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.

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.