Chemokine Receptor CCR2 Is Protective toward Outer Hair Cells in Chronic Suppurative Otitis Media.

Chronic suppurative otitis media (CSOM) is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. Previously, we discovered that outer hair cell (OHC) loss occurred in the basal turn of the cochlea and that macrophages are the major immune cells associated with OHC loss in CSOM. Macrophage-associated cytokines are upregulated. Specifically, CCL-2, an important member of the MCP family, is elevated over time following middle ear infection. CCR2 is a common receptor of the MCP family and the unique receptor of CCL2. CCR2 knockout mice (CCR2-/-) have been used extensively in studies of monocyte activation in neurodegenerative diseases. In the present study, we investigated the effect of CCR2 deletion on the cochlear immune response and OHC survival in CSOM. The OHC survival rate was 84 ± 12.5% in the basal turn of CCR2+/+ CSOM cochleae, compared with was 63 ± 19.9% in the basal turn of CCR2-/- CSOM cochleae (p ≤ 0.05). Macrophage numbers were significantly reduced in CCR2-/- CSOM cochleae compared with CCR2+/+ CSOM cochleae (p ≤ 0.001). In addition, CCL7 was upregulated, whereas IL-33 was downregulated, in CCR2-/- CSOM cochleae. Finally, the permeability of the blood-labyrinth barrier in the stria vascularis remained unchanged in CCR2-/- CSOM compared with CCR2+/+ CSOM. Taken together, the data suggest that CCR2 plays a protective role through cochlear macrophages in the CSOM cochlea.

Modulating the unfolded protein response with ISRIB mitigates cisplatin ototoxicity.

Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin, and UPR marker gene expression and cell death measured. Treatment with ISRIB (Integrated Stress Response InhIBitor), a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested for its ability to reduce apoptosis in HEK cells, hair-cell death in cochlear cultures, and hearing loss using an in vivo mouse model of cisplatin ototoxicity. Finally, to evaluate whether ISRIB might interfere with cisplatin chemoeffectiveness, we tested it in head and neck squamous cell carcinoma (HNSCC) cell-based assays of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose-response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatin's cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.

A cochlear progenitor pool influences patterning of the mammalian sensory epithelium via MYBL2.

During embryonic development, Wnt signaling influences both proliferation and sensory formation in the cochlea. How this dual nature of Wnt signaling is coordinated is unknown. In this study, we define a novel role for a Wnt-regulated gene, Mybl2, which was already known to be important for proliferation, in determining the size and patterning of the sensory epithelium in the murine cochlea. Using a quantitative spatial analysis approach and analyzing Mybl2 loss-of-function, we show that Mybl2 promoted proliferation in the inner sulcus domain but limited the size of the sensory domain by influencing their adjoining boundary position via Jag1 regulation during development. Mybl2 loss-of-function simultaneously decreased proliferation in the inner sulcus and increased the size of the sensory domain, resulting in a wider sensory epithelium with ectopic inner hair cell formation during late embryonic stages. These data suggest that progenitor cells in the inner sulcus determine boundary formation and pattern the sensory epithelium via MYBL2.

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection.

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.

Speech intelligibility prediction based on a physiological model of the human ear and a hierarchical spiking neural network.

A speech intelligibility (SI) prediction model is proposed that includes an auditory preprocessing component based on the physiological anatomy and activity of the human ear, a hierarchical spiking neural network, and a decision back-end processing based on correlation analysis. The auditory preprocessing component effectively captures advanced physiological details of the auditory system, such as retrograde traveling waves, longitudinal coupling, and cochlear nonlinearity. The ability of the model to predict data from normal-hearing listeners under various additive noise conditions was considered. The predictions closely matched the experimental test data under all conditions. Furthermore, we developed a lumped mass model of a McGee stainless-steel piston with the middle-ear to study the recovery of individuals with otosclerosis. We show that the proposed SI model accurately simulates the effect of middle-ear intervention on SI. Consequently, the model establishes a model-based relationship between objective measures of human ear damage, like distortion product otoacoustic emissions, and speech perception. Moreover, the SI model can serve as a robust tool for optimizing parameters and for preoperative assessment of artificial stimuli, providing a valuable reference for clinical treatments of conductive hearing loss.

Temporal fine structure sensitivity measured with pulse-spreading harmonic complexes.

Two experiments investigated sensitivity to temporal fine structure (TFS) in a group of normal hearing participants. The stimuli were bandpass filtered pulse-spreading harmonic complexes (PSHCs) with a regular envelope repetition rate and a phase adjusted so that the TFS peaks were progressively shifted across envelope periods. For up-PSHCs, the TFS peaks were advanced, yielding a rising pitch percept, while for down-PSHCs, the peaks were delayed, yielding a falling pitch percept. Experiment 1 showed that in a fixed frequency region, there was a range of rates for which the direction of the pitch change could be identified. Cochlear model simulations suggested that participants may use either place-of-excitation and/or temporal cues to perform this task. Experiment 2 showed that there was an envelope rate below which down-PSHCs and up-PSHCs could not be discriminated. This lower envelope rate limit of TFS sensitivity significantly increased with increases in frequency region and was similar to the lower rate limit of melodic pitch. The results in high frequency regions suggest that TFS cues are available up to 10 kHz when the rank of the lowest component present in the passband is 18, and all harmonics are presumably unresolved.

Activated tissue-resident macrophages contribute to hair cell insults in noise-induced hearing loss in mice.

Macrophages serve as the primary immune cell population and assume a pivotal role in the immune response within the damaged cochleae. Yet, the origin and role of macrophages in response to noise exposure remain controversial. Here, we take advantage of Ccr2RFP/+ Cx3cr1GFP/+ dual-reporter mice to identify the infiltrated and tissue-resident macrophages. After noise exposure, we reveal that activated resident macrophages change in morphology, increase in abundance, and migrate to the region of hair cells, leading to the loss of outer hair cells and the damage of ribbon synapses. Meanwhile, peripheral monocytes are not implicated in the noise-induced hair cell insults. These noise-induced activities of macrophages are abolished by inhibiting TLR4 signaling, resulting in alleviated insults of hair cells and partial recovery of hearing. Our findings indicate cochlear resident macrophages are pro-inflammatory and detrimental players in acoustic trauma and introduce a potential therapeutic target in noise-induced hearing loss.

TUBB4B is essential for the cytoskeletal architecture of cochlear supporting cells and motile cilia development.

Microtubules are essential for various cellular processes. The functional diversity of microtubules is attributed to the incorporation of various α- and ß-tubulin isotypes encoded by different genes. In this work, we investigated the functional role of ß4B-tubulin isotype (TUBB4B) in hearing and vision as mutations in TUBB4B are associated with sensorineural disease. Using a Tubb4b knockout mouse model, our findings demonstrate that TUBB4B is essential for hearing. Mice lacking TUBB4B are profoundly deaf due to defects in the inner and middle ear. Specifically, in the inner ear, the absence of TUBB4B lead to disorganized and reduced densities of microtubules in pillar cells, suggesting a critical role for TUBB4B in providing mechanical support for auditory transmission. In the middle ear, Tubb4b-/- mice exhibit motile cilia defects in epithelial cells, leading to the development of otitis media. However, Tubb4b deletion does not affect photoreceptor function or cause retinal degeneration. Intriguingly, ß6-tubulin levels increase in retinas lacking ß4B-tubulin isotype, suggesting a functional compensation mechanism. Our findings illustrate the essential roles of TUBB4B in hearing but not in vision in mice, highlighting the distinct functions of tubulin isotypes in different sensory systems.

Targeting the NLRP3 inflammasome in cochlear macrophages protects against hearing loss in chronic suppurative otitis media.

The activation of the NLRP3 inflammasome has been linked to several inflammatory and autoinflammatory diseases. Despite cases of potential hearing improvement in immune-mediated diseases, direct evidence of the efficacy of targeting this mechanism in the inner ear is still lacking. Previously, we discovered that macrophages are associated with Sensorineural Hearing loss (SNHL) in Chronic Suppurative Otitis Media (CSOM), the leading cause of this permanent hearing loss in the developing world and incurring costs of $4 to $11 billion dollars in the United States. However, the underlying mechanism remained unknown. Here, we investigate how macrophages drive permanent hearing loss in CSOM. We first confirmed the occurrence of NLRP3 inflammasome activation in cochlear macrophages in CSOM. We then revealed that Outer Hair Cells (OHCs) were protected in CSOM by macrophage depletion and subsequently confirmed the same protection in the NLRP3 knockout condition. Furthermore, we showed that therapeutic inhibition of NLRP3 inflammasome activation and downstream inhibition of IL-1ß protects OHCs in CSOM. Collectively, our data demonstrates that the main driver for hearing loss in CSOM is NLRP3 inflammasome activation in cochlear macrophages and this is therapeutically targetable, leading the way for the development of interventions to prevent the leading cause of permanent hearing loss and a costly disease in the developed world.

A pore locus in the E1 domain differentially regulates Cx26 and Cx30 hemichannel function.

Connexins (Cxs) function as gap junction (GJ) channels and hemichannels that mediate intercellular and transmembrane signaling, respectively. Here, we investigated the proximal segment of the first extracellular loop, E1, of two closely related Cxs, Cx26 and Cx30, that share widespread expression in the cochlea. Computational studies of Cx26 proposed that this segment of E1 contains a parahelix and functions in gating. The sequence of the parahelix is identical between Cx26 and Cx30 except for an Ala/Glu difference at position 49. We show through cysteine-scanning and mutational analyses that position 49 is pore-lining and interacts with the adjacent Asp50 residue to impact hemichannel functionality. When both positions 49 and 50 are charged, as occurs naturally in Cx30, the hemichannel function is dampened. Co-expression of Cx30 with Cx26(D50N), the most common mutation associated with keratitis-ichthyosis-deafness syndrome, results in robust hemichannel currents indicating that position 49-50 interactions are relevant in heteromerically assembled hemichannels. Cysteine substitution at position 49 in either Cx26 or Cx30 results in tonic inhibition of hemichannels, both through disulfide formation and high-affinity metal coordination, suggestive of a flexible region of the pore that can narrow substantially. These effects are absent in GJ channels, which exhibit wild-type functionality. Examination of postnatal cochlear explants suggests that Cx30 expression is associated with reduced propagation of Ca2+ waves. Overall, these data identify a pore locus in E1 of Cx26 and Cx30 that impacts hemichannel functionality and provide new considerations for understanding the roles of these connexins in cochlear function.

Two new mouse alleles of Ocm and Slc26a5.

The genes Ocm (encoding oncomodulin) and Slc26a5 (encoding prestin) are expressed strongly in outer hair cells and both are involved in deafness in mice. However, it is not clear if they influence the expression of each other. In this study, we characterise the auditory phenotype resulting from two new mouse alleles, Ocmtm1e and Slc26a5tm1Cre. Each mutation leads to absence of detectable mRNA transcribed from the mutant allele, but there was no evidence that oncomodulin regulates expression of prestin or vice versa. The two mutants show distinctive patterns of auditory dysfunction. Ocmtm1e homozygotes have normal auditory brainstem response thresholds at 4 weeks old followed by progressive hearing loss starting at high frequencies, while heterozygotes show largely normal thresholds until 6 months of age, when signs of worse thresholds are detected. In contrast, Slc26a5tm1Cre homozygotes have stable but raised thresholds across all frequencies tested, 3 to 42 kHz, at least from 4 to 8 weeks old, while heterozygotes have raised thresholds at high frequencies. Distortion product otoacoustic emissions and cochlear microphonics show deficits similar to auditory brainstem responses in both mutants, suggesting that the origin of hearing impairment is in the outer hair cells. Endocochlear potentials are normal in the two mutants. Scanning electron microscopy revealed normal development of hair cells in Ocmtm1e homozygotes but scattered outer hair cell loss even at 4 weeks old when thresholds appeared normal, indicating that there is not a direct relationship between numbers of outer hair cells present and auditory thresholds.

The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress.

Noise-induced hidden hearing loss (HHL) is a newly uncovered form of hearing impairment that causes hidden damage to the cochlea. Patients with HHL do not have significant abnormalities in their hearing thresholds, but they experience impaired speech recognition in noisy environments. However, the mechanisms underlying HHL remain unclear. In this study, we developed single-cell transcriptome profiles of the cochlea of mice with HHL, detailing changes in individual cell types. Our study revealed a transient threshold shift, reduced auditory brainstem response wave I amplitude, and decreased number of ribbon synapses in HHL mice. Our findings suggest elevated oxidative stress and GDF15 expression in cochlear hair cells of HHL mice. Notably, the upregulation of GDF15 attenuated oxidative stress and auditory impairment in the cochlea of HHL mice. This suggests that a therapeutic strategy targeting GDF15 may be efficacious against HHL.

A Subcortical Model for Auditory Forward Masking with Efferent Control of Cochlear Gain.

Previous physiological and psychophysical studies have explored whether feedback to the cochlea from the efferent system influences forward masking. The present work proposes that the limited growth-of-masking (GOM) observed in auditory nerve (AN) fibers may have been misunderstood; namely, that this limitation may be due to the influence of anesthesia on the efferent system. Building on the premise that the unanesthetized AN may exhibit GOM similar to more central nuclei, the present computational modeling study demonstrates that feedback from the medial olivocochlear (MOC) efferents may contribute to GOM observed physiologically in onset-type neurons in both the cochlear nucleus and inferior colliculus (IC). Additionally, the computational model of MOC efferents used here generates a decrease in masking with longer masker-signal delays similar to that observed in IC physiology and in psychophysical studies. An advantage of this explanation over alternative physiological explanations (e.g., that forward masking requires inhibition from the superior paraolivary nucleus) is that this theory can explain forward masking observed in the brainstem, early in the ascending pathway. For explaining psychoacoustic results, one strength of this model is that it can account for the lack of elevation in thresholds observed when masker level is randomly varied from interval-to-interval, a result that is difficult to explain using the conventional temporal window model of psychophysical forward masking. Future directions for evaluating the efferent mechanism as a contributing mechanism for psychoacoustic results are discussed.

The caspase-inhibitor Emricasan efficiently counteracts cisplatin- and neomycin-induced cytotoxicity in cochlear cells.

Cisplatin is a chemotherapeutic agent widely used to treat solid tumors. However, it can also be highly ototoxic, resulting in high-frequency hearing loss. Cisplatin causes degeneration of hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear, which are essential components of the hearing process and cannot be regenerated in mammals. As the affected cells primarily die by apoptosis, we tested several anti-apoptotic small molecules to protect these cells from drug-induced toxicity. We found that the general caspase inhibitor Emricasan could significantly counteract the toxic effects of cisplatin in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, phoenix auditory cells, and primary SGNs. Importantly, the anti-cytotoxic effect in neuronal cells was even more pronounced than the effect of sodium thiosulfate (STS), which is currently the only approved prevention option for cisplatin-induced ototoxicity. Finally, we tested the protective effect of Emricasan treatment in the context of another ototoxic drug, i.e., the aminoglycoside antibiotic neomycin, and again found a significant increase in cell viability when the cultures were co-treated with Emricasan. These results suggest a promising strategy to prevent ototoxicity in patients by temporarily blocking the apoptotic pathway when applying cisplatin or aminoglycoside antibiotics. KEY MESSAGES: Anti-apoptotic small molecules can reduce cisplatin-induced toxicity. Emricasan can effectively exert its anti-apoptotic effect on cochlear cells. Strong protection from cisplatin- and neomycin-induced cytotoxicity with Emricasan. Sodium thiosulfate and Emricasan provide similar protective effects to cisplatin-treated cells. Emricasan is more potent than sodium thiosulfate in reducing neomycin-induced cytotoxicity.

Calcitriol alleviates noise-induced hearing loss by regulating the ATF3/DUSP1 signalling pathway.

BACKGROUND: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. METHODS: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. RESULTS: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database （GTRD）and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. CONCLUSION: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

Evaluation of a Slim Modiolar Electrode Array: A Temporal Bone Study.

HYPOTHESIS: Evaluation of the Slim Modiolar (SM) electrode in temporal bones (TB) will elucidate the electrode's insertion outcomes. BACKGROUND: The SM electrode was designed for atraumatic insertion into the scala tympani, for ideal perimodiolar positioning and with a smaller caliber to minimize interference with cochlear biological processes. METHODS: The SM electrode was inserted into TBs via a cochleostomy. First, the axial force of insertion was measured. Next, TBs were inserted under fluoroscopy to study insertion dynamics, followed by histologic evaluation of electrode placement and cochlear trauma. A subset of TBs were inserted with the Contour Advance (CA) electrode for comparison. RESULTS: Sixteen of 22 insertions performed to measure the axial force of insertion had flat or near zero insertion force profiles. Six insertions had increased insertion forces, which were attributed to improper sheath depth before electrode insertion. Under real-time fluoroscopy, 23 of 25 TBs had uneventful insertion and good perimodiolar placement. There was 1 scala vestibuli insertion due to suboptimal cochleostomy position and 1 tip roll over related to premature electrode deployment. When compared with the CA electrode, 14 of 15 insertions with the SM electrode resulted in a more perimodiolar electrode position. No evidence of trauma was found in histologic evaluation of the 24 TBs with scala tympani insertions. CONCLUSION: TB evaluation revealed that the SM electrode exerts minimal insertion forces on cochlear structures, produces no histologic evidence of trauma, and reliably assumes the perimodiolar position. Nonstandard cochleostomy location, improper sheath insertion depth, or premature deployment of the electrode may lead to suboptimal outcomes.

Hyperglycemia-induced oxidative stress exacerbates mitochondrial apoptosis damage to cochlear stria vascularis pericytes via the ROS-mediated Bcl-2/CytC/AIF pathway.

OBJECTIVES: Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss. METHODS: We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes. RESULTS: Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis. DISCUSSION: Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.

Research on sound quality prediction of vehicle interior noise using the human-ear physiological model.

In order to improve the prediction accuracy of the sound quality of vehicle interior noise, a novel sound quality prediction model was proposed based on the physiological response predicted metrics, i.e., loudness, sharpness, and roughness. First, a human-ear sound transmission model was constructed by combining the outer and middle ear finite element model with the cochlear transmission line model. This model converted external input noise into cochlear basilar membrane response. Second, the physiological perception models of loudness, sharpness, and roughness were constructed by transforming the basilar membrane response into sound perception related to neuronal firing. Finally, taking the calculated loudness, sharpness, and roughness of the physiological model and the subjective evaluation values of vehicle interior noise as the parameters, a sound quality prediction model was constructed by TabNet model. The results demonstrate that the loudness, sharpness, and roughness computed by the human-ear physiological model exhibit a stronger correlation with the subjective evaluation of sound quality annoyance compared to traditional psychoacoustic parameters. Furthermore, the average error percentage of sound quality prediction based on the physiological model is only 3.81%, which is lower than that based on traditional psychoacoustic parameters.

Cochlear Implantation: Small Cochlear Diameter May Indicate Degree of Abnormality.

Cochlear size variation was first reported in 1884, and since then, there have been various reports confirming the same. Yet, there is no single report that has displayed the wide variations in the cochlear size in a single layout capturing the cochlea in the oblique coronal view/ cochlear view. Basal turn diameter (A-value) was measured in the oblique coronal plane using the OTOPLAN® otological preplanning tool in 104 computed tomography (CT) scans of the temporal bones of cochlear implant (CI) recipients in a tertiary CI center. All CT scans with an image resolution of at least 0.5 mm and identified as having cochleae with normal anatomy were included in this study. A 3-dimensional (3D) segmentation was performed using the 3D slicer and visualized to evaluate the impact of cochlear size on the number of turns studied. The A-value was found to vary between 7.3 mm and 10.4 mm among the studied patients. Three-dimensional segmentation of the inner ear revealed only 2 turns of the cochlea in 4 ears, with A-values of 7.3, 8.8, 7.8, and 7.7 mm. One ear had only 11 /2 turns of the cochlea, with an A-value of 7.9 mm. As a further advancement in the assessment of cochlear size as determined by the A-value, 3D segmentation of the complete inner ear provides a full picture of the number of cochlear turns. Three-dimensional segmentation of the entire inner ear could help improve the preoperative planning of CI surgery and have implications for electrode array selection. Cochlear size could be a predictor of the number of cochlear turns, even in cases that look normal from the radiological findings. The findings of this study could help in improving the preoperative planning for a more successful CI surgery by differentiating between the normal and abnormal cochlea.