Publications by authors named "Jeon Lee"

70 Publications

Assessing outcomes of ear molding therapy by health care providers and convolutional neural network.

Sci Rep 2021 09 9;11(1):17875. Epub 2021 Sep 9.

Department of Plastic Surgery, UT Southwestern, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.

Ear molding therapy is a nonsurgical technique to correct certain congenital auricular deformities. While the advantages of nonsurgical treatments over otoplasty are well-described, few studies have assessed aesthetic outcomes. In this study, we compared assessments of outcomes of ear molding therapy for 283 ears by experienced healthcare providers and a previously developed deep learning CNN model. 2D photographs of ears were obtained as a standard of care in our onsite photography studio. Physician assistants (PAs) rated the photographs using a 5-point Likert scale ranging from 1(poor) to 5(excellent) and the CNN assessment was categorical, classifying each photo as either "normal" or "deformed". On average, the PAs classified 75.6% of photographs as good to excellent outcomes (scores 4 and 5). Similarly, the CNN classified 75.3% of the photographs as normal. The inter-rater agreement between the PAs ranged between 72 and 81%, while there was a 69.6% agreement between the machine model and the inter-rater majority agreement between at least two PAs (i.e., when at least two PAs gave a simultaneous score < 4 or ≥ 4). This study shows that noninvasive ear molding therapy has excellent outcomes in general. In addition, it indicates that with further training and validation, machine learning techniques, like CNN, have the capability to accurately mimic provider assessment while removing the subjectivity of human evaluation making it a robust tool for ear deformity identification and outcome evaluation.
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http://dx.doi.org/10.1038/s41598-021-97310-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429730PMC
September 2021

The Drosophila ribosome protein S5 paralog RpS5b promotes germ cell and follicle cell differentiation during oogenesis.

Development 2021 10 4;148(19). Epub 2021 Oct 4.

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Emerging evidence suggests that ribosome heterogeneity may have important functional consequences in the translation of specific mRNAs within different cell types and under various conditions. Ribosome heterogeneity comes in many forms, including post-translational modification of ribosome proteins (RPs), absence of specific RPs and inclusion of different RP paralogs. The Drosophila genome encodes two RpS5 paralogs: RpS5a and RpS5b. While RpS5a is ubiquitously expressed, RpS5b exhibits enriched expression in the reproductive system. Deletion of RpS5b results in female sterility marked by developmental arrest of egg chambers at stages 7-8, disruption of vitellogenesis and posterior follicle cell (PFC) hyperplasia. While transgenic rescue experiments suggest functional redundancy between RpS5a and RpS5b, molecular, biochemical and ribo-seq experiments indicate that RpS5b mutants display increased rRNA transcription and RP production, accompanied by increased protein synthesis. Loss of RpS5b results in microtubule-based defects and in mislocalization of Delta and Mindbomb1, leading to failure of Notch pathway activation in PFCs. Together, our results indicate that germ cell-specific expression of RpS5b promotes proper egg chamber development by ensuring the homeostasis of functional ribosomes.
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http://dx.doi.org/10.1242/dev.199511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513607PMC
October 2021

Cerebral Venous Thrombosis and Persistent Pulsatile Tinnitus After Sigmoid Sinus Resurfacing Surgery.

Ear Nose Throat J 2021 Aug 19:1455613211038269. Epub 2021 Aug 19.

Department of Otorhinolaryngology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.

We report a case with rare complication of cerebral venous thrombosis, as well as an incomplete response, after sigmoid sinus resurfacing surgery for pulsatile tinnitus (PT). A 24-year-old female patient with PT originating from the sigmoid sinus underwent sigmoid sinus resurfacing surgery. The tinnitus was immediately resolved, but it recurred with headache 5 days after surgery. A cerebral venous thrombosis was identified and treated, but PT persisted, although its frequency and loudness decreased. Sigmoid sinus resurfacing surgery is a safe and effective method to treat PT, but in some patients, it can cause serious complications and/or persistent tinnitus. In our patient, factors such as changes in blood viscosity due to warfarin intake or increased blood flow due to weight loss may have influenced the persistence of the tinnitus. It is important to identify the various associated factors and the weight of each of these factors to provide more tailored treatment of PT for individual patients in the future and to reduce complications and increase the effectiveness of sigmoid sinus resurfacing surgery.
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http://dx.doi.org/10.1177/01455613211038269DOI Listing
August 2021

Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer.

Cell Rep 2021 Aug;36(5):109491

Department of Medicine, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA; UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA. Electronic address:

The exocyst is an evolutionarily conserved protein complex that regulates vesicular trafficking and scaffolds signal transduction. Key upstream components of the exocyst include monomeric RAL GTPases, which help mount cell-autonomous responses to trophic and immunogenic signals. Here, we present a quantitative proteomics-based characterization of dynamic and signal-dependent exocyst protein interactomes. Under viral infection, an Exo84 exocyst subcomplex assembles the immune kinase Protein Kinase R (PKR) together with the Hippo kinase Macrophage Stimulating 1 (MST1). PKR phosphorylates MST1 to activate Hippo signaling and inactivate Yes Associated Protein 1 (YAP1). By contrast, a Sec5 exocyst subcomplex recruits another immune kinase, TANK binding kinase 1 (TBK1), which interacted with and activated mammalian target of rapamycin (mTOR). RALB was necessary and sufficient for induction of Hippo and mTOR signaling through parallel exocyst subcomplex engagement, supporting the cellular response to virus infection and oncogenic signaling. This study highlights RALB-exocyst signaling subcomplexes as mechanisms for the integrated engagement of Hippo and mTOR signaling in cells challenged by viral pathogens or oncogenic signaling.
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http://dx.doi.org/10.1016/j.celrep.2021.109491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383154PMC
August 2021

Characterization of Primary Muscle Tension Dysphonia Using Acoustic and Aerodynamic Voice Metrics.

J Voice 2021 Jul 16. Epub 2021 Jul 16.

Department of Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, New York.

Objectives/hypothesis: The objectives of this study were to (1) identify optimal clusters of 15 standard acoustic and aerodynamic voice metrics recommended by the American Speech-Language-Hearing Association (ASHA) to improve characterization of patients with primary muscle tension dysphonia (pMTD) and (2) identify combinations of these 15 metrics that could differentiate pMTD from other types of voice disorders.

Study Design: Retrospective multiparametric METHODS: Random forest modeling, independent t-tests, logistic regression, and affinity propagation clustering were implemented on a retrospective dataset of 15 acoustic and aerodynamic metrics.

Results: Ten percent of patients seen at the New York University (NYU) Voice Center over two years met the study criteria for pMTD (92 out of 983 patients), with 65 patients with pMTD and 701 of non-pMTD patients with complete data across all 15 acoustic and aerodynamic voice metrics. PCA plots and affinity propagation clustering demonstrated substantial overlap between the two groups on these parameters. The highest ranked parameters by level of importance with random forest models-(1) mean airflow during voicing (L/sec), (2) mean SPL during voicing (dB), (3) mean peak air pressure (cmH2O), (4) highest F0 (Hz), and (5) CPP mean vowel (dB)-accounted for only 65% of variance. T-tests showed three of these parameters-(1) CPP mean vowel (dB), (2) highest F0 (Hz), and (3) mean peak air pressure (cmH2O)-were statistically significant; however, the log2-fold change for each parameter was minimal.

Conclusion: Computational models and multivariate statistical testing on 15 acoustic and aerodynamic voice metrics were unable to adequately characterize pMTD and determine differences between the two groups (pMTD and non-pMTD). Further validation of these metrics is needed with voice elicitation tasks that target physiological challenges to the vocal system from baseline vocal acoustic and aerodynamic ouput. Future work should also place greater focus on validating metrics of physiological correlates (eg, neuromuscular processes, laryngeal-respiratory kinematics) across the vocal subsystems over traditional vocal output measures (eg, acoustics, aerodynamics) for patients with pMTD.

Level Of Evidence: II.
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http://dx.doi.org/10.1016/j.jvoice.2021.05.019DOI Listing
July 2021

Concerns and breakthroughs of combining ionic liquids with microwave irradiation for the synthesis of Ru nanoparticles via decarbonylation.

J Colloid Interface Sci 2021 Oct 20;599:828-836. Epub 2021 Apr 20.

Smart Energy and Nano Photonics R&D Group, Korea Institute of Industrial Technology (KITECH), Gwangju 61012, South Korea. Electronic address:

Hypothesis: Combination of microwave irradiation (MWI) and ionic liquids (IL) is widely used for the synthesis of nanoparticles (NP) via decarbonylation of zero-valent metal carbonyl precursors. However, we carefully raise a question as to whether this combination is always beneficial. Upon MWI, highly-absorbing materials such as ILs would be subject to local intense heating, likely resulting in the occurrence of localized chemical decomposition. The decomposition is expected to influence the growth mechanism of NPs due to changes in the electrostatic and steric effects. If the assumption is valid, it should be possible to decompose IL and destabilize the NPs by modifying the amplitude of the incident microwaves. In other words, it should also be possible to control the particle aggregation by circumventing the decomposition of the IL.

Experiments: A series of comparative studies were conducted using a model system (i.e. [BMIm][BF] and Ru(CO)). Variables were systematically controlled. After MWI, the decrease in colloidal stability of NPs was identified.

Findings: In the formation of Ru NPs via decarbonylation, the association between incident microwave intensity, chemical decomposition of IL, and initiation of particle aggregation has been demonstrated. Conditions that can accelerate or alleviate the decomposition and the aggregation are also corroborated.
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http://dx.doi.org/10.1016/j.jcis.2021.04.046DOI Listing
October 2021

Occult parotid involvement in early-stage squamous cell carcinoma of the external auditory canal.

Head Neck 2021 09 3;43(9):2655-2662. Epub 2021 May 3.

Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, South Korea.

Background: The importance of elective parotidectomy in early-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) is not well established.

Methods: A retrospective study of 43 patients with early-stage SCC of the EAC who underwent parotidectomy in conjunction with lateral temporal bone resection at three centers.

Results: Overall occult parotid involvement (OPI) rate in early-stage SCC of the EAC was 13.9% (6/43). When considering both the anteroposterior position and the bony-cartilaginous position, patients with SCC in both the anterior wall and cartilaginous portion exhibited significantly higher OPI than other locations (37.5% vs. 0%, p = 0.001), with an increase in the OPI predictive value.

Conclusion: SCC located in either the anterior wall of the EAC or the cartilaginous portion of the EAC or both simultaneously showed a high prevalence of OPI, and elective parotidectomy should be considered in those patients.
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http://dx.doi.org/10.1002/hed.26729DOI Listing
September 2021

Auditory experience, for a certain duration, is a prerequisite for tinnitus: lessons from subjects with unilateral tinnitus in the better-hearing ear.

Prog Brain Res 2021 14;260:223-233. Epub 2020 Aug 14.

Department of Otorhinolaryngology, Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

Tinnitus has traditionally been considered an otologic disorder; however, recent advances in auditory neuroscience have shifted investigations toward the brain. The Bayesian brain model explains tinnitus as an auditory phantom percept. According to the model, the brain works to reduce environmental uncertainty, and thus the absence of auditory information due to hearing loss may cause auditory phantom percepts, i.e., tinnitus. As in animal studies, our recent human observational study revealed the absence of ipsilesional tinnitus in subjects with congenital single-sided deafness, suggesting that auditory experience is a prerequisite for the generation of tinnitus. Prompted by anecdotal cases, we hypothesized that subjects with acquired hearing loss would not develop tinnitus if their duration of auditory experience was not sufficiently long. We retrospectively enrolled 22 subjects with acquired asymmetric hearing loss and unilateral tinnitus in better ear (TBE). Twenty-two hearing threshold-matched controls with tinnitus in worse ear (TWE) were selected from our database of tinnitus patients. All 22 TBE subjects reported that their acquired hearing loss developed before the age of 20, and the reported duration of auditory deprivation in the ear without tinnitus in the TBE group was significantly longer than that of the TWE group. In other words, the TBE group with limited auditory experience in the worse ear did not develop tinnitus in the worse ear while subjects with enough auditory experiences in the worse ear developed ipsilesional tinnitus in the TWE group. These preliminary results support our hypothesis that both auditory experience itself, and an individually variable critical duration of auditory deprivation, are prerequisites for the generation of tinnitus.
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http://dx.doi.org/10.1016/bs.pbr.2020.07.013DOI Listing
November 2021

Blood biomarker discovery for autism spectrum disorder: A proteomic analysis.

PLoS One 2021 24;16(2):e0246581. Epub 2021 Feb 24.

Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States of America.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Given the lack of specific pharmacological therapy for ASD and the clinical heterogeneity of the disorder, current biomarker research efforts are geared mainly toward identifying markers for determining ASD risk or for assisting with a diagnosis. A wide range of putative biological markers for ASD is currently being investigated. Proteomic analyses indicate that the levels of many proteins in plasma/serum are altered in ASD, suggesting that a panel of proteins may provide a blood biomarker for ASD. Serum samples from 76 boys with ASD and 78 typically developing (TD) boys, 18 months-8 years of age, were analyzed to identify possible early biological markers for ASD. Proteomic analysis of serum was performed using SomaLogic's SOMAScanTM assay 1.3K platform. A total of 1,125 proteins were analyzed. There were 86 downregulated proteins and 52 upregulated proteins in ASD (FDR < 0.05). Combining three different algorithms, we found a panel of 9 proteins that identified ASD with an area under the curve (AUC) = 0.8599±0.0640, with specificity and sensitivity of 0.8217±0.1178 and 0.835±0.1176, respectively. All 9 proteins were significantly different in ASD compared with TD boys, and were significantly correlated with ASD severity as measured by ADOS total scores. Using machine learning methods, a panel of serum proteins was identified that may be useful as a blood biomarker for ASD in boys. Further verification of the protein biomarker panel with independent test sets is warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246581PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904196PMC
July 2021

The Effects of Preoperative Audiovisual Speech Perception on the Audiologic Outcomes of Cochlear Implantation in Patients with Postlingual Deafness.

Audiol Neurootol 2021 22;26(3):149-156. Epub 2020 Dec 22.

Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea,

Introduction: Patients with postlingual deafness usually depend on visual information for communication, and their lipreading ability could influence cochlear implantation (CI) outcomes. However, it is unclear whether preoperative visual dependency in postlingual deafness positively or negatively affects auditory rehabilitation after CI. Herein, we investigated the influence of preoperative audiovisual per-ception on CI outcomes.

Method: In this retrospective case-comparison study, 118 patients with postlingual deafness who underwent unilateral CI were enrolled. Evaluation of speech perception was performed under both audiovisual (AV) and audio-only (AO) conditions before and after CI. Before CI, the speech perception test was performed under hearing aid (HA)-assisted conditions. After CI, the speech perception test was performed under the CI-only condition. Only patients with a 10% or less preoperative AO speech perception score were included.

Results: Multivariable regression analysis showed that age, gender, residual hearing, operation side, education level, and HA usage were not correlated with either postoperative AV (pAV) or AO (pAO) speech perception. However, duration of deafness showed a significant negative correlation with both pAO (p = 0.003) and pAV (p = 0.015) speech perceptions. Notably, the preoperative AV speech perception score was not correlated with pAO speech perception (R2 = 0.00134, p = 0.693) but was positively associated with pAV speech perception (R2 = 0.0731, p = 0.003).

Conclusion: Preoperative dependency on audiovisual information may positively influence pAV speech perception in patients with postlingual deafness.
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http://dx.doi.org/10.1159/000509969DOI Listing
July 2021

Functional characterization of 67 endocytic accessory proteins using multiparametric quantitative analysis of CCP dynamics.

Proc Natl Acad Sci U S A 2020 12 30;117(50):31591-31602. Epub 2020 Nov 30.

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;

Clathrin-mediated endocytosis (CME) begins with the nucleation of clathrin assembly on the plasma membrane, followed by stabilization and growth/maturation of clathrin-coated pits (CCPs) that eventually pinch off and internalize as clathrin-coated vesicles. This highly regulated process involves a myriad of endocytic accessory proteins (EAPs), many of which are multidomain proteins that encode a wide range of biochemical activities. Although domain-specific activities of EAPs have been extensively studied, their precise stage-specific functions have been identified in only a few cases. Using single-guide RNA (sgRNA)/dCas9 and small interfering RNA (siRNA)-mediated protein knockdown, combined with an image-based analysis pipeline, we have determined the phenotypic signature of 67 EAPs throughout the maturation process of CCPs. Based on these data, we show that EAPs can be partitioned into phenotypic clusters, which differentially affect CCP maturation and dynamics. Importantly, these clusters do not correlate with functional modules based on biochemical activities. Furthermore, we discover a critical role for SNARE proteins and their adaptors during early stages of CCP nucleation and stabilization and highlight the importance of GAK throughout CCP maturation that is consistent with GAK's multifunctional domain architecture. Together, these findings provide systematic, mechanistic insights into the plasticity and robustness of CME.
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http://dx.doi.org/10.1073/pnas.2020346117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749282PMC
December 2020

Hearing Rehabilitation with Combined Electroacoustic Stimulation and Ossiculoplasty.

J Audiol Otol 2021 Apr 16;25(2):110-114. Epub 2020 Nov 16.

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

We report a case of hearing rehabilitation following combined cochlear implantation and ossiculoplasty. A 71-year-old patient visited the clinic for right-sided mixed hearing loss. We targeted neural and conductive components, performing two different operations simultaneously. At two months post-operative, the patient showed satisfactory results with respect to hearing threshold and speech comprehension. Our experience suggests that careful evaluation of patients and consideration of the diverse array of available treatment strategies can be used to provide personalized rehabilitation with maximal effectiveness. To the best of our knowledge, this is the first report to take such an integrated approach to treat hearing impairment and is thus likely to have clinical importance for otologists.
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http://dx.doi.org/10.7874/jao.2020.00136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062243PMC
April 2021

Automatic Facial Recognition System Assisted-facial Asymmetry Scale Using Facial Landmarks.

Otol Neurotol 2020 09;41(8):1140-1148

Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Republic of Korea.

Objectives: This study aimed to demonstrate the application of our automated facial recognition system to measure facial nerve function and compare its effectiveness with other conventional systems and provide a preliminary evaluation of deep learning-facial grading systems.

Study Design: Retrospective, observational.

Setting: Tertiary referral center, hospital.

Patients: Facial photos taken from 128 patients with facial paralysis and two persons with no history of facial palsy were analyzed.

Intervention: Diagnostic.

Main Outcome Measures: Correlation with Sunnybrook (SB) and House-Brackmann (HB) grading scales.

Results: Our results had good reliability and correlation with other grading systems (r = 0.905 and 0.783 for Sunnybrook and HB grading scales, respectively), while being less time-consuming than Sunnybrook grading scale.

Conclusions: Our objective method shows good correlation with both Sunnybrook and HB grading systems. Furthermore, this system could be developed into an application for use with a variety of electronic devices, including smartphones and tablets.
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http://dx.doi.org/10.1097/MAO.0000000000002735DOI Listing
September 2020

Effect of Cochlear Implantation on Hearing Fluctuation in Patients with Biallelic SLC26A4 Variants.

Audiol Neurootol 2021 2;26(2):111-120. Epub 2020 Sep 2.

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

Introduction: Fluctuating hearing loss is a distinctive feature caused by SLC26A4 variants. We investigated whether cochlear implantation had protective or deleterious effect on hearing fluctuation in patients with biallelic SLC26A4 variants.

Methods: Patients with biallelic SLC26A4 variants (N = 16; age = 10.24 ± 9.20 years) who had unilateral cochlear implantation and consecutive postsurgical, bilateral pure-tone audiograms more than 3 times were selected. We retrospectively reviewed the patients' medical records from 2008 to 2019 obtained from a tertiary medical center and used the auditory threshold change (Shift) over time as a marker of hearing fluctuation. Fluctuation events were counted, and the Shift of the implanted and contralateral ears was compared using logistic regression with a generalized estimating equation and linear mixed model. A total of 178 values were included.

Results: The odds of fluctuating hearing frequency were 11.185-fold higher in the unimplanted ears than in the implanted ears postoperatively (p = 0.001). The extent of fluctuation at 250 and 500 Hz was also significantly lower in the implanted ears than in the unimplanted ears after adjusting for every other effect (p = 0.003 and p < 0.001, respectively). Notably, higher residual hearing was rather associated with lesser fluctuation in frequency and the extent of fluctuation at 500 Hz, indicating residual hearing function is not the positive predictor for hearing fluctuation.

Conclusion: In patients with biallelic SLC26A4 variants, cochlear implantation may reduce the frequency and extent of hearing fluctuations.
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http://dx.doi.org/10.1159/000508858DOI Listing
June 2021

Neural Networks to Predict Radiographic Brain Injury in Pediatric Patients Treated with Extracorporeal Membrane Oxygenation.

J Clin Med 2020 Aug 22;9(9). Epub 2020 Aug 22.

Children's Health Dallas, Dallas, TX 75201, USA.

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model's performance. These findings lay the foundation for further areas of research directions.
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http://dx.doi.org/10.3390/jcm9092718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565544PMC
August 2020

Effects of Vibrant Soundbridge on tinnitus accompanied by sensorineural hearing loss.

PLoS One 2020 4;15(2):e0228498. Epub 2020 Feb 4.

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

Objectives: Tinnitus is a common symptom among patients with hearing loss, and many studies have reported successful tinnitus suppression with hearing devices. Active middle ear implantation of the Vibrant Soundbridge (VSB) is a good alternative to existing hearing devices. This study evaluated the effects of VSB implantation on tinnitus and sought to identify the main audiological factor that affects tinnitus suppression.

Methods: The study participants were 16 adults who had tinnitus with sensorineural hearing loss, and who underwent VSB implantations. Pure-tone audiometry; word recognition test; tinnitus handicap inventory (THI); and visual analog scale (VAS) assessment of loudness, awareness, and annoyance were performed before and 12 months after surgery. Changes in hearing threshold, word recognition scores (WRS), THI scores, and VAS scores were analyzed.

Results: VAS scores for loudness (mean difference: 1.9, 95% CI: 0.6, 3.1), awareness (mean difference: 1.6, 95% CI: 0.4, 2.8), and annoyance (mean difference: 1.7, 95% CI: 0.7, 2.8) showed significant improvements from baseline to 12 months after surgery. In addition, THI scores showed a significant decrease (mean difference: 13.8, 95% CI: 2.9, 24.9). The average hearing threshold level, WRS, and most comfortable level (MCL) also showed significant improvements at 12 months after surgery (mean difference: 17.3, 95% CI: 13.3, 21.3; mean difference: -7.6, 95% CI: -15.1, -0.1; mean difference: 26.3, 95% CI: 22.9, 29.6, respectively). Among the aforementioned factors, changes in MCL were best correlated with those in THI scores (mean difference: 2.55, 95% CI: 0.90, 4.21).

Conclusion: A VSB implant is beneficial to subjects with tinnitus accompanied by sensorineural hearing loss. The changes in THI scores best correlated with those in MCL. This improvement may represent a masking effect that contributes to tinnitus suppression in patients with VSB implants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228498PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999863PMC
April 2020

Identifying Ear Abnormality from 2D Photographs Using Convolutional Neural Networks.

Sci Rep 2019 12 3;9(1):18198. Epub 2019 Dec 3.

Department of Plastic Surgery, UT Southwestern, 5323 Harry Hines Blvd., Dallas, TX, 75390, United States.

Quantifying ear deformity using linear measurements and mathematical modeling is difficult due to the ear's complex shape. Machine learning techniques, such as convolutional neural networks (CNNs), are well-suited for this role. CNNs are deep learning methods capable of finding complex patterns from medical images, automatically building solution models capable of machine diagnosis. In this study, we applied CNN to automatically identify ear deformity from 2D photographs. Institutional review board (IRB) approval was obtained for this retrospective study to train and test the CNNs. Photographs of patients with and without ear deformity were obtained as standard of care in our photography studio. Profile photographs were obtained for one or both ears. A total of 671 profile pictures were used in this study including: 457 photographs of patients with ear deformity and 214 photographs of patients with normal ears. Photographs were cropped to the ear boundary and randomly divided into training (60%), validation (20%), and testing (20%) datasets. We modified the softmax classifier in the last layer in GoogLeNet, a deep CNN, to generate an ear deformity detection model in Matlab. All images were deemed of high quality and usable for training and testing. It took about 2 hours to train the system and the training accuracy reached almost 100%. The test accuracy was about 94.1%. We demonstrate that deep learning has a great potential in identifying ear deformity. These machine learning techniques hold the promise in being used in the future to evaluate treatment outcomes.
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http://dx.doi.org/10.1038/s41598-019-54779-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890688PMC
December 2019

Temporomandibular Joint Herniation: Review of the Literature.

Otol Neurotol 2020 01;41(1):e1-e6

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

Objective: To define clear clinical characteristics and management strategies of herniation of temporomandibular joint (TMJ) into the external auditory canal (EAC).

Data Source: MEDLINE, PubMed, and EMBASE databases.

Study Selection: A search was conducted using the keywords "temporomandibular joint" and "herniation" with all of their synonyms. Literature selection criteria included articles published in English, and articles dating back no further than 1970.

Results: Forty articles regarding 51 cases were eligible for critical appraisal. According to the previously published papers, TMJ herniation has following characteristics; symptoms are nonspecific, but a distinguishable feature is a protruding mass into the EAC that can be seen to appear and disappear as the mouth opens and closes. High-resolution computed tomography scans are sensitive to the bony defect and are helpful in diagnosing TMJ herniation. In the surgical treatment of TMJ herniation, wall reconstruction rather than simple mass excision could be a safe and long-lasting strategy.

Conclusions: Herniation of TMJ into the EAC is a rare condition, but can be encountered in the clinic at any time. This literature review could be helpful in the diagnosis and treatment of TMJ herniation into the EAC.
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http://dx.doi.org/10.1097/MAO.0000000000002459DOI Listing
January 2020

Is Early Progression to Bilateral Involvement in Menière's Disease a Poor Prognostic Indicator?

Otol Neurotol 2019 12;40(10):1333-1338

Department of Otorhinolaryngology, Yonsei University College of Medicine.

Objective: To investigate differences in the clinical features of bilateral Menière's disease (BMD) with early and late bilateral involvement.

Study Design: A retrospective case-comparison study.

Setting: Tertiary referral center.

Patients: In total, 25 patients with definite BMD were enrolled. Patients with bilateral involvement with a transition interval shorter than 1 month were considered to have synchronous BMD, whereas the others had metachronous BMD.

Interventions: We investigated differences in prognosis as defined by changes in the number of vertigo attacks after treatment, demographics, comorbidities, and inner ear function according to the transition interval from unilateral to bilateral involvement.

Main Outcome Measure: We investigated other appropriate cut-off values in the interval from first- to second-ear involvement to predict poor prognosis.

Results: Receiver operating characteristic curve analysis revealed that a cut-off value of < 18-month interval exhibited maximum sensitivity and specificity for predicting poor prognosis. According to this value, we categorized patients into the early bilateral involvement group (EBIG, < 18 months' interval) and the late bilateral involvement group (LBIG, ≥ 18 months' interval). Patients with synchronous BMD and patients in the EBIG group exhibited poorer prognosis compared with patients with metachronous BMD and those in LBIG (p = 0.011 and p ≤ 0.001). Demographics, hearing threshold, vestibular deficit, and comorbidities were not significantly different between the two groups (p > 0.05). None of the patients exhibited systemic autoimmune disease.

Conclusion: BMD with early bilateral progression exhibited poorer prognosis compared with late bilateral progression.
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http://dx.doi.org/10.1097/MAO.0000000000002368DOI Listing
December 2019

Lessons From an Analysis of Newborn Hearing Screening Data for Children With Cochlear Implants.

Otol Neurotol 2019 10;40(9):e909-e917

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

Objectives: The aims of the study are to identify the limitations of the current newborn hearing screening (NHS) programs and provide recommendations for better protocols.

Study Design: Retrospective analysis.

Setting: Tertiary referral center.

Patients: The study participants were 185 children who received cochlear implants (CIs) at ≤5 years of age.

Interventions: Therapeutic and rehabilitative.

Main Outcome Measures: The results of NHS, screening tools used, age, and hearing thresholds at which hearing loss was confirmed, causes of the hearing loss, age of CI insertion, aided pure-tone audiogram findings, and language development level were analyzed.

Results: NHS data was available for 109 children, and 24 patients (22.0%) had passed NHS for both ears. Hearing loss was confirmed considerably later in children who had passed NHS than in children who were referred for further evaluation (p < 0.01). The most common cause for hearing loss in the NHS-pass group was SLC26A4 mutations (41.7%). Patients in the NHS-pass group received CIs considerably later than those in the NHS-referred group (p < 0.01). Among patients with SLC26A4 mutations, the language development level was significantly lower in the NHS-pass group than in the NHS-referred group (p < 0.01).

Conclusions: Careful counseling regarding NHS results is necessary for parents to understand that the absence of hearing loss at birth does not mean that the child will not develop hearing loss later in life. Genetic testing for SLC26A4 mutations may be necessary in regions with a high incidence of these mutations, such as East Asia.
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http://dx.doi.org/10.1097/MAO.0000000000002339DOI Listing
October 2019

Which Patients With a Unilateral Hearing Aid for Symmetric Sensorineural Hearing Loss Have Auditory Deprivation?

Clin Exp Otorhinolaryngol 2020 Feb 16;13(1):23-28. Epub 2019 Jul 16.

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

Objectives: The aim of study is to find conditions that aggravate auditory deprivation in patients with symmetric hearing loss after unilateral digital, non-linear hearing aid (HA).

Methods: In the retrospective case-comparison study, we assessed 47 patients with symmetric sensorineural hearing loss (SNHL), wearing unilateral conventional HAs. Audiological outcomes were assessed >1 year after HA fitting (mean duration, 31.0 months). Pure-tone audiometry in HA-aided and HA-unaided conditions was performed over time. Word recognition score (WRS) was evaluated at the most comfortable listening level.

Results: The initial pure tone average of four frequency thresholds at 500, 1,000, 2,000, and 4,000 Hz (PTA4) did not show a difference of >5 dB HL between HA-aided and HA-unaided ears. WRS progressively decreased for both HA-aided and HA-unaided ears although the extent of decrease was significantly greater for HA-unaided (7.6%) than for HA-aided ears (5.1%, P<0.05). Notably, auditory deprivation in HA-unaided ears was significantly greater in patients with an initial PTA4 ≥53 dB HL (P<0.001).

Conclusion: Bilateral HAs are strongly recommended, particularly for patients with moderate to severe SNHL to prevent auditory deprivation in the contralateral ear.
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http://dx.doi.org/10.21053/ceo.2019.00402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010494PMC
February 2020

Intratympanic Membrane Congenital Cholesteatoma Removal Using an Endoscopic System: A Case Report.

Ear Nose Throat J 2019 Apr-May;98(4):188-189. Epub 2019 Jan 28.

1 Department of Otorhinolaryngology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.

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http://dx.doi.org/10.1177/0145561318823319DOI Listing
December 2019

Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study.

Breast Cancer Res Treat 2019 Jul 24;176(2):419-427. Epub 2019 Apr 24.

Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, 25 Simgok-ro 100 beon-gil, Seo-gu, Incheon, 22711, Republic of Korea.

Purpose: Alongside the modern trend of delaying childbirth, the high incidence of breast cancer among young women is causing significant pregnancy-related problems in Korea. We estimated the incidence of childbirth for young Korean breast cancer survivors compared with women who did not have breast cancer using a nationally representative dataset.

Methods: Using a database from the National Health Insurance Service in South Korea, we analyzed 109,680 women who were between 20 and 40 years old between 2007 and 2013. They were prospectively followed, and childbirth events were recorded until December 31, 2015. We compared childbirth rates and characteristics between the breast cancer survivors and the noncancer controls.

Results: Compared to 10,164 childbirths among 91,400 women without breast cancer (incidence rate: 22.3/1000), 855 childbirths occurred among 18,280 breast cancer survivors (incidence rate: 9.4/1000); the adjusted hazard ratio (HR) for childbirth was 0.41 (95% CI 0.38-0.44). Chemotherapy, endocrine therapy, and target therapy were associated with the decreasing childbirths among survivors, with corresponding adjusted HRs of 0.61 (0.53-0.70), 0.44 (0.38-0.51), and 0.62 (0.45-0.86), respectively. Breast cancer survivors had a lower probability of full-term delivery and a higher frequency of preterm labor than controls, with corresponding adjusted ORs of 0.78 (0.68-0.90) and 1.33 (1.06-1.65), respectively.

Conclusions: We showed that a history of breast cancer has a negative effect on childbirth among young premenopausal women in Korea. Breast cancer survivors should be aware that they have a higher risk for preterm labor and are less likely to have a full-term delivery than women without a history of breast cancer.
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http://dx.doi.org/10.1007/s10549-019-05244-6DOI Listing
July 2019

A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

Cell Rep 2018 12;25(12):3530-3542.e5

Department of Urology, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using an iterative process of single-cell RNA sequencing (scRNA-seq) and flow cytometry on ∼98,000 cells taken from different anatomical regions. Immunohistochemistry with newly derived cell type-specific markers revealed the distribution of each epithelial and stromal cell type on whole mounts, revising our understanding of zonal anatomy. Based on discovered cell surface markers, flow cytometry antibody panels were designed to improve the purification of each cell type, with each gate confirmed by scRNA-seq. The molecular classification, anatomical distribution, and purification tools for each cell type in the human prostate create a powerful resource for experimental design in human prostate disease.
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http://dx.doi.org/10.1016/j.celrep.2018.11.086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411034PMC
December 2018

SWI/SNF component restrains pancreatic neoplasia formation.

Gut 2019 07 12;68(7):1259-1270. Epub 2018 Oct 12.

Children's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Objective: is commonly mutated in pancreatic ductal adenocarcinoma (PDAC), but the functional effects of mutations in the pancreas are unclear. Understanding the molecular mechanisms that drive PDAC formation may lead to novel therapies.

Design: Concurrent conditional deletion and activation mutations were modelled in mice. Small-interfering RNA (siRNA) and CRISPR/Cas9 were used to abrogate in human pancreatic ductal epithelial cells.

Results: We found that pancreas-specific loss in mice was sufficient to induce inflammation, pancreatic intraepithelial neoplasia (PanIN) and mucinous cysts. Concurrent activation accelerated the development of cysts that resembled intraductal papillary mucinous neoplasm. Lineage-specific deletion confirmed compartment-specific tumour-suppressive effects. Duct-specific loss promoted dilated ducts with occasional cyst and PDAC formation. Heterozygous acinar-specific loss resulted in accelerated PanIN and PDAC formation with worse survival. RNA-seq showed that loss induced gene networks associated with activity and protein translation. knockdown in human pancreatic ductal epithelial cells induced increased MYC expression and protein synthesis that was abrogated with knockdown. ChIP-seq against H3K27ac demonstrated an increase in activated enhancers/promoters.

Conclusions: suppresses pancreatic neoplasia in a compartment-specific manner. In duct cells, this process appears to be associated with MYC-facilitated protein synthesis.
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http://dx.doi.org/10.1136/gutjnl-2017-315490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499717PMC
July 2019

Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice.

Biomol Ther (Seoul) 2019 01;27(1):107-116

Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea.

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in deficient cells, indicating that is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.
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http://dx.doi.org/10.4062/biomolther.2018.090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319556PMC
January 2019

Evidence Based Tailored Parotidectomy in Treating External Auditory Canal Carcinoma.

Sci Rep 2018 08 14;8(1):12112. Epub 2018 Aug 14.

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

Carcinoma of the external auditory canal (EAC) is a rare tumor and little information is available regarding parotid gland in surgically treating EAC carcinomas. This study aimed to investigate the mode of parotid involvement in EAC carcinoma through staging and histopathological analysis, and to establish surgical guidelines for the parotid gland management when there is no clinical evidence of parotid involvement. Sixty-five patients with EAC carcinoma who underwent temporal bone resection and any type of parotidectomy simultaneously were retrospectively reviewed. The rate of direct parotid invasion and parotid nodal involvement was analyzed according to the stage and histopathological findings. Among the 65 patients, 39 were confirmed to have squamous cell carcinoma (SCC) and 26 were confirmed to have adenoid cystic carcinoma (ACC). Direct parotid invasion occurred in 7 of 39 patients with SCC, only in the advanced stages, and in 15 of 26 patients with ACC, regardless of stage. Metastasis to the parotid node was noted in 6 patients with advanced-stage SCC, whereas no patient with ACC showed parotid nodal metastasis. For adequate tumor control with low risk of surgical complications, evidence based tailored parotidectomy should be applied. With no evidence of parotid involvement, an elective parotidectomy can be excluded in early SCC, whereas a total parotidectomy is recommended for advanced SCC. In ACC, basal resection of the parotid gland rather than a superficial or total parotidectomy should be performed at all disease stages.
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http://dx.doi.org/10.1038/s41598-018-30536-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092432PMC
August 2018

Truncated Adenomatous Polyposis Coli Mutation Induces Asef-Activated Golgi Fragmentation.

Mol Cell Biol 2018 09 15;38(17). Epub 2018 Aug 15.

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Adenomatous polyposis coli (APC) is a key molecule to maintain cellular homeostasis in colonic epithelium by regulating cell-cell adhesion, cell polarity, and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (Asef). The APC-activated Asef stimulates the small GTPase, which leads to decreased cell-cell adherence and cell polarity, and enhanced cell migration. In colorectal cancers, while truncated APC constitutively activates Asef and promotes cancer initiation and progression, regulation of Asef by full-length APC is still unclear. Here, we report the autoinhibition mechanism of full-length APC. We found that the armadillo repeats in full-length APC interact with the APC residues 1362 to 1540 (APC-2,3 repeats), and this interaction competes off and inhibits Asef. Deletion of APC-2,3 repeats permits Asef interactions leading to downstream signaling events, including the induction of Golgi fragmentation through the activation of the Asef-ROCK-MLC2. Truncated APC also disrupts protein trafficking and cholesterol homeostasis by inhibition of SREBP2 activity in a Golgi fragmentation-dependent manner. Our study thus uncovers the autoinhibition mechanism of full-length APC and a novel gain of function of truncated APC in regulating Golgi structure, as well as cholesterol homeostasis, which provides a potential target for pharmaceutical intervention against colon cancers.
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http://dx.doi.org/10.1128/MCB.00135-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094051PMC
September 2018

Benefits of Bimodal Hearing With Cochlear and Middle Ear Implants: Preliminary Results in Four Patients.

Otol Neurotol 2018 07;39(6):e422-e428

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

Objective: Conventional hearing aids have some limitations in overcoming a large air-bone gap or in cases of severe high-frequency hearing loss. The authors aimed to evaluate the benefit of a new bimodal hearing configuration combining cochlear implantation (CI) and middle ear implant (MEI) in patients with severe mixed conductive and ski-slope hearing loss.

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Four patients with severe to profound hearing loss, who underwent CI in one ear and MEI in the other, were enrolled.

Intervention: Audiological outcomes were assessed at least 6 months after the MEI/CI operation. Pure-tone audiometry (PTA) in unaided, CI-aided, and MEI-aided conditions were measured.

Main Outcome Measures: Average threshold changes in bands of frequencies (<1 kHz, ≥1 kHz) were compared between MEI-aided and HA-aided conditions. The Korean version of the Hearing-in-Noise Test (K-HINT), and speech perception score in noisy and quiet conditions were evaluated in the bimodal configuration (i.e., MEI with CI).

Results: MEI-aided PTA was especially increased in high-frequency areas (≥1 kHz). Speech perception in noisy and quiet conditions demonstrated better scores in the bimodal configuration. K-HINT also demonstrated better scores in the bimodal configuration.

Conclusions: There is an increasing number of patients with unilateral CI and residual hearing in the contralateral ear. The benefits of a new bimodal hearing configuration with CI and MEI were demonstrated in patients with severe high-frequency hearing loss or mixed conductive hearing loss in the contralateral ear.
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http://dx.doi.org/10.1097/MAO.0000000000001820DOI Listing
July 2018

The effects of smartphone multitasking on gait and dynamic balance.

J Phys Ther Sci 2018 Feb 28;30(2):293-296. Epub 2018 Feb 28.

Department of Physical Therapy, Uiduk University: 261 Donghae-daero, Gangdong-myeon, Gyeongju-si, Gyeongsangbuk-do, Republic of Korea.

[Purpose] This study was performed to analyze the influence of smartphone multitasking on gait and dynamic balance. [Subjects and Methods] The subjects were 19 male and 20 female university students. There were 4 types of gait tasks: General Gait (walking without a task), Task Gait 1 (walking while writing a message), Task Gait 2 (walking while writing a message and listening to music), Task Gait 3 (walking while writing a message and having a conversation). To exclude the learning effect, the order of tasks was randomized. The Zebris FDM-T treadmill system (Zebris Medical GmbH, Germany) was used to measure left and right step length and width, and a 10 m walking test (10MWT) was conducted for gait velocity. In addition, a Timed Up and Go test (TUG) was used to measure dynamic balance. All the tasks were performed 3 times, and the mean of the measured values was analyzed. [Results] There were no statistically significant differences in step length and width. There were statistically significant differences in the 10MWT and TUG tests. [Conclusion] Using a smartphone while walking decreases a person's dynamic balance and walking ability. It is considered that accident rates are higher when using a smartphone.
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http://dx.doi.org/10.1589/jpts.30.293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851367PMC
February 2018
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