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Journal of the Association for Research in Otolaryngology

○ Springer Science and Business Media LLC

Preprints posted in the last 30 days, ranked by how well they match Journal of the Association for Research in Otolaryngology's content profile, based on 15 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

1
Refractoriness-Based Masking Yields Threshold-Specific Human Auditory Nerve Responses

Chen, F.; Stoll, T. J.; Jones, G. R.; Maddox, R. K.

2026-09-25 neuroscience 10.64898/2026.09.19.752910 medRxiv
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Distinct auditory nerve (AN) fiber populations with varying thresholds and vulnerabilities to synaptopathy are observable in animal models, but standard non-invasive human measures lack the resolution to differentiate these groups of fibers. This fundamental limitation hinders the translation of findings in animals to human auditory pathologies. To overcome this, we developed a novel refractoriness-masking paradigm to non-invasively isolate threshold-specific AN fiber responses in humans. By presenting rapid click trains with cumulatively rising levels (45 to 105 dB peSPL) at a 250-microsecond inter-click interval, we sequentially masked lower-threshold fibers. Using a tympanic membrane electrode, we recorded compound action potentials (CAPs) in adults with normal hearing and isolated threshold-specific responses via waveform subtraction. Our results demonstrated that the isolated CAPs exhibited decreased latencies with increasing levels and a non-linear amplitude growth, plateauing at 90 dB peSPL before sharply increasing at 105 dB peSPL. This pattern reflects the sequential recruitment of AN fiber that were not effectively recruited by the preceding clicks. Validate conditions, in which the final two clicks had equal levels, produced substantially smaller CAPs, consistent with response suppression by refractoriness. Overall, this paradigm establishes a human measurement approach for characterizing level-threshold-dependent AN responses, providing a potential way to better investigate different AN pathologies, such as cochlear synaptopathy or auditory neuropathy.

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LGR5 and SOX2 expressing progenitor cells in the adult and aged human and mouse inner ear have the potential to produce Myosin 7A positive cells in vitro

Fenton, G. E.; Pieper, T.; Cleypool, C.; Sgroi, S.; Rousset, F.; de Heus, C.; Liv, N.; Thomeer, H. G.; Senn, P.; Stokroos, R. J.; Straatman, L. V.; Smith Cortinez, N.

2026-09-24 neuroscience 10.64898/2026.09.18.752313 medRxiv
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Hearing loss and deafness as a result of hair cell loss cannot be restored due to the incapacity of spontaneous regeneration of these cells. Compounds that manipulate key signaling pathways can potentially regenerate cochlear hair cells. In order to test different compounds that promote hair cell regeneration in vitro models can be used. Three-dimensional cultures have allowed the expansion and experimentation of human and mouse inner ear organoids. This is mainly performed in the embryonic or the early postnatal developmental stage. However, since the majority of patients with hearing loss are adult, it is crucial to understand the adult inner ear regenerative capacity. Here, we evaluated progenitor cell markers in the adult human and mouse inner ear and the generation, expansion and differentiation of cochlear organoids derived from the adult human and mouse inner ear. Cochlear and vestibular sensory epithelium from adult humans; and from adult and aged mice express the progenitor markers SOX2 and LGR5; and can generate organoids in vitro. By optimizing the culture conditions, organoids derived from the cochlea and vestibular organ from adult human and adult and aged mouse differentiated to Myosin 7A positive cells. This indicates that the adult inner ear has regenerative capacity. These findings are encouraging for future regenerative therapies to cure hair cell-related hearing loss and deafness.

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A rapid, machine-learning readout of cochlear neural degeneration that transfers from animals to humans

Andrino, L. S.; Gall, R.; Klara, J.; Akcakaya, M.; Bartlett, E. L.; Parthasarathy, A.

2026-09-30 neuroscience 10.64898/2026.09.24.754199 medRxiv
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Standard hearing tests miss cochlear neural degeneration (CND), the loss of synapses between inner hair cells and auditory nerve fibers that may underlie unexplained hearing difficulty in roughly one in ten adults. Envelope following responses (EFRs) can index this neural loss noninvasively, but conventional protocols are too slow for clinical use. We tested a dynamic amplitude-modulated (dAM) EFR that sweeps the full modulation spectrum in a single brief stimulus. In Mongolian gerbils with histologically verified CND, dAM EFRs revealed selective deficits at fast modulation rates without threshold elevation. A machine-learning classifier distinguished young from middle-aged animals with high accuracy; additionally, its most informative feature, power near 400-500 Hz, tracked synapse counts, indicating a readout of cochlear neural health rather than age. Applied without retraining to 56 human listeners, the gerbil-trained classifier separated age groups above chance. dAM EFRs thus offer a rapid, objective and clinically viable marker of CND.

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Repeated Inertial Stimulation Reveals Divergent Plasticity in Peripheral and Central Vestibular Pathways

Naqvi, S. D.; Niwa, M.; Braun, R. D.; Hali, M.; Apawu, A. K.; Holt, A. G.

2026-09-28 neuroscience 10.64898/2026.09.22.752866 medRxiv
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The vestibular system consists of peripheral end organs that provide the brain with temporally precise information about head position in space required for motor coordination and postural stability. Irregular vestibular afferents of the inner ear are particularly sensitive to rapid changes in acceleration, or jerk, which is necessary for making quick, corrective movements and postural adjustments. Vestibular short-latency evoked potentials (VsEPs) are waveforms that provide a measure of synchronous irregular afferent activity originating from peripheral (early peaks) and central (later peaks) vestibular pathways. These VsEPs are elicited by head jerk stimuli, commonly used preclinically. Previous studies have shown that early VsEP waves are dependent upon jerks of an adequate intensity, number, and duration. However, less is known about jerk characteristics necessary for generation of reliable VsEP signals centrally (later peaks). The present study examines the precise temporal dynamics of peripheral and central vestibular centers across a broad range of mechanical vestibular load in rats. We found differential changes in synchrony and timing driven by jerk repetition, intensity, and duration between early and late VsEP waves representing distinct anatomical components of the vestibular circuit. Our results suggest that central components are uniquely sensitive to jerk duration, intensity, and repetition, indicating a disconnect between peripheral and central neuronal recruitment, adaptive plasticity, and time-frequency dynamics. This work provides a foundation for using VsEP to assess jerk-induced physiological vestibular dysfunction and to understand how central relays differentially adapt to variations of mechanical vestibular stress compared with the precise, high-fidelity transmission observed in the periphery.

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A nonlinear time-domain finite-element model of the human middle ear subjected to intense sound waves

Mohammadi, H.; Tubelli, A.; Puria, S.; Cheng, J. T.

2026-09-24 bioengineering 10.64898/2026.09.23.753568 medRxiv
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Computational models of the middle ear are typically developed within the linear range of the middle ear's response, which corresponds to typical sounds in daily life. Understanding middle-ear biomechanics under high-intensity sounds is also important for assessing potential auditory damage under adverse conditions. In this study, a finite-element (FE) model of the human middle ear plus the external ear canal is presented, employing a first-order Ogden hyperelastic material formulation and time-domain nonlinear analysis to capture nonlinear deformation of soft tissues and the resulting middle-ear response. The model was analyzed using pure-tone pressure excitations applied at the ear canal entrance over the 80 Hz to 8 kHz frequency range and 110 to 180 dB sound pressure levels (SPL). The ear canal pressure near the tympanic membrane (TM) and full-field three-dimensional response of the middle ear structures were examined. Across the investigated frequency range, the simulated middle-ear motion exhibited a transition from predominantly piston-like behavior at low frequencies, up to 1 kHz, to increasingly intricate multi-modal and multi-directional vibration patterns at higher frequencies. Nonlinear behaviors became increasingly significant at high frequencies and high stimulus levels, including compressive/expansive pressure-displacement relationships, waveform distortions, and the emergence of non-harmonic spectral components. The model developed in this study provides a computational framework for studying nonlinear sound transmission through the middle ear and its implications for high-intensity acoustic exposure. The findings contribute to a better understanding of middle-ear mechanics under adverse conditions and support future investigations of acoustic trauma and hearing protection strategies.

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Auditory brainstem response amplitude predicts age-related forward masking temporal-processing deficits in normal-hearing listeners

Huang, C. G.; Costantino, M.; Soleimanpour, R.; Beinke, T.; Anderson, S.; Goupell, M. J.

2026-09-25 neuroscience 10.64898/2026.09.21.753073 medRxiv
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Aging has profound effects on sensory systems, such that older adults can report problems in hearing despite having normal audiometric thresholds. While it is known that older listeners have poorer temporal processing than younger listeners, there is limited understanding of how these deficits interact with effects of sound level, in particular when they are above conversational level (e.g., > 65 dB SPL). Here we wanted to investigate the link between temporal processing and sound level as a function of age in normal-hearing listeners. Using a forward-masking paradigm, auditory brainstem responses (ABRs) and behavioral detection thresholds were measured at different masker levels. It was found that with increasing age and masker sound level, the Wave V amplitudes of older listeners decreased and directly correlated with behavioral detection thresholds of the probe stimulus in the forward-masking paradigm. These results elucidate the fundamental effects of aging on temporal processing and its interactions with sound level in the central auditory system. The results of this study have clinical implications for the concept of normal hearing in the aging population and how older listeners may struggle in different listening environments that are not captured by simple audiometry. Further delineating the important effects of aging will pave the way for earlier clinical diagnosis of hearing disorders and personalized treatments for different forms of age-related hearing loss.

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KDM6A Haploinsufficiency Is Insufficient to Disrupt Cochlear Structure and Auditory Function in Mouse Models of Kabuki Syndrome Type 2

Shimizu, Y.; Wakamori, S.; Smith, L.; Behnammanesh, G.; Honkura, Y.; Suzuki, J.; Bird, J. E.; Katori, Y.; Someya, S.

2026-10-12 developmental biology 10.64898/2026.10.09.757851 medRxiv
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Objective: Kabuki syndrome type 2 (KS2) is a rare X-linked disorder caused by pathogenic variants in KDM6A and is frequently associated with hearing impairment. Because auditory phenotypes include sensorineural, conductive, and mixed hearing loss, we examined whether Kdm6a deficiency directly impairs cochlear morphology or auditory function in mice. Methods: We generated Nestin-Cre; Kdm6a conditional mutants and a germline-derived global Kdm6a deletion model using Sox2-Cre-mediated germline recombination. Auditory function and cochlear morphology were assessed by auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and histological analyses. Results: Whole-body hemizygous or homozygous Kdm6a deletion resulted in embryonic lethality. Analyses therefore focused on Nestin-Cre; Kdm6aflox/Y males and females carrying a germline-derived heterozygous Kdm6a deletion. In Nestin-Cre mutants, ABR thresholds, wave I amplitudes and latencies, and DPOAE measures at 8, 16, and 32 kHz were comparable with littermate controls at 4 and 8 weeks. In heterozygous deletion females, ABR thresholds, wave I amplitudes and latencies at 4-64 kHz and DPOAE measures at 8, 16, and 32 kHz were comparable with male and female wild-type controls. No overt cochlear pathology was observed in either model. Conclusion: Kdm6a deficiency in the viable mouse models examined did not produce overt cochlear pathology or baseline auditory dysfunction. These findings suggest that partial Kdm6a loss alone is insufficient to produce a robust primary cochlear phenotype in young mice and highlight the potential contributions of non-cochlear, developmental, central, and later-onset mechanisms to hearing impairment in KS2. Clinically, these findings support careful evaluation for potentially treatable middle-ear disease.

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Spatial hearing in adults with sequential bilateral cochlear implants: a longitudinal prospective cohort study

Valzolgher, C.; Ghiselli, S.; Epifania, M. O.; Gullotta, J.; Zanetti, D.; Lilli, G.; Di Berardino, F.; Pozzi, M.; Ciorba, A.; Borin, M.; Brunelli, N.; Musumano, L. B.; Frau, G. N.; Tromballi, G.; Chini, A.; Rosi, T.; Malerba, P.; Cuda, D.; Pavani, F.

2026-10-06 otolaryngology 10.64898/2026.10.01.26364332 medRxiv
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Bilateral cochlear implantation (BCI) can improve spatial hearing in adults with bilateral hearing loss, but the early development of spatial hearing following sequential BCI remains poorly understood. This prospective longitudinal study investigated changes in spatial hearing experience in 23 adults undergoing sequential BCI, assessed before and at ~1, 3, and 8 months after bilateral implantation under two conditions: spontaneous and restrained head movements. Using a motion-tracking system combined with virtual reality, sound localization was assessed through absolute and signed errors, along with self-reported localization confidence and listening effort. Subjective spatial hearing was also assessed using the Speech, Spatial and Qualities of Hearing Scale (SSQ). Localization performance improved by 1 month after bilateral implantation, as evidenced by a reduction of absolute error and in the bias toward the first-implanted ear. Participants reported greater localization confidence and lower listening effort at 1 month, although these changes were not consistently maintained at later follow-ups. SSQ scores showed improved spatial hearing at 1 month, speech perception at 3 months, and sound clarity and discriminability at 8 months. Compared with head-restrained condition, accuracy and confidence improved when spontaneous head rotations were allowed. The temporal trajectories of localization bias, confidence, and effort were modulated by the duration of experience with the first CI. These findings indicate that changes in spatial hearing can emerge soon after second CI activation. They further highlight the contribution of spontaneous head movements and previous CI experience, and support the use of complementary measures to monitor the early development of bilateral listening.

9
Novel Co-expression of Group I Metabotropic Glutamate Receptor During Mouse Cochlear Nucleus Development

Sakano, H.; Wheeler, J.; Lam, J.; Vo, E.; Gibson, R.; Langevin, J.; Yu, X.; Rubel, E. W.; Wang, Y.

2026-10-01 neuroscience 10.64898/2026.09.29.755315 medRxiv
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Metabotropic glutamate receptors (mGluR) are G-protein coupled receptors that regulate neuroplasticity and have been shown to play a role in auditory processing. However, not much is known about the expression of mGluRs during cochlear nucleus development in the context of Fragile X syndrome (FXS). FXS is the most common heritable form of intellectual disability and autism and is associated with auditory processing deficits including hypersensitivity. Audiogenic seizure is a notable feature of the Fmr1 knock-out (KO) mouse model for FXS, in which mGluR5 has been shown to be necessary. In this study, we investigated the expression of eight metabotropic glutamate receptors (mGluRs) in the cochlear nucleus at both young and adult ages and in wildtype and Fmr1 KO mice. While it is established that mGluR1 is the predominantly expressed mGluR in adult cochlear nucleus, we report the following new finding that mGluR5 is the more abundant receptor during early development. The expression of Group II and III mGluRs (2,3,4,6,7,8) was relatively stable during development. We show that mGluR1 and mGluR5 are co-expressed across multiple neuron types. Fmr1 genotype did not have statistically significant impact on the expression pattern of mGluRs in cochlear nucleus. Although hearing onset occurs during this mGluR5 to 1 transition period, mGluR expression patterns were not impacted by cochlear activity. We conclude that there is an mGluR5 is to mGluR1 transition that occurs within cochlear nucleus neurons during the critical period closure that is intrinsic to neuronal development.

10
Direct optogenetic activation of inner hair cells improves the efficiency and fidelity of auditory encoding

Li, W.; Bordier, V.; Schorscher-Petcu, A.; Lubetzki, J.; Pirrone, T.; Barral, J.

2026-09-29 neuroscience 10.64898/2026.09.24.751732 medRxiv
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Severe hearing impairment affects approximately 5% of the global population, with a prevalence projected to increase over the coming decades. Cochlear implant devices pose a neuroprosthetic treatment option to allow sound perception and speech comprehension. However, users are limited in the spectrum of auditory information they can regain because electrical stimulation of the auditory nerve generates a broad spread of current and limits the transmission of sound frequency information. Recently, optogenetic stimulation of the cochlear nerve has emerged as a promising alternative for hearing restoration. Because light can be precisely confined in space, optogenetic stimulation of the cochlea permits to activate auditory neurons within smaller tonotopic regions, thereby improving the encoding of sound frequencies compared to electrical stimulation. However, this approach is limited in terms of dynamic range and ability to follow rapidly varying inputs, thus preventing faithful transmission of auditory information. Here, we developed an alternative approach targeting directly sensory inner hair cells with optogenetics. We demonstrate that this approach decreases the amount of light energy necessary to evoke auditory responses. Direct stimulation of hair cells increases the dynamic range of intensities encoded by neurons in subcortical auditory areas and improves the temporal fidelity of optogenetic responses. Finally, a biophysical model of the auditory system suggests that preserving the synapses between inner hair cells and auditory neurons greatly improves the encoding performance of an optical cochlear implant. Together, our results suggest that targeting sensory inner hair cells is a promising approach for hearing restoration through an optical implant.

11
Serum Electrolyte Concentrations Are Associated With Motor Nerve Conduction Velocity in Children

Broser, P. J.

2026-10-11 neuroscience 10.64898/2026.10.07.757353 medRxiv
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Axonal action potential propagation critically depends on tightly regulated intra and extracellular electrolyte concentrations and acid base homeostasis. Experimental studies have demonstrated that changes in extracellular sodium, potassium, and calcium concentrations alter axonal excitability and conduction properties. However, it remains unknown whether small variations in electrolyte concentrations within the physiological range are associated with measurable changes in nerve conduction velocity in humans. In this study, data from neurologically healthy children who underwent both nerve conduction studies and blood gas analysis were analyzed to investigate the relationship between electrolyte concentrations and median motor nerve conduction velocity. Nerve conduction velocity was significantly negatively correlated with ionized calcium concentration and positively correlated with sodium concentration, whereas no significant correlation was observed for potassium. In an a priori defined multiple linear regression model, ionized calcium, sodium, and bicarbonate remained significantly associated with nerve conduction velocity after correction for multiple testing. These findings indicate that even small variations in electrolyte concentrations within the physiological range are associated with measurable differences in peripheral nerve conduction velocity and suggest an additional contribution of acid base status to nerve conduction.

12
Objective markers of altered neural gain dissociate tinnitus and self-reported listening problems in individuals with exceptional hearing thresholds

O'Donohue, M. P.; Mikiel-Hunter, J.; Hernandez-Perez, H.; McAlpine, D.; Faundez-Astudillo, J.-P.

2026-10-08 neuroscience 10.64898/2026.10.01.755864 medRxiv
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Many individuals experience problems that are undetected by standard hearing tests, such as persistent tinnitus and difficulties understanding speech in background noise. Here, we report evidence of altered neural gain in young adults with self-reported listening problems despite exceptional hearing thresholds. Individuals reporting persistent tinnitus (the daily percept of sound in the absence of an external source) exhibited elevated thresholds of the middle ear muscle reflex, suggestive of altered gain in brainstem reflexive circuits, and reduced cortical responses to auditory spatial cues conveyed in the temporal fine structure of low-frequency sounds. Moreover, in both groups, greater self-reported speech-in-noise difficulties were associated with higher magnitude cortical responses, particularly at the highest stimulus intensity, consistent with elevated neural gain. Using a conceptual model, we demonstrate how damage to high-threshold auditory nerve fibres innervating cochlear nuclei can account for reduced activity of binaural neurons sensitive to the temporal fine structure of low-frequency sounds, generating a compensatory increase in neural gain in higher brain centres that impacts listening in complex environments.

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Retinal arteriolar tortuosity as a candidate genetic window to inner-ear microvasculature: distributed sharing with blood pressure at CSK and PAWR and a roadmap for larger hearing GWAS

yang, l.; liu, y.

2026-10-11 genetic and genomic medicine 10.64898/2026.10.08.26365030 medRxiv
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Background: The inner ear is supplied by the labyrinthine artery, which is functionally close to an end artery with limited collateral reserve. Microvascular abnormalities have been implicated in sudden sensorineural hearing loss (SSNHL) and age-related hearing loss, yet inner-ear microvasculature cannot be assessed in vivo and current hearing genome-wide association studies (GWAS) are underpowered. We evaluated the shared genetic architecture of retinal arteriolar tortuosity (retina_AT) with blood pressure, cerebral small vessel disease (cSVD) and hearing phenotypes, and examined whether retinal microvasculature could serve as a candidate genetic window to inner-ear microvasculature. Methods: We used linkage-disequilibrium score regression (LDSC) to estimate SNP heritability for 19 phenotypes and genome-wide genetic correlations (rg) for 11 prespecified pairs. We ran approximate Bayes-factor colocalization (coloc.abf) between 19 independent retinal loci and systolic blood pressure (SBP), together with 95% credible-set fine-mapping, UCSC gene annotation, colocalization with GTEx aortic and tibial-artery expression QTL (eQTL) data and with white-matter hyperintensities (WMH), hearing-GWAS power calculations, and univariable and multivariable Mendelian randomization (MR) of blood pressure and heart rate on hearing. Results: Only retina_AT with SBP was significant genome-wide (rg = 0.10, P = 4.2x10, FDR q = 0.00042). The strongest retinal locus, 13q34, did not colocalize (PP.H3 = 0.996; peaks about 267 kb apart; allelic heterogeneity), whereas two secondary loci colocalized strongly--CSK at 15q24 (PP.H4 = 0.98; 3/3 credible variants within CSK) and PAWR at 12q21 (PP.H4 = 0.99; 3/5 within PAWR)--supported by tissue-matched, moderate eQTL evidence (PP.H4 = 0.71-0.75). At 13q34, retina_AT with WMH was an adequately powered null (PP.H4 = 0.019; only this region and phenotype were tested). On the hearing side, sharing of the blood-pressure magnitude (rg {approx} 0.10) was a near-powered null (about 1.5-fold larger sample needed for 80% power under that assumption, versus about 15-fold for weak rg {approx} 0.03 sharing), and rg [≥] 0.12 was excluded; MR found no robust causal effect. Conclusions: Retinal arteriolar tortuosity shows limited, distributed genetic sharing with blood pressure at the vascular-tone genes CSK and PAWR; no sharing with WMH was observed at 13q34 (only this region was tested). Retinal microvasculature may serve as a candidate genetic window to inner-ear microvasculature, but this analogy awaits direct testing by larger, vessel-oriented hearing GWAS and inner-ear tissue functional studies.

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Vestibular signals enhance the temporal precision of predictive movements to musical rhythms

Yamazaki, R.; Ushiyama, J.

2026-09-29 neuroscience 10.64898/2026.09.24.754009 medRxiv
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Humans exhibit head movements synchronized with musical rhythms, frequently observed during instrument playing or dancing (e.g., hip hop). We conjectured that vestibular input from head movements could aid motor execution anticipatory of musical rhythms, known as sensorimotor synchronization (SMS). To examine this, we applied subthreshold galvanic vestibular stimulation (GVS) simultaneously with musical beats while healthy adults performed SMS to those beats. We designed a GVS waveform where the current rose steeply before each beat onset, which was expected to trigger intense vestibular afferent firing before the beats (as actual head movements would). Participants flexed their index finger in synchrony with the beats of syncopated auditory rhythms. In GVS trials, the SMS timing variability was significantly lower than in trials without GVS, suggesting that vestibular input stabilizes SMS to musical beats. Additionally, a control experiment using a waveform with a gradually increasing current revealed no significant difference in SMS variability between trials with and without GVS. This study provides causal evidence that the vestibular system is involved in synchronized movement to music. In addition, the results suggest that a specific parameter of the GVS waveform could influence predictive motor execution anticipatory of upcoming auditory events.

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Diagnostic Accuracy of Fine Needle Aspiration Cytology in Thyroid Diseases: Comparison with Histopathological Findings in Hawassa, Ethiopia

Nisro, A. M.; Geremew, T. T.; Tadele, A. K.; Fenta, B. D.; Engida, G. G.; Lukas, F. Y.; Tesgera, T. G.; Alem, A. T.

2026-10-21 pathology 10.64898/2026.10.16.26365726 medRxiv
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Introduction: Thyroid diseases are major health problems and among the most common endocrine disorders worldwide, including in Ethiopia. They are characterized by alterations in hormone secretion, enlargement of the thyroid gland, or both. Fine needle aspiration cytology is an important initial screening tool, and histopathologic examination is essential for the definitive diagnosis of thyroid disease. This study aimed to compare the diagnostic accuracy of fine needle aspiration cytology with histopathology in identifying thyroid diseases. Methods: A cross-sectional study was conducted at three health facilities in Hawassa City, Ethiopia, involving 304 patients who underwent both thyroid fine needle aspiration cytology and histopathologic examination of the same site between 30th October 2024 and 29th October 2025. FNAC results were classified using the Bethesda system, with histopathology as the gold standard. Data were entered into Kobo Toolbox, exported to SPSS version 27, and analyzed using cross-tabulation and chi-square ({chi}{superscript 2}) tests to determine diagnostic accuracy. Result: 304 patient records were included in the study. The fine needle aspiration cytology was determinate/diagnostic in 81.6% of cases. The study revealed the sensitivity and specificity of fine needle aspiration cytology to be 88.2% (CI 77.6-95.1%) and 94.4% (CI 90.6-97.1%), respectively. The false negative and false positive rates in this study were 2.4% and 4.4%, respectively. The positive predictive value was 80.3% (CI 68.7-89.3%), and the negative predictive value was 96.8% (CI 93.8-98.7%). The accuracy of fine needle aspiration cytology in differentiating benign from malignant thyroid lesions was 93.1%. Conclusion: FNAC demonstrated strong agreement with histopathology and remains a reliable, cost-effective first-line diagnostic tool for thyroid disease, particularly in resource-limited settings. Strengthening sample handling, ultrasound guidance, and adherence to Bethesda criteria may further improve diagnostic precision

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Visualising large audiological data beyond the audiogram for auditory phenotyping

Encina-Llamas, G.; Kjaerbol, E.; Kressner, A. A.

2026-09-28 otolaryngology 10.64898/2026.09.24.26363901 medRxiv
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The pure-tone audiogram remains the cornerstone of hearing assessment, yet it captures only part of the functional consequences of cochlear damage. Most phenotyping schemes rely solely on the audiogram, which cannot detect hidden suprathreshold dysfunction when thresholds are normal. How best to represent audiological data - as discrete phenotypes or as a continuous space - remains unresolved. Using a retrospective database from the Copenhagen Hearing and Balance Centre, Rigshospitalet (Denmark; 1995-2022; 251986 ear-session units from 81883 adults with normal or sensorineural audiograms), we compared linear (PCA) and non-linear (UMAP) embeddings of the audiogram alone and with word recognition in quiet (WRSmax-Q). Here we show that a linear embedding suffices for the audiogram, but a non-linear one becomes advantageous once suprathreshold measures are added. PCA compressed the audiogram onto two interpretable axes, overall level and slope, explaining 91.5% of the variance, with ears forming a continuous cloud that published reference schemes tiled into overlapping regions. For the audiogram alone, UMAP recovered the same organisation. WRSmax-Q varied widely among ears with similar audiograms; adding it left the PCA unchanged but reorganised the UMAP. A synthetic experiment illustrated this: ears with identical audiograms but different WRSmax-Q separated under UMAP, not PCA. Combining thresholds with WRSmax-Q, UMAP yielded a continuous representation - a prototype Hearing Loss Map - where each ear's position reflects threshold and suprathreshold measures. Representing hearing loss as a location in a continuous space rather than as discrete categories may better reflect its graded nature, with clinical relevance for individual patients.

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Thyroid Dysfunction in Male Patients at Asia Med Laboratory, Herat, Afghanistan July 2021-Jan 2022

Tamkin, N.; Habibi, M.; Leming, M.

2026-09-24 pathology 10.64898/2026.09.19.752850 medRxiv
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Objective: Hyperthyroidism and hypothyroidism related to iodine deficiency are major public health concerns in Afghanistan. This study aimed to assess the frequency of thyroid dysfunction among male patients referred for thyroid testing and its association with age, and to examine monthly trends in thyroid dysfunction at Asia Med Laboratory in Herat, Afghanistan, from July 2021 to January 2022. Methods: A retrospective analysis was conducted on 250 male patients aged 0-69 years. We measured Serum TSH, total T4, and total T3 levels, and thyroid status was classified using age specific reference ranges. In addition, the frequency of thyroid dysfunction was analyzed across age groups with monthly trends of thyroid state. Results: Overall, the euthyroid state consisted of 69.2% of participants, 24.8% with overt hypothyroidism, 3.2% with overt hyperthyroidism, and 2.8% with subclinical hyperthyroidism. Thyroid status differed significantly by age (p = 0.0135), with hypothyroidism increasing in older age groups and reaching its highest proportion among men aged 60-69 years (55.6%). Euthyroidism predominated in patients aged 10-39 years, while hyperthyroidism across age groups remained relatively infrequent. After September 2021, a threefold increase was observed in the total number of male patients referred for thyroid testing. During this period, the proportion of hyperthyroidism increased slightly, whereas hypothyroidism cases declined. Conclusion: In conclusion, hypothyroidism was more frequent with older age. The rise in absolute case numbers after September 2021 likely reflects increased patient referrals, underscoring the need for ongoing monitoring of thyroid function. The study may assist in the early management of thyroid disorders and in reducing their complications.

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A Unified and Interpretable Geometric Optimization Framework for Intelligent Automated Implant Planning in CBCT from Single to Consecutive Multiple Missing Teeth

Zeng, Z.; Jiang, Y.; Li, J.; Cao, H.; Lu, Y.; Zhu, H.; Xiong, J.; Tang, Z.; Hu, N.; Ma, H.

2026-10-05 dentistry and oral medicine 10.64898/2026.10.03.26364640 medRxiv
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Automated dental implant planning using artificial intelligence (AI) faces challenges in interpretability, safety assurance, and applicability beyond single-tooth cases. This paper presents a unified explainable framework for cone-beam computed tomography (CBCT) that handles both single-tooth and consecutive multiple missing teeth. The method combines nnU-Net-based anatomical segmentation with a transparent geometric optimization pipeline. Implant placement is formulated as a lexicographic multi-objective constrained optimization problem that enforces clinical safety margins while balancing bone engagement, mesiodistal spacing, and buccolingual position. For multi-tooth cases, a global coordination strategy ensures inter-implant parallelism, minimum spacing, and a common insertion path. The framework was validated on 20 single-tooth and 9 consecutive multi-tooth cases. The AI plans achieved a centroid distance of 1.60+/-1.05 mm for single-tooth cases and 1.22+/-0.32 mm for multi-tooth cases, with approximately 7 degrees axial angle difference. All plans achieved 100% compliance with predefined safety thresholds. In a Turing-style test, experts were unable to distinguish AI from human intelligence (HI) plans under blinded conditions. By decoupling perception from reasoning and embedding clinical knowledge as explicit constraints, the framework offers an interpretable and clinically trustworthy solution for computer-aided implant dentistry.

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Attention Is All You Need: A Universal Augmented Reality Surgical Navigation Framework

Zhao, D.; Qiu, Y.; Guo, Y.; Luo, X.; Liu, Y.; Li, X.; Chen, H.; Cai, X.; Tian, T.

2026-09-25 dentistry and oral medicine 10.64898/2026.09.20.26363284 medRxiv
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Hard-tissue surgery requires precise spatial control, while conventional computer-assisted navigation presents guidance separately from the operative field. Augmented reality can bring navigation information closer to the surgeon, but how best to translate this information into intuitive intraoperative guidance remains underexplored. We therefore developed an augmented reality navigation system (ANS) that translates real-time deviations from the planned trajectory into co-located holographic action cues. Evaluation comprised typodont and ex vivo porcine experiments, a randomized crossover study in 40 dental trainees, and eight clinical cases. In porcine mandibles, ANS showed lower angular deviation than static and dynamic navigation (1.78 vs 6.42 and 4.02 degrees). Among trainees, accuracy was comparable with dynamic navigation, while workload was lower (29.18 vs 33.15), usability higher (73.13 vs 68.88), and visual-focus ratings improved (3.55 vs 2.28). Clinical cases supported feasibility. These findings support co-located action guidance as an alternative interface paradigm for surgical navigation.

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Multidimensional Electroglottographic Characterization of Immediate Responses to Straw Phonation: A Pilot Methodological Study in Singers

Little, M.; Oren, L.

2026-10-09 physiology 10.64898/2026.10.08.757648 medRxiv
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Semi-occluded vocal tract (SOVT) exercises are widely used in voice training and therapy, but their immediate electroglottographic (EGG) effects remain incompletely characterized. In this pilot methodological study, six female community singers completed a no-straw baseline recording and then 1-min straw-phonation exercises with four straws (Household metal, Metal VoiceStraw, plastic, and paper), each followed by a no-straw EGG recording. Thirty 1s recordings were analyzed with a standardized pipeline including contact quotient (CQ), waveform skewness, contact-phase rise/fall timing, temporal skewness (s_t), a normalized derivative asymmetry index (NDAI), average-cycle morphology, and EGG spectral descriptors. Relative to baseline, group-mean CQ was higher after all four straws (by 0.027-0.058), waveform skewness and NDAI were lower, and the EGG spectral centroid was lower (by 9.6-15.3%). Contact-phase timing asymmetry did not change consistently: s_t exceeded baseline after three straws and fell below it after one, and the rise/fall ratio decreased in three to five of six participants depending on the straw. Four participants ranked the Metal VoiceStraw first and two ranked paper first. Because every straw condition followed the baseline, warm-up and order effects cannot be separated from straw effects. These hypothesis-generating results identify CQ, waveform skewness, and EGG spectral centroid as candidate endpoints for a larger controlled study