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A long short-term memory (LSTM) model is introduced to predict missing datapoints of dissolved oxygen (DO) in an eel (Anguilla japonica) recirculating aquaculture system. Field experiments allow to determine periodic patterns in DO data corresponding to day-night cycles and a DO decrease after feeding. To improve the accuracy of DO prediction by using a training-to-test data ratio of 5:1, training with data in sequential and reverse orders is performed and evaluated. The LSTM model used to predict DO levels in the fish tank has an error of approximately 3.25%. The proposed LSTM model trained on DO data has a high applicability and may support water quality control in aquaculture farms.

Abstract Advances in next-generation sequencing technologies have led to elucidation of sensorineural hearing loss genetics and associated clinical impacts. However, studies on the functional pathogenicity of variants of uncertain significance (VUS), despite their close association with clinical phenotypes, are lacking. Here we identified compound heterozygous variants in ESRRB transcription factor gene linked to DFNB35, specifically a novel splicing variant (NM_004452.4(ESRRB): c.397 + 2T>G) in trans with a missense variant (NM_004452.4(ESRRB): c.1144C>T p.(Arg382Cys)) whose pathogenicity remains unclear. The splicing variant (c.397 + 2T>G) caused exon 4 skipping, leading to premature stop codon formation and nonsense-mediated decay. The p.(Arg382Cys) variant was classified as a VUS due to its particularly higher allele frequency among East Asian population despite disease-causing in-silico predictions. However, functional assays showed that p.(Arg382Cys) variant disrupted key intramolecular interactions, leading to protein instability. This variant also reduced transcriptional activity and altered expression of downstream target genes essential for inner ear function, suggesting genetic contribution to disease phenotype. This study expanded the phenotypic and genotypic spectrum of ESRRB in DFNB35 and revealed molecular mechanisms underlying ESRRB-associated DFNB35. These findings suggest that variants with high allele frequencies can also possess functional pathogenicity, providing a breakthrough for cases where VUS, previously unexplored, could be reinterpreted by elucidating their functional roles and disease-causing characteristics.

Abstract The relationship between tinnitus and body composition in specific regions has not been extensively investigated. This study aimed to identify associations between tinnitus and body composition. Individuals with data on physical and otological examination findings, and bioelectrical impedance analysis were included from the ninth Korea National Health and Nutritional Examination Survey. They were divided into a tinnitus group and a non-tinnitus group. Participants with tinnitus were further classified into acute or chronic tinnitus group. The tinnitus group showed significantly higher body fat percentages in each region (arms: P = 0.014; legs: P = 0.029; trunk: P = 0.008; whole body: P = 0.010) and waist circumference (P = 0.007) than the non-tinnitus group, and exhibited lower leg muscle percentage (P = 0.038), total body fluid percentage (P = 0.010), and intracellular fluid percentage (P = 0.009) than the non-tinnitus group in men. Furthermore, men with chronic tinnitus showed a significantly higher trunk fat percentage (P = 0.015) and waist circumference (P = 0.043), and lower intracellular fluid percentage (P = 0.042) than their counterparts without tinnitus. No significant differences in body composition were observed among the groups in the female population. In men, body composition may be associated with tinnitus.

Abstract While volatile organic compounds (VOCs) impair various organs, their influence on hearing loss (HL) has not been extensively researched. We aimed to identify the association between VOCs and HL or high-frequency hearing loss (HFHL). We extracted data on age, sex, pure tone audiometry, hypertension, occupational noise exposure, and creatinine-corrected urine VOC metabolite concentrations from the eighth Korea National Health and Nutrition Survey. Among the VOC metabolites, N-acetyl-S-(benzyl)-L-cysteine (BMA, P = 0.004), N-acetyl-S-(phenyl)-l-cysteine (SPMA, P = 0.027), and N-acetyl-S-(3,4-dihydroxybutyl)-l-cysteine (DHBMA, P

Abstract Hearing loss affects some nutrient intake. Disabling hearing loss may exacerbate these issues. We aimed to evaluate nutrient intake and assess deficiencies based on functional hearing status. The study included 6907 participants with information on demographic factors, nutrient intake, weight, height, disease status, and hearing level in the eighth Korea National Health and Nutrition Examination Survey, conducted from 2019 to 2021. We categorized the participants into 3 groups based on their functional hearing status: bilateral hearing, unilateral hearing, and disabling hearing loss. The disabling hearing loss group showed lower intake of most major nutrients (P

Abstract Background TMC1, which encodes transmembrane channel-like protein 1, forms the mechanoelectrical transduction (MET) channel in auditory hair cells, necessary for auditory function. TMC1 variants are known to cause autosomal dominant (DFNA36) and autosomal recessive (DFNB7/11) non-syndromic hearing loss, but only a handful of TMC1 variants underlying DFNA36 have been reported, hampering analysis of genotype-phenotype correlations. Methods In this study, we retrospectively reviewed 338 probands in an in-house database of genetic hearing loss, evaluating the clinical phenotypes and genotypes of novel TMC1 variants associated with DFNA36. To analyze the structural impact of these variants, we generated two structural models of human TMC1, utilizing the Cryo-EM structure of C. elegans TMC1 as a template and AlphaFold protein structure database. Specifically, the lipid bilayer-embedded protein database was used to construct membrane-embedded models of TMC1. We then examined the effect of TMC1 variants on intramolecular interactions and predicted their potential pathogenicity. Results We identified two novel TMC1 variants related to DFNA36 (c.1256T > C:p.Phe419Ser and c.1444T > C:p.Trp482Arg). The affected subjects had bilateral, moderate, late-onset, progressive sensorineural hearing loss with a down-sloping configuration. The Phe419 residue located in the transmembrane domain 4 of TMC1 faces outward towards the channel pore and is in close proximity to the hydrophobic tail of the lipid bilayer. The non-polar-to-polar variant (p.Phe419Ser) alters the hydrophobicity in the membrane, compromising protein-lipid interactions. On the other hand, the Trp482 residue located in the extracellular linker region between transmembrane domains 5 and 6 is anchored to the membrane interfaces via its aromatic rings, mediating several molecular interactions that stabilize the structure of TMC1. This type of aromatic ring-based anchoring is also observed in homologous transmembrane proteins such as OSCA1.2. Conversely, the substitution of Trp with Arg (Trp482Arg) disrupts the cation-π interaction with phospholipids located in the outer leaflet of the phospholipid bilayer, destabilizing protein-lipid interactions. Additionally, Trp482Arg collapses the CH-π interaction between Trp482 and Pro511, possibly reducing the overall stability of the protein. In parallel with the molecular modeling, the two mutants degraded significantly faster compared to the wild-type protein, compromising protein stability. Conclusions This results expand the genetic spectrum of disease-causing TMC1 variants related to DFNA36 and provide insight into TMC1 transmembrane protein-lipid interactions.

Abstract When medical genetic syndromes are influenced by allelic hierarchies, mutant alleles have distinct effects on clinical phenotypes. Genotype–phenotype correlations for Usher syndrome type 2 (USH2) suggest that the USH2A gene exhibits an allelic hierarchy. Here, we analyzed the phenotypes and genotypes of 16 South Korean patients with USH2A biallelic variants to investigate an allelic hierarchy from audiological and ophthalmological perspectives. Using whole exome and genome sequencing, 18 mutant alleles, including 4 novel alleles, were identified and implicated in USH2A-related disorders. Truncated alleles were linked to earlier onset of subjective hearing loss and more severe thresholds; biallelic truncated alleles had more severe effects. Truncated alleles were also associated with retinal structure degeneration and severe functional deterioration. However, younger patients (aged

Pathogenic structure variations (SVs) are associated with various types of cancer and rare genetic diseases. Recent studies have used Cas9 nuclease with paired guide RNAs (gRNAs) to generate targeted chromosomal rearrangements, focusing on producing fusion proteins that cause cancer, whereas research on precision genome editing for rectifying SVs is limited. In this study, we identified a novel complex genomic rearrangement (CGR), specifically an EYA1 inversion with a deletion, implicated in branchio-oto-renal/branchio-oto syndrome. To address this, two CRISPR-based approaches were tested. First, we used Cas9 nuclease and paired gRNAs tailored to the patient’s genome. The dual CRISPR-Cas9 system induced efficient correction of paracentric inversion in patient-derived fibroblast, and effectively restored the expression of EYA1 mRNA and protein, along with its transcriptional activity required to regulate the target gene expression. Additionally, we used CRISPR activation (CRISPRa), which leads to the upregulation of EYA1 mRNA expression in patient-derived fibroblasts. Moreover, CRISPRa significantly improved EYA1 protein expression and transcriptional activity essential for target gene expression. This suggests that CRISPRa-based gene therapies could offer substantial translational potential for approximately 70% of disease-causing EYA1 variants responsible for haploinsufficiency. Our findings demonstrate the potential of CRISPR-guided genome editing for correcting SVs, including those with EYA1 CGR linked to haploinsufficiency.

In general, for livestock building, a simple system for controlling the HVAC system that is based only on the indoor air temperature is applied. This study evaluated the applicability of temperature humidity index (THI)-based ventilation systems installed in livestock buildings using a building energy simulation model. Based on the monitoring data of an actual pig house, the integrated predictive performance of the indoor temperature and humidity of the building energy simulation model was calibrated. Additionally, the indoor environment of the existing temperature-based control and THI-controlled ventilation systems was compared through simulations. The average THI and the section exceeding the THI threshold were both lower compared to the existing system. This was because the part load ratio of the fans of the THI-controlled ventilation system was higher than that of the existing system, indicating better ventilation. These results suggest that THI-based ventilation systems can overcome the limitations of existing temperature-based systems and effectively improve the thermal stress management of livestock buildings. This study portrays that the indoor environment can be improved by simply changing control variables, while presenting the field applicability and research value of THI-based control systems in the management of livestock environments.

Abstract POU4F3, a member of the POU family of transcription factors, commonly causes autosomal dominant deafness. Exome sequencing was used to identify four novel variants in POU4F3 (NM_002700.2), including c.564dupA: p.Ala189SerfsTer26, c.743T > C:p.Leu248Pro, c.879C > A:p.Phe293Leu, and c.952G > A:p.Val318Met, and diverse aspects of the molecular consequences of their protein expression, stability, subcellular localization, and transcriptional activity were investigated. The expression of three mutant proteins, encoded by missense variants, was reduced compared to the wild-type protein, demonstrating that the mutants were unstable and vulnerable to degradation. Additionally, all the mutant proteins had distinct subcellular localization patterns. A mutant protein carrying p.Ala189SerfsTer26, in which both mono- and bi-partite nuclear localization signals were disrupted, showed abnormal subcellular localization. Resultantly, all the mutant proteins significantly reduced the transcriptional activity required to regulate the downstream target gene expression. Furthermore, we identified the altered expression of 14 downstream target genes associated with inner ear development using patient-derived lymphoblastoid cell lines. There was a significant correlation of the expression profile between patient-derived cells and the cochlear hair cells, which provided a breakthrough for cases where the collection of human cochlear samples for transcriptome studies was unfeasible. This study expanded the genotypic spectrum of POU4F3 in DFNA15, and further refined the molecular mechanisms underlying POU4F3-associated DFNA15.

Abstract Branchio-oto-renal (BOR)/branchio-otic (BO) syndrome is a rare disorder and exhibits clinically heterogenous phenotypes, marked by abnormalities in the ear, branchial arch, and renal system. Sporadic cases of atypical BOR/BO syndrome have been recently reported; however, evidence on genotype–phenotype correlations and molecular mechanisms of those cases is lacking. We herein identified five SIX1 heterozygous variants (c.307dupC:p.Leu103Profs*51, c.373G>A:p.Glu125Lys, c.386_391del:p.Tyr129_Cys130del, c.397_399del:p.Glu133del, and c.501G>C:p.Gln167His), including three novel variants, through whole-exome sequencing in five unrelated Korean families. All eight affected individuals with SIX1 variants displayed non-syndromic hearing loss (DFNA23) or atypical BO syndrome. The prevalence of major and minor criteria for BOR/BO syndrome was significantly reduced among individuals with SIX1 variants, compared to 15 BOR/BO syndrome families with EYA1 variants. All SIX1 variants interacted with the EYA1 wild-type; their complexes were localized in the nucleus except for the p.Leu103Profs*51 variant. All mutants also showed obvious but varying degrees of reduction in DNA binding affinity, leading to a significant decrease in transcriptional activity. This study presents the first report of SIX1 variants in South Korea, expanding the genotypic and phenotypic spectrum of SIX1 variants, characterized by DFNA23 or atypical BO syndrome, and refines the diverse molecular aspects of SIX1 variants according to the EYA1–SIX1–DNA complex theory.

ObjectivesSymptomatic vestibulopathy impairs patients' lives. However, few studies have explored the lives of patients with compensated or asymptomatic vestibulopathy. This study investigated the quality of life (QOL), psychological health, and physical function of patients with vestibulopathy.Materials and methodsUsing the eighth Korea National Health and Nutrition Examination Survey database, we included individuals with data on demographic factors, diabetes, hypertension, dizziness experiences, pure-tone audiometry, video head impulse test (vHIT), Health-related Quality of Life Instrument with 8 Items, General Anxiety Disorder 7-item scale, stress, and walking and sitting times. Participants were classified into the following groups: an uncompensated group with abnormal vHIT result and chronic dizziness, a compensated group with abnormal vHIT result and a history of dizziness, an asymptomatic group with abnormal vHIT result and no history of dizziness, and a normal group without abnormal vHIT result or a history of dizziness.ResultsUncompensated vestibulopathy was more common in older individuals and women. The uncompensated group showed impairments in climbing stairs (P < 0.001), pain (P < 0.001), vitality (P = 0.001), working (P < 0.001), depression (P < 0.001), sleep (P = 0.001), happiness (P = 0.002), anxiety (P = 0.006), and stress (P = 0.003). The compensated group showed deficits in pain (P < 0.001), work (P = 0.006), sleep (P = 0.001), and happiness (P = 0.001). The asymptomatic group had no deficits in QOL, psychological health, or physical function. These tendencies were similar after controlling for age and gender.ConclusionVestibulopathy with a history of dizziness has a long-lasting impact on QOL and emotional status, even after compensation. Uncompensated vestibulopathy has a significant effect on QOL and mental health. Notably, though, the compensated group also showed a reduction in QOL. Appropriate interventions for each category of patients should be provided based on their impaired functions.

Abstract Background Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner ear function. Unlike the recessively inherited Wolfram syndrome, WFS1 heterozygous variants cause DFNA6/14/38 and wolfram-like syndrome, characterized by autosomal dominant nonsyndromic hearing loss, optic atrophy, and diabetes mellitus. Here, we identified two WFS1 heterozygous variants in three DFNA6/14/38 families using exome sequencing. We reveal the pathogenicity of the WFS1 variants based on three-dimensional (3D) modeling and structural analysis. Furthermore, we present cochlear implantation (CI) outcomes in WFS1-associated DFNA6/14/38 and suggest a genotype-phenotype correlation based on our results and a systematic review. Methods We performed molecular genetic test and evaluated clinical phenotypes of three WFS1-associated DFNA6/14/38 families. A putative WFS1–NCS1 interaction model was generated, and the impacts of WFS1 variants on stability were predicted by comparing intramolecular interactions. A total of 62 WFS1 variants associated with DFNA6/14/38 were included in a systematic review. Results One variant is a known mutational hotspot variant in the endoplasmic reticulum (ER)-luminal domain WFS1(NM_006005.3) (c.2051 C > T:p.Ala684Val), and the other is a novel frameshift variant in transmembrane domain 6 (c.1544_1545insA:p.Phe515LeufsTer28). The two variants were pathogenic, based on the ACMG/AMP guidelines. Three-dimensional modeling and structural analysis show that non-polar, hydrophobic substitution of Ala684 (p.Ala684Val) destabilizes the alpha helix and contributes to the loss of WFS1-NCS1 interaction. Also, the p.Phe515LeufsTer28 variant truncates transmembrane domain 7–9 and the ER-luminal domain, possibly impairing membrane localization and C-terminal signal transduction. The systematic review demonstrates favorable outcomes of CI. Remarkably, p.Ala684Val in WFS1 is associated with early-onset severe-to-profound deafness, revealing a strong candidate variant for CI. Conclusions We expanded the genotypic spectrum of WFS1 heterozygous variants underlying DFNA6/14/38 and revealed the pathogenicity of mutant WFS1, providing a theoretical basis for WFS1-NCS1 interactions. We presented a range of phenotypic traits for WFS1 heterozygous variants and demonstrated favorable functional CI outcomes, proposing p.Ala684Val a strong potential marker for CI candidates.

Abstract Determining the etiology of severe-to-profound sensorineural hearing loss (SP-SNHL) in pediatric subjects is particularly important in aiding the decision for auditory rehabilitation. We aimed to update the etiologic spectrum of pediatric SP-SNHL by combining internal auditory canal (IAC)-MRI with comprehensive and state-of-the-art genetic testings. From May 2013 to September 2020, 119 cochlear implantees under the age of 15 years with SP-SNHL were all prospectively recruited. They were subjected to genetic tests, including exome sequencing, and IAC-MRI for etiologic diagnosis. Strict interpretation of results were made based on ACMG/AMP guidelines and by an experienced neuroradiologist. The etiology was determined in of 65.5% (78/119) of our cohort. If only one of the two tests was done, the etiologic diagnostic rate would be reduced by at least 21.8%. Notably, cochlear nerve deficiency (n = 20) detected by IAC-MRI topped the etiology list of our cohort, followed by DFNB4 (n = 18), DFNB1 (n = 10), DFNB9 (n = 10) and periventricular leukomalacia associated with congenital CMV infection (n = 8). Simultaneous application of state-of-the-art genetic tests and IAC-MRI is essential for etiologic diagnosis, and if lesions of the auditory nerve or central nerve system are carefully examined on an MRI, we can identify the cause of deafness in more than 65% of pediatric SP-SNHL cases.

In this study, the internal environment such as the air temperature, humidity, and wall temperature of the underground utility tunnel, was analyzed. The current status and problems of the air conditioning system were examined by analyzing the capacity of the exhaust fan and the air velocity inside the utility tunnel. The field experiment showed that the utility tunnel has a relative humidity of 95% or higher for most sections during summer. The deviation of the internal air temperature was about $4~^{\circ }\text{C}$ depending on the section, and the dew condensation occurred. However, most of the exhaust fans has a capacity below the standard minimum air velocity of 2.5m $\cdot \text{s}^{-1}$ . In particular, in the section where dew condensation occurred, the air velocity was 0.26 to 0.97 $\text{m}\cdot \text{s}^{-1}$ , indicating the presence of stagnant air inside the facility. Therefore, this study attempted to minimize dew condensation by calculating the proper exhaust fan capacity using computational fluid dynamics and installing circulation fans and duct systems in the section where the dew condensation occurred. As a result, when a circulation fan was installed, it was possible to increase the air velocity inside the utility tunnel, and the relative humidity could be reduced by about 78%. By installing a duct, the direct supply of external air or the discharge of internal humid air was simulated for the section where dew condensation occurred. The result showed that the relative humidity could be reduced by about 78% when the duct system was operated in the intake direction.

Tinnitus can be defined as the conscious perception of phantom sounds in the absence of corresponding external auditory signals. Tinnitus can develop in the setting of sudden sensorineural hearing loss (SSNHL), but the underlying mechanism is largely unknown. Using electroencephalography, we investigated differences in afferent node capacity between 15 SSNHL patients without tinnitus (NT) and 30 SSNHL patients with tinnitus (T). Where the T group showed increased afferent node capacity in regions constituting a “triple brain network” [default mode network (DMN), central executive network (CEN), and salience network (SN)], the NT group showed increased information flow in regions implicated in temporal auditory processing and noise-canceling pathways. Our results demonstrate that when all components of the triple network are activated due to sudden-onset auditory deprivation, tinnitus ensues. By contrast, auditory processing-associated and tinnitus-suppressing networks are highly activated in the NT group, to overcome the activation of the triple network and effectively suppress the generation of tinnitus.

Objectives Malformations of the inner ear account for approximately 20% of cases of congenital deafness. In current practice, straight arrays with circumferential electrodes (i.e., full-banded electrodes) are widely used in severely malformed cochleae. However, the unpredictability of the location of residual spiral ganglion neurons in such malformations argues against obligatorily using full-banded electrodes in all cases. Here, we present our experience of electrically evoked compound action potential (ECAP) and radiography-based selection of an appropriate electrode for severely malformed cochleae. Methods Three patients with severely malformed cochleae, showing cochlear hypoplasia type II (CH-II), incomplete partition type I (IP-I), and cochlear aplasia with a dilated vestibule (CADV), respectively, were included, and the cochlear nerve deficiency (CND) was evaluated. A full-banded electrode (CI24RE(ST)) and slim modiolar electrode (CI632) were alternately inserted to compare ECAP responses and electrode position. Results In patient 1 (CH-II with CND), who had initially undergone cochlear implantation (CI) using a lateral wall electrode (CI422), revision CI was performed due to incomplete insertion of CI422 and resultant unsatisfactory performance by explanting the CI422 and re-inserting the CI24RE(ST) and CI632 sequentially. Although both electrodes elicited reliable ECAP responses with correct positioning, CI24RE(ST) showed overall lower ECAP thresholds compared to CI632; thus, CI24RE(ST) was selected. In patient 2 (IP-I with CND), CI632 elicited superior ECAP responses relative to CI24RE(ST), with correct positioning of the electrode; CI632 was chosen. In patient 3 (CADV), CI632 did not elicit an ECAP response, while meaningful ECAP responses were obtained with the CI24RE(ST) array once correct positioning was achieved. All patients’ auditory performance markedly improved postoperatively. Conclusion The ECAP and radiography-based strategy to identify an appropriate electrode may be useful for severely malformed cochleae, leading to enhanced functional outcomes. The practice of sticking to full-banded straight electrodes may not always be optimal for IP-I and CH-II.

Abstract Surgical plugging to treat superior semicircular canal dehiscence (SCD) has been proven to impede the effect of the third mobile window, abating cochleovestibular symptoms. Knowledge of superior semicircular canal (SC)-plugging status has been proposed to serve as a guide for adjuvant treatment. Here, we investigated disturbances in the inner ear fluid space following SC plugging using a novel three-dimensional (3D) reconstruction-based method. This approach used a semi-automatic segmentation algorithm and a direct volume rendering method derived from conventional magnetic resonance images. The variable extents of filling defects at the sites of SC plugging and the positional relation of the defect to the ampulla and common crus were identified. The success group exhibited markedly reduced volumes following surgery, whereas the failure group displayed no changes in volume. These results indicate that the success or failure of SC plugging was related to 3D volume changes in the labyrinth fluid signal. Collectively, this study presents individualized SC-plugging statuses using a novel 3D reconstruction-based method and it facilitates future work regarding easy-to-measure 3D volume changes. This current technology also aids in the exploration of pathologic changes in various targets of interest.

Abstract The slim modiolar electrode has been reported to ensure better modiolar proximity than previous conventional perimodiolar electrodes and consistently high scala tympani localization. Nonetheless, variability in modiolar proximity exists even among slim modiolar electrodes, still leaving room for further improvement of modiolar proximity, which may positively affect functional outcomes. Given this, the pull-back maneuver was reported to increase the modiolar proximity of slim modiolar electrodes in a cadaveric study, but in vivo repositioning effects remain to be established. Here we identified that the pull-back maneuver led to better modiolar proximity than conventional insertion while maintaining a similar angular insertion depth. Notably, the reduced electrode-modiolus distance from the pull-back maneuver was associated with significantly lower impedances across electrodes postoperatively as well as reduced intraoperative electrophysiological thresholds than conventional insertion. Among adult cochlear implant recipients, this maneuver resulted in significantly better sentence recognition scores at three months postoperatively when compared to those with a conventional insertion; however, this benefit was not observed at later intervals. Collectively, slim modiolar electrodes with the pull-back maneuver further enhance the modiolar proximity, possibly leading to better open-set sentence recognition, at least in the early postoperative stage.

A clinical diagnosis of Ménière's disease (MD) is made based on medical history and audiometry findings. The 1995 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines requires histopathological confirmation of endolymphatic hydrops (EH) for a diagnosis of “certain” MD. Symptoms such as dizziness and ear fullness are important diagnostic features; however, the descriptions provided by patients are frequently vague and non-specific. A recently developed magnetic resonance imaging (MRI) protocol to document EH is, therefore, useful for the evaluation of inner ear status in patients with MD. In this study, patients with MD were assessed using MRI and the HYDROPS (HYbriD of Reversed image Of Positive endolymph signal and native image of positive perilymph Signal) protocol to investigate the effectiveness of MRI for visualization of the endolymphatic space in the diagnosis of MD by correlating clinical laboratory parameters with the grade of EH. Of the 123 patients with MD recruited in this study, 80 had definite MD, 11 had probable MD, and 32 had possible MD based on the 1995 AAO-HNS guidelines. The EH grade based on HYDROPS MRI was determined independently by two otorhinolaryngologists and compared with several clinical parameters, including the diagnostic scale of MD (1995 AAO-HNS guidelines), pure tone average (PTA), low tone average (LTA), canal paresis (CP) on the caloric test, and disease duration. Cochlear hydrops and vestibular hydrops were detected in 58 and 80% of 80 definite MD ears, in 33 and 58% of 12 probable MD ears, and in 5 and 27% of 37 possible MD ears, respectively. The proportion of higher hydrops grades increased significantly with grade according to the MD diagnostic scale (p < 0.0001). Both PTA and LTA were significantly higher in patients with hydrops grade 2 than hydrops grade 0 in both the cochlea and the vestibule. CP was significantly higher in patients with grade 2 than grade 0 vestibular hydrops. Disease duration was not associated with hydrops grade. Radiological evaluation of MD using the HYDROPS protocol is useful for evaluation of the extent and severity of EH in the diagnosis of MD based on its pathophysiological mechanism.

Objectives We, herein, report two novel USH2A variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL). Methods Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis. Results We identified the following variants of USH2A from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C>T: p.R2723X) and a missense variant (c.1823G>A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G>A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as “uncertain significance” and “pathogenic,” respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant. Conclusion Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring USH2A variants, suggesting that USH2A should also be included in the candidate gene of cochlear implantation. A specific combination of USH2A variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of USH2A variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with USH2A will be helpful for genetic counseling and treatment starategy.

ObjectiveThe pathogenesis of hearing loss in autoinflammatory disorders due to activation of the inflammasome remains incompletely understood. Previously no animals expressing mutant Nlrp3 (NOD-, LRR- and pyrin domain-containing protein 3) survived to an age when hearing evaluation was possible due to embryonic lethality. We aimed to establish a novel mouse model that manifests quantifiable hearing loss with other syndromic features due to alteration of Nlrp3 and investigate the audiologic and histopathologic phenotype in the cochlea to clarify how the genetic alterations of NLRP3 could induce autoinflammatory hearing loss.MethodsTo induce inner ear expression of the mutant Nlrp3, Nlrp3D301NneoR mice were bred with Gfi1Cre knock-in mice for conditional mutant Nlrp3 activation in the cochlea and hematopoietic cells. Hearing thresholds were measured. Hematoxylin-eosin sections of the cochlea, brain, kidney, and liver were examined under light microscopy. Immunohistochemical analyses using polyclonal anti-NLRP3 antibodies on cochlear whole-mount preparations and frozen sections were performed.ResultsWe, for the first time in the literature, established a mouse model that manifests quantifiable hearing loss due to Nlrp3 alteration. ABR recordings of Nlrp3D301NneoR/+; Gfi1Cre/+ mice, albeit with limited life expectancy, exhibited severe to profound hearing loss at postnatal day 20 (P20). There was overall overexpression of mutant Nlrp3, and mutant Nlrp3 expression was noted in the spiral prominence, the outer sulcus region (Claudius cells and outer sulcus cells), the organ of Corti, the inner sulcus, and the spiral ganglion neurons in the cochlea. The hematoxylin-eosin sections of Nlrp3D301NneoR/+; Gfi1Cre/+ mice cochleae at P12 exhibited a disorganized organ of Corti between the outer hair cells/supporting Deiters' cells and basilar membrane compared with the normal phenotype mice, leading to a collapsed Nuel's space. This morphologic feature gradually returned to normal by P15. Varying degrees of inflammation with lymphocytic infiltrations were observed in the brain, kidney, and liver.ConclusionWe report the first mutant Nlrp3 overexpression mouse model (Nlrp3D301NneoR/+; Gfi1Cre/+) that shows obvious overexpression of Nlrp3 in the cochlea, a transient developmental lag of the cochlea, and severe to profound hearing loss. We expect that this mouse line, which models human autoinflammatory hearing loss, could provide a valuable tool to elucidate the underlying pathogenic mechanism of inflammasome activation-mediated hearing loss.

Venous pulsatile tinnitus (PT) is characterized by an auditory perception of pulse-synchronous sound, suppressed by compression of the ipsilateral internal jugular vein. We sought to determine the preoperative prognostic significance of the effect of ipsilateral neck manual compression on the PT loudness and audiometric changes in patients with sigmoid sinus dehiscences (SS-Deh) and diverticula (SS-Div) by comparing postoperative improvements in ipsilateral low-frequency hearing loss (LFHL) in pure-tone audiogram (PTA) and PT symptoms. Twenty-two subjects with PT originating from SS-Deh/Div were recruited. Air-conduction hearing thresholds were measured using PTA at three time points: twice preoperatively (with neutral neck position and with ipsilateral manual compression of internal jugular vein) and once at 3-months postoperatively with neutral neck position. We defined a positive neck compression effect as a threshold improvement of ≥ 10 dB HL at 250 or 500 Hz after manual neck compression. All but two subjects presented with ipsilateral LFHL in the neutral position. The average hearing threshold in the neutral position markedly improved after manual neck compression, indicating that LFHL originated from the masking effect of venous PT. All subjects had subjective improvements in PT and LFHL after sigmoid sinus surgeries, confirming that LFHL resulted from the masking effect of PT. Additionally, improvement of LFHL after neck compression could be regarded as a positive prognostic indicator after surgery. Collectively, elimination of PT loudness and improvement of LFHL with manual compression over the ipsilateral neck may suggest the venous origin of the PT and predict a favorable outcome following repair of SS-Deh/SS-Div.

There are still debates about timing and effectiveness of cochlear implants (CI) in pediatric subjects with significant residual hearing who do not belong to traditional indication of CI. In this study, we aimed to investigate the outcomes of CI, specifically on improvement of pronunciation, among hearing-impaired children already with a substantial degree of language skills as evaluated by Categories of Auditory Perception (CAP) scores or sentence score. Our cohort comprised pediatric CI recipients from July 2018 through October 2020. Among them, cases with CAP scores of 5 or 6 preoperatively were defined as "borderline cases". We investigated prevalence and etiologies, and compared speech evaluation data preoperatively and postoperatively at three time points (3, 6 and 9-12 months after implantation). Among 86 pediatric CI recipients, 13 subjects (15.12%) had language development that reached CAP scores of 5 or 6 before implantation. Postoperative speech evaluation data 6 months after implantation revealed significant improvement of pronunciation (Urimal Test of Articulation and Phonation scores: UTAP), Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and word perception scores, but not of CAP and sentence perception scores. Notably, the significant improvement of pronunciation based on UTAP scores outstripped that of other speech parameters and this continued steadily up to one-year postoperatively. The result of the study serves as evidence for what to expect from cochlear implantation in hearing-impaired children who have already achieved a substantial degree of language development in terms of CAP scores or sentence perception scores, preoperatively.

Because of the poor environment inside fattening pig houses due to high humidity, ammonia gas, and fine dust, it is hard to accumulate reliable long-term data using sensors. Therefore, it is necessary to conduct research for filling in the missing environmental data inside fattening pig houses. Thus, this research aimed to develop a model for predicting the missing data of the air temperature inside fattening pig houses using a long short-term memory (LSTM) model, which is one of the artificial neural networks (ANNs). Firstly, the internal and external environmental data of the fattening pig house were monitored to develop the LSTM models for data filling of the missing data and to validate the developed LSTM model. The LSTM model for data filling of the missing data was developed by learning the measured temperature inside the pig house. The LSTM model developed in this study was validated by comparing the air temperature data predicted by the LSTM model with the air temperature data measured in the fattening pig house. The LSTM model was accurate within a 3.5% error rate for the internal air temperature. Finally, the accuracy and applicability of the developed LSTM model were evaluated according to the order of learning data and the length of the missing data. In the future, for information and communication technologies (ICTs) and the convergence and application of smart farms, the LSTM models developed in this study may contribute to the accumulation of reliable long-term data at the fattening pig house.

Objectives. To investigate the neurocognition of aged patients with chronic tinnitus and reveal the possible association between tinnitus severity and cognitive function, with attention to mild cognitive impairment (MCI). Methods. Fifty-eight elderly patients (≥65 years old) with chronic tinnitus (≥6 months) were prospectively enrolled in this study. All patients assessed the neurocognitive batteries including the Korean version of the patient health questionnaire-9 (K-PHQ-9), the Lawton instrumental activities of daily living scale (K-IADL), and the Montreal cognitive assessment (MoCA-K). After initial evaluation to exclude moderate or severe cognitive impairment by a psychiatrist, the patients were classified into two groups: MCI and non-MCI, according to the MoCA-K scores (cutoff value, 22/23). All patients underwent audiological examinations including psychoacoustic tests of tinnitus. Results. Of 58 patients, 10 (17.2%) met the MCI criteria. The tinnitus handicap inventory (THI) score in the MCI group was significantly higher than that in the non-MCI group. Based on multivariate regression analysis, a significant association between tinnitus severity and MoCA-K score was also detected. Specifically, bothersome tinnitus (THI score ≥30) was closely linked to the presence of MCI. Meanwhile, the impact of MCI on both K-PHQ-9 and K-IADL scores was not evident in patients with chronic tinnitus. Conclusion. Tinnitus severity appears to be a potential independent determinant for predicting the MCI, suggesting the underlying mechanism between chronic tinnitus and cognitive deficit. Given that MCI highly links to dementia, the evaluation of cognitive functions in aged patients with chronic tinnitus need to be considered at the initial assessment of tinnitus.

Eurasian tree sparrow data from the 4th National Ecosystem Survey (2014 ~ 2018) were used for sparrows, which are known to decrease by about one third over 40 years. Data on altitude and land type among GIS factors in the Eurasian tree sparrow Recorded 6 Metropolitan City(Incheon, Daejeon, Daegu, Gwangju, Ulsan, Busan) of Republic of Korea were generated. As a result, altitudes and land types were generated for 578 Eurasian tree sparrow.

We compared the therapeutic efficacy of facial nerve decompression (FND) and conservative treatment in patients with Bell’s palsy through a systematic review and meta-analysis. Primary database search was performed in PubMed, Medline, and Embase. After screening, 13 studies were assessed for their eligibility. Among them, seven studies employing either the House-Brackmann grading system (HBGS) or May’s classification (modified HBGS) were selected for quantitative and qualitative analysis. Based on May’s classification, the degree of recovery was classified into complete (HBGS I), fair (HBGS II–III), or failed (HBGS IV–VI) recovery. The outcomes were assessed between 6 and 12 months after surgery. The estimated pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random effects model. Cohorts were comprised of patients who underwent FND (n=202, 53.0%) and conservative treatments (n=179, 47.0%). In pooled analysis, the rate of complete recovery was significantly higher in the FND group than in the control group (OR, 2.06; 95% CI, 1.22 to 3.48; P=0.007) showing neither heterogeneity nor publication bias. Meanwhile, the rates of fair recovery (OR, 0.71; 95% CI, 0.42 to 1.21; P=0.208) and failed recovery (OR, 0.60; 95% CI, 0.22 to 1.67; P=0.327) in the FND group were similar to that in the control group. In subgroup analyses, there was no significant difference in the OR according to the operation timing and surgical approach. FND can be a possible treatment option for patients with complete Bell’s palsy, especially for complete recovery, which provide insights on decision-making and outcome prediction. However, FND should be determined carefully given the risk of small study effects and possible complications.

Objectives. Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. Methods. Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. Results. There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. Conclusion. EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.

Although efficacies and proportions of tympanoplasty performed via endoscopic ear surgery (EES) have gradually introduced, it remains unclear whether total EES is a good alternative to microscopic ear surgery (MES). Herein, we aimed to compare therapeutic effects of EES and MES in patients receiving tympanoplasty or myringoplasty. A search of MEDLINE, PubMed, and Embase databases was conducted to compare the efficacies of EES and MES. Two investigators independently reviewed all studies and extracted data with a standardized form. We assessed risk of bias and calculated pooled odds ratio (OR) estimates with a 95% confidence interval (CI). Thirteen studies (607 EES patients and 678 MES patients) met inclusion criteria for quantitative meta-analysis. In pooled analysis, those who undergo EES have 0.99 times the OR of graft success compared to those with MES (95% CI, 0.84 to 1.16; P=0.894). In qualitative analysis, comparable hearing improvement was observed between the two groups, despite inconsistent audiometric evaluation. The air-bone gaps (ABGs) improved 2.02 dB less in EES than in MES (mean difference of improvements of ABGs, 2.02; 95% CI, –3.84 to –0.20; P=0.029); however, substantial heterogeneity and publication bias limited the integrity of this analysis. Further, EES significantly decreased canalplasty rate, wound complications, and operation time, compared to MES. Moreover, patients receiving EES reported higher cosmetic satisfaction than patients receiving MES. EES can be a good alternative to MES in terms of comparable graft success rate and hearing outcomes in patients receiving tympanoplasty or myringoplasty. Moreover, EES was less invasive, resulting in higher cosmetic satisfaction, reduced morbidity, and shorter operation time. Our results may affect decision-making and outcome prediction in cases of EES; however, confirmation is needed to clarify potential bias.

The Seocheon Tidal Flat is an important staging and wintering site for the Far East Russian population of Swan Goose (Anser cygnoides) in the East Asian–Australasian Flyway. However, rapid environmental changes for tourism in this area can threaten the survival of this vulnerable population by hindering sufficient rest and wintering; therefore, establishing protection strategies based on Swan Goose behavioral characteristics is necessary. Here, we estimated Swan Goose core home ranges and habitat use based on GPS tracking data collected at the Seocheon Tidal Flat in South Korea from 2017–2018. The home range of Swan Geese was estimated to be an area from Yubu Island in the south to Janggu Bay in the north; however, the core home range and habitat use characteristics differed significantly between daytime and nighttime (Day: 59.9 km2, Night: 40.3 km2, on average, 100% MCP). During the day (08:00–18:00), Swan Geese mostly spent time resting or feeding on tidal flats, especially those around tidal channels or paddy fields near Janggu Bay, whereas they mostly rested on sand dunes near Yubu Island along with the mudflats at Janggu Bay at night. Our results provide practical information on the habitat use of wintering Swan Geese population over time and indicate that Yubu Island is an important resting place. Hence, these results can contribute to evaluating threats to Swan Geese and establishing management and protection strategies for the Seocheon Tidal Flat, a major wintering site for the Far East Russian population of Swan Geese.

The internal rearing environment of livestock houses has become an important issue in the last few years due to the rapid increase in meat consumption. As the number of days of heat waves increase continuously, problems caused by abnormal weather changes steadily occurred. Thus, the main goal of this study is to develop a technology that can automatically calculate heat stress for livestock by considering weather forecast data. Specifically, a web-based heat stress forecasting system for the evaluation of heat stress in broilers was developed. The field experiments were carried out at the selected broiler house to measure and analyze the external weather, the internal environment, and the ventilation flow rate of fans used in tunnel ventilation. The developed model was validated by comparing the field and simulated thermal environment values. Based on a reliable model, Land-Atmosphere Modeling Package (LAMP) weather forecast data was used to show the stress index on the internal rearing environment with a heat stress index suitable for South Korea. When the users input the farm location, structure and equipment, and rearing information, users responded after receiving heat stress from the broiler raised in a mechanically ventilated broiler house.

Background and Objectives: Many otologists face a dilemma in the decision-making process of surgical management of patients with cochlear nerve (CN) aplasia. The goal of this study is to provide fresh evidence on cochlear implantation (CI) results in patients with CN aplasia. Materials and Methods: We scrutinized functional outcomes in 37 ears of 21 children with bilateral CN aplasia who underwent unilateral or bilateral CI based on cross-sectional and longitudinal assessments. Results: The Categories of Auditory Performance (CAP) scores gradually improved throughout the 3-year follow-up; however, variable outcomes existed between individuals. Specifically, 90% of recipients with a 1-year postoperative CAP score ≤1 could not achieve a CAP score over 1 even at 3-year postoperative evaluation, while the recipients with a 1-year postoperative CAP score >1 had improved auditory performance, and 72.7% of them were able to achieve a CAP score of 4 or higher. Meanwhile, intraoperative electrically evoked compound action potential was not correlated with postoperative CAP score. Conclusions: Our results further refine previous studies on the clinical feasibility of CI as the first treatment modality to elicit favorable auditory performance in children with CN aplasia. However, special attention should be paid to pediatric patients with an early postoperative CAP score ≤1 for identification of unsuccessful cochlear implants and switching to auditory brainstem implants.

As the pig industry develops rapidly, various problems are increasing both inside and outside pig houses. In particular, in the case of pig houses, it is difficult to solve the main problems even if automation and mechanization are applied with Information and Communications Technologies (ICT). The air recirculation technology can be applied as a technology that can solve these typical problems in the pig industry, such as growth environment, livestock disease, odor emission, energy cost, and pig productivity. The air recirculated ventilation system (ARVS) can minimize the inflow of air from the outdoors and recycle the internal thermal energy of the pig house. The ARVS consists of (1) an air scrubber module, (2) an external air mixing module, (3) a UV cleaning module, (4) a solar heat module, and (5) an air distribution module. In this study, the growth environment of piglets was predicted using a numerical model when the ARVS was applied. Since the concept of air recirculation was used, numerous equations for predicting the internal environment should be iteratively calculated. Furthermore, it was necessary to determine the optimum condition of the modules by applying various boundary conditions. Therefore, the model was designed for numerical analysis based on the balance equations of environmental factors inside the piglet room. For each module, the module coefficient and equations were considered based on the previous studies. The analysis was conducted according to the system diagram of each module, and the growth environment inside the piglet room was evaluated according to the various environmental conditions. As a result of calculating the numerical model, the ventilation rate of 40 CMM or more was advantageous to properly maintaining the gas environment. In the summer season, it was necessary to additionally use the cooling device and dehumidifier. In the winter season, when using a heat exchanger and solar module, was more advantageous for maintaining air temperature inside the piglet room.

A Venlo-type greenhouse with a continuous roof vent (CR-Venlo greenhouse) was proposed by the Ministry of Agriculture, Food and Rural Affairs, South Korea (2019) for natural ventilation even during summers. It is ventilated through the buoyancy effect of the heated air using the high eave elevation. However, the CR-Venlo greenhouse was not distributed domestically, and its ventilation efficiency was not quantitatively evaluated. We aimed to analyze the natural ventilation efficiency of the greenhouse according to the eave height, using computational-fluid-dynamics. The simulation model was analyzed for hot summer conditions. The target greenhouse is ventilated only through the roof vent with all roof windows open; therefore, the air introduced through the roof window is easily exhausted. To evaluate the efficiency of ventilation, the external air entering through the roof window was calculated and evaluated. The amount of incoming air varied greatly with the location of the span and average temperature of the greenhouse; The temperature of the crop zone decreased lognormally with increasing height of the eave. Moreover, the ventilation efficiency of CR-Venlo greenhouse could be increased by improving the ventilation structure such as a shape, position or combination of roof window.

Sensorineural hearing loss is one of the most common inherited sensory disorders. Functional classifications of deafness genes have shed light on genotype- and mechanism-based pharmacological approaches and on gene therapy strategies. In this study, we characterized the clinical phenotypes and genotypes of non-syndromic deafness caused by transcription factor (TF) gene variants, one of the functional classifications of genetic hearing loss. Of 1280 probands whose genomic DNA was subjected to molecular genetic testing, TF genes were responsible for hearing loss in 2.6%. Thirty-three pathogenic variants, including nine novel variants, accounting for non-syndromic deafness were clustered in only four TF genes (POU3F4, POU4F3, LMX1A, and EYA4), which is indicative of a narrow molecular etiologic spectrum of TF genes, and the functional redundancy of many other TF genes, in the context of non-syndromic deafness. The audiological and radiological characteristics associated with the four TF genes differed significantly, with a wide phenotypic spectrum. The results of this study reveal the genetic load of TF gene alterations among a cohort with non-syndromic hearing loss. Additionally, we have further refined the clinical profiles associated with TF gene variants as a basis for a personalized, genetically tailored approach to audiological rehabilitation.

As the pig industry develops rapidly, various problems are appearing both inside and outside the pig houses. In particular, in the case of pig houses, it is difficult to solve the main problems even if automation and mechanization are applied with ICT technology. The main current issues are: (1) preventing infectious diseases amongst livestock, (2) reducing the emission of harmful gas and odors, (3) improving the growth environment inside the pig house, (4) reducing energy costs, (5) improving the farm management and operating system, and 6) improving the livestock product quality. Air recirculation technology can be applied as a technology that can solve these typical problems in the pig industry. An air-recirculated ventilation system can minimize the inflow of air from outdoors and recycle the internal thermal energy of the pig house. The air-recirculated ventilation system consists of (1) an air scrubber module, (2) external air-mixing module, (3) UV cleaning module, (4) solar heat module, and (5) air-distribution module. First, in this study, the field data were collected to analyze the main problems of the target piglet house for the application of the air-recirculated ventilation system. In addition, a computational fluid dynamics (CFD) model was developed and validated for seasonal aerodynamic analysis. The applicability of the air-recirculated ventilation system was evaluated based on the CFD computed results for various environmental conditions. As a result of evaluating the internal environment according to the ventilation rates and external-air-mixing ratio of the air-recirculated ventilation system, the required ventilation rate and external air-mixing ratio to maintain the proper temperature and gas concentration were determined.

The cortical auditory evoked potential (CAEP)-based P1 component acts as a biomarker for cochlear implantation (CI) outcomes in children with auditory neuropathy spectrum disorder (ANSD). To date, early intervention primarily before the age of two years and six months of CI usage is necessary and sufficient to achieve age-appropriate cortical maturation and good prognosis. However, varying degrees of neural dyssynchrony, resulting from the etiological heterogeneity of ANSD, may preclude uniform application of this hypothesis to ensure auditory cortical maturation. Thus, a focused evaluation of those carrying OTOF variants, which may be the salient molecular etiology of prelingual ANSD, would circumvent the issue of heterogeneity. Here, we sought to provide a much better understanding of the brain perspectives (i.e., P1 maturation) in OTOF-associated ANSD subjects and set the stage for an optimal strategy to enhance language development. We conducted a preliminary study comprising 10 subjects diagnosed with OTOF-related ANSD who underwent CI by a single surgeon and subsequently underwent measurements of the P1 component. We observed that DFNB9 subjects who received CI after 2 years of age exhibited "absent" or "anomalous" P1 components that correspond to delayed language development. However, timely implantation, as early as 12 months of age per se, might be insufficient to achieve age-appropriate cortical maturation of DFNB9 in cases with six to seven months of device use. This suggests the importance of sustained rehabilitation in DFNB9 than in other etiologies. Indeed, an additional follow-up study showed that a reduction in P1 latency was linked to an improvement in auditory performance. Collectively, our results suggest that central auditory maturation and successful outcome of CI in DFNB9 may have more demanding requirements, that is, earlier implantation and more sustained rehabilitation. We believe that the current study opens a new path toward genome-based neuroimaging in the field of hearing research.

Just as the human brain works in a Bayesian manner to minimize uncertainty regarding external stimuli, a deafferented brain due to hearing loss attempts to obtain or “fill in” the missing auditory information, resulting in auditory phantom percepts (i.e., tinnitus). Among various types of hearing loss, sudden sensorineural hearing loss (SSNHL) has been extensively reported to be associated with tinnitus. However, the reason that tinnitus develops selectively in some patients with SSNHL remains elusive, which led us to hypothesize that patients with SSNHL with tinnitus (SSNHL-T) and those without tinnitus (SSNHL-NT) may exhibit different cortical activity patterns. In the current study, we compared resting-state quantitative electroencephalography findings between 13 SSNHL-T and 13 SSNHL-NT subjects strictly matched for demographic characteristics and hearing thresholds. By performing whole-brain source localization analysis complemented by functional connectivity analysis, we aimed to determine the as-yet-unidentified cortical oscillatory signatures that may reveal potential prerequisites for the perception of tinnitus in patients with SSNHL. Compared with the SSNHL-NT group, the SSNHL-T group showed significantly higher cortical activity in Bayesian inferential network areas such as the frontopolar cortex, orbitofrontal cortex (OFC), and pregenual anterior cingulate cortex (pgACC) for the beta 3 and gamma frequency bands. This suggests that tinnitus develops in a brain with sudden auditory deafferentation only if the Bayesian inferential network updates the missing auditory information and the pgACC-based top-down gatekeeper system is actively involved. Additionally, significantly increased connectivity between the OFC and precuneus for the gamma frequency band was observed in the SSNHL-T group, further suggesting that tinnitus derived from Bayesian inference may be linked to the default mode network so that tinnitus is regarded as normal. Taken together, our preliminary results suggest a possible mechanism for the selective development of tinnitus in patients with SSNHL. Also, these areas could serve as the potential targets of neuromodulatory approaches to preventing the development or prolonged perception of tinnitus in subjects with SSNHL.

Tinnitus is a conscious auditory perception in the absence of an external stimulus. Despite previous reports of a recognized association between tinnitus and cognitive deficits, the effects of tinnitus on functional and structural brain changes associated with cognitive deficits remain unknown. We aimed to investigate the changes in glucose metabolism and gray matter (GM) volume in subjects diagnosed with mild cognitive impairment (MCI) depending on tinnitus. Twenty-three subjects were subclassified into MCI with the chronic tinnitus (MCI_T) and MCI without tinnitus (MCI_NT) groups. Encouraged by the identification of neural substrates associated with tinnitus and cognitive deficits, we correlated the extent of tinnitus severity with the changes in glucose metabolism and GM volume and conducted a glucose metabolic connectivity study. Compared to the MCI_NT group, the MCI_T group showed significantly lower metabolism in the right superior temporal pole and left fusiform gyrus. Additionally, the GM volume in the right insula was markedly lower in the MCI_T group compared to the MCI_NT group. Moreover, correlation analyses in metabolism or GM volumes revealed specific brain regions associated with the cognitive decline with increasing tinnitus severity. Metabolic connectivity analysis revealed that MCI_NT had markedly strengthened intra-hemispheric connectivity in the frontal, parietal, and occipital regions than did MCI_T. Furthermore, MCI_NT showed a strong negative association between the parietal and temporal and parietal and limbic regions, but the association was not observed in MCI_T. These findings indicate that tinnitus may cause metabolic and structural changes in the brain and alters complex inter- or intra-hemispheric networks in MCI. Considering the impact of MCI on accelerating dementia, these results provide a valuable basis on which yet-to-be-identified neurodegenerative markers of tinnitus can be refined.

Superior semicircular canal dehiscence (SCD), which is characterized by a “third mobile window” in the inner ear, causes various vestibular and auditory symptoms and signs. Surgical plugging of the superior semicircular canal (SC) can eliminate the symptoms associated with increased perilymph mobility due to the presence of the third window. However, the natural course of vestibular function after surgical plugging remains unknown. Therefore, we explored longitudinal vestibular function after surgery in 11 subjects with SCD who underwent SC plugging using the middle cranial fossa approach. Changes in vestibulo-ocular reflex (VOR) gain in all planes were measured over 1 year with the video head impulse test. We also evaluated surgical outcomes, including changes in symptoms, audiometric results, and electrophysiological tests, to assess whether plugging eliminated third mobile window effects. The mean VOR gain for the plugged SC decreased from 0.81 ± 0.05 before surgery to 0.65 ± 0.08 on examinations performed within 1 week after surgery but normalized thereafter. Four of seven subjects who were able to perform both VOR tests before surgery and immediately after surgery had pathologic values (SC VOR gain < 0.70). Conversely, the mean VOR gain in the other canals remained unchanged over 1 year. The majority of symptoms and signs were absent or markedly decreased at the last follow-up evaluation, and no complications associated with the surgery were reported. Surgical plugging significantly attenuated the air-bone gap, in particular at low frequencies, because of increased bone conduction thresholds and deceased air conduction thresholds. Moreover, surgical plugging significantly increased vestibular-evoked myogenic potential thresholds and decreased the ratio of summating potential to action potential in plugged ears. Postoperative heavily T2-weighted images were available for two subjects and showed complete obliteration of the T2-bright signal intensity in the patent SC lumen in preoperative imaging based on filling defect at the site of plugging. Our results suggest that successful plugging of dehiscent SCs is closely associated with a transient, rather than persistent, disturbance of labyrinthine activity exclusively involved in plugged SCs, which may have clinical implications for timely and individualized vestibular rehabilitation.

Energy management of a building-integrated rooftop greenhouse (BiRTG) is considered one of the important factors. Accordingly, the interest in energy simulation models has increased. Energy load computed from the simulation model can be used for appropriate capacity calculation and optimal operation of the environmental control system. In particular, because the thermal environment of greenhouses is sensitive to the external weather environment, dynamic energy simulations, such as building energy simulation (BES), play an essential role in understanding the complex mechanisms of heat transfer in greenhouses. Depending on the type and crop density, there is a significant difference in the thermal energy loads of greenhouses. Furthermore, ventilation is also an important factor affecting the energy input of the greenhouse. Therefore, this study aimed to design and validate BES models considering the crop and ventilation characteristics of a naturally ventilated greenhouse before designing and evaluating a BES model for the BiRTG. First, the BES module for the greenhouse and crop models was designed using field-measured data, and the ventilation characteristics were analysed using computational fluid dynamics (CFD). The greenhouse BES model was designed and then validated by comparing air temperature (Ta) and relative humidity (RH) measured at the greenhouse with the BES-computed results of the greenhouse model. The results showed that the average absolute error of Ta was 1.57 °C and RH was 7.7%. The R2 of the designed BES model for Ta and RH were 0.96 and 0.89, respectively. These procedures and sub-modules developed were applied to the energy load calculation of BiRTG.

Building-integrated rooftop greenhouses (BiRTGs) are innovative vertical farms consisting of a greenhouse on the roof of a building. BiRTGs can provide environmental benefits by recycling energy, carbon dioxide, and water between the greenhouse and the building. Moreover, BiRTGs can reduce cooling and heating loads by reducing the exposure of the building surface to heat gains/losses through the roof. However, the benefits of BiRTGs have not yet been completely elucidated from an energy perspective. This study aimed to analyse the energy-saving efficiency of BiRTGs using building energy simulations (BES) and computational fluid dynamics (CFD) techniques. BES is a calculation method for analysing the heating and cooling loads of buildings; however, it was difficult to consider time-dependent changes in the ventilation characteristics in the BES model. CFD can be used to calculate more detailed ventilation characteristics of an experimental facility. Thus, CFD and the BES were combined to obtain more accurate BES-based data. The BES-computed annual energy load for a single-span greenhouse in which tomatoes were grown was 490,128 MJ, whereas the annual energy load for growing tomatoes in a BiRTG resulted in a 5.2% reduction, on average (464,673 MJ). The energy-saving effects were positive from October to April because the BiRTG helped transmit heat energy transmitted from the building to the greenhouse. Regarding the total energy load in the BiRTG after alternating the air temperature management (ATM), the heating energy load was reduced in the winter. ATM was expected to apply from November to March, with average energy savings of 11.8%.

The duck industry ranks sixth as one of the fastest-growing major industries for livestock production in South Korea. However, there are few studies quantitatively predicting the internal thermal and moisture environment of duck houses. In this study, high-accuracy recurrent neural network (RNN) models were used to predict the internal air temperature and relative humidity of mechanically and naturally ventilated duck houses. The models were developed according to the type of duck houses, seasons, and environmental variables by learning the monitoring data of the internal and external environments. The optimal sequence length of learning data for the development of the RNN model was selected as 120 min. As a result of the validation, both air temperature and relative humidity could be accurately predicted within 1% error. In addition, simplified RNN models were additionally developed by learning only from the data of external air temperature, relative humidity, and duck weight, which are relatively easy to acquire at the farms. The accuracy of the simplified RNN models was similar to the basic model for predicting the internal air temperature and relative humidity of duck houses in real time. In the future, for the convergence of information and communications technologies (ICTs) and application of smart farms in duck houses, the RNN models of duck houses developed in this study can be applied to predict and control the internal environments of duck houses using the model predictive control (MPC) technique.

Although tinnitus retraining therapy (TRT) based on Jastreboff’s classical neurophysiological model is efficacious in most patients, its effects on the cortical activity changes responsible for the improvement of tinnitus are still unclear. In this study, we compared pre- and post-TRT resting-state quantitative electroencephalography (rs-qEEG) findings to identify power changes that could explain TRT-induced improvements. Thirty-seven patients with severe tinnitus were enrolled in the study, and rs-qEEG data recorded before the initial TRT sessions and 6 months after TRT were compared. In addition, associations between the changes in qEEG and percentage improvements in Tinnitus Handicap Inventory (THI) scores and numeric rating scale (NRS) scores of tinnitus loudness and tinnitus perception were examined. The mean THI score decreased significantly 6 months after the initial TRT session. Also, significant improvements were observed 6 months after the initial TRT session compared with the pre-treatment scores in NRS loudness, distress, and perception. As compared with the pre-TRT status, post-TRT 6 months status showed significantly decreased powers in the left primary and secondary auditory cortices for the gamma frequency band. Changes in the alpha 1 frequency band power in the right insula and orbitofrontal cortex (OFC) appeared to be positively correlated with the percentage changes in NRS distress. These results suggested that TRT improved tinnitus-related distress by reducing the power of the top-down autonomic response modulator or peripheral physiological responses to emotional experiences. That is, TRT induced habituation via modulation of functional connections between the auditory system and the limbic and autonomic nervous systems. Our results confer additional basis for understanding the neurophysiological model and the newly suggested integrative model of tinnitus by De Ridder et al. (2014) in the context of the long-term efficacy of TRT.

To utilize the energy in the thermal effluent, many attempts have been made to use the thermal effluent for agricultural facilities such as greenhouses. As the first step, it is important to estimate the energy loads of the greenhouse for deciding a suitable scale for the heating and cooling. Then, it is available to estimate the energy efficiency of the thermal effluent heat pump system installed in the greenhouse. Therefore, the main objectives of this study were to design and validate an energy model of the experimental greenhouse growing Irwin mangoes and to estimate the annual and maximum energy loads using building energy simulation (BES). Field experiments were conducted in a multi-span plastic-covered greenhouse growing Irwin mangoes to measure the internal environments of the greenhouse and crop characteristics. The energy exchange model of the greenhouse considering crop, cladding, heat pump was developed using BES. The BES model was validated using the data measured at field experiments. The designed model was found to be able to provide satisfactory estimates of the changes of the internal air temperature of the greenhouse (R2 = 0.94 and d = 0.97). The hourly energy loads computed by using the validated model were used to analyse the periodic and maximum energy loads according to the growth stage of the cultivated crops. Finally, the energy costs were compared according to the type of energy source based on the calculated annual energy loads. The average energy cost when using the thermal effluent—heat pump system was found to be 68.21% lower than that when a kerosene boiler was used.

A substantial reduction in the environmental impacts related to the construction and operation of agricultural buildings is needed to adapt to the continuing development of agriculture. The life cycle assessment (LCA) is a methodology used to quantify the environmental impact of different processes involved in the production and therefore has been increasingly applied to assess the environmental burden. However, most LCA-related research studies have focused on the overall environmental impact of the entire system without considering the energy load of the agricultural buildings. By integrating the LCA tool with other design tools such as the building energy simulation (BES), the identification of environmental hotspots and the mitigation options become possible during the design process. Thus, the objective of the paper was to identify the current integration approaches used to combine BES and LCA results to assess the environmental impact of different heating systems such as absorption heat pump (AHP) using energy from thermal effluent, electricity-powered heat pump and kerosene-powered boilers used in a conventional multi-span Korean greenhouse. The assessment result revealed that the environmental impact caused using a kerosene-powered boiler is largest in terms of the acidification potential (AP), global warming potential (GWP) and Eutrophication Potential (EP) of 1.15 × 100 kg SO2-eq, 1.13 × 102 kg CO2-eq and 1.62 × 10−1 kg PO4-eq, respectively. Detailed analysis of the result showed that the main contributor for greenhouse gas emission was caused by the type, amount and source of energy used to heat the greenhouse, which contributed to a maximum of 86.59% for case 1, 96.69% for case 2 and a maximum of 96.47% for case 3, depending on the type of greenhouse gas being considered.

With the rise in livestock production, the odour concentration emitted from livestock facilities has significantly increased. For this reason, odour complaints have become a major issue. The dispersion of the odour into the atmosphere is affected by various factors (wind speed, wind direction, atmospheric stability, terrain condition, ventilation type, and so on). Thus, a thorough analysis on the factor influencing odour dispersion is necessary to establish regulations and policies for odour management. Therefore, this research aimed to evaluate odour dispersion generated from a pig house with complex terrain using computational fluid dynamics (CFD) and to statistically determine the key factor for odour dispersion. By comparing CFD-computed results with field-measured data, an appropriate grid size, time step, and turbulence model of the CFD model were determined. Considering various factors, case studies were performed using the validated CFD model. The CFD-computed results showed that odour dispersion distance at the level of 1 OU m−3 ranged from 129.7 to 1488.1 m. The prediction of odour dispersion distance varies with the change of factor being analysed. Finally, the statistical analysis showed that the most influential factor that affected odour dispersion distance was the wind speed with a t-value: −9.057.

Routine application of next-generation sequencing in clinical settings is often limited by time- and cost-prohibitive complex filtering steps. Despite the previously introduced genotyping kit that allows screening of the 11 major recurring variants of sensorineural hearing loss (SNHL) genes in the Korean population, the demand for phenotype- and variant-specific screening kits still remains. Herein, we developed a new real-time PCR-based kit (U-TOP™ HL Genotyping Kit Ver2), comprising six variants from two auditory neuropathy spectrum disorder (ANSD) genes (OTOF and ATP1A3) and five variants from three SNHL genes (MPZL2, COCH, and TMC1), with a distinct auditory phenotype, making this the first genotyping kit dedicated to ANSD. The concordance rate with Sanger sequencing, sensitivity, and specificity of this genotyping kit were all 100%, suggesting reliability. The kit not only allows timely and cost-effective identification of recurring OTOF variants, but it also allows timely detection of cochlear nerve deficiency for those without OTOF variants. Herein, we provide a clinical guideline for an efficient, rapid, and cost-effective etiologic diagnosis of prelingual ANSD. Our study provides a good example of continuing to update new key genetic variants, which will continuously be revealed through NGS, as targets for the newly developed genotyping kit.