Comparison of clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea.

OBJECTIVES: This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA). DESIGN: Cohort study. SETTING: Single tertiary care centre. PARTICIPANTS: This study included 190 patients with OSA who underwent multilevel upper airway surgery between September 2012 and September 2021. The patients were divided into two groups according to the proportion of each respiratory event: hypopnea-predominant (n = 102) and apnea-predominant (n = 88). MAIN OUTCOME MEASURES: The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery. RESULTS: The apnea-predominant group included more male patients and had higher AHI, respiratory disturbance index (RDI) and oxygen desaturation index (ODI) than the hypopnea-predominant group. Both groups showed significant improvements in AHI, apnea index, RDI, supine AHI, REM AHI, non-REM AHI, ODI, lowest O2 saturation and Epworth Sleepiness Scale scores following the surgery. Notably, hypopnea index increased after surgery in the apnea-predominant OSA group. Although the improvement in the absolute value of AHI by surgery was significantly greater in the apnea-predominant group than in the hypopnea-predominant group, the two groups showed no significant difference in the percentage improvement in AHI from baseline AHI. CONCLUSION: Patients with apnea-predominant OSA had more severe disease than those with hypopnea-predominant OSA; however, surgical outcomes, as evaluated by percentage AHI improvement, were comparable between the two groups. In addition, multilevel upper airway surgery may induce the transition from apnea to hypopnea in patients with apnea-predominant OSA.

Graphene Via Contact Architecture for Vertical Integration of vdW Heterostructure Devices.

Two-dimensional (2D) devices and their van der Waals (vdW) heterostructures attract considerable attention owing to their potential for next-generation logic and memory applications. In addition, 2D devices are projected to have high integration capabilities, while maintaining nanoscale thickness. However, the fabrication of 2D devices and their circuits is challenging because of the high precision required to etch and pattern ultrathin 2D materials for integration. Here, the fabrication of a graphene via contact architecture to electrically connect graphene electrodes (or leads) embedded in vdW heterostructures is demonstrated. Graphene via contacts comprising of edge and fluorinated graphene (FG) electrodes are fabricated by successive fluorination and plasma etching processes. A one-step fabrication process that utilizes the graphene contacts is developed for a vertically integrated complementary inverter based on n- and p-type 2D field-effect transistors (FETs). This study provides a promising method to fabricate vertically integrated 2D devices, which are essential in 2D material-based devices and circuits.

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

INTRODUCTION: Fluctuating hearing loss is a distinctive feature caused by SLC26A4 variants. We investigated whether cochlear implantation had protective or deleterious effect on hearing fluctuation in patients with biallelic SLC26A4 variants. METHODS: Patients with biallelic SLC26A4 variants (N = 16; age = 10.24 ± 9.20 years) who had unilateral cochlear implantation and consecutive postsurgical, bilateral pure-tone audiograms more than 3 times were selected. We retrospectively reviewed the patients' medical records from 2008 to 2019 obtained from a tertiary medical center and used the auditory threshold change (Shift) over time as a marker of hearing fluctuation. Fluctuation events were counted, and the Shift of the implanted and contralateral ears was compared using logistic regression with a generalized estimating equation and linear mixed model. A total of 178 values were included. RESULTS: The odds of fluctuating hearing frequency were 11.185-fold higher in the unimplanted ears than in the implanted ears postoperatively (p = 0.001). The extent of fluctuation at 250 and 500 Hz was also significantly lower in the implanted ears than in the unimplanted ears after adjusting for every other effect (p = 0.003 and p < 0.001, respectively). Notably, higher residual hearing was rather associated with lesser fluctuation in frequency and the extent of fluctuation at 500 Hz, indicating residual hearing function is not the positive predictor for hearing fluctuation. CONCLUSION: In patients with biallelic SLC26A4 variants, cochlear implantation may reduce the frequency and extent of hearing fluctuations.

Impact of Organic Molecule-Induced Charge Transfer on Operating Voltage Control of Both n-MoS2 and p-MoTe2 Transistors.

Since transition metal dichalcogenide (TMD) semiconductors are found as two-dimensional van der Waals materials with a discrete energy bandgap, many TMD based field effect transistors (FETs) are reported as prototype devices. However, overall reports indicate that threshold voltage ( Vth) of those FETs are located far away from 0 V whether the channel is p- or n-type. This definitely causes high switching voltage and unintended OFF-state leakage current. Here, a facile way to simultaneously modulate the Vth of both p- and n-channel FETs with TMDs is reported. The deposition of various organic small molecules on the channel results in charge transfer between the organic molecule and TMD channels. Especially, HAT-CN molecule is found to ideally work for both p- and n-channels, shifting their Vth toward 0 V concurrently. As a proof of concept, a complementary metal oxide semiconductor (CMOS) inverter with p-MoTe2 and n-MoS2 channels shows superior voltage gain and minimal power consumption after HAT-CN deposition, compared to its initial performance. When the same TMD FETs of the CMOS structure are integrated into an OLED pixel circuit for ambipolar switching, the circuit with HAT-CN film demonstrates complete ON/OFF switching of OLED pixel, which was not switched off without HAT-CN.

Self-controllable proteinic antibacterial coating with bacteria-triggered antibiotic release for prevention of periprosthetic infection.

Periprosthetic infection is a devastating postimplantation complication in which a biofilm layer harboring invasive microorganisms forms around orthopedic implants, leading to severe implant failure and patient morbidity. Despite the development of several infection-triggered antibiotic release approaches, most current antibacterial coatings are susceptible to undesired antibiotic leakage or mechanical disintegration during prosthesis installation. Herein, we propose a self-controllable proteinic antibacterial coating capable of both long-lasting adherence onto titanium implant substrates over the implant fixation period and instantaneous bacterial eradication. Importantly, the pH-dependent reversible metal coordination of mussel adhesive protein (MAP) enabled bacterial concentration-dependent antibiotic delivery in response to infection-induced acidification. In addition, the MAP coating exhibited superior self-healable adhesive properties and scratch resistance, which enabled to avert issues associated with mechanical damages, including peeling and cracking, often occurring in conventional implant coating systems. The gentamicin-loaded MAP coating exhibited complete inhibition of bacterial growth in vivo against Staphylococcus aureus penetrations during implantation surgery (immediate infection) and even 4 weeks after implantation (delayed infection). Thus, our antibiotic-loaded MAP hydrogel coating can open new avenues for self-defensive antibiotic prophylaxis to achieve instant and sustainable bacteriocidal activity in orthopedic prostheses. © 2017 Elsevier Inc. All rights reserved.

Boltzmann Switching MoS2 Metal-Semiconductor Field-Effect Transistors Enabled by Monolithic-Oxide-Gapped Metal Gates at the Schottky-Mott Limit.

A gate stack that facilitates a high-quality interface and tight electrostatic control is crucial for realizing high-performance and low-power field-effect transistors (FETs). However, when constructing conventional metal-oxide-semiconductor structures with two-dimensional (2D) transition metal dichalcogenide channels, achieving these requirements becomes challenging due to inherent difficulties in obtaining high-quality gate dielectrics through native oxidation or film deposition. Here, a gate-dielectric-less device architecture of van der Waals Schottky gated metal-semiconductor FETs (vdW-SG MESFETs) using a molybdenum disulfide (MoS2) channel and surface-oxidized metal gates such as nickel and copper is reported. Benefiting from the strong SG coupling, these MESFETs operate at remarkably low gate voltages, <0.5 V. Notably, they also exhibit Boltzmann-limited switching behavior featured by a subthreshold swing of ≈60 mV dec-1 and negligible hysteresis. These ideal FET characteristics are attributed to the formation of a Fermi-level (EF) pinning-free gate stack at the Schottky-Mott limit. Furthermore, authors experimentally and theoretically confirm that EF depinning can be achieved by suppressing both metal-induced and disorder-induced gap states at the interface between the monolithic-oxide-gapped metal gate and the MoS2 channel. This work paves a new route for designing high-performance and energy-efficient 2D electronics.

Clinical Characteristics and Surgical Outcomes of Obstructive Sleep Apnea Patients With Mixed Apnea Components.

OBJECTIVE: This study was aimed to investigate clinical implications of mixed apnea (MA) in patients with obstructive sleep apnea (OSA), particularly whether surgical outcomes differ between OSA patients with and without MA events. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary medical center. METHODS: Eighty-eight patients with OSA who underwent multilevel upper airway surgery were included. Patients were divided into 2 groups according to the presence of MA events: "pure group" (n = 30) and "mixed group" (n = 58). The clinical characteristics and surgical outcomes were compared between the 2 groups. RESULTS: The mixed group included more males (P = .020) and hypertensive patients (P = .009) and had a higher apnea-hypopnea index (AHI; P < .001) than the pure group. The surgical success rate was lower in the mixed group (29.3%) than in the pure group (73.3%; P < .001). Furthermore, the postoperative improvements in total AHI (P < .001), supine AHI (P < .001), and oxygen desaturation index (P = .006) were lower in the mixed group than in the pure group. Logistic regression analysis confirmed that the presence of MA (P = .002) was an independent predictor of poor surgical outcomes in patients with OSA. CONCLUSION: OSA patients with MA showed different clinical features and poor surgical outcomes compared to those without MA. These results imply that OSA with MA components may have a distinct pathophysiology, and the presence of MA should be considered in the surgical treatment of OSA.

Negative Photoresponse Switching via Electron-Hole Recombination at The Type III Junction of MoTe2 Channel/SnS2 Top Layer.

Extensive study on 2D van der Waals (vdW) heterojunctions has primarily focused on PN diodes for fast-switching photodetection, while achieving the same from 2D channel phototransistors is rare despite their other advantages. Here, a high-speed phototransistor featuring a type III junction between p-MoTe2 channel and n-SnS2 top layer is designed. The photodetecting device operates with a basis of negative photoresponse (NPR), which originates from the recombination of photoexcited electrons in n-SnS2 and accumulated holes in the p-MoTe2 channel. For the NPR to occur, high-energy photons capable of exciting SnS2 (band gap ≈2.2 eV) are found to be effective because lower-energy photons simply penetrate the SnS2 top layer only to excite MoTe2 , leading to normal positive photoresponse (PPR) which is known to be slow due to the photogating effects. The NPR transistor showcases 0.5 ms fast photoresponses and a high responsivity over 5000 A W-1 . More essentially, such carrier recombination mechanism is clarified with three experimental evidences. The phototransistor is finally modified with Au contact on n-SnS2 , to be a more practical device displaying voltage output. Three different photo-logic states under blue, near infrared (NIR), and blue-NIR mixed photons are demonstrated using the voltage signals.

Diagnosis of Eosinophilic Otitis Media Using Blood Eosinophil Levels.

Eosinophilic otitis media (EOM) is a rare middle ear disease with unfavorable outcomes. Under the current diagnostic criteria of EOM, it is challenging to suspect EOM before tympanostomy. Therefore, this study attempted to use blood eosinophil levels for the differential diagnosis of EOM from other conditions. Three disease groups with features of recurrent otorrhea were categorized, which included the following: EOM (n = 9), granulomatosis with polyangiitis (GPA, n = 12), and primary ciliary dyskinesia (PCD, n = 6). Clinical and radiological characteristics were analyzed in the three groups. Patients who underwent ventilation tube insertion due to serous otitis media were enrolled as the control group (n = 225) to evaluate the diagnostic validity of blood eosinophilia. The EOM group showed a significantly higher blood eosinophil concentration (p < 0.001) and blood eosinophil count (p < 0.001) compared to the GPA and PCD groups. The estimated sensitivity and specificity for diagnosing EOM from OME patients who underwent ventilation tube insertion were 100% and 95.6%, respectively. In addition, EOM tended to have protympanic space soft tissue density and a relatively clear retrotympanic space in temporal bone computerized tomography. Blood eosinophil evaluation is a significant clinical indicator of EOM. Furthermore, the assessment of exclusive protympanic soft tissue density can provide an additional diagnostic clue.

Self-Assembled TaOX/2H-TaS2 as a van der Waals Platform of a Multilevel Memristor Circuit Integrated with a ß-Ga2O3 Transistor.

Two-dimensional (2D)-layered material tantalum disulfide (2H-TaS2) is known to be a van der Waals conductor at room temperature. Here, 2D-layered TaS2 has been partially oxidized by utraviolet-ozone (UV-O3) annealing to form a 12-nm-thin TaOX on conducting TaS2, so that the TaOX/2H-TaS2 structure might be self-assembled. Utilizing the TaOX/2H-TaS2 structure as a platform, each device of a ß-Ga2O3 channel MOSFET and a TaOX memristor has been successfully fabricated. An insulator structure of Pt/TaOX/2H-TaS2 shows good a dielectric constant (k ∼ 21) and strength (∼3 MV/cm) of achieved TaOX, which is enough to support a ß-Ga2O3 transistor channel. Based on the quality of TaOX and low trap density of the TaOX/ß-Ga2O3 interface, which is achieved via another UV-O3 annealing, excellent device properties such as little hysteresis (<∼0.04 V), band-like transport, and a steep subthreshold swing of ∼85 mV/dec are achieved. With a Cu electrode on top of the TaOX/2H-TaS2 structure, the TaOX acts as a memristor operating around ∼2 V for nonvolatile bipolar and unipolar mode memories. The functionalities of the TaOX/2H-TaS2 platform become more distinguished finally when the Cu/TaOX/2H-TaS2 memristor and ß-Ga2O3 MOSFET are integrated to form a resistive memory switching circuit. The circuit nicely demonstrates the multilevel memory functions.

Visualization of the relationship between electrogustometry and whole mouth test using multidimensional scaling.

Interpreting the relationship between different taste function tests of different stimuli, such as chemical and electrical stimulation, is still poorly understood. This study aims to analyze visually as well as quantitatively how to interpret the relationship of results between taste function tests using different stimuli. Patients who underwent the whole mouth test and Electrogustometry (EGM) at a tertiary medical center between August 2018 and December 2018 were reviewed retrospectively with electronic medical records. Of the 110 patients, a total of 86 adults who self-reported that their taste function was normal through a questionnaire were enrolled. EGM measured the thresholds of the chorda tympani (CT) and glossopharyngeal nerve (GL) area of the tongue. The whole mouth test measured detection and recognition thresholds for sweet, salty, bitter, sour, and umami taste. Statistical analyses of Pearson's, Spearman's rank and polyserial correlation and multidimensional scaling (MDS) was performed. The EGM threshold for the average value of both CT regions and the recognition threshold of the whole mouth test were significantly correlated in sweet, salty, bitter, and sour taste (r = 0.244-0.398, P < 0.05), and the detection threshold was correlated only significant in sweet (r = 0.360, P = 0.007). In the MDS analysis results, the three-dimensional (D) solution was chosen over the 2-D solution because of the lower stress. Detection-, recognition threshold of whole mouth test and EGM thresholds of CT and GL area, those were standardized by Z-score, formed well-distinguished sections in the MDS analyses. The EGM threshold of the CT area was closer to the detection and recognition thresholds than the EGM threshold of the GL area. In general, the EGM threshold was closer to the recognition threshold than the detection threshold for each taste. Overall, visualization of the relationship of whole mouth test and EGM by MDS was in good agreement with quantitative analysis. EGM and whole mouth test seem to reflect different aspects of taste. However, when interpreting the EGM results, the EGM threshold of the CT area will show more similarity to the recognition threshold than the detection threshold for the whole mouth test.

Low-temperature growth of MoS2 on polymer and thin glass substrates for flexible electronics.

Recent advances in two-dimensional semiconductors, particularly molybdenum disulfide (MoS2), have enabled the fabrication of flexible electronic devices with outstanding mechanical flexibility. Previous approaches typically involved the synthesis of MoS2 on a rigid substrate at a high temperature followed by the transfer to a flexible substrate onto which the device is fabricated. A recurring drawback with this methodology is the fact that flexible substrates have a lower melting temperature than the MoS2 growth process, and that the transfer process degrades the electronic properties of MoS2. Here we report a strategy for directly synthesizing high-quality and high-crystallinity MoS2 monolayers on polymers and ultrathin glass substrates (thickness ~30 µm) at ~150 °C using metal-organic chemical vapour deposition. By avoiding the transfer process, the MoS2 quality is preserved. On flexible field-effect transistors, we achieve a mobility of 9.1 cm2 V-1 s-1 and a positive threshold voltage of +5 V, which is essential for reducing device power consumption. Moreover, under bending conditions, our logic circuits exhibit stable operation while phototransistors can detect light over a wide range of wavelengths from 405 nm to 904 nm.

Is obstructive sleep apnea associated with erythrocytosis? A systematic review and meta-analysis.

Objective: The aim of this systematic review and meta-analysis was to investigate the association between obstructive sleep apnea (OSA) and erythrocytosis. Methods: The PubMed, Web of Science, and Cochrane Library databases were searched for articles examining hematocrit values in patients with OSA and control individuals published till September 1, 2021. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated, and subgroup analyses were performed. Results: Eleven eligible studies with a total of 4608 patients with OSA were included in this meta-analysis. Pooled outcomes revealed that hematocrit values were significantly higher in patients with OSA than in controls (SMD, 0.19; 95% CI, 0.08-0.29; p < .01). When studies were stratified by disease severity, the significant differences in hematocrit values between patients and controls were only observed in the severe OSA group (SMD, 0.34; 95% CI, 0.08-0.59; p < .01), but not in the mild and moderate OSA groups. In subgroup analyses according to sex and publication year, significant differences in hematocrit values between patients and controls remained stable in studies with only female patients (SMD, 0.25; 95% CI, 0.12-0.38; p < .01) and in studies published after 2012 (SMD, 0.17; 95% CI, 0.06-0.28, p < .01). Conclusion: Our meta-analysis revealed that the hematocrit value was significantly increased in patients with OSA, particularly in severe patients, compared with that in controls. However, the elevation was modest, and the hematocrit value is expected to be within the normal range in patients with OSA. These data suggest that OSA leads to slight increases in hematocrit but does not cause clinically significant erythrocytosis.

Efficient Photon Extraction in Top-Emission Organic Light-Emitting Devices Based on Ampicillin Microstructures.

The desire to enhance the efficiency of organic light-emitting devices (OLEDs) has driven to the investigation of advanced materials with fascinating properties. In this work, the efficiency of top-emission OLEDs (TEOLEDs) is enhanced by introducing ampicillin microstructures (Amp-MSs) with dual phases (α-/ß-phase) that induce photoluminescence (PL) and electroluminescence (EL). Moreover, Amp-MSs can adjust the charge balance by Fermi level (EF ) alignment, thereby decreasing the leakage current. The decrease in the wave-guided modes can enhance the light outcoupling through optical scattering. The resulting TEOLED demonstrates a record-high external quantum efficiency (EQE) (maximum: 68.7% and average: 63.4% at spectroradiometer; maximum: 44.8% and average: 42.6% at integrating sphere) with a wider color gamut (118%) owing to the redshift of the spectrum by J-aggregation. Deconvolution of the EL intensities is performed to clarify the contribution of Amp-MSs to the device EQE enhancement (optical scattering by Amp-MSs: 17.0%, PL by radiative energy transfer: 9.1%, and EL by J-aggregated excitons: 4.6%). The proposed TEOLED outperforms the existing frameworks in terms of device efficiency.

Tunicate-Inspired Photoactivatable Proteinic Nanobombs for Tumor-Adhesive Multimodal Therapy.

Near-IR (NIR) light-responsive multimodal nanotherapeutics have been proposed to achieve improved therapeutic efficacy and high specificity in cancer therapy. However, their clinical application is still elusive due to poor biometabolization and short retention at the target site. Here, innovative photoactivatable vanadium-doped adhesive proteinic nanoparticles (NPs) capable of allowing biological photoabsorption and NIR-responsive anticancer therapeutic effects to realize trimodal photothermal-gas-chemo-therapy treatments in a highly biocompatible, site-specific manner are proposed. The photoactivatable tumor-adhesive proteinic NPs can enable efficient photothermal conversion via tunicate-inspired catechol-vanadium complexes as well as prolonged tumor retention by virtue of mussel protein-driven distinctive adhesiveness. The incorporation of a thermo-sensitive nitric oxide donor and doxorubicin into the photoactivatable adhesive proteinic NPs leads to synergistic anticancer therapeutic effects as a result of photothermal-triggered "bomb-like" multimodal actions. Thus, this protein-based phototherapeutic tumor-adhesive NPs have great potential as a spatiotemporally controllable therapeutic system to accomplish effective therapeutic implications for the complete ablation of cancer.

One-stage cochlear implantation in patients with chronic otitis media using canal wall up mastoidectomy.

BACKGROUND: Cochlear implantation (CI) with subtotal petrosectomy was recommended to avoid the complications for patients with chronic otitis media (COM). OBJECTIVES: To evaluate the surgical outcomes of CI in patients with COM using a one-stage operation with canal wall up mastoidectomy (CWUM). METHODS: Thirty-five patients with COM who underwent CI with CWUM as a one-stage between 2009 and 2017 were participated. They divided into those with inactive COM and active COM. The anatomical success rate, postoperative complication, and hearing outcomes were analyzed. RESULTS: Twenty-four patients had inactive COM and seven with active COM. Three of the 31 patients (9.7%) had otorrhea from the ear undergone surgery. Two of these three patients had myringitis after CI and their symptoms improved after conservative management. Although infection of the tympanic membrane in the third patient was controlled after conservative management, a perforation was left. Postoperative otorrhea occurred in two patients (8.3%) in the inactive COM group and one patient (14.3%) in the active COM group. CONCLUSION: This study indicates that infection control and successful implantation can be achieved through a one-stage CI operation with CWUM in selected patients with COM.HIGHLIGHTSAlthough COM was once considered a contraindication to CI, CI in patients with COM has been made feasible by STP before CI or simultaneously with CI.Simultaneous CI with CWUM was performed for 31 patients with COM.Three patients (9.7%) had minor complications after the surgery and only one patient experienced device explantation which was due to device failure.

Outcomes of multilevel upper airway surgery, including tongue base resection, in patients with torus mandibularis.

By affecting the tongue position and oropharyngeal airway volume, torus mandibularis is an anatomical factor associated with obstructive sleep apnea (OSA). This study aimed to investigate the influence of torus mandibularis on the surgical outcomes of multilevel upper airway surgery with tongue base resection (TBR) in patients with OSA. Patients with OSA who underwent palatal surgery and TBR were retrospectively analyzed. The patients were divided into two groups according to the presence or absence of torus mandibularis upon physical examination or on computed tomography images. The anatomical characteristics of the upper airway and pre/postoperative polysomnography were analyzed. The control and torus mandibularis groups comprised 69 and 35 patients, respectively, with all of them showing improved sleep quality after surgery. Apnea-hypopnea index (AHI) scores decreased from 42.1 ± 22.2 preoperatively to 23.9 ± 21.4 postoperatively in the control group (p < 0.001), and from 45.2 ± 19.9 to 22.5 ± 13.5 in the torus mandibularis group (p < 0.001). Comparing the postoperative changes in AHI, the AHI of the torus mandibularis group improved by 22.7 ± 23.4, whereas that of the control group improved by 18.1 ± 19.6 (p = 0.296). Sleep efficiency improved from 90.0 ± 7.5 to 92.8 ± 6.8 in the control group, and from 90.3 ± 8.7 to 93.6 ± 6.5 in the torus mandibularis group; however, there was no statistical difference between the two groups (p = 0.816). The presence of torus mandibularis did not appear to significantly affect the surgical results in OSA patients, but it did elicit significant changes in polysomnographic parameters compared with the control group. Therefore, following the identification of torus mandibularis in OSA patients, TBR should be considered as part of planning, as it may help to predict surgical outcomes.

Bone Graft Biomineral Complex Coderived from Marine Biocalcification and Biosilicification.

Bone graft materials have been mainly developed based on inorganic materials, including calcium phosphate. However, these graft materials usually act as osteoconductive rather than osteoinductive scaffolds. To improve bone reconstruction, a combination of several materials has been proposed. However, there are still no alternatives that can completely replace the existing animal-derived bone graft materials. In this work, a marine-inspired biomineral complex was suggested as a potential bone graft material. The proposed biosilicified coccolithophore-derived coccoliths using bioengineered mussel adhesive proteins show osteopromotive ability through the synergistic effects of osteoconductivity from calcium carbonate and osteoinductivity from silica. Its possibility of use as a bone substitute was determined by evaluating the in vitro osteogenic behaviors of multipotent mesenchymal stem cells and in vivo bone regeneration in a rat calvarial defect model. Therefore, the marine-inspired biomineral complex developed in this study could be successfully used for bone tissue engineering.

Heterogeneity of MYO15A variants significantly determine the feasibility of acoustic stimulation with hearing aid and cochlear implant.

Autosomal recessive nonsyndromic hearing loss 3 (DFNB3) mainly leads to congenital and severe-to-profound hearing impairment, which is caused by variants in MYO15A. However, audiological heterogeneity in patients with DFNB3 hinders precision medicine in hearing rehabilitation. Here, we aimed to elucidate the heterogeneity of the auditory phenotypes of MYO15A variants according to the affected domain and the feasibilities for acoustic stimulation. We conducted whole-exome sequencing for 10 unrelated individuals from seven multiplex families with DFNB3; 11 MYO15A variants, including the novel frameshift c.900delT (p.Pro301Argfs*143) and nonsense c.4879G > T (p.Glu1627*) variants, were identified. In seven probands, residual hearing at low frequencies was significantly higher in the groups with one or two N-terminal frameshift variants in trans conformation compared to that in the group without these variants. This is consistent with the 56 individuals from the previously published reports that carried a varying number of N-terminal truncating variants in MYO15A. In addition, patients with missense variants in the second FERM domain had better hearing at low frequencies than patients without these variants. Subsequently, acoustic stimulation provided by devices such as hearing aids or cochlear implants was feasible in patients with one or two N-terminal truncating variants or a second FERM missense variant. In conclusion, N-terminal or second FERM variants in MYO15A allow the practical use of acoustic stimulation through hearing aids or electroacoustic stimulation for aural rehabilitation.