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MAPK pathway mutations affect one-fifth of head and neck squamous cell carcinoma (HNSCC). Unexpectedly, MAPK pathway aberrations are associated with remarkably long patient survival, even among patients with TP53 mutations (median ∼14 yr). We explored underlying outcome-favoring mechanisms with omics followed by preclinical models. Strikingly, multiple hotspot and non-hotspot MAPK mutations (A/BRAF, HRAS, MAPK1, and MAP2K1/2) all abrogated ErbB3 activation, a well-established HNSCC progression signal. Inhibitor studies functionally defined ERK activity negatively regulating phospho-ErbB3 in MAPK-mutants. Furthermore, pan-pathway immunoprofiling investigations identified MAPK-mutant tumors as the only "CD8+ T-cell-inflamed" tumors inherently bearing high-immunoreactive, constitutive cytolytic tumor microenvironments. Immunocompetent MAPK-mutant HNSCC models displayed active cell death and massive CD8+ T-cell recruitment in situ. Consistent with CD8+ T-inflamed phenotypes, MAPK-mutant HNSCC patients, independent of tumor-mutational burden, survived 3.3-4 times longer than WT patients with anti-PD1/PD-L1 immunotherapies. Similar prognosticity was noted in pan-cancers. We uncovered clinical, signaling, and immunological uniqueness of MAPK-mutant HNSCC with potential biomarker utilities predicting favorable patient survival.

Objectives: Our study aimed to investigate the feasibility of using high‐density surface electromyography (HD‐sEMG) for swallowing assessment by comparing the quantitative parameters and topographic patterns of HD‐sEMG between post‐irradiated patients and healthy individuals. Methods: Ten healthy volunteers and ten post‐irradiated nasopharyngeal carcinoma patients were recruited. 96‐channel HD‐sEMG was recorded although each participant consumed different consistencies of food (thin and thick liquid, puree, congee, and soft rice). Dynamic topography was generated from the root mean square (RMS) of the HD‐sEMG signals to illustrate the anterior neck muscle function in the swallowing process. The averaged power of muscles and the symmetry of swallowing patterns were assessed by objective parameters including average RMS, Left/Right Energy Ratio, and Left/Right Energy Difference. Results: The study showed different swallowing patterns between patients with dysphagia and healthy individuals. The mean RMS values were higher in the patient group compared to the healthy group, but the difference was not statistically significant. Asymmetrical patterns were shown in patients with dysphagia. Conclusion: HD‐sEMG is a promising technique that could be used to quantitatively evaluate the average power of neck muscles and the symmetry of swallowing activities in patients with swallowing difficulties. Level of Evidence: Level 3 Laryngoscope, 133:2920–2928, 2023 [ABSTRACT FROM AUTHOR]

This paper is concerned with the stability analysis and stabilization of periodic piecewise positive systems. By constructing a time‐scheduled copositive Lyapunov function with a time segmentation approach, an equivalent stability condition, determined via linear programming, for periodic piecewise positive systems is established. Based on the asymptotic stability condition, the spectral radius characterization of the state transition matrix is proposed. The relation between the spectral radius of the state transition matrix and the convergent rate of the system is also revealed. An iterative algorithm is developed to stabilize the system by decreasing the spectral radius of the state transition matrix. Finally, numerical examples are given to illustrate the results. [ABSTRACT FROM AUTHOR]

Objectives: The role of traditional nuclear medicine studies in the management of malignant otitis externa (MOE) is unclear and there are ongoing debates regarding their diagnostic value. The authors perform a systematic review and meta-analysis to assess the sensitivity and specificity of traditional nuclear medicine studies in the diagnosis of MOE.Methods: In accordance with PRISMA guidelines, a query of the Medline, Embase, Web of Science, and Cochrane databases was undertaken. The primary outcomes of interest were the sensitivity and specificity of traditional nuclear medicine studies to detect MOE.Results: Of the initial 1317 hits from the four databases, 20 articles with a combined 608 patients were ultimately included in the review. The pooled sensitivities for Technetium-99 and Gallium-67 were 85.1% (95% CI, 72.0-98.1%) and 71.2% (95% CI, 55.1-87.3%) respectively. The available evidence suggested poor specificity of these modalities, but was insufficient for meta-analysis. Neither modality was shown to be effective in the assessment of disease resolution.Conclusion: The sensitivities of Technetium-99 and Gallium-67 to detect MOE are less favorable than was initially thought. Given this finding and their poor specificity, lack of anatomic resolution, unproven ability to detect disease resolution and variable availability, this review does not support the routine use of these studies in the management of MOE.Level Of Evidence: N/A Laryngoscope, 130:1812-1816, 2020. [ABSTRACT FROM AUTHOR]

Objective: To assess interobserver agreement and intraobserver reproducibility when assessing the nasopharynx for malignancy under white light and narrow band imaging endoscopy because the decision to biopsy hinges on the examiner's perceived chance of malignancy.Methods: An interobserver and intraobserver agreement study utilizing white light and narrow band endoscopic images of the nasopharynx. The setting was an academic referral hospital. Participants were 156 adults with suspected nasopharyngeal carcinoma who underwent white light and narrow band imaging endoscopy and biopsy. Images of the nasopharynges were subsequently scored for malignancy by four otolaryngologists. The nasopharynx was scored on 4-point scales under white light and narrow band imaging endoscopy for the likelihood of malignancy or abnormality, respectively.Results: Intraclass correlation coefficients for intraobserver agreement for nasopharyngeal malignancy for four observers under white light were 0.86, 0.89, 0.79 and 0.88 (mean 0.855), respectively; and under narrow band imaging they were 0.64, 0.68, 0.64, and 0.66 (mean 0.655), respectively (all P values < 0.001). The coefficient for interobserver reliability under white light was 0.79 (95% confidence interval [CI] 0.76-0.82; P < 0.001), which indicated strong agreement. The coefficient for interobserver reliability under narrow band imaging was 0.56 (95% CI 0.50-0.61; P < 0.001), which indicated moderate agreement.Conclusions: Intraobserver and interobserver agreement for nasopharyngeal malignancy was strong on white light endoscopy but only moderate on narrow band imaging endoscopy. Agreement may be improved by adopting a standard set of assessment guidelines, including an objective detailed morphological analysis under white light and vasculature analysis under narrow band imaging.Level Of Evidence: 2a Laryngoscope, 129:1374-1379, 2019. [ABSTRACT FROM AUTHOR]