Publications by authors named "Eunjung Lee"

263 Publications

Association between Soft-Drink Intake and Obesity, Depression, and Subjective Health Status of Male and Female Adults.

Int J Environ Res Public Health 2021 Oct 3;18(19). Epub 2021 Oct 3.

Food and Nutrition Major, School of Wellness Industry Convergence, Hankyong National University, Anseong-si 17579, Gyeonggi-do, Korea.

This study explores the association between soft-drink intake and obesity, depression, and subjective health status in male and female adults. Soft-drink consumption has become a serious public health issue worldwide. Participants of this study were selected ( = 3086) from the respondents in the Seventh Korea National Health and Nutrition Examination Survey 2016 and divided into the non-soft-drink group (men, 502; women, 1117) and the soft-drink group (men, 684; women, 783). Soft-drink intake data were obtained, using a validated quantitative food frequency questionnaire and the 24 h dietary recall. Total energy intake and fat density were significantly higher, but the nutrient densities of carbohydrate, total dietary fiber, and micronutrients were significantly lower in the soft-drink group than in the non-soft-drink group. In men, soft-drink intake was found to be significantly associated with a lower risk of depression. Conversely, in women, soft-drink intake was found to be significantly associated with the higher risks of depression, obesity, and poor subjective health status. Therefore, less frequent soft-drink intake may prevent obesity and depression in Korean women.
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http://dx.doi.org/10.3390/ijerph181910415DOI Listing
October 2021

Diagnosing thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology with the deep convolutional neural network.

Sci Rep 2021 Oct 8;11(1):20048. Epub 2021 Oct 8.

Department of Radiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

To compare the diagnostic performances of physicians and a deep convolutional neural network (CNN) predicting malignancy with ultrasonography images of thyroid nodules with atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) results on fine-needle aspiration (FNA). This study included 202 patients with 202 nodules ≥ 1 cm AUS/FLUS on FNA, and underwent surgery in one of 3 different institutions. Diagnostic performances were compared between 8 physicians (4 radiologists, 4 endocrinologists) with varying experience levels and CNN, and AUS/FLUS subgroups were analyzed. Interobserver variability was assessed among the 8 physicians. Of the 202 nodules, 158 were AUS, and 44 were FLUS; 86 were benign, and 116 were malignant. The area under the curves (AUCs) of the 8 physicians and CNN were 0.680-0.722 and 0.666, without significant differences (P > 0.05). In the subgroup analysis, the AUCs for the 8 physicians and CNN were 0.657-0.768 and 0.652 for AUS, 0.469-0.674 and 0.622 for FLUS. Interobserver agreements were moderate (k = 0.543), substantial (k = 0.652), and moderate (k = 0.455) among the 8 physicians, 4 radiologists, and 4 endocrinologists. For thyroid nodules with AUS/FLUS cytology, the diagnostic performance of CNN to differentiate malignancy with US images was comparable to that of physicians with variable experience levels.
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http://dx.doi.org/10.1038/s41598-021-99622-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501016PMC
October 2021

An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States.

Clin Gastroenterol Hepatol 2021 Oct 5. Epub 2021 Oct 5.

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA. Electronic address:

Background: /Aims: Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US.

Methods: On March 5-6, 2020 a Summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. Following this Summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This White Paper represents a consensus statement prepared by the writing group.

Results: The burden of GC is highly inequitably distributed in the US, and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecological studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention), and the majority of observational data (for secondary prevention) are derived from non-US sources.

Conclusions: There exists substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.
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http://dx.doi.org/10.1016/j.cgh.2021.09.039DOI Listing
October 2021

Comprehensive characterization of viral integrations and genomic aberrations in HBV-infected intrahepatic cholangiocarcinomas.

Hepatology 2021 Sep 3. Epub 2021 Sep 3.

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

Background And Aims: Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. We sought to identify the landscape and mechanism of HBV integration, along with the genomic architecture of HBV-infected iCCA tumors.

Approach And Results: We profiled a cohort of 108 HBV-infected iCCAs using whole-genome sequencing, deep sequencing, and RNA sequencing, together with pre-constructed datasets of HBV-infected hepatocellular carcinoma (HBV-HCC; n=167) and combined hepatocellular cholangiocarcinoma (HBV-cHCC/CCA; n=59), and conventional (n=154) and fluke-related iCCAs (n=16). Platforms based on primary iCCA cell lines to evaluate the functional effects of chimeric transcripts were also used. We found that HBV had inserted at multiple sites in the iCCA genomes in 45 (41.7%) of the tumors. Recurrent viral integration breakpoints were found at 9 different sites. The most common insertional hotspot (7 tumors) was in the TERT promoter, where insertions and mutations (11 tumors) were mutually exclusive, and were accompanied by promoter hyperactivity. Recurrent HBV integration events (5 tumors) were also detected in FAT2, and were associated with enrichment of epithelial-mesenchymal transition-related genes. A distinctive intergenic insertion, between DMRTA1 and LINC01239 (chr9p21.3), had oncogenic effects through activation of the mTOR/4EBP/S6K pathway. Regarding the mutational profiles of primary liver cancers, the overall landscape of HBV-iCCA was closer to that of nonviral conventional iCCA, than to HBV-HCC and HBV-cHCC/CCA.

Conclusions: Our findings provide insight into the behavior of iCCAs driven by various pathogenic mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.
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http://dx.doi.org/10.1002/hep.32135DOI Listing
September 2021

Rates and patterns of clonal oncogenic mutations in the normal human brain.

Cancer Discov 2021 Aug 13. Epub 2021 Aug 13.

Genetics and Genomics, Boston Children's Hospital

While oncogenic mutations have been found in non-diseased, proliferative non-neural tissues, their prevalence in the human brain is unknown. Targeted sequencing of genes implicated in brain tumors in 418 samples derived from 110 individuals of varying ages, without tumor diagnoses, detected oncogenic somatic single-nucleotide variants (sSNVs) in 5.4% of the brains, including IDH1 R132H. These mutations were largely present in subcortical white matter and enriched in glial cells, and surprisingly, were less common in older individuals. A depletion of high-allele frequency sSNVs representing macroscopic clones with age was replicated by analysis of bulk RNAseq data from 1,816 non-diseased brain samples ranging from fetal to old age. We also describe large clonal copy number variants, and that sSNVs show mutational signatures resembling those found in gliomas, suggesting that mutational processes of the normal brain drive early glial oncogenesis. This study helps understand the origin and early evolution of brain tumors.
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http://dx.doi.org/10.1158/2159-8290.CD-21-0245DOI Listing
August 2021

Non-steroidal Anti-inflammatory Drug Use and Risk of Age-Related Macular Degeneration in the California Teachers Study.

Drugs Aging 2021 Sep 26;38(9):817-828. Epub 2021 Jul 26.

Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.

Purpose: The aim of this study was to examine whether use of regular aspirin and/or other non-steroidal anti-inflammatory drugs (NSAIDs) is associated with the development of age-related macular degeneration (AMD).

Methods: In the California Teachers Study cohort (N = 88,481) we identified diagnoses of AMD up to December 31, 2012 by linkage to statewide hospital discharge records. Aspirin, ibuprofen, other NSAIDs, and acetaminophen use and comprehensive risk factor information were collected via self-administered questionnaires at baseline in 1995-1996 and a follow-up questionnaire in 2005-2006. We employed Cox proportional hazard regression to model AMD risk.

Results: We did not find any associations between AMD and frequency and duration of aspirin or ibuprofen use reported at baseline. In the subsample with more specific information on medication use, we observed a 20% decrease in risk of AMD among low-dose aspirin users (HR 0.81, 95% CI 0.70-0.95) and a 55% decrease among cyclooxygenase-2 (COX-2) inhibitor users (HR 0.45, 95% CI 0.26-0.78) during 6.3 years of average follow-up.

Conclusion: The decrease in risk of intermediate- or late-stage AMD among women who reported regular use of low-dose aspirin or specific COX-2 inhibitors suggests a possible protective role for medications with COX-2 inhibitory properties or aspirin at doses used for cardiovascular disease prevention.
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http://dx.doi.org/10.1007/s40266-021-00885-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419134PMC
September 2021

Resisting the politics of the pandemic and racism to foster humanity.

Qual Soc Work 2021 Mar;20(1-2):225-232

School of Social Work, Dalhousie University, Halifax, NS, Canada.

Following the World Health Organization (WHO) declaration of COVID-19 as a pandemic in March 2020, a state of emergency was announced in many countries. This has had significant impacts on individuals, communities, and various systems-as-whole locally, nationally and globally. Among the various impacts the pandemic has on people, we would like to invite social workers who deeply care about social justice and equity to pause and reflect on how some populations are unjustly subject to pandemic related stigma and racism; how racist politics play out to maintain extreme nationalism and exclusion; and how we can resist these politics of the pandemic to foster humanity and equity.
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http://dx.doi.org/10.1177/1473325020973313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261382PMC
March 2021

Impacts of Side Effects to BNT162b2 and the First Dose of ChAdOx1 Anti-SARS-CoV-2 Vaccination on Work Productivity, the Need for Medical Attention, and Vaccine Acceptance: A Multicenter Survey on Healthcare Workers in Referral Teaching Hospitals in the Republic of Korea.

Vaccines (Basel) 2021 Jun 14;9(6). Epub 2021 Jun 14.

Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Korea.

To establish a successful anti-SARS-CoV-2 vaccination strategy, it is necessary to take possible tradeoffs into account. We conducted a survey on vaccinated healthcare workers (HCWs) inthree referral teaching hospitals in the Republic of Korea. We investigated the frequency of vaccination side effects (SEs), the impact on their work productivity, the need for medical attention, and vaccine acceptance. Three groups of HCWs were surveyed: 1406 who had received the first dose of BNT162b2 (BNT162b2#1), 1168 who had received the second dose of BNT162b2 (BNT162b2#2), and 1679 who had received the first dose of ChAdOx1 (ChAdOx1#1). More SEs and impact on work productivity were reported in ChAdOx1#1 than in the other two groups. However, among individuals aged ≥40 years, no significant difference of absence from work was found between ChAdOx1#1 and BN162b2#2 (4.4%, 31/699 vs. 3.0%, 12/405; = 0.26), and none were hospitalized. Older HCWs in ChAdOx1#1 showed intention to receive the second dose of the vaccine. Although the incidence of SEs and their impacts were greater after the first dose of ChAdOx1 than BNT162b2 in young people, significant impact of SEs seemed to be rare in individuals aged ≥40 years, regardless of the vaccine they received.
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http://dx.doi.org/10.3390/vaccines9060648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232011PMC
June 2021

Comprehensive identification of transposable element insertions using multiple sequencing technologies.

Nat Commun 2021 06 22;12(1):3836. Epub 2021 Jun 22.

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.

Transposable elements (TEs) help shape the structure and function of the human genome. When inserted into some locations, TEs may disrupt gene regulation and cause diseases. Here, we present xTea (x-Transposable element analyzer), a tool for identifying TE insertions in whole-genome sequencing data. Whereas existing methods are mostly designed for short-read data, xTea can be applied to both short-read and long-read data. Our analysis shows that xTea outperforms other short read-based methods for both germline and somatic TE insertion discovery. With long-read data, we created a catalogue of polymorphic insertions with full assembly and annotation of insertional sequences for various types of retroelements, including pseudogenes and endogenous retroviruses. Notably, we find that individual genomes have an average of nine groups of full-length L1s in centromeres, suggesting that centromeres and other highly repetitive regions such as telomeres are a significant yet unexplored source of active L1s. xTea is available at https://github.com/parklab/xTea .
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http://dx.doi.org/10.1038/s41467-021-24041-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219666PMC
June 2021

Risk factors for isolation of multi-drug resistant organisms in coronavirus disease 2019 pneumonia: A multicenter study.

Am J Infect Control 2021 10 17;49(10):1256-1261. Epub 2021 Jun 17.

Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea. Electronic address:

Objectives: Superimposed multi-drug resistant organisms (MDROs) co-infection can be associated with worse outcomes in patients with severe coronavirus disease 2019 (COVID-19), even if these patients were managed with strict airborne and contact precautions. Identifying risk factors for isolation of MDROs is critical to COVID-19 treatment.

Methods: All eligible adult patients with confirmed COVID-19 pneumonia from 10 hospitals in the Republic of Korea between February 2020 and May 2020 were retrospectively enrolled. Using this cohort, epidemiology and risk factors for isolation of MDROs were evaluated.

Results: Of 152 patients, 47 with microbial culture results were included. Twenty isolates of MDROs from 13 (28%) patients were cultured. Stenotrophomonas maltophilia (5 isolates) was the most common MDRO, followed by methicillin-resistant staphylococcus aureus (4 isolates). MDROs were mostly isolated from sputum samples (80%, 16/20). The median time from hospitalization to MDRO isolation was 28 days (interquartile range, 18-38 days). In-hospital mortality was higher in patients with MDRO isolation (62% vs 15%; P = .001). Use of systemic corticosteroids after diagnosis of COVID-19 (adjusted odds ratio [aOR]: 15.07; 95% confidence interval [CI]: 2.34-97.01; P = .004) and long-term care facility (LTCF) stay before diagnosis of COVID-19 (aOR: 6.09; 95% CI: 1.02-36.49; P = .048) were associated with MDRO isolation.

Conclusions: MDROs were isolated from 28% of COVID-19 pneumonia patients with culture data and 8.6% of the entire cohort. Previous LTCF stay and adjunctive corticosteroid use were risk factors for the isolation of MDROs. Strict infection prevention strategies may be needed in these COVID-19 patients with risk factors.
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http://dx.doi.org/10.1016/j.ajic.2021.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251653PMC
October 2021

Evidence of Cooperation between Hippo Pathway and Mutation in Thyroid Carcinomas.

Cancers (Basel) 2021 May 12;13(10). Epub 2021 May 12.

Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 Andar, São Paulo, SP 04039-032, Brazil.

Thyroid cancer incidences have been steadily increasing worldwide and are projected to become the fourth leading cancer diagnosis by 2030. Improved diagnosis and prognosis predictions for this type of cancer depend on understanding its genetic bases and disease biology. mutations have been found in a wide range of thyroid tumors, from benign to aggressive thyroid carcinomas. Based on that and in vivo studies, it has been suggested that cooperates with other driver mutations to induce tumorigenesis. This study aims to identify genetic alterations or pathways that cooperate with the mutation in the pathogenesis of thyroid cancer. From a cohort of 120 thyroid carcinomas, 11 -mutated samples were identified. The samples were subjected to RNA-Sequencing analyses. The mutation analysis in our eleven -positive cases uncovered that four genes that belong to the Hippo pathway were mutated. The gene expression analysis revealed that this pathway was dysregulated in the -positive samples. We additionally explored the mutational status and expression profiling of 60 -positive papillary thyroid carcinomas (PTC) from The Cancer Genome Atlas (TCGA) cohort. Altogether, the mutational landscape and pathway enrichment analysis (gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genome (KEGG)) detected the Hippo pathway as dysregulated in -positive thyroid carcinomas. Finally, we suggest a crosstalk between the Hippo and other signaling pathways, such as Wnt and BMP.
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http://dx.doi.org/10.3390/cancers13102306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151534PMC
May 2021

Promotion of healthcare personnel vaccinations among newly employed doctors and nurses: Evidence-guided strategy.

Vaccine 2021 06 20;39(26):3480-3485. Epub 2021 May 20.

Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.

Objective: Healthcare personnel vaccinations are important to prevent vaccine-preventable diseases in hospitals. We evaluated the seroprevalence, vaccination rates, and barriers to vaccination among newly employed nurses and doctors.

Methods: A cross-sectional study was conducted at a university hospital in the Republic of Korea from 2017 to 2020. The immune status for hepatitis B virus (HBV), varicella zoster virus (VZV), and hepatitis A virus (HAV) was tested. HBV, VZV, measles, mumps, and rubella (MMR) vaccinations were mandatory. HAV and tetanus-diphtheria-pertussis (Tdap) vaccinations were also recommended by specialists. A web-based survey on factors affecting vaccination completion was conducted.

Results: For the 668 participants, the mean age was 26 ± 2 (±SD) years. Seroprevalence was 86% for HBV, 93% for VZV, and 59% for HAV. Vaccine completion rates were 40% for HBV, 70% for VZV, 65% for MMR, 42% for HAV, and 70% for Tdap. Overall compliance for mandatory vaccines was 54%. A total of 402 subjects who had worked for over one year were surveyed, with a 22% response rate. More than 50% of respondents gave the following reasons for not receiving recommend vaccines: 1) they were busy (77%), 2) vaccination process was complicated (68%), and 3) they simply forgot about vaccination (55%). Healthcare personnel agreed to be frequently informed of immunization requirements and for monitoring of vaccination rates.

Conclusion: Vaccination compliance among newly employed doctors and nurses was 54%. Active interventions such as simplifying the vaccination process and frequent notifications are needed to achieve optimal immunization rates.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.025DOI Listing
June 2021

Novel Alzheimer's disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers.

Transl Psychiatry 2021 05 19;11(1):296. Epub 2021 May 19.

Clinical Genomics Center, Samsung Medical Center, Seoul, South Korea.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry. Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles. We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status. Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E-07) and rs12594991 (P = 2.03E-07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population. In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations.
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http://dx.doi.org/10.1038/s41398-021-01412-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134477PMC
May 2021

A trauma-informed approach in Canadian mental health policies: A systematic mapping review.

Health Policy 2021 07 20;125(7):899-914. Epub 2021 Apr 20.

Factor-Inwentash Faculty of Social Work, University of Toronto, 246 Bloor Street West, Toronto, ON, Canada M5S 1A1.

Trauma is a hidden epidemic and a public health concern in Canada and globally. To address the pervasiveness of trauma in general and clinical populations, a trauma-informed approach (TIA) has been widely promoted in the field of mental health (MH). This study explores how a TIA has been incorporated in Canadian MH policies across all provinces and territories, and in both government and non-government organizations. A systematic mapping review in multiple search sites resulted in a total of 60 TIA policy documents in MH policies. The findings indicated that despite the broad range of the search period which went back as far as the 1980s, TIA policies started emerging in 2010 in the field of Canadian MH. Our research findings also showed an increased understanding of a broad definition and various types of trauma and an acknowledgement of its causes and impacts on multiple levels. This highlighted the importance of all levels of services in TIA. Through this search, we identified the widespread use of different terminologies to refer to TIA. This may create confusion about what TIA means in policy, research, and practice. We propose areas for improvement such as including experiences of marginalized populations, explicitly centering cultural and gender sensitive approaches in TIA policy initiatives, clarifying the standard definition of TIA and its implementation services, and establishing indicators and evaluation methods for future research and policy directions.
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http://dx.doi.org/10.1016/j.healthpol.2021.04.008DOI Listing
July 2021

The Use of a Light-Emitting Diode Device for Neck Rejuvenation and Its Safety on Thyroid Glands.

J Clin Med 2021 Apr 19;10(8). Epub 2021 Apr 19.

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

Home-use light-emitting diodes (LEDs) are attracting growing attention regarding their anti-aging effects. Although most previous studies on the use of LED devices as a form of low-level laser therapy reported no significant adverse events, questions regarding the safety of using a light source on secretory tissues have been raised. This study aimed to assess the safety and efficacy of a home-use LED device for neck skin rejuvenation, particularly regarding its effect on thyroid gland morphology and function. Thyroid function tests and ultrasonographic analyses showed no significant changes after 16 weeks of LED use. Evaluation using the Lemperle wrinkle scale and global improvement scales by both investigators and subjects showed significant improvement after 16 weeks of daily application, as well as 8 weeks after discontinuation. Biophysical parameters, such as hydration, elasticity, and density, also showed significant improvements. Hence, the long-term use of the LED device was safe and effective for neck rejuvenation, and showed no significant side effects on the adjacent thyroid and parathyroid glands.
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http://dx.doi.org/10.3390/jcm10081774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073506PMC
April 2021

A Versatile Surface Modification Method via Vapor-phase Deposited Functional Polymer Films for Biomedical Device Applications.

Biotechnol Bioprocess Eng 2021 Apr 1:1-14. Epub 2021 Apr 1.

Department of Chemical and Biomolecular Engineering, Korea Advanced of Institute of Science and Technology, Daejeon, 34141 Korea.

For last two decades, the demand for precisely engineered three-dimensional structures has increased continuously for the developments of biomaterials. With the recent advances in micro- and nano-fabrication techniques, various devices with complex surface geometries have been devised and produced in the pharmaceutical and medical fields for various biomedical applications including drug delivery and biosensors. These advanced biomaterials have been designed to mimic the natural environments of tissues more closely and to enhance the performance for their corresponding biomedical applications. One of the important aspects in the rational design of biomaterials is how to configure the surface of the biomedical devices for better control of the chemical and physical properties of the bioactive surfaces without compromising their bulk characteristics. In this viewpoint, it of critical importance to secure a versatile method to modify the surface of various biomedical devices. Recently, a vapor phase method, termed initiated chemical vapor deposition (iCVD) has emerged as damage-free method highly beneficial for the conformal deposition of various functional polymer films onto many kinds of micro- and nano-structured surfaces without restrictions on the substrate material or geometry, which is not trivial to achieve by conventional solution-based surface functionalization methods. With proper structural design, the functional polymer thin film via iCVD can impart required functionality to the biomaterial surfaces while maintaining the fine structure thereon. We believe the iCVD technique can be not only a valuable approach towards fundamental cell-material studies, but also of great importance as a platform technology to extend to other prospective biomaterial designs and material interface modifications for biomedical applications.
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http://dx.doi.org/10.1007/s12257-020-0269-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013202PMC
April 2021

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

J Korean Med Sci 2021 Mar 22;36(11):e83. Epub 2021 Mar 22.

Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain.

Methods: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values.

Results: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; = 0.007).

Conclusion: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.
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http://dx.doi.org/10.3346/jkms.2021.36.e83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985289PMC
March 2021

Heparin-mediated electrostatic immobilization of bFGF functional polymer films for enhanced self-renewal of human neural stem cells.

J Mater Chem B 2021 03;9(8):2084-2091

Department of Chemical and Biomolecular Engineering & KI for NanoCentury, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Daejeon 34141, Republic of Korea.

Preserving the self-renewal capability of undifferentiated human neural stem cells (hNSCs) is one of the crucial prerequisites for efficient hNSC-based regenerative medicine. Considering that basic fibroblast growth factor (bFGF) is one of the key contributing factors in maintaining the self-renewal property of hNSCs, the bioactivity and stability of bFGF in the hNSC culture should be regulated carefully. In this study, we developed a functional polymer film of poly(glycidyl methacrylate (GMA)-co-N,N-dimethylaminoethyl methacrylate (DMAEMA)) (coGD, or p(GMA-co-DMAEMA)) via initiated chemical vapor deposition (iCVD), which facilitated a stable, electrostatic adsorption of heparin and subsequent immobilization of bFGF. The bFGF-immobilized coGD surface substantially enhanced the proliferation rate and neurosphere forming ability of hNSCs compared to tissue culture plate (TCP). The expression of the stemness markers of hNSCs such as NESTIN and SOX-2 was also upregulated prominently on the coGD surface. Also, the hNSCs cultured on the coGD surface showed enhanced neurogenesis upon spontaneous differentiation. The immobilized bFGF on the coGD surface stimulated the expression of bFGF receptors and subsequently activated the mitogen-activated protein kinase (MAPK) pathway, attributed to the increase in self-renewal property of hNSCs. Our results indicate that the coGD surface allowed in situ heparin-mediated bFGF immobilization, which served as a robust platform to generate hNSC neurospheres with enhanced self-renewal and differentiation capabilities and thereby will prompt an advance in the field of therapeutics of neurodegenerative diseases.
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http://dx.doi.org/10.1039/d0tb02799eDOI Listing
March 2021

Implications of US radiomics signature for predicting malignancy in thyroid nodules with indeterminate cytology.

Eur Radiol 2021 Jul 18;31(7):5059-5067. Epub 2021 Jan 18.

Department of Radiology, Research Institute of Radiological Science, and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, South Korea.

Objectives: The purpose of this study was to evaluate the role of the radiomics score using US images to predict malignancy in AUS/FLUS and FN/SFN nodules.

Methods: One hundred fifty-five indeterminate thyroid nodules in 154 patients who received initial US-guided FNA for diagnostic purposes were included in this retrospective study. A representative US image of each tumor was acquired, and square ROIs covering the whole nodule were drawn using the Paint program of Windows 7. Texture features were extracted by in-house texture analysis algorithms implemented in MATLAB 2019b. The LASSO logistic regression model was used to choose the most useful predictive features, and ten-fold cross-validation was performed. Two prediction models were constructed using multivariable logistic regression analysis: one based on clinical variables, and the other based on clinical variables with the radiomics score. Predictability of the two models was assessed with the AUC of the ROC curves.

Results: Clinical characteristics did not significantly differ between malignant and benign nodules, except for mean nodule size. Among 730 candidate texture features generated from a single US image, 15 features were selected. Radiomics signatures were constructed with a radiomics score, using selected features. In multivariable logistic regression analysis, higher radiomics score was associated with malignancy (OR = 10.923; p < 0.001). The AUC of the malignancy prediction model composed of clinical variables with the radiomics score was significantly higher than the model composed of clinical variables alone (0.839 vs 0.583).

Conclusions: Quantitative US radiomics features can help predict malignancy in thyroid nodules with indeterminate cytology.
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http://dx.doi.org/10.1007/s00330-020-07670-3DOI Listing
July 2021

Three-Dimensional Spheroid Culture on Polymer-Coated Surface Potentiate Stem Cell Functions via Enhanced Cell-Extracellular Matrix Interactions.

ACS Biomater Sci Eng 2020 04 9;6(4):2240-2250. Epub 2020 Mar 9.

Department of Chemical and Biomolecular Engineering and KI for Nano Century, Korea Advanced of Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.

The aggregation of mesenchymal stem cells (MSCs) into three-dimensional (3D) spheroids has emerged as a promising therapeutic candidate for the treatment of a variety of diseases. In spite of the numerous 3D culture methods suggested recently for MSC spheroid generation, it is still elusive to fully reflect real stem cell niches; this effort majorly suffers from a lack of cell-extracellular matrix (ECM) interactions within the 3D spheroids. In this study, we develop a simple but versatile method for generating human MSC (hMSC) spheroids by culturing the cells on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). Interestingly, the pV4D4-coated surface allows a dynamic cell adhesion to the polymer surface while developing the formation of 3D spheroids. The corresponding mechanotransduction promotes the expression of the endogenous ECM and, in turn, results in a remarkable improvement in self-renewal abilities, pro-angiogenic potency, and multilineage differentiation capabilities. This observation highlights the significance of our method compared to the conventional spheroid-generating methods in terms of recreating the ECM-rich microenvironment. We believe the developed surface can serve as a versatile but reliable method for stem cell-based tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01738DOI Listing
April 2020

Infectious Diseases Physician Workforce in Korea.

J Korean Med Sci 2020 Dec 21;35(49):e428. Epub 2020 Dec 21.

Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.

This study aimed to evaluate the infectious disease (ID) physician workforce in Korea. We investigated the acquisition of ID physicians from 1992 to 2019 with their current working place in the Health Care System. We defined ID physicians working at general or tertiary-care hospitals as active ID physicians. A total 275 physicians acquired ID as a sub-specialty. Among the 275, 242 were active ID physicians. The density of active ID physicians was 0.47 per 100,000 population. Of all the 17 administrative districts, 11 (64.7%) fell short of 0.47, and 131 medical institutions employed the service of ID physicians. The median number of beds per adult ID physician was 372 (interquartile range, 280-507). It is essential to secure human resources to respond to emerging infectious diseases and perform the inherent work of ID physicians.
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http://dx.doi.org/10.3346/jkms.2020.35.e428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752260PMC
December 2020

Remodeling of Adhesion Network within Cancer Spheroids via Cell-Polymer Interaction.

ACS Biomater Sci Eng 2020 10 10;6(10):5632-5644. Epub 2020 Sep 10.

Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.

3D spheroids are considered as the improved model to mimic the distinct arrangements of the cells . To date, low-attachment surfaces have been most widely used to induce the spontaneous aggregation of cells in suspension by simply tuning the relative strength of the cell-cell adhesion over cell-substrate adhesion. However, aggregating cancer cells into 3D clusters should mean more than just adjoining the cells in the physical proximity. The tumor cell functionality is strongly affected by the adhesion networks between cancer cells and extracellular matrix (ECM). Here, we performed an in-depth analysis of how the nonmetastatic breast cancer cells (MCF7) can be transformed to gain invasive phenotypes through compact aggregation into 3D spheroids on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). By comparing the adhesion networks and invasion dynamics between 3D spheroids cultured on the pV4D4 surface with those cultured on conventional ultra-low-attachment (ULA) dishes, we report that only spheroids on the pV4D4 display active and sporadic cell-surface binding activities via dynamic protrusions, which correlates strongly with an increase in integrin β1. Moreover, localized laminin expression at the core of the pV4D4-cultured spheroids confirms the prominence of the intimate integrin-laminin interactions prompted by the exposure to pV4D4. This study suggests that structurally and functionally dissimilar 3D spheroids can be generated from the same type of cells on the surfaces of different physicochemical properties without any chemical treatment or genetic manipulation.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00977DOI Listing
October 2020

Negative Conversion Rate of SARS-CoV-2 Infection-Reply.

JAMA Intern Med 2021 04;181(4):566-567

Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.

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http://dx.doi.org/10.1001/jamainternmed.2020.7204DOI Listing
April 2021

Artificial intelligence to predict the BRAFV600E mutation in patients with thyroid cancer.

PLoS One 2020 25;15(11):e0242806. Epub 2020 Nov 25.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, South Korea.

Purpose: To investigate whether a computer-aided diagnosis (CAD) program developed using the deep learning convolutional neural network (CNN) on neck US images can predict the BRAFV600E mutation in thyroid cancer.

Methods: 469 thyroid cancers in 469 patients were included in this retrospective study. A CAD program recently developed using the deep CNN provided risks of malignancy (0-100%) as well as binary results (cancer or not). Using the CAD program, we calculated the risk of malignancy based on a US image of each thyroid nodule (CAD value). Univariate and multivariate logistic regression analyses were performed including patient demographics, the American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TIRADS) categories and risks of malignancy calculated through CAD to identify independent predictive factors for the BRAFV600E mutation in thyroid cancer. The predictive power of the CAD value and final multivariable model for the BRAFV600E mutation in thyroid cancer were measured using the area under the receiver operating characteristic (ROC) curves.

Results: In this study, 380 (81%) patients were positive and 89 (19%) patients were negative for the BRAFV600E mutation. On multivariate analysis, older age (OR = 1.025, p = 0.018), smaller size (OR = 0.963, p = 0.006), and higher CAD value (OR = 1.016, p = 0.004) were significantly associated with the BRAFV600E mutation. The CAD value yielded an AUC of 0.646 (95% CI: 0.576, 0.716) for predicting the BRAFV600E mutation, while the multivariable model yielded an AUC of 0.706 (95% CI: 0.576, 0.716). The multivariable model showed significantly better performance than the CAD value alone (p = 0.004).

Conclusion: Deep learning-based CAD for thyroid US can help us predict the BRAFV600E mutation in thyroid cancer. More multi-center studies with more cases are needed to further validate our study results.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242806PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688114PMC
January 2021

Pleural Cryptococcosis in a Patient with AIDS.

J Korean Med Sci 2020 Nov 16;35(44):e392. Epub 2020 Nov 16.

Department of Pathology, Soonchunhyang University Seoul Hospital, Seoul, Korea.

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http://dx.doi.org/10.3346/jkms.2020.35.e392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669458PMC
November 2020

Ultrasonography-Based Radiomics of Screening-Detected Ductal Carcinoma In Situ According to Visibility on Mammography.

Ultrasound Q 2020 Nov 13;37(1):23-27. Epub 2020 Nov 13.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, College of Medicine, Yonsei University, Seoul, Korea.

Abstract: Ductal carcinoma in situ (DCIS) has different prognostic factors according to the detection modality. The purpose of this study was to compare parameters from a radiomic analysis of ultrasonography (US) images for DCIS detected on screening mammography (MMG) and US and detected on screening US only. A total of 154 surgically confirmed DCIS visible on US were included. Regions of interest were drawn onto US images of DCIS, and texture analysis was performed. Lesions were classified into those detected by both US and MMG (the US-MMG group) and those detected by US only (the US group). Analysis parameters were compared between the US-MMG group and the US group. Ninety-six lesions were included in the US-MMG group and 58 lesions in the US group. Energy, entropy, maximum, mean absolute deviation, range, SD, and variance were significantly higher in the US-MMG group than the US group. Kurtosis, skewness, and uniformity were significantly lower in the US-MMG group than the US group. Among the 22 gray-level cooccurrence matrix parameters, 18, 21, 22, 20, and 21 parameters were significantly different between the 2 groups in 0, 45, 90, and 135 degrees and the average value. Among the 11 gray-level run-length matrix parameters, 6, 6, 7, 7, and 6 parameters were significantly different in 0, 45, 90, and 135 degrees and the average value. Inverse variance and gray-level nonuniformity were the most different features between the 2 groups. Screening-detected DCIS showed different radiomic features according to the detection modality.
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http://dx.doi.org/10.1097/RUQ.0000000000000538DOI Listing
November 2020

HiTea: a computational pipeline to identify non-reference transposable element insertions in Hi-C data.

Bioinformatics 2021 05;37(8):1045-1051

Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.

Hi-C is a common technique for assessing 3D chromatin conformation. Recent studies have shown that long-range interaction information in Hi-C data can be used to generate chromosome-length genome assemblies and identify large-scale structural variations. Here, we demonstrate the use of Hi-C data in detecting mobile transposable element (TE) insertions genome-wide. Our pipeline Hi-C-based TE analyzer (HiTea) capitalizes on clipped Hi-C reads and is aided by a high proportion of discordant read pairs in Hi-C data to detect insertions of three major families of active human TEs. Despite the uneven genome coverage in Hi-C data, HiTea is competitive with the existing callers based on whole-genome sequencing (WGS) data and can supplement the WGS-based characterization of the TE-insertion landscape. We employ the pipeline to identify TE-insertions from human cell-line Hi-C samples.

Availability And Implementation: HiTea is available at https://github.com/parklab/HiTea and as a Docker image.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa923DOI Listing
May 2021

Combining radiomics with ultrasound-based risk stratification systems for thyroid nodules: an approach for improving performance.

Eur Radiol 2021 Apr 9;31(4):2405-2413. Epub 2020 Oct 9.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 03722, Seoul, Korea.

Objectives: To develop a radiomics score using ultrasound images to predict thyroid malignancy and to investigate its potential as a complementary tool to improve the performance of risk stratification systems.

Methods: We retrospectively included consecutive patients who underwent fine-needle aspiration (FNA) for thyroid nodules that were cytopathologically diagnosed as benign or malignant. Nodules were randomly assigned to a training and test set (8:2 ratio). A radiomics score was developed from the training set, and cutoff values based on the maximum Youden index (Rad_maxY) and for 5%, 10%, and 20% predicted malignancy risk (Rad_5%, Rad_10%, Rad_20%, respectively) were applied to the test set. The performances of the American College of Radiology (ACR) and the American Thyroid Association (ATA) guidelines were compared with the combined performances of the guidelines and radiomics score with interpretations from expert and nonexpert readers.

Results: A total of 1624 thyroid nodules from 1609 patients (mean age, 50.1 years [range, 18-90 years]) were included. The radiomics score yielded an AUC of 0.85 (95% CI: 0.83, 0.87) in the training set and 0.75 (95% CI: 0.69, 0.81) in the test set (Rad_maxY). When the radiomics score was combined with the ACR or ATA guidelines (Rad_5%), all readers showed increased specificity, accuracy, and PPV and decreased unnecessary FNA rates (all p < .05), with no difference in sensitivity (p > .05).

Conclusion: Radiomics help predict thyroid malignancy and improve specificity, accuracy, PPV, and unnecessary FNA rate while maintaining the sensitivity of the ACR and ATA guidelines for both expert and nonexpert readers.

Key Points: • The radiomics score yielded an AUC of 0.85 and 0.75 in the training and test set, respectively. • For all readers, combining a 5% predicted malignancy risk cutoff for the radiomics score with the ACR and ATA guidelines significantly increased specificity, accuracy, and PPV and decreased unnecessary FNA rates, with no decrease in sensitivity. • Radiomics can help predict malignancy in thyroid nodules in combination with risk stratification systems, by improving specificity, accuracy, and PPV and unnecessary FNA rates while maintaining sensitivity for both expert and nonexpert readers.
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http://dx.doi.org/10.1007/s00330-020-07365-9DOI Listing
April 2021

Selective activation of the estrogen receptor-β by the polysaccharide from Cynanchum wilfordii alleviates menopausal syndrome in ovariectomized mice.

Int J Biol Macromol 2020 Dec 28;165(Pt A):1029-1037. Epub 2020 Sep 28.

Research Group of Traditional Food, Korea Food Research Institute, Wanju 55365, Republic of Korea. Electronic address:

The menopausal syndrome caused by rapid changes in hormone levels greatly influences the quality of life of women. Though hormone replacement therapy (HRT) is widely used to treat the menopausal syndrome, it exhibits many side effects, including the risk of thrombosis, cardiovascular diseases, and increased incidence of breast cancer; thus, diversifying the interest for phytotherapy-based materials as alternatives to HRT. Here, we isolated a crude polysaccharide fraction (CWPF) from Cynanchum wilfordii root that alleviated the ovariectomy-induced uterine atrophy and bone loss without changes in plasma estradiol concentration in mice. Increased plasma levels of follicle-stimulating hormone (FSH), alkaline phosphatase (ALP), osteocalcin (OC) in ovariectomized mice were also reduced to normal levels by CWPF administration. We found that the inhibitory effects of CWPF on menopausal symptoms were mediated by the estrogen receptor β (ER-β) specific activation, not ER-α. Moreover, CWPF treatment suppressed the phosphorylation of Akt, suggesting that CWPF alleviates post-menopausal symptoms by regulating ER-β related Akt signaling pathway. These results demonstrate that the polysaccharides corresponding to CWPF among the water-soluble extracts of CW could be used as a beneficial herbal alternative for the development of therapeutic agents to prevent menopausal syndrome in women.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.09.165DOI Listing
December 2020

Diagnosis of thyroid nodules on ultrasonography by a deep convolutional neural network.

Sci Rep 2020 09 17;10(1):15245. Epub 2020 Sep 17.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

The purpose of this study was to evaluate and compare the diagnostic performances of the deep convolutional neural network (CNN) and expert radiologists for differentiating thyroid nodules on ultrasonography (US), and to validate the results in multicenter data sets. This multicenter retrospective study collected 15,375 US images of thyroid nodules for algorithm development (n = 13,560, Severance Hospital, SH training set), the internal test (n = 634, SH test set), and the external test (n = 781, Samsung Medical Center, SMC set; n = 200, CHA Bundang Medical Center, CBMC set; n = 200, Kyung Hee University Hospital, KUH set). Two individual CNNs and two classification ensembles (CNNE1 and CNNE2) were tested to differentiate malignant and benign thyroid nodules. CNNs demonstrated high area under the curves (AUCs) to diagnose malignant thyroid nodules (0.898-0.937 for the internal test set and 0.821-0.885 for the external test sets). AUC was significantly higher for CNNE2 than radiologists in the SH test set (0.932 vs. 0.840, P < 0.001). AUC was not significantly different between CNNE2 and radiologists in the external test sets (P = 0.113, 0.126, and 0.690). CNN showed diagnostic performances comparable to expert radiologists for differentiating thyroid nodules on US in both the internal and external test sets.
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http://dx.doi.org/10.1038/s41598-020-72270-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498581PMC
September 2020
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