Variability of Maximum Glottal Angle on Clinical Sniff Task Differs in Patients With Functional and Organic Laryngeal Pathologies Compared to Healthy Controls.

OBJECTIVES: Practitioners rely heavily on flexible endoscopic visualization of the true vocal folds during a repeated "sniff-ee" maneuver to assess vocal fold mobility. However, the human eye lacks the temporal and spatial precision required to accurately gauge fine differences in maximal glottal angle. This study compared differences in maximal glottal angle variables during "sniff-ee" maneuvers across patients with various voice and laryngeal breathing disorders. METHODS: We retrospectively measured glottal angle from flexible laryngoscopy examinations in six groups of patients with voice and upper airway disorders: laryngeal dystonia/essential tremor (LD/ET), vocal fold lesions, vocal fold atrophy, paradoxical vocal fold motion disorder (PVFMD), muscle tension dysphonia (MTD), and healthy controls. Maximum glottal angle (GAMAX) and average glottal angle (GAAVG) were calculated during three serial "sniff-ee" maneuvers for all participants. Individual disorder groups (MTD, PVFMD, LD/ET, atrophy, and lesion) and broader disorder types (functional and organic) were compared to healthy controls using simple linear regression analyses. RESULTS: No significant difference in either GAMAX or GAAVG was found between controls and the disorder subgroups or broader disorder type (function and organic). However, there were statistically significant differences in the variability of GAMAX in both PVFMD (6.2° more variability; P < 0.001) and LD/ET (5.8° more variability; P < 0.001) compared to healthy controls. CONCLUSION: Patients diagnosed with LD/ET and PVFMD both demonstrated significantly more variability in their GAMAX compared to healthy controls, suggesting that movement consistency or coordination may be relatively compromised in these patient groups. Further research is warranted to investigate the sensitivity and specificity of glottal angle variability in diagnosing PVFMD and LD in clinical or research settings. LEVEL OF EVIDENCE: 4 SHORT SUMMARY: Laryngeal examinations from five patient groups were compared to those from healthy controls. Patients with paradoxical vocal fold motion disorder and laryngeal movement disorders exhibited significantly greater variability of glottal angle during sniff maneuver compared to healthy controls.

Current Practices in Voice Data Collection and Limitations to Voice AI Research: A National Survey.

INTRODUCTION: Accuracy and validity of voice AI algorithms rely on substantial quality voice data. Although commensurable amounts of voice data are captured daily in voice centers across North America, there is no standardized protocol for acoustic data management, which limits the usability of these datasets for voice artificial intelligence (AI) research. OBJECTIVE: The aim was to capture current practices of voice data collection, storage, analysis, and perceived limitations to collaborative voice research. METHODS: A 30-question online survey was developed with expert guidance from the voicecollab.ai members, an international collaborative of voice AI researchers. The survey was disseminated via REDCap to an estimated 200 practitioners at North American voice centers. Survey questions assessed respondents' current practices in terms of acoustic data collection, storage, and retrieval as well as limitations to collaborative voice research. RESULTS: Seventy-two respondents completed the survey of which 81.7% were laryngologists and 18.3% were speech language pathologists (SLPs). Eighteen percent of respondents reported seeing 40%-60% and 55% reported seeing >60 patients with voice disorders weekly (conservative estimate of over 4000 patients/week). Only 28% of respondents reported utilizing standardized protocols for collection and storage of acoustic data. Although, 87% of respondents conduct voice research, only 38% of respondents report doing so on a multi-institutional level. Perceived limitations to conducting collaborative voice research include lack of standardized methodology for collection (30%) and lack of human resources to prepare and label voice data adequately (55%). CONCLUSION: To conduct large-scale multi-institutional voice research with AI, there is a pertinent need for standardization of acoustic data management, as well as an infrastructure for secure and efficient data sharing. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1333-1339, 2024.

A Photoactivatable Luminescent Motif through Ring-Flipping Isomerization for Multiple Photopatterning.

Photoactivatable luminescent materials have garnered enormous attention in the field of intelligent responsive materials, yet their design and applications remain challenging due to the limited variety of photoactivatable motifs. In the work described herein, we discovered a new photoactivatable luminescent motif that underwent ring-flipping isomerization under UV irradiation. The emission of this motif exhibited a rapid transformation from dark yellow to bright green, accompanied by a significant enhancement of quantum yield from 1.9% to 34.2%. Experimental and theoretical studies revealed that the effective intramolecular motion (EIM) was crucial to the distinct luminescence performance between two isomers. In addition, polymers containing this motif were achieved through a one-pot alkyne polymerization, exhibiting both photofluorochromic and photo-cross-linking properties. Furthermore, multiple types of photopatterning, including luminescent encryption, fluorescent grayscale imaging, and high-resolution photolithographic patterns, were realized. This work developed a new photoactivatable luminescent motif and demonstrated its potential applications in both small molecules and macromolecules, which will help in the future design of photoactivatable luminescent materials.

Laryngeal Anatomy, Molecular Biology, Cause, and Risk Factors for Laryngeal Cancer.

Laryngeal cancer is declining in incidence in many parts of the world, as smoking becomes a less common habit. However, challenging cases of laryngeal cancer still exist and require expertise from otolaryngologists. This article reviews the relevant anatomy and lymphatic drainage pathways of the larynx because they pertain to cancer spread. The molecular and immune landscapes of laryngeal cancer, which are tightly linked to smoking, are also discussed.

Defining the Performance of Clinician's Ability to Screen for Laryngeal Mass From Voice.

OBJECTIVE: Defining a clinician's ability to perceptually identify mass from voice will inform the feasibility, design priorities, and performance standards for tools developed to screen for laryngeal mass from voice. This study defined clinician ability of and examined the impact of expertise on screening for laryngeal mass from voice. STUDY DESIGN: Task comparison study between experts and nonexperts rating voices for the probability of a laryngeal mass. SETTING: Online, remote. METHODS: Experts (voice-focused speech-language pathologists and otolaryngologists) and nonexperts (general medicine providers) rated 5-s/i/voice samples (with pathology defined by laryngoscopy) for the probability of laryngeal mass via an online survey. The intraclass correlation coefficient (ICC) estimated interrater and intrarater reliability. Diagnostic performance metrics were calculated. A linear mixed effects model examined the impact of expertise and pathology on ratings. RESULTS: Forty clinicians (21 experts and 19 nonexperts) evaluated 344 voice samples. Experts outperformed nonexperts, with a higher area under the curve (70% vs 61%), sensitivity (49% vs 36%), and specificity (83% vs 77%) (all comparisons p < .05). Interrater reliability was fair for experts and poor for nonexperts (ICC: 0.48 vs 0.34), while intrarater reliability was excellent and good, respectively (ICC: 0.9 and 0.6). The main effects of expertise and underlying pathology were significant in the linear model (p < .001). CONCLUSION: Clinicians demonstrate inadequate performance screening for laryngeal mass from voice to use auditory perception for dysphonia triage. Experts' superior performance indicates that there is acoustic information in a voice that may be utilized to detect laryngeal mass based on voice.

Quantifying and Improving the Performance of Speech Recognition Systems on Dysphonic Speech.

OBJECTIVE: This study seeks to quantify how current speech recognition systems perform on dysphonic input and if they can be improved. STUDY DESIGN: Experimental machine learning methods based on a retrospective database. SETTING: Single academic voice center. METHODS: A database of dysphonic speech recordings was created and tested against 3 speech recognition platforms. Platform performance on dysphonic voice input was compared to platform performance on normal voice input. A custom speech recognition model was trained on voice from patients with spasmodic dysphonia or vocal cord paralysis. Custom model performance was compared to base model performance. RESULTS: All platforms performed well on normal voice, and 2 platforms performed significantly worse on dysphonic speech. Accuracy metrics on dysphonic speech returned values of 84.55%, 88.57%, and 93.56% for International Business Machines (IBM) Watson, Amazon Transcribe, and Microsoft Azure, respectively. The secondary analysis demonstrated that the lower performance of IBM Watson and Amazon Transcribe was driven by performance on spasmodic dysphonia and vocal fold paralysis. Thus, a custom model was built to increase the accuracy of these pathologies on the Microsoft platform. Overall, the performance of the custom model on dysphonic voices was 96.43% and on normal voices was 97.62%. CONCLUSION: Current speech recognition systems generally perform worse on dysphonic speech than on normal speech. We theorize that poor performance is a consequence of a lack of dysphonic voices in each platform's original training dataset. We address this limitation with transfer learning used to increase the performance of these systems on all dysphonic speech.

A Computer Simulation Model to Analyze the Application Process for Competitive Residency Programs.

BACKGROUND: The residency match process for competitive specialties hinders programs' ability to holistically review applications. OBJECTIVE: A computer simulation model of the residency application process was created to test the hypotheses that (1) it is advantageous to medical students to apply to the maximum number of programs under the current system, and (2) including a medical student's residency program preferences at the beginning of the application process improves the efficiency of the system for applicants and programs as quantified by the number of interview invitations received. METHODS: The study was conducted in 2016 using 2014 Otolaryngology Match data. A computer model was created to perform simulations for multiple scenarios to test the hypotheses. Students were assigned scores representing easy and hard metrics and program preferences, simulating a mixture of individual student preference and general program popularity. RESULTS: We modeled a system of 99 otolaryngology residency programs with 292 residency spots and 460 student applicants. While it was individually advantageous for an applicant to apply to the maximum number of programs, this led to a poor result for the majority of students when all applicants undertook the strategy. The number of interview invitations improved for most applicants when preference was revealed. CONCLUSIONS: Offering applicants an option to provide program preference improves the practical number of interview invitations. This enables programs to review applicants holistically-instead of using single parameters such as United States Medical Licensing Examination scores-which facilitates a selection of applicants who will be successful in residency.

Native State Volume Fluctuations in Proteins as a Mechanism for Dynamic Allostery.

Allostery enables tight regulation of protein function in the cellular environment. Although existing models of allostery are firmly rooted in the current structure-function paradigm, the mechanistic basis for allostery in the absence of structural change remains unclear. In this study, we show that a typical globular protein is able to undergo significant changes in volume under native conditions while exhibiting no additional changes in protein structure. These native state volume fluctuations were found to correlate with changes in internal motions that were previously recognized as a source of allosteric entropy. This finding offers a novel mechanistic basis for allostery in the absence of canonical structural change. The unexpected observation that function can be derived from expanded, low density protein states has broad implications for our understanding of allostery and suggests that the general concept of the native state be expanded to allow for more variable physical dimensions with looser packing.

A Bayesian Network Model of Head and Neck Squamous Cell Carcinoma Incorporating Gene Expression Profiles.

Radiation therapy allows precision targeting of certain groups of lymph nodes and is a treatment for metastatic head and neck squamous cell carcinoma. In current practice, there is approximately 15% probability that physicians inadvertently treat healthy tissue or leave the cancerous lymph nodes untreated. The aim of this work is to improve the accuracy of medical decision-making by extending existing predictive models to capture the probabilities of finding cancerous lymph nodes at each of the six image-based surgical neck level using a patient's genetic profile, primary tumor site and tumor size. Our model was trained with publicly available data extracted from the Cancer Genome Atlas (TCGA) and validated against the TCGA dataset both with and without genetic information. Results show that genetic profile data improves model accuracy. These findings suggest that our predictive model may improve the accuracy of clinical decision-making, especially for patients with more advanced metastasis. However, more data is needed to ensure significance of the proposed effects, as well as to improve accuracy of the overall model.

Development of a Novel Markov Chain Model for the Prediction of Head and Neck Squamous Cell Carcinoma Dissemination.

Prediction of microscopic tumor spread to regional lymph nodes can assist in radiation planning for cancer treatment. However, it is still challenging to predict tumor spread. In this paper, we present a unique approach to modeling how tumor cells disseminate to form regional metastases. This involves leveraging well established knowledge resources and commonly held notions of how cancer spreads. Using patient data, we utilized our approach to create a model of metastasis for the subset of head and neck squamous cell carcinoma that arises in the mucosa of the lateral tongue. The model was created using a training set extracted from the clinical records of 50 patients with tumors of this type who presented to the University of Washington head and tumor board over a three and half year period. The test sets consist of four case series drawn from the literature.

Conservation of side-chain dynamics within a protein family.

The question of protein dynamics and its relevance to function is currently a topic of great interest. Proteins are particularly dynamic at the side-chain level on the time scale of picoseconds to nanoseconds. Here, we present a comparison of NMR-monitored side-chain motion between three PDZ domains of approximately 30% sequence identity and show that the side-chain dynamics display nontrivial conservation. Methyl (2)H relaxation was carried out to determine side-chain order parameters (S(2)), which were found to be more similar than naively expected from sequence, local packing, or a combination of the two. Thus, the dynamics of a rather distant homologue appears to be an excellent predictor of a protein's side-chain dynamics and, on average, better than current structure-based methods. Fast side-chain dynamics therefore display a high level of organization associated with global fold. Beyond simple conservation, the analysis herein suggests that the pattern of side-chain flexibility has significant contributions from nonlocal elements of the PDZ fold, such as correlated motions, and that the conserved dynamics may directly support function.

CspA regulates pigment production in Staphylococcus aureus through a SigB-dependent mechanism.

We report that the cold shock protein CspA of Staphylococcus aureus is required for maximal production of pigment. Results from transcriptional studies revealed that loss of CspA resulted in decreased expression of genes needed for the biosynthesis of 4,4'-diaponeurosporene and the alternative sigma factor SigB.