Search Results (4,237)

Hearing loss affects millions and is often caused by irreversible damage to mechanosensory hair cells. Humans and other mammals lack the capacity to regenerate damaged hair cells; however zebrafish, Danio rerio, can regenerate hair cells that are present in the ear and mechanosensory neuromasts, making this animal an ideal model for understanding hair cell regenerative mechanisms. This study investigates the role of the GDP-fucose biosynthesis gene GDP-mannose 4,6-dehydratase (gmds) in regulating neuromast hair cell regeneration in zebrafish. Fucosylation is required for Notch signalling, a critical negative regulator of hair cell regeneration, and we therefore hypothesized that loss of gmds function would enhance hair cell regeneration. We demonstrate increased hair cell number in gmds mutants, and increased hair cell number following chemical ablation of hair cells with neomycin. Additionally, gmds mutants exhibited accelerated neuromast and hair cell regeneration, achieving complete restoration faster than wild-type siblings. Pharmacological inhibition of Notch signalling further enhanced hair cell regeneration in wild-type siblings but less so in gmds mutants, indicating that Notch signalling may partially regulate hair cell regeneration downstream of gmds. These findings highlight the importance of GDP-fucose biosynthesis in regulating hair cell number and regeneration, likely partially dependent on Notch signalling. Full article

Hearing loss is a major health burden, often caused by ototoxic drugs such as cisplatin and gentamicin. Effective therapy is limited by the poor penetrability of drugs into inner ear compartments. This study aimed to develop and test magnetic cationic liposomes as nanocarriers for targeted corticosteroid delivery to auditory hair cells. Carboxymethyl chitosan–coated liposomes were prepared by the lipid film hydration method, incorporating magnetic nanoparticles and dexamethasone phosphate in their aqueous core. The optimal liposomal formulation, in terms of size, zeta potential, and drug leakage over time, was selected and tested in an in vitro model of drug-induced ototoxicity. HEI-OC1 cells exposed to cisplatin or gentamicin were co-treated with the liposomal formulations, and viability, mitochondrial membrane potential, and β-galactosidase activity were assessed. The results demonstrated that magnetic, polymer-coated liposomes protected against cytotoxicity by preserving mitochondrial function and significantly reducing senescence. These findings provide a proof of concept for magnetically responsive liposomal systems as potential therapeutic platforms for preventing or treating drug-associated hearing loss. Full article

In response to the inability to quickly assess wind noise performance during the early stages of automotive styling design, this paper proposes a method for predicting interior wind noise by integrating automotive point cloud models with the Gray Wolf Optimization Residual Network model (GWO-ResNet). Based on wind tunnel test data under typical operating conditions, the point cloud model of the test vehicle is compressed using an auto-encoder and used as input features to construct a nonlinear mapping model between the whole vehicle point cloud and the wind noise level at the driver’s left ear. Through adaptive optimization of key hyperparameters of the ResNet model using the gray wolf optimization algorithm, the accuracy and generalization of the prediction model are improved. The prediction results on the test set indicate that the proposed GWO-ResNet model achieves prediction results that are consistent with the actual measured values for the test samples, thereby validating the effectiveness of the proposed method. A comparative analysis with traditional ResNet models, GWO-LSTM models, and LSTM models revealed that the GWO-ResNet model achieved Mean Absolute Percentage Error (MAPE) and mean squared error (MSE) of 9.72% and 20.96, and 9.88% and 19.69, respectively, on the sedan and SUV test sets, significantly outperforming the other comparison models. The prediction results on the independent validation set also demonstrate good generalization ability and stability (MAPE of 10.14% and 10.15%, MSE of 23.97 and 29.15), further proving the reliability of this model in practical applications. The research results provide an efficient and feasible technical approach for the rapid evaluation of wind noise performance in vehicles and provide a reference for wind noise control in the early design stage of vehicles. At the same time, due to the limitations of the current test data, it is impossible to predict the wind noise during the actual driving of the vehicle. Subsequently, the wind noise during actual driving can be predicted by the test data of multiple working conditions. Full article

Introduction: Noggin encoding (NOG) gene plays a critical role in early embryogenesis and development of bones, joints, cartilage, eyes, and neural tissue. The NOG gene encodes the noggin protein. Noggin is the only secreted inhibitor of bone morphogenetic protein (BMP) that is associated with abnormal phenotypes in humans. The most commonly observed manifestations of NOG gene mutations include bilateral conductive hearing loss, proximal symphalangism, broad thumbs, hyperopia, and a distinct facial appearance. This genetic disorder was first reported in 1990 by Teunissen and Cremers. Since then, various phenotypic presentations of NOG mutation have been reported, leading to the introduction of the term NOG-related symphalangism spectrum disorder (NOG-SSD). Case report: In this report, we describe a family (mother and daughter) with bilateral mixed hearing loss. Both patients had hyperopia, distinct facial appearance with hemicylindrical nose, broad thumbs, and syndactyly of the second and third toes. Genetic testing confirmed a NOG gene mutation. Bilateral stapedotomy was successfully performed, resulting in significant hearing improvement. However, due to sensorineural component of hearing loss, complete hearing recovery was only achieved with the use of hearing aids. Discussion: The etiology of the sensorineural component of hearing loss in NOG-SSD remains unclear. In animal models, the NOG gene is essential for inner ear development, while in humans, only middle ear malformations have been reported. The phenotypic variability observed in individuals with NOG mutations is very wide, suggesting that the sensorineural component of hearing loss could represent one of the possible manifestations. Conclusions: Conductive hearing loss is the primary manifestation of the NOG-SSD, and all previously reported cases of NOG gene mutations have presented exclusively with conductive hearing loss. It is possible that additional genetic factors, not necessarily directly related to the NOG gene but present in this family, contribute to the development of the sensorineural component of hearing loss, although thorough genetic testing did not reveal any additional mutation. This is, to our knowledge, the first report of mixed hearing loss associated with a NOG mutation confirmed preoperatively. Further studies are needed to determine whether the sensorineural component represents a primary manifestation or arises from secondary mechanisms. Full article

Yield components are the most important breeding objectives, directly determining maize high-yield breeding. It is well known that these traits are controlled by a large number of quantitative trait loci (QTL). Therefore, deeply understanding the genetic basis of yield components and identifying key regulatory candidate genes can lay the foundation for maize marker-assisted selection (MAS) breeding. In this study, our aim was to identify the key genomic regions that regulate maize yield component formation through bioinformatic methods. Herein, 554 original QTLs related to 11 yield components, including ear length (EL), hundred-kernel weight (HKW), ear weight (EW), cob weight (CW), ear diameter (ED), cob diameter (CD), kernel row number (KRN), kernel number per row (KNR), kernel length (KL), grain weight per plant (GW), and kernel width (KW) in maize, were collected from the MaizeGDB, national center for biotechnology information (NCBI), and China national knowledge infrastructure (CNKI) databases. The consensus map was then constructed with a total length of 7154.30 cM. Approximately 80.32% of original QTLs were successfully projected on the consensus map, and they were unevenly distributed on the 10 chromosomes (Chr.). Moreover, 44 meta-QTLs (MQTLs) were identified by the meta-analysis. Among them, 39 MQTLs controlled two or more yield components, except for the MQTL4 in Chr. 1, which was associated with HKW; MQTL11 in Chr. 2, which was responsible for EL; MQTL19 in Chr. 3, which was related to KRN; MQTL26 in Chr. 5, which was involved in HKW; and MQTL36 in Chr. 7, which regulated EL. These findings were consistent with the Pearson correlation results, indicating that these traits exhibited co-linked heredity phenomena. Meanwhile, 159 candidate genes were found in all of the above MQTLs intervals, of which, 29 genes encoded E3 ubiquitin protein ligase, which was related with kernel size and weight. Other genes were involved in multiple metabolic processes, including plant hormones signaling transduction, plant growth and development, sucrose–starch synthesis and metabolism, and reproductive growth. Overall, the results will provide reliable genetic resources for high-yield molecular breeding in maize. Full article

Background and Objectives: Sensorineural hearing loss (SNHL) is influenced by various causes, including thyroid diseases. For example, hypothyroidism and thyroid autoimmunity can damage the inner ear through hormonal, immune, and vascular mechanisms. Vestibular disorders like Ménière’s disease (MD) and benign paroxysmal positional vertigo (BPPV) also show possible associations with thyroid dysfunction. Materials and Methods: A review following PRISMA guidelines searched PubMed, Scopus, and Google Scholar for studies linking thyroid disorders with inner ear dysfunction. Results: Out of 985 screened records, 30 studies met inclusion criteria, involving various thyroid disorders, primarily hypothyroidism and autoimmune thyroiditis. Scientific evidence supports a correlation between hypothyroidism and hearing impairment. However, some studies also suggest a link between hyperthyroidism and inner ear disorders, particularly focusing on the role of autoimmunity in this context. Concerning vestibular dysfunction, the available studies are less abundant and support a significant association between thyroid disease and Meniere’s disease. Conclusions: There is a clear correlation between hypothyroidism and auditory function. A substantial body of literature also supports an association with vestibular disorders, although some discrepancies remain. Further research is needed to elucidate the underlying pathophysiological mechanisms (e.g., autoimmune, vascular, metabolic) involved with this correlation. Full article

Background/Objectives: Complete blood count tests are inexpensive and widely available and may help identify low-grade inflammation in otolaryngologic (Ear, Nose and Throat, ENT) diseases, such as facial paralysis and hearing loss. This study aimed to describe the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), and lymphocyte-to-monocyte ratio (LMR) in ENT diseases and to provide preliminary evidence supporting further research. Methods: Data from 62 patients with ENT diseases were analyzed in a cross-sectional design. Results: The prevalence of ENT diseases was higher in women (63%) and adults (85.5%), highlighting vertigo, hearing loss, and septal deviation. Most marker values were within normal ranges; however, NLR values were elevated in patients with either septal deviation or vertigo, and ELR values were increased in cases of allergic or infectious rhinitis and sinusitis. In contrast, LMR values were at the lower normal limits in patients with septal deviation. Conclusions: These findings highlight the need for further studies to clarify the role of these biomarkers in chronic conditions and morphological alterations associated with ENT diseases, using more complex study designs. Full article

Background/Objectives: Spanish-speaking patients face persistent barriers in accessing equitable audiological care, particularly when standardized language-appropriate tools are lacking. Two Spanish-language sentence recognition tests, the Spanish AzBio Sentence (SAzB) and the Latin American Hearing in Noise Test (LAH), are commonly used to evaluate speech perception in adults with hearing loss. However, performance differences between these measures may influence referral decisions for hearing intervention, such as cochlear implantation. This study compared test performance under varying noise and spatial conditions to guide appropriate test selection and reduce the risk of misclassification that may contribute to healthcare disparities. Methods: Twenty-one bilingual Spanish/English speaking adults with normal bilateral hearing completed speech perception testing using both the SAzB and LAH. Testing was conducted under two spatial configurations: (1) speech and noise presented from the front (0° azimuth) and (2) speech to the simulated poorer ear and noise to the better ear (90°/270° azimuth). Conditions included quiet and three signal-to-noise ratios (+10, +5, and 0 dB). Analyses included paired t-tests and one-way ANOVAs. Results: Participants scored significantly higher on the LAH than on the SAzB across all SNR conditions and configurations, with ceiling effects observed for the LAH. SAzB scores varied by language dominance, while LAH scores did not. No other differences were observed based on any further demographic information. Conclusions: The SAzB provides a more challenging and informative assessment of speech perception in noise. Relying on easier tests like the LAH may obscure real-world difficulties and delay appropriate referrals for hearing loss intervention, including cochlear implant evaluation. Selecting the most appropriate test is critical to avoiding under-referral and ensuring Spanish-speaking patients receive equitable and accurate care. Full article

Background: This study aimed to evaluate the clinical effectiveness of dupilumab and its impact on CRSwNP and type 2 inflammatory biomarkers in patients with severe uncontrolled asthma, with or without comorbidities, within a real-life cohort. Methods: This was a single-center, prospective, and observational real-life study conducted at the Severe Asthma Unit of Germans Trias i Pujol University Hospital. The objective of this study was to assess the real-world response to dupilumab treatment in patients with severe asthma, with or without nasal polyposis, bronchiectasis, obesity, or switching from another biologic drug for their asthma. Results: The ACT score significantly increased (13.7 vs. 20.6; p = 0.001), while the number of exacerbations decreased (3.1 vs. 0.7; p = 0.005). Patients with CRSwNP showed an increase in the ACT score (13.1 vs. 19.8; p = 0.011) and a decrease in the number of exacerbations (3.0 vs. 1.3; p = 0.217). Patients with nasal polyps showed an increase in both SNOT22 (78.3 vs. 38.3; p = 0.013) and global VAS (8 vs. 4.2; p = 0.028). Patients with bronchiectasis receiving dupilumab showed an increase in the ACT score (12.7 vs. 21.3; p = 0.039) and a marked decrease in the number of exacerbations (2.8 vs. 0; p = 0.025). Obese patients treated with dupilumab showed an improvement in the ACT score (14.1 vs. 21.3; p = 0.044) and a decrease in the rate of exacerbations (3.2 vs. 1.3; p = 0.030). Patients with rhinoconjunctivitis receiving dupilumab showed an increase in the ACT score (13.4 vs. 19.1; p = 0.017) and a decrease in the number of exacerbations (3.3 vs. 0.8; p = 0.024). Conclusions: Dupilumab is a highly effective treatment for severe asthma, showing significant improvements in lung function, reductions in exacerbations, and enhanced quality of life for patients with and without nasal polyps. The results of this real-life study support dupilumab as a valuable addition to the therapeutic armamentarium for asthma, particularly for those with type 2 inflammation despite the presence of comorbidities such as bronchiectasis or obesity, or for patients in whom a previous biologic treatment failed. Full article

Introduction: Canine sinonasal aspergillosis (SNA) can present singular as a primary disease or secondary to concurrent sinonasal pathology. We hypothesized that treatment response and prognosis differ between both forms, particularly when sinusitis is present. Methods: In this retrospective study, 30 dogs with SNA were categorized as either group pA (primary aspergillosis) or group sA (secondary aspergillosis; with additional sinonasal pathology). History, diagnostics, endoscopic therapeutic intervention of affected nose and sinus, and follow-up data were analyzed. Results: Group pA included 19/30 dogs (63%), with 15 dogs (79%) showing concurrent sinusitis. Group sA included 11/30 dogs (37%; additional conditions: foreign bodies, dental pathologies, frontal bone fracture). Only 2/11 sA dogs (18%) had sinusitis. Follow-ups in group pA were more frequent than in group sA (p = 0.04). Need for re-treatments differed significantly between groups (p = 0.02) and in dogs with sinusitis, regardless of group (p < 0.001). In group sA, treating the underlying condition plus single endoscopic debridement ± antifungal therapy led to clinical resolution in 11 of 12 dogs (92%). Conclusions: Primary SNA is frequently associated with sinusitis, requires aggressive repeated antifungal therapy, and may not achieve a definitive cure. Secondary SNA is usually confined to the nasal cavity, responds well to underlying condition treatment, carries better prognosis, and requires fewer antifungal treatments. Full article

Advancements in electroencephalography (EEG) technology and feature extraction methods have paved the way for wearable, non-invasive systems that enable continuous sleep monitoring outside clinical environments. This study presents the development and evaluation of an EEG-based acquisition system for sleep staging, which can be adapted for wearable applications. The system utilizes a custom experimental setup with the ADS1299EEG-FE-PDK evaluation board to acquire EEG signals from the forehead and in-ear regions under various conditions, including visual and auditory stimuli. Afterward, the acquired signals were processed to extract a wide range of features in time, frequency, and non-linear domains, selected based on their physiological relevance to sleep stages and disorders. The feature set was reduced using the Minimum Redundancy Maximum Relevance (mRMR) algorithm and Principal Component Analysis (PCA), resulting in a compact and informative subset of principal components. Experiments were conducted on the Bitbrain Open Access Sleep (BOAS) dataset to validate the selected features and assess their robustness across subjects. The feature set extracted from a single EEG frontal derivation (F4-F3) was then used to train and test a two-step deep learning model that combines Long Short-Term Memory (LSTM) and dense layers for 5-class sleep stage classification, utilizing attention and augmentation mechanisms to mitigate the natural imbalance of the feature set. The results—overall accuracies of 93.5% and 94.7% using the reduced feature sets (94% and 98% cumulative explained variance, respectively) and 97.9% using the complete feature set—demonstrate the feasibility of obtaining a reliable classification using a single EEG derivation, mainly for unobtrusive, home-based sleep monitoring systems. Full article

Dermal tissue samples are a rich source of germplasm because they can be readily collected, frozen as part of a genebank collection, digested and cultured, and used for a variety of purposes such as genotyping or other forms of genetic research. Derived fibroblasts can also be used for somatic cell nuclear transfer, and the remaining cells can be frozen for future use. However, collection of tissues with ear notchers, scalpels, or biopsy punches can be problematic because tissue handling and the tool surfaces can contaminate the samples. Therefore, the modification of the Allflex Tissue Sampling Unit (TSU) system was explored to determine if the technology can empower rapid collection of clean samples that are easily identifiable and portable. Results indicate that the TSU system was efficient, and samples that were collected and processed for tissue culture resulted in successful derivations of fibroblasts from 7 of 11 animals. Thus, the TSU system appears to be a viable option for collecting and preserving dermal tissue for genebanking and other applications where simple, rapid collection of large quantities of samples is required. Full article

Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and typically has a favorable prognosis. However, a subset of patients experience aggressive disease, recurrence, or treatment resistance, underscoring the need for more precise diagnostic and therapeutic strategies. Advances in molecular profiling have improved the management of thyroid cancer by enabling risk-adapted treatment and targeted interventions. This narrative review offers a clinically focused synthesis of the current role of molecular diagnostics and personalized therapeutics in DTC. We examine key genetic alterations and their diagnostic, prognostic, and therapeutic implications, and discuss how molecular markers enhance traditional risk stratification systems, informing surgical decisions, radioactive iodine (RAI) use, and surveillance. The growing role of targeted therapies, such as tyrosine kinase inhibitors and agents against specific oncogenic drivers, is reviewed, particularly for RAI-refractory DTC. We also address real-world challenges in implementing precision medicine, including access, cost, and standardization. Future directions, such as liquid biopsy, artificial intelligence, and multi-omic integration, are explored as tools to achieve fully personalized care. This review aims to bridge the gap between molecular discovery and clinical application, offering practical insights for endocrinologists, surgeons, oncologists, and multidisciplinary teams managing DTC. Full article

The first monographic exhibition dedicated to Vittore Carpaccio (ca. 1460–1525) in the US, and the first outside of Italy, was hosted at the National Gallery of Art in Washington, DC, from 20 Nov 2022 to 23 February 2023 (from where it went to Venice). Building on the research of art historians and experts on Venice and the larger Mediterranean region in the early modern period, this paper examines Carpaccio’s depiction of various “Turks” in some of the large narrative painting cycles (teleri) commissioned by the devotional confraternities (scuole) in Renaissance Venice. While Carpaccio’s and the larger Venetian familiarity with Islam, including Turks, has been studied, this paper compares various female figures in the St. Stephen cycle with those in his St. George cycle, situating them in the larger historical context of the commissioning scuole (Scuola di Santo Stefano and Scuola di San Giorgio degli Schiavoni, respectively). While attempting to uncover the significance, if not the identities, of a few individuals who stand out from the crowd, this paper urges caution when attempting to discern social history from a painting, much as we take literary texts (particularly those written well before our own times) with a grain of salt. Full article

Dysferlin direct protein–protein interactions (PPI) previously have been elucidated with surface plasmon resonance (SPR) and predicted to underlie membrane repair in mechanotransducing myofibrils. In mechanotransducing inner ear hair cells, dysferlin is detected with Z-stack confocal immunofluorescence in the stereocilia and their inserts in the tectorial membrane (TM) co-localizing with FKBP8, consistent with the SPR determination of tight, positively Ca²⁺-dependent interaction. FKBP8, a direct binding partner of mechanotransducing TMC1, when overexpressed, evokes an elevation in anti-apoptotic BCL2, inhibition of ryanodine receptor (RYR) activity, and a consequent reduction in Ca²⁺ release. RYR3 has now been immunolocalized to the tip of the TM in close association with a third-row outer hair cell (OHC) stereociliary BCL2-positive insertion. Dysferlin, annexin A2, and Alzheimer’s proteins BACE1 and amyloid precursor protein (APP) are also accumulated in these stereociliary insertions. RYR2 and RYR1 have been immunolocalized to the TM core, in position to influence TM Ca²⁺. Dysferlin PPI pathways also intersect with AD protein pathways in the spiral ganglion (SG). Dysferlin segregates with FKBP8, BACE1, and RYR3 in the interiors of SG type I cell bodies. RYR1, RYR2, PSEN1, BCL2, and caspase 3 are primarily confined to plasma membrane sites. RYR3 pathways traverse the plasma membrane to the cell body interior. Western analysis of dysferlinopathy proteins links FKBP8 and BCL2 overexpression with RYR inhibition, indicative of dysferlin targets that are ameliorative in AD. Full article