Publications by authors named "Seung Ho Shin"

99 Publications

Characterization of DNA lesions associated with cell-free DNA by targeted deep sequencing.

BMC Med Genomics 2021 Jul 28;14(1):192. Epub 2021 Jul 28.

GENINUS Inc, Seoul, 05836, Korea.

Background: Recently, a next-generation sequencing (NGS)-based method has been used for the successful detection of circulating tumor DNA (ctDNA) in various cancer types. Thus, the use of NGS on liquid biopsies will improve cancer diagnosis and prognosis. However, the low-allelic fraction of ctDNA poses a challenge for the sensitive and specific detection of tumor variants in cell-free DNA (cfDNA). To distinguish true variants from false positives, the characteristics of errors that occur during sample preparation and sequencing need to be elucidated.

Methods: We generated capture-based targeted deep sequencing data from plasma cfDNA and peripheral blood leucocyte (PBL) gDNA to profile background errors. To reveal cfDNA-associated DNA lesions, background error profiles from two sample types were compared in each nucleotide substitution class.

Results: In this study, we determined the prevalence of single nucleotide substitutions in cfDNA sequencing data to identify DNA damage preferentially associated with cfDNA. On comparing sequencing errors between cfDNA and cellular genomic DNA (gDNA), we observed that the total substitution error rates in cfDNA were significantly higher than those in gDNA. When the substitution errors were divided into 12 substitution error classes, C:G>T:A substitution errors constituted the largest difference between cfDNA and gDNA samples. When the substitution error rates were estimated based on the location of DNA-fragment substitutions, the differences in error rates of most substitution classes between cfDNA and gDNA samples were observed only at the ends of the DNA fragments. In contrast, C:G>T:A substitution errors in the cfDNA samples were not particularly associated with DNA-fragment ends. All observations were verified in an independent dataset.

Conclusions: Our data suggested that cytosine deamination increased in cfDNA compared to that in cellular gDNA. Such an observation might be due to the attenuation of DNA damage repair before the release of cfDNA and/or the accumulation of cytosine deamination after it. These findings can contribute to a better understanding of cfDNA-associated DNA damage, which will enable the accurate analysis of somatic variants present in cfDNA at an extremely low frequency.
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http://dx.doi.org/10.1186/s12920-021-01040-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317339PMC
July 2021

Beneficial Effects of a Specially Designed Home Meal Replacement on Cardiometabolic Parameters in Individuals with Obesity: Preliminary Results of a Randomized Controlled Clinical Trial.

Nutrients 2021 Jun 24;13(7). Epub 2021 Jun 24.

Department of Family Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea.

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention ( = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).
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http://dx.doi.org/10.3390/nu13072171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308396PMC
June 2021

Optimal First-Line Therapy for Acute Low-Tone Sensorineural Hearing loss.

J Audiol Otol 2021 Jun 30. Epub 2021 Jun 30.

Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, Seoul, Korea.

Background And Objectives: We aimed to analyze treatment outcomes following different initial management approaches and confirm treatment regimens for acute low-tone sensorineural hearing loss (ALHL) that would yield the best results.

Subjects And Methods: We retrospectively analyzed the medical records of 106 patients with ALHL who visited a university hospital's otology clinic from March 2013 to June 2019. Pure-tone averages at the initial visit and at 2 and 4 weeks after the initial visit were evaluated.

Results: Forty-nine patients were enrolled in this study; of them, 41 (83.7%) exhibited complete recovery (CR) at 2 weeks and 43 (87.8%) exhibited CR at 1 month after the initial visit. Regression analysis revealed that CR at 2 weeks after the initial visit was associated with diuretic use [Exp(B): 10.309, 95% confidence interval (CI): 1.007-100]. An initial daily low-dose steroid use was marginally significant [Exp(B): 1.042, 95% CI: 0.997-1.092; p=0.066]. Isolated diuretic use [Exp(B): 25.641, 95% CI: 1.121-90.909; p=0.039] was an independent, good prognostic factor at 1 month after the initial visit. However, other treatment regimens did not affect the final results.

Conclusions: A combination of initial daily administration of ≤30 mg prednisolone plus diuretics was sufficient as the first-line treatment for ALHL. High-dose steroids and salvage intratympanic steroid injections can be applied as a second choice; however, the predicted outcome would not be good in that case.
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http://dx.doi.org/10.7874/jao.2021.00269DOI Listing
June 2021

Association between ischemic stroke and seropositive rheumatoid arthritis in Korea: A nationwide longitudinal cohort study.

PLoS One 2021 17;16(5):e0251851. Epub 2021 May 17.

Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, South Korea.

The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan-Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02-1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07-1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05-1.97) and 1.66 (95% CI, 1.16-2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11-1.95) and 1.43 (95% CI, 1.07-1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251851PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128246PMC
May 2021

γ-Oryzanol Improves Exercise Endurance and Muscle Strength by Upregulating PPARδ and ERRγ Activity in Aged Mice.

Mol Nutr Food Res 2021 07 3;65(14):e2000652. Epub 2021 Jun 3.

Natural Materials and Metabolism Research Group, Korea Food Research Institute, Wanju, 55365, Republic of Korea.

Scope: γ-Oryzanol, a well-known antioxidant, has been used by body builders and athletes to boost strength and increase muscle gain, without major side effects. However, the effect of γ-Oryzanol on sarcopenia and the underlying molecular mechanism is poorly understood.

Results: Aged mice fed with the γ-Oryzanol diet do not show significant changes in muscle weight, but show increased running endurance as well as improved grip strength. The expression and activity of PPARδ and ERRγ are increased in skeletal muscle of γ-Oryzanol supplemented mice. γ-Oryzanol upregulates oxidative muscle fibers by MEF2 transcription factor, and PGC-1α and ERRα expressions. Fatty acid oxidation related genes and mitochondria biogenesis are upregulated by γ-Oryzanol. In addition, γ-Oryzanol inhibits TGF-β-Smad-NADPH oxidase 4 pathway and inflammatory cytokines such as TNF-α, IL-1β, IL-6, and p65 NF-κB subunit, which cause skeletal muscle weakness. Collectively, γ-Oryzanol attenuates muscle weakness pathway and increases oxidative capacity by increasing PPARδ and ERRγ activity, which contributes to enhance strength and improve oxidative capacity in muscles, consequently enhancing exercise capacity in aged mice. Particularly, γ-Oryzanol directly binds to PPARδ.

Conclusions: These are the first findings showing that γ-Oryzanol enhances skeletal muscle function in aged mice by regulating PPARδ and ERRγ activity without muscle gain.
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http://dx.doi.org/10.1002/mnfr.202000652DOI Listing
July 2021

Effects of Groove Sealing of the Posterior Occlusal Surface and Offset of the Internal Surface on the Internal Fit and Accuracy of Implant Placements Using 3D-Printed Surgical Guides: An In Vitro Study.

Polymers (Basel) 2021 Apr 11;13(8). Epub 2021 Apr 11.

Department of Prosthodontics, Yonsei University College of Dentistry, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, Korea.

This study evaluated the internal fit and the accuracy of the implant placement position in order to determine how the surface shape of the tooth and the offset influence the accuracy of the surgical guide. The acquired digital data were analyzed in three dimensions using 3D inspection software. The obtained results confirmed that the internal fit was better in the groove sealing (GS) group (164.45 ± 28.34 μm) than the original shape (OS) group (204.07 ± 44.60 μm) ( < 0.001), and for an offset of 100 μm (157.50 ± 17.26 μm) than for offsets of 30 μm (206.48 ± 39.12 μm) and 60 μm (188.82 ± 48.77 μm) ( < 0.001). The accuracy of implant placement was better in the GS than OS group in terms of the entry (OS, 0.229 ± 0.092 mm; GS, 0.169 ± 0.061 mm; < 0.001), apex (OS, 0.324 ± 0.149 mm; GS, 0.230 ± 0.124 mm; < 0.001), and depth (OS, 0.041 ± 0.027 mm; GS, 0.025 ± 0.022 mm; < 0.001). In addition, the entries (30 μm, 0.215 ± 0.044 mm; 60 μm, 0.172 ± 0.049 mm; 100 μm, 0.119 ± 0.050 mm; < 0.001) were only affected by the amount of offset. These findings indicate that the accuracy of a surgical guide can be improved by directly sealing the groove of the tooth before manufacturing the surgical guide or setting the offset during the design process.
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http://dx.doi.org/10.3390/polym13081236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070577PMC
April 2021

Effects of Postcuring Temperature on the Mechanical Properties and Biocompatibility of Three-Dimensional Printed Dental Resin Material.

Polymers (Basel) 2021 Apr 7;13(8). Epub 2021 Apr 7.

Department of Prosthodontics, Yonsei University College of Dentistry, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, Korea.

Three-dimensional (3D) printing is an attractive technology in dentistry. Acrylic-based 3D printed resin parts have to undergo postcuring processes to enhance their mechanical and biological properties, such as UV-light and thermal polymerization. However, no previous studies have revealed how the postcuring temperature influences the biocompatibility of the produced parts. Therefore, we postprocessed 3D printed denture teeth resin under different postcuring temperatures (40, 60 and 80 °C) for different periods (15, 30, 60, 90 and 120 min), and evaluated their flexural properties, Vickers hardness, cell cytotoxicity, cell viability, and protein adsorption. In addition, confocal laser scanning was used to assess the condition of human gingival fibroblasts. It was found that increasing the postcuring temperature significantly improved the flexural strength and cell viability. The flexural strength and cell viability were 147.48 ± 5.82 MPa (mean ± standard deviation) and 89.51 ± 7.09%, respectively, in the group cured at 80 °C for 120 min, which were higher than the values in the 40 and 60 °C groups. The cell cytotoxicity increased in the 40 °C groups and for longer cultivation time. Confocal laser scanning revealed identifiable differences in the morphology of fibroblasts. This study has confirmed that the postcuring temperature influences the final mechanical and biological properties of 3D printed resin.
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http://dx.doi.org/10.3390/polym13081180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067535PMC
April 2021

Sleeve insert scan body to predict implant placement position by using implant surgical guides: A dental technique.

J Prosthet Dent 2021 Feb 1. Epub 2021 Feb 1.

Assistant Professor, Department of Prosthodontics, Oral Research Science Center, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address:

In studies that assessed the accuracy of implant surgical guides, evaluations were based on the placement position of the implant by using a manufactured surgical guide. However, such assessments could involve errors that may occur during implant placement. Therefore, evaluating the 3-dimensional accuracy of the fabrication of the implant surgical guide itself is not enough. In the evaluation method described in this article, location-related information is obtained by connecting a scan body to the sleeve of the surgical guide instead of directly placing the implant. This helps to evaluate the accuracy of the surgical guide without errors in the placement of an implant.
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http://dx.doi.org/10.1016/j.prosdent.2020.12.004DOI Listing
February 2021

Dental students' perceptions on a simulated practice using patient-based customised typodonts during the transition from preclinical to clinical education.

Eur J Dent Educ 2021 Jan 29. Epub 2021 Jan 29.

Department of Prosthodontics, Yonsei University College of Dentistry, Seoul, Korea.

Purpose/objectives: Dental students experience difficulties during the transition from preclinical to clinical curriculum. In order to help the students to adapt to the clinical education programme, a simulated practice using patient-based customised models was introduced in this study to prepare for their first clinical practice.

Methods: This study included 45 third-year predoctoral students (D3 students) who were about to perform the preparation of a single crown abutment on their first patient. After practicing abutment preparation using simulated models and providing the actual treatment to their own patient, the students were surveyed to investigate their perceptions on the simulated practice using the 3D-printed customised typodont model. The statistical analysis of the quantitative data and the thematic analysis of the qualitative data were conducted.

Results: Regarding this simulation, more than 80% of the students gave positive feedback on their practice of (a) operative positions and postures, (b) finger rest, (c) occlusal reduction, (d) axial reduction and (e) proximal reduction. Student responses on the open-ended questions about how they perceived the usefulness of this simulation were categorised as "First clinical case," "Patient-based model" and "Realistic simulation environment." In addition, a number of improvements of the simulation were also suggested by the students including the typodont and the manikin.

Conclusions: This study gives insights into the significance of simulated practice using patient-based customised typodonts as a transitional education tool and its direction of development in the field of restorative treatments accompanied by irreversible tooth preparations.
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http://dx.doi.org/10.1111/eje.12672DOI Listing
January 2021

Natural Antioxidant and Anti-Inflammatory Compounds in Foodstuff or Medicinal Herbs Inducing Heme Oxygenase-1 Expression.

Antioxidants (Basel) 2020 Nov 27;9(12). Epub 2020 Nov 27.

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Korea.

Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme that catalyzes heme group degradation. Decreased level of HO-1 is correlated with disease progression, and HO-1 induction suppresses development of metabolic and neurological disorders. Natural compounds with antioxidant activities have emerged as a rich source of HO-1 inducers with marginal toxicity. Here we discuss the therapeutic role of HO-1 in obesity, hypertension, atherosclerosis, Parkinson's disease and hepatic fibrosis, and present important signaling pathway components that lead to HO-1 expression. We provide an updated, comprehensive list of natural HO-1 inducers in foodstuff and medicinal herbs categorized by their chemical structures. Based on the continued research in HO-1 signaling pathways and rapid development of their natural inducers, HO-1 may serve as a preventive and therapeutic target for metabolic and neurological disorders.
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http://dx.doi.org/10.3390/antiox9121191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761319PMC
November 2020

Evaluation of the 3D Printing Accuracy of a Dental Model According to Its Internal Structure and Cross-Arch Plate Design: An In Vitro Study.

Materials (Basel) 2020 Nov 28;13(23). Epub 2020 Nov 28.

Department of Prosthodontics, Yonsei University College of Dentistry, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, Korea.

The amount of photopolymer material consumed during the three-dimensional (3D) printing of a dental model varies with the volume and internal structure of the modeling data. This study analyzed how the internal structure and the presence of a cross-arch plate influence the accuracy of a 3D printed dental model. The model was designed with a U-shaped arch and the palate removed (Group U) or a cross-arch plate attached to the palate area (Group P), and the internal structure was divided into five types. The trueness and precision were analyzed for accuracy comparisons of the 3D printed models. Two-way ANOVA of the trueness revealed that the accuracy was 135.2 ± 26.3 µm (mean ± SD) in Group U and 85.6 ± 13.1 µm in Group P. Regarding the internal structure, the accuracy was 143.1 ± 46.8 µm in the 1.5 mm-thick shell group, which improved to 111.1 ± 31.9 µm and 106.7 ± 26.3 µm in the roughly filled and fully filled models, respectively. The precision was 70.3 ± 19.1 µm in Group U and 65.0 ± 8.8 µm in Group P. The results of this study suggest that a cross-arch plate is necessary for the accurate production of a model using 3D printing regardless of its internal structure. In Group U, the error during the printing process was higher for the hollowed models.
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http://dx.doi.org/10.3390/ma13235433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729473PMC
November 2020

Evaluation of the Color Stability of 3D-Printed Crown and Bridge Materials against Various Sources of Discoloration: An In Vitro Study.

Materials (Basel) 2020 Nov 26;13(23). Epub 2020 Nov 26.

Department of Prosthodontics, Yonsei University College of Dentistry, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, Korea.

Recent advances in three-dimensional (3D) printing have introduced new materials that can be utilized for dental restorations. Nonetheless, there are limited studies on the color stability of restorations using 3D-printed crowns and bridge resins. Herein, the color stability of conventional computer-aided design/computer-aided manufacturing (CAD/CAM) blocks and 3D-printing resins was evaluated and assessed for their degrees of discoloration based on material type, colorant types (grape juice, coffee, curry, and distilled water (control group)), and storage duration (2, 7, and 30 days) in the colorants. Water sorption, solubility, and scanning electron microscope (SEM) analyses were conducted. A three-way ANOVA analysis showed that all three factors significantly affected the color change of the materials. Notably, the discoloration (ΔE) was significantly higher in all 3D printing resins (4.74-22.85 over the 30 days) than in CAD/CAM blocks (0.64-4.12 over the 30 days) following immersion in all colorants. 3D-printing resins showed color differences above the clinical limit (2.25) following storage for 7 days or longer in all experimental groups. Curry was the most prominent colorant, and discoloration increased in almost all groups as the storage duration increased. This study suggests that discoloration must be considered when using 3D printing resins for restorations.
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http://dx.doi.org/10.3390/ma13235359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731151PMC
November 2020

Effects of Post-Curing Time on the Mechanical and Color Properties of Three-Dimensional Printed Crown and Bridge Materials.

Polymers (Basel) 2020 Nov 23;12(11). Epub 2020 Nov 23.

Department of Prosthodontics, Yonsei University College of Dentistry, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, Korea.

Three-dimensional (3D) printing is increasingly being utilized in the dental field. After fabricating a prosthesis using a 3D printed resin, a post-curing process is required to improve its mechanical properties, but there has been insufficient research on the optimal post-curing conditions. We used various 3D printed crown and bridge materials in this study, and evaluated the changes in their properties according to post-curing time by evaluating the flexural strength, Weibull modulus, Vickers hardness, color change, degree of conversion, and biocompatibility. The obtained results confirmed that the strength of the 3D printed resin increased when it was post-cured for 60-90 min. The Vickers hardness, the degree of conversion, and biocompatibility of the 3D printed resins increased significantly around the beginning of the post-curing time, and then increased more gradually as the post-curing time increased further. It was observed that the color tone also changed as the post-curing time increased, with some groups showing a ΔE value of ≥ 2.25, which can be recognized clinically. This study has confirmed that, after the printing process of a 3D printed resin was completed, a sufficient post-curing time of at least 60 min is required to improve the overall clinical performance of the produced material.
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http://dx.doi.org/10.3390/polym12112762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700600PMC
November 2020

GSK3β-Mediated Expression of CUG-Translated WT1 Is Critical for Tumor Progression.

Cancer Res 2021 02 12;81(4):945-955. Epub 2020 Nov 12.

College of Medicine, Zhengzhou University, Henan, China.

The () gene is well known as a chameleon gene. It plays a role as a tumor suppressor in Wilms' tumor but also acts as an oncogene in other cancers. Previously, our group reported that a canonical AUG starting site for the WT1 protein (augWT1) acts as a tumor suppressor, whereas a CUG starting site for the WT1 protein (cugWT1) functions as an oncogene. In this study, we report an oncogenic role of cugWT1 in the AOM/DSS-induced colon cancer mouse model and in a urethane-induced lung cancer model in mice lacking cugWT1. Development of chemically-induced tumors was significantly depressed in cugWT1-deficient mice. Moreover, glycogen synthase kinase 3β promoted phosphorylation of cugWT1 at S64, resulting in ubiquitination and degradation of the cugWT1 associated with the F-box WD repeat-containing protein 8. Overall, our findings suggest that inhibition of cugWT1 expression provides a potential candidate target for therapy. SIGNIFICANCE: These findings demonstrate that CUG-translated WT1 plays an oncogenic role , and GSK3β-mediated phosphorylation of cugWT1 induces its ubiquitination and degradation in concert with FBXW8.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1880DOI Listing
February 2021

Feasibility of Asynchronous and Automated Telemedicine in Otolaryngology: Prospective Cross-Sectional Study.

JMIR Med Inform 2020 Oct 19;8(10):e23680. Epub 2020 Oct 19.

Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: COVID-19 often causes respiratory symptoms, making otolaryngology offices one of the most susceptible places for community transmission of the virus. Thus, telemedicine may benefit both patients and physicians.

Objective: This study aims to explore the feasibility of telemedicine for the diagnosis of all otologic disease types.

Methods: A total of 177 patients were prospectively enrolled, and the patient's clinical manifestations with otoendoscopic images were written in the electrical medical records. Asynchronous diagnoses were made for each patient to assess Top-1 and Top-2 accuracy, and we selected 20 cases to conduct a survey among four different otolaryngologists to assess the accuracy, interrater agreement, and diagnostic speed. We also constructed an experimental automated diagnosis system and assessed Top-1 accuracy and diagnostic speed.

Results: Asynchronous diagnosis showed Top-1 and Top-2 accuracies of 77.40% and 86.44%, respectively. In the selected 20 cases, the Top-2 accuracy of the four otolaryngologists was on average 91.25% (SD 7.50%), with an almost perfect agreement between them (Cohen kappa=0.91). The automated diagnostic model system showed 69.50% Top-1 accuracy. Otolaryngologists could diagnose an average of 1.55 (SD 0.48) patients per minute, while the machine learning model was capable of diagnosing on average 667.90 (SD 8.3) patients per minute.

Conclusions: Asynchronous telemedicine in otology is feasible owing to the reasonable Top-2 accuracy when assessed by experienced otolaryngologists. Moreover, enhanced diagnostic speed while sustaining the accuracy shows the possibility of optimizing medical resources to provide expertise in areas short of physicians.
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http://dx.doi.org/10.2196/23680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575342PMC
October 2020

Clinical Experience with Treatment of Aquafilling Filler-Associated Complications: A Retrospective Study of 146 Cases.

Aesthetic Plast Surg 2020 12 16;44(6):1997-2007. Epub 2020 Sep 16.

Department of Plastic and Reconstructive Surgery, Korea University College of Medicine, Inchon-ro 73, Seongbuk-gu, Seoul, 02841, Republic of Korea.

Background: Aquafilling filler is used for breast and buttock augmentation, which are the most commonly performed cosmetic surgery procedures. However, complications after using Aquafilling filler for breast augmentation have been reported, and there are concerns regarding its use in large areas, such as the buttocks. We provide our experience with complications after breast augmentation and buttock augmentation using Aquafilling filler.

Methods: This observational cohort study analyzed the data of 399 patients treated for filler-related complications at our institutes from September 2015 to November 2019. Of these patients, 146 underwent surgery to remove Aquafilling filler from the breast or buttock.

Results: The mean time between Aquafilling filler use and complication onset was 38.5 ± 10.2 months. The average amount of filler material removed from one side of the breast or buttock was 285.5 ± 95.8 mL (range 150-750 mL). The most common complications were induration and masses (83.6%), followed by pain (52.1%), firmness (24.7%), asymmetry (10.3%), migration (8.2%), mastitis (6.8%), dimpling (6.2%), fever (3.4%), and sepsis (n = 1). After treatment, there was no recurrence of infection, and the patient satisfaction level based on the visual analogue scale was 8.0 ± 0.9.

Conclusions: Although Aquafilling filler is easily injectable and has long-term clinical effects, complications can occur. Furthermore, there are concerns regarding its toxicity and influence on the surrounding tissues. Hence, further research studies on Aquafilling filler and evidence regarding its long-term safety are needed.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-020-01889-7DOI Listing
December 2020

HI-511 overcomes melanoma drug resistance targeting AURKB and BRAF V600E.

Theranostics 2020 1;10(21):9721-9740. Epub 2020 Aug 1.

The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, USA.

Melanoma is an aggressive tumor of the skin and drug resistance is still a major problem in melanoma therapy. Novel targets and effective agents to overcome drug resistant melanoma are urgently needed in clinical therapy. Gene Expression Omnibus (GEO) database analysis, pathway enrichment analysis, and survival rate analysis were utilized to identify a candidate target. An anchorage-independent cell growth assay, flow cytometry, Western blot, and a xenograft mouse model were used to study the function of Aurora kinase B (AURKB) in both drug-sensitive and drug-resistant melanoma. Next, HI-511, a novel dual-target inhibitor targeting both AURKB and BRAF V600E, was designed and examined by an kinase assay. Methods as indicated above in addition to a BRAF V600E/PTEN-loss melanoma mouse model were used to demonstrate the effect of HI-511 on melanoma development and . AURKB is highly expressed in melanoma and especially in vemurafenib-resistant melanoma and the expression was correlated with patient survival rate. Knocking down inhibited cell growth and induced apoptosis in melanoma, which was associated with the BRAF/MEK/ERKs and PI3-K/AKT signaling pathways. Importantly, we found that HI-511, a novel dual-target inhibitor against AURKB and BRAF V600E, suppresses both vemurafenib-sensitive and vemurafenib-resistant melanoma growth and by inducing apoptosis and mediating the inhibition of the BRAF/MEK/ERKs and PI3K/AKT signaling pathways. AURKB is a potential target for melanoma treatment. HI-511, a novel dual-target inhibitor against both AURKB and BRAF V600E, could achieve durable suppression of melanoma growth, even drug-resistant melanoma growth.
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http://dx.doi.org/10.7150/thno.44342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449901PMC
May 2021

Synthetic lethality by targeting the RUVBL1/2-TTT complex in mTORC1-hyperactive cancer cells.

Sci Adv 2020 Jul 31;6(31):eaay9131. Epub 2020 Jul 31.

Division of Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.

Despite considerable efforts, mTOR inhibitors have produced limited success in the clinic. To define the vulnerabilities of mTORC1-addicted cancer cells and to find previously unknown therapeutic targets, we investigated the mechanism of piperlongumine, a small molecule identified in a chemical library screen to specifically target cancer cells with a hyperactive mTORC1 phenotype. Sensitivity to piperlongumine was dependent on its ability to suppress RUVBL1/2-TTT, a complex involved in chromatin remodeling and DNA repair. Cancer cells with high mTORC1 activity are subjected to higher levels of DNA damage stress via c-Myc and displayed an increased dependency on RUVBL1/2 for survival and counteracting genotoxic stress. Examination of clinical cancer tissues also demonstrated that high mTORC1 activity was accompanied by high RUVBL2 expression. Our findings reveal a previously unknown role for RUVBL1/2 in cell survival, where it acts as a functional chaperone to mitigate stress levels induced in the mTORC1-Myc-DNA damage axis.
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http://dx.doi.org/10.1126/sciadv.aay9131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399646PMC
July 2020

Optimal modified lateral shearing interferometer with axial range extension by using a dual optical plate.

Appl Opt 2020 Aug;59(23):6838-6847

We present a method to extend the axial range of digital holographic microscopy based on the optimal modified lateral shearing interferometer (MLSI). The proposed system can extend the axial range by using a dual optical plate. The interference pattern with two spatial wavelengths is generated by the plate with different thicknesses. These spatial wavelengths transfer a dual spatial frequency into the Fourier plane by using FFT. Two phases are extracted by a dual spatial frequency and combined to create a synthetic wavelength, which is applied to measure the micrometer-scale object without phase unwrapping. Also, the noise-reducing algorithm is used to reduce phase noise caused by the amplified noise of the synthetic wavelength. The experimental result confirms the feasibility of the optimal MLSI by using a dual optical plate.
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http://dx.doi.org/10.1364/AO.394757DOI Listing
August 2020

CDK12 and PAK2 as novel therapeutic targets for human gastric cancer.

Theranostics 2020 15;10(14):6201-6215. Epub 2020 May 15.

Department of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, China.

Gastric cancer remains the second leading cause of cancer-related death, and the third in mortality due to lack of effective therapeutic targets for late stage cancer patients. This study aims to identify potential druggable target biomarkers as potential therapeutic options for patients with gastric cancer. Immunohistochemistry of human gastric tumor tissues was conducted to determine the expression level of cyclin-dependent kinase 12 (CDK12). Multiple and assays such as RNAi, mass spectrometry, computer docking models, kinase assays, cell xenograft NU/NU mouse models (CDXs) and patient-derived xenograft NOD/SCID mouse models (PDXs) were conducted to study the function and molecular interaction of CDK12 with p21 activated kinase 2 (PAK2), as well as to find CDK12 inhibitors as potential treatment options for human gastric cancer. Here we identified that CDK12 is a driver gene in human gastric cancer growth. Mechanistically, CDK12 directly binds to and phosphorylates PAK2 at T134/T169 to activate MAPK signaling pathway. We further identified FDA approved clinical drug procaterol can serve as an effective CDK12 inhibitor, leading to dramatic restriction of cancer cell proliferation and tumor growth in human gastric cancer cells and PDXs. Our data highlight the potential of CDK12/PAK2 as therapeutic targets for patients with gastric cancer, and we propose procaterol treatment as a novel therapeutic strategy for human gastric cancer.
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http://dx.doi.org/10.7150/thno.46137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255043PMC
May 2021

Machine learning approach for prediction of hearing preservation in vestibular schwannoma surgery.

Sci Rep 2020 04 28;10(1):7136. Epub 2020 Apr 28.

Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.

In vestibular schwannoma patients with functional hearing status, surgical resection while preserving the hearing is feasible. Hearing levels, tumor size, and location of the tumor have been known to be candidates of predictors. We used a machine learning approach to predict hearing outcomes in vestibular schwannoma patients who underwent hearing preservation surgery: middle cranial fossa, or retrosigmoid approach. After reviewing the medical records of 52 patients with a pathologically confirmed vestibular schwannoma, we included 50 patient's records in the study. Hearing preservation was regarded as positive if the postoperative hearing was within serviceable hearing (50/50 rule). The categorical variable included the surgical approach, and the continuous variable covered audiometric and vestibular function tests, and the largest diameter of the tumor. Four different algorithms were lined up for comparison of accuracy: support vector machine(SVM), gradient boosting machine(GBM), deep neural network(DNN), and diffuse random forest(DRF). The average accuracy of predicting hearing preservation ranged from 62% (SVM) to 90% (DNN). The current study is the first to incorporate machine learning methodology into a prediction of successful hearing preservation surgery. Although a larger population may be needed for better generalization, this study could aid the surgeon's decision to perform a hearing preservation approach for vestibular schwannoma surgery.
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http://dx.doi.org/10.1038/s41598-020-64175-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188896PMC
April 2020

Is an Ultrasonic and Bipolar Integrated Energy Device More Useful Than a Conventional Electric Device in Head and Neck Free Flap Reconstruction? A Prospective Comparison.

J Oral Maxillofac Surg 2020 Aug 21;78(8):1437.e1-1437.e9. Epub 2020 Feb 21.

Assistant Professor, Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Purpose: Thunderbeat (TB) is an integrated energy device incorporating ultrasonic and bipolar technology that provides rapid cut and precision dissection and reliable vessel sealing compared with conventional electrosurgery (ES). The present study compared the surgical outcomes of TB and ES for harvesting the anterolateral thigh free flap (ALTFF).

Patients And Methods: The present prospective cohort study compared TB and ES in patients who had undergone head and neck reconstruction using ALTFFs. The baseline characteristics, including age, gender, body mass index, primary tumor site (recipient site), and T stage, were measured. Patients who had undergone reconstruction after previous unsuccessful head and neck cancer treatment using radiation were included in the salvage surgery group. The primary outcome variables were the harvesting time, blood loss, and flap failure. The interval until the start of an oral diet and the percutaneous endoscopic gastrostomy (PEG) insertion rate were analyzed to compare the functional outcomes. After identifying the confounding variables, multivariate approaches were used to adjust for the confounding variables.

Results: No significant differences were found in the demographics and disease-related factors such as age, gender, body mass index, anatomic distribution, and T stage of the primary disease, between the 2 groups. The operation time and bleeding volume were reduced by 32.4 and 33.1%, respectively, in the TB group compared with those in the control group. The postoperative drainage volume, duration, flap failure rate, and intensive care unit and total hospital stays were nearly identical between the 2 groups. No statistically significant differences were found in the functional outcomes (PEG insertion and oral diet start day) between the 2 groups.

Conclusions: The results of the present study have shown that TB is a useful supportive tool for head and neck reconstruction surgery because it decreases the operation time with surgical outcomes comparable to those with conventional ES.
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http://dx.doi.org/10.1016/j.joms.2020.02.017DOI Listing
August 2020

Alpha-Linolenic Acid-Enriched Butter Promotes Fatty Acid Remodeling and Thermogenic Activation in the Brown Adipose Tissue.

Nutrients 2020 Jan 3;12(1). Epub 2020 Jan 3.

Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.

Supplementation with -3 long-chain (LC) polyunsaturated fatty acids (PUFA) is known to promote thermogenesis via the activation of brown adipose tissue (BAT). Agricultural products that are biofortified with -linolenic acid (ALA), the precursor of -3 LC PUFA, have been launched to the market, but their impact on BAT function is unknown. This study aimed to evaluate the effects of ALA-biofortified butter on lipid metabolism and thermogenic functions in the BAT. C57BL/6 mice were fed a high-fat diet containing ALA-biofortified butter (n3Bu, 45% calorie from fat) for ten weeks in comparison with the isocaloric high-fat diets prepared from conventional butter or margarine. The intake of n3Bu significantly reduced the whitening of BAT and increased the thermogenesis in response to acute-cold treatment. Also, n3Bu supplementation is linked with the remodeling of BAT by promoting bioconversion into -3 LC PUFA, FA elongation and desaturation, and mitochondrial biogenesis. Taken together, our results support that ALA-biofortified butter is a novel source of -3 PUFA, which potentiates the BAT thermogenic function.
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http://dx.doi.org/10.3390/nu12010136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019653PMC
January 2020

NCM 1921, a Mixture of Several Ingredients, Including Fatty Acids and Choline, Attenuates Atopic Dermatitis in 1-Chloro-2,4-Dinitrobenzene-Treated NC/Nga Mice.

Nutrients 2020 Jan 7;12(1). Epub 2020 Jan 7.

Institute of Traditional Medicine & Bioscience, Daejeon University, Daejeon 34520, Korea.

Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. In this study, we evaluated the effects of a mixture (NCM 1921) of omega-3 butter, omega-3 beef tallow oil, omega-3 lard oil, caprylic acid, lauric acid, choline, and Fe on AD in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. NCM 1921 significantly ameliorated the macroscopic and microscopic signs and reduced skin thickness and mast cell incorporation in the skin lesions of mice with DNCB-induced AD. Furthermore, it reduced serum immunoglobulin E levels; reduced the number of IgE-producing B cells, peripheral blood mononuclear cells, white blood cells, and differential white blood cells; and increased the number of lymphocytes. NCM 1921 normalized the total cell number in dorsal skin tissue, the axillary lymph node, and spleen following DNCB exposure and reduced the number of CD23+/B220+ cells in the axillary lymph node and CD3+ cells in dorsal skin tissue. Moreover, it reduced the levels of interleukin (IL)-4 and IL-13 but increased the levels of interferon-γ in anti-CD3-stimulated splenocytes. Immunohistofluorescence staining showed that NCM 1921 treatment significantly increased claudin1, filaggrin, and Sirt1 protein expressions in AD skin lesions. These results suggest that NCM 1921 could be a valuable remedy for the treatment of AD.
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http://dx.doi.org/10.3390/nu12010165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019988PMC
January 2020

α-Linolenic acid-enriched butter attenuated high fat diet-induced insulin resistance and inflammation by promoting bioconversion of n-3 PUFA and subsequent oxylipin formation.

J Nutr Biochem 2020 02 12;76:108285. Epub 2019 Nov 12.

Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE. Electronic address:

α-Linolenic acid (ALA) is an essential fatty acid and the precursor for long-chain n-3 PUFA. However, biosynthesis of n-3 PUFA is limited in a Western diet likely due to an overabundance of n-6 PUFA. We hypothesized that dietary reduction of n-6/n-3 PUFA ratio is sufficient to promote the biosynthesis of long-chain n-3 PUFA, leading to an attenuation of high fat (HF) diet-induced obesity and inflammation. C57BL/6 J mice were fed a HF diet from ALA-enriched butter (n3Bu, n-6/n-3=1) in comparison with isocaloric HF diets from either conventional butter lacking both ALA and LA (Bu, n-6/n-3=6), or margarine containing a similar amount of ALA and abundant LA (Ma, n-6/n-3=6). Targeted lipidomic analyses revealed that n3Bu feeding promoted the bioconversion of long-chain n-3 PUFA and their oxygenated metabolites (oxylipins) derived from ALA and EPA. The n3Bu supplementation attenuated hepatic TG accumulation and adipose tissue inflammation, resulting in improved insulin sensitivity. Decreased inflammation by n3Bu feeding was attributed to the suppression of NF-κB activation and M1 macrophage polarization. Collectively, our work suggests that dietary reduction of the n-6/n-3 PUFA ratio, as well as total n-3 PUFA consumed, is a crucial determinant that facilitates n-3 PUFA biosynthesis and subsequent lipidomic modifications, thereby conferring metabolic benefits against obesity-induced inflammation and insulin resistance.
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http://dx.doi.org/10.1016/j.jnutbio.2019.108285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995772PMC
February 2020

A generation process for a three-dimensional digital cast that simulates the oral cavity by using an existing maxillary obturator.

J Prosthet Dent 2020 Mar 12;123(3):531-534. Epub 2019 Jul 12.

Associate Professor, Department of Prosthodontics, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address:

To simulate the current oral status of patients, including maxillofacial defects, the digital method described uses a method based on multisource data. These include data recorded from scans made with and without wearing an obturator and data obtained by scanning the surgical or interim obturator. This method eliminates the need for preliminary impressions and complex border-molding steps during the process of creating a definitive obturator, thereby greatly simplifying the fabrication process.
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http://dx.doi.org/10.1016/j.prosdent.2019.01.015DOI Listing
March 2020

Inhibition of LTA4H by bestatin in human and mouse colorectal cancer.

EBioMedicine 2019 Jun 10;44:361-374. Epub 2019 May 10.

The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of America; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China. Electronic address:

Background: Our preclinical data showed that the leukotriene A4 hydrolase (LTA4H) pathway plays a role in colorectal cancer (CRC). High expression of LTA4H and leukotriene B4 receptor type 1 (BLT1) were also associated with CRC survival probability. Clinical samples were evaluated to determine whether LTA4H could serve as a therapeutic target and whether leukotriene B4 (LTB4) could be used as a biomarker for evaluating the efficacy of bestatin in CRC.

Methods: Patients with Stage I-III CRC did or did not receive bestatin prior to surgery. Evaluable pairwise CRC patient blood samples were collected to evaluate LTB4 concentration. Tissues were processed by immunohistochemistry to detect the LTA4H pathway and Ki-67 expression. We also determined whether LTA4H or BLT1 was associated with CRC survival probability and explored the mechanism of bestatin action in CRC.

Findings: Samples from 13 CRC patients showed a significant decrease in LTB4, the LTA4H signaling pathway, and Ki-67 in the bestatin-treated group compared with the untreated group. LTA4H and BLT1 are overexpressed in CRC and associated with CRC survival probability. Bestatin effectively inhibited LTB4 and tumorigenesis in the Apc and CRC patient-derived xenograft mouse model.

Interpretation: These results demonstrate that LTB4 could serve as a biomarker for evaluating bestatin efficacy in CRC and the antitumor effects of bestatin through its targeting of LTA4H and support further studies focusing on LTA4H inhibition in CRC.
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http://dx.doi.org/10.1016/j.ebiom.2019.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604047PMC
June 2019

Performance evaluation of commercial library construction kits for PCR-based targeted sequencing using a unique molecular identifier.

BMC Genomics 2019 Mar 14;20(1):216. Epub 2019 Mar 14.

Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, South Korea.

Background: Target enrichment is a critical component of targeted deep next-generation sequencing for the cost-effective and sensitive detection of mutations, which is predominantly performed by either hybrid selection or PCR. Despite the advantages of efficient enrichment, PCR-based methods preclude the identification of PCR duplicates and their subsequent removal. Recently, this limitation was overcome by assigning a unique molecular identifier(UMI) to each template molecule. Currently, several commercial library construction kits based on PCR enrichment are available for UMIs, but there have been no systematic studies to compare their performances. In this study, we evaluated and compared the performances of five commercial library kits from four vendors: the Archer® Reveal ctDNA™ 28 Kit, NEBNext Direct® Cancer HotSpot Panel, Nugen Ovation® Custom Target Enrichment System, Qiagen Human Comprehensive Cancer Panel(HCCP), and Qiagen Human Actionable Solid Tumor Panel(HASTP).

Results: We evaluated and compared the performances of the five kits using 50 ng of genomic DNA for the library construction in terms of the library complexity, coverage uniformity, and errors in the UMIs. While the duplicate rates for all kits were dramatically decreased by identifying unique molecules with UMIs, the Qiagen HASTP achieved the highest library complexity based on the depth of unique coverage indicating superb library construction efficiency. Regarding the coverage uniformity, the kits from Nugen and NEB performed the best followed by the kits from Qiagen. We also analyzed the UMIs, including errors, which allowed us to adjust the depth of unique coverage and the length required for sufficient complexity. Based on these comparisons, we selected the Qiagen HASTP for further performance evaluations. The targeted deep sequencing method based on PCR target enrichment combined with UMI tagging sensitively detected mutations present at a frequency as low as 1% using 6.25 ng of human genomic DNA as the starting material.

Conclusion: This study is the first systematic evaluation of commercial library construction kits for PCR-based targeted deep sequencing utilizing UMIs. Because the kits displayed significant variability in different quality metrics, our study offers a practical guideline for researchers to choose appropriate options for PCR-based targeted sequencing and useful benchmark data for evaluating new kits.
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http://dx.doi.org/10.1186/s12864-019-5583-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416880PMC
March 2019

Analysis of circulating tumor DNA by targeted ultra-deep sequencing across various non-Hodgkin lymphoma subtypes.

Leuk Lymphoma 2019 09 18;60(9):2237-2246. Epub 2019 Feb 18.

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

Although targeted deep sequencing of cell-free DNA (cfDNA) was recently used to investigate tumor somatic mutations in particular subtypes of non-Hodgkin lymphomas (NHLs), the immense genetic heterogeneity across subtypes poses a hurdle to design a universal gene panel applicable for diverse subtypes of NHLs. We designed a panel targeting 66 genes associated with NHLs and performed targeted deep sequencing to analyze plasma cfDNA from patients with various subtypes of NHLs. Genetic profiling in plasma cfDNA using the method resulted in 88.0% sensitivity and >99% specificity in detecting mutations present at a frequency greater than 20% in the tumor biopsies. Furthermore, the level of ctDNA significantly decreased and increased depending on designated clinical responses to therapy and disease progression. These results demonstrated that ctDNA sensitively indicated the presence of cancer and reliably correlated with tumor burden, suggesting potential utility of the method for patients with various subtypes of NHLs.
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http://dx.doi.org/10.1080/10428194.2019.1573998DOI Listing
September 2019

Can an average of thresholds at 2 kHz and 4 kHz substitute for the threshold at 3 kHz in pure tone audiometry? A study based on the Korean National Health and Nutrition Examination Survey 2010-2012.

PLoS One 2018 7;13(8):e0201867. Epub 2018 Aug 7.

Department of Otorhinolaryngology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.

Background: When evaluating hearing disability in medicolegal cases, an average of thresholds at several frequencies is calculated using pure tone audiometry. Occasionally, there are instances in which thresholds at certain frequencies are omitted. One typical example is the threshold at 3 kHz (H3k). The American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium (1995) suggested that the average of thresholds at 2 kHz and 4 kHz (H24k) could replace H3k for a comparison of results between studies. However, to the best of our knowledge, there is no report in the literature that compares H3k and H24k.

Objective: This study aimed to investigate the agreement between H3k and H24k.

Methods: This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012, which was conducted by the Korean government. A total of 18,472 participants (unweighted) who represented 39,357,497 Koreans (weighted) were included. To verify the agreement of H3k and H24k, a paired t-test, Cohen's d, Pearson's correlation, Cronbach's coefficient, intraclass correlation coefficient (ICC), a Bland-Altman plot, and linear regression analysis were used.

Results: The means of H3k and H24k were 16.2 dBHL and 16.6 dBHL, respectively. They were significantly different in a paired t-test (p<0.0001), which resulted from the large sample size. In contrast, the effect size (Cohen's d) was 0.02, which meant that the two groups nearly overlapped. The means showed strong correlation: Pearson's correlation coefficient = 0.92, Cronbach's alpha = 0.96, and ICC = 0.92. A strong linear predictive relationship between H3k and H24k was found: y = -0.6821 + 1.0186x, where x = H24k, y = H3k, and p<0.0001. However, the Bland-Altman plot showed large upper and lower limits of agreement (LOA) of 15.0 dBHL and -15.8 dBHL, respectively. Irrespective of age and degree of the four-tone average (0.5, 1, 2, and 3 kHz) hearing loss or thresholds at 2 kHz, 3 kHz, and 4 kHz, the absolute LOAs were greater than 10 dBHL.

Conclusions: Despite a very strong correlation between the two thresholds, H3k and H24k showed clinically large LOAs. Therefore, it would be improper to substitute H24k for H3k in an individual requesting a hearing disability rating. However, since the overall means of the H3k and H24k samples were nearly equal, H24k can replace H3k for a mean comparison of results between studies. This result supports the 1995 Committee on Hearing and Equilibrium guideline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201867PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080789PMC
February 2019
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