASIL and cysteine-sparing NOTCH3 mutations and those with CADASIL and cysteine-involving NOTCH3 mutations.

Methods: We retrospectively reviewed medical records of patients with CADASIL admitted to the Asan Medical Center between September 1999 and September 2017. We compared clinical and brain magnetic resonance imaging (MRI) characteristics based on the presence or absence of cysteine-involving NOTCH3 gene mutations. We compared white matter change frequencies and grades in specific spatial regions between the groups according to age-related white matter change (ARWMC) scores. We evaluated the presence, number, and anatomical distributions of cerebral microbleeds according to the microbleed anatomical rating scale.

Results: We reviewed data from 79 patients (55 cysteine-involving, 24 cysteine-sparing NOTCH3 mutations). Clinical symptoms and signs did not differ significantly between the groups. The white matter change frequency and ARWMC scores (adjusted for age and stroke risk factors) in the anterior temporal lobes were lower in cysteine-sparing patients than in cysteine-involving patients. Frequencies and grades of the other brain region's white matter changes and cerebral microbleeds were similar between the groups.

Conclusions: Patients with CADASIL and cysteine-sparing NOTCH3 mutations showed less involvement of the anterior temporal lobes in brain MRI than those with CADASIL and cysteine-involving NOTCH3 mutations, although both groups showed similar clinical characteristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234797PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302479PMC
August 2020

Cilostazol restores autophagy flux in bafilomycin A1-treated, cultured cortical astrocytes through lysosomal reacidification: roles of PKA, zinc and metallothionein 3.

Sci Rep 2020 06 8;10(1):9175. Epub 2020 Jun 8.

Department of Neurology, University of Ulsan College of Medicine, Seoul, Korea; Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Cilostazol, a phosphodiesterase 3 inhibitor, reduces the amyloid-beta (Aβ) burden in mouse models of Alzheimer disease by as yet unidentified mechanisms. In the present study, we examined the possibility that cilostazol ameliorates lysosomal dysfunction. Astrocytes treated with bafilomycin A1 (BafA1) exhibited markedly reduced DND-189 and acridine orange (AO) fluorescence, indicating reduced lysosomal acidity. In both cases, BafA1-induced alkalization was reversed by addition of cilostazol, dibutyryl cAMP or forskolin. All three agents significantly increased free zinc levels in lysosomes, and addition of the zinc chelator TPEN abrogated lysosomal reacidification. These treatments did not raise free zinc levels or reverse BafA1-mediated lysosomal alkalization in metallothionein 3 (Mt3)-null astrocytes, indicating that the increases in zinc in astrocytes were derived mainly from Mt3. Lastly, in FITC-Aβ-treated astrocytes, cilostazol reversed lysosomal alkalization, increased cathepsin D activity, and reduced Aβ accumulation in astrocytes. Cilostazol also reduced mHtt aggregate formation in GFP-mHttQ74-expressing astrocytes. Collectively, our results present the novel finding that cAMP/PKA can overcome the v-ATPase blocking effect of BafA1 in a zinc- and Mt3-dependent manner.
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http://dx.doi.org/10.1038/s41598-020-66292-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280249PMC
June 2020

Development of cellulose-based conductive fabrics with electrical conductivity and flexibility.

PLoS One 2020 4;15(6):e0233952. Epub 2020 Jun 4.

Department of Clothing and Textiles, Sookmyung Women's University, Seoul, South Korea.

This study aimed to produce cellulose-based conductive fabrics with electrical conductivity and flexibility. Bacterial cellulose (BC) and three chemical cellulose (CC), namely methyl cellulose (MC), hydroxypropyl cellulose (HPMC) and carboxymethyl cellulose (CMC) were in situ polymerized with aniline and the four conductive cellulose fabrics were compared and evaluated. Matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy analysis confirmed that three CC-PANI composites displayed longer and more stable polymerization pattern than BC-PANI because of the different polymerization method: bulk polymerization for BC-PANI and emulsion polymerization for CC-PANI, respectively. The electrical conductivity of BC-PANI and CC-PANI were ranging from 0.962 × 10-2 S/cm to 2.840 × 10-2 S/cm. MC-PANI showed the highest electrical conductivity among the four conductive cellulose fabrics. The flexibility and crease recovery results showed that MC-PANI had the highest flexibility compared to BC-PANI, HPMC-PANI, and CMC-PANI. These results have confirmed that the electrical conductivity and flexibility were influenced by the type of cellulose, and MC-PANI was found to have the best performance in the electrical conductivity and flexibility.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233952PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272206PMC
August 2020

Clinical implication of serum biomarkers and patient age in inflammatory demyelinating diseases.

Ann Clin Transl Neurol 2020 06 4;7(6):992-1001. Epub 2020 Jun 4.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Objectives: Serum synaptic proteins levels may change with age-related neurodegeneration, affecting their clinical implications as a disease biomarker. We aimed to investigate neuronal and astroglial markers in patients with multiple sclerosis (MS) and aquaporin-4 antibody-seropositive neuromyelitis optica spectrum disorders (NMOSD) to compare the clinical implications of these markers according to age.

Methods: Using single-molecule array assays, we measured neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in sera from consecutive patients with MS (n = 117) and NMOSD (n = 63). For each disease, we assessed correlations between these markers and disease severity (Expanded Disability Status Scale [EDSS]) scores according to three age groups (≤44, 45-54, and ≥55 years).

Results: Although serum GFAP levels were significantly higher in patients with NMOSD than those with MS, levels of both serum markers revealed significant positive correlations with EDSS scores in both diseases. In MS patients, the degrees of correlation between serum NfL (or GFAP) levels and EDSS scores were similar across all age groups. However, in NMOSD patients, positive GFAP-EDSS correlations were distinctively stronger in the youngest than in the oldest group. Conversely, there were no positive NfL-EDSS correlations in NMOSD in the youngest group, but there were significant in the oldest group.

Interpretation: The degrees to which serum NfL and GFAP levels reflect disease severity vary significantly with patient age in NMOSD, but not in MS. These findings suggest that the pathological processes and progression differ between the diseases; hence, serum biomarker levels may need to be interpreted differently according to patient age and disease type.
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http://dx.doi.org/10.1002/acn3.51070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317646PMC
June 2020

Choroid plexus changes on magnetic resonance imaging in multiple sclerosis and neuromyelitis optica spectrum disorder.

J Neurol Sci 2020 08 15;415:116904. Epub 2020 May 15.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objective: To investigate alterations in the choroid plexus in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using brain magnetic resonance imaging (MRI).

Methods: We prospectively recruited consecutive patients with MS or NMOSD from July 2018 to February 2019. The inclusion criterion was brain MRI within three months from onset of acute neurological symptoms. The thickness and enhancement ratio of the choroid plexus on gadolinium-enhanced T1-weighted images of patients with MS (n = 51), patients with NMOSD (n = 32), and healthy controls (HCs, n = 28) were compared.

Results: MRI in patients with MS or NMOSD showed a comparably thick but more enhanced choroid plexus compared with that of HCs. In the axial view, enhancement ratios of the lateral ventricle of MS and NMOSD patients and HCs were 1.64 ± 0.34, 1.65 ± 0.25, and 1.39 ± 0.17, respectively (P > .999 for MS vs. NMOSD; P = .001 for MS vs. HCs; P = .001 for NMOSD vs. HCs).

Conclusions: The choroid plexus was significantly more enhanced on brain MRI of patients with MS or NMOSD than on that of HCs, suggesting the involvement of the choroid plexus in the autoimmune inflammatory processes in MS and NMOSD.
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http://dx.doi.org/10.1016/j.jns.2020.116904DOI Listing
August 2020