The impact of COVID-19 and vaccination status on outcomes in veterans with head and neck squamous cell carcinoma.

BACKGROUND: The impact of both COVID-19 infection and vaccination status on patients with head and neck squamous cell carcinoma (HNSCC) remains unknown. OBJECTIVE: To determine the impact of COVID-19 infection and vaccination status on 60-day mortality, cardiovascular, and respiratory complications in patients with a prior diagnosis of HNSCC. METHODS: This was a retrospective cohort study through the Veterans Affairs (VA) Corporate Data Warehouse of Veterans with HNSCC who were tested for COVID-19 during any inpatient VA medical center admission. A cohort of patients was created of Veterans with a diagnosis of HNSCC of the oral cavity,oropharynx, hypopharynx, larynx, and nasopharynx based on International Classification of Disease (ICD) codes. Data collected included clinical/demographic data, vaccination status, and incidence of 60-day mortality, 60-day cardiovascular complication (including myocardial infarction, venous thromboembolism, cerebrovascular accident), and 60-day respiratory complication (including acute respiratory failure, acute respiratory distress syndrome, and pneumonia). The interactions between COVID-19 infection, vaccination status, morbidity and mortality were investigated. RESULTS: Of the 14 262 patients with HNSCC who were tested for COVID-19 during inpatient admission, 4754 tested positive (33.3%), and 9508 (67.7%) tested negative. Patients who tested positive demonstrated increased 60-day mortality (4.7% vs. 2.0%, respectively; p < 0.001), acute respiratory failure (ARF; 15.4% vs. 7.1%, p < 0.001), acute respiratory distress syndrome (ARDS; 0.9% vs. 0.2%, p < 0.001), and pneumonia (PNA; 20.0% vs. 6.4%, p < 0.001) compared to those who never tested positive, respectively. Patients who received COVID-19 vaccination between 2 weeks and 6 months prior to a positive test demonstrated decreased rates of ARF (13.2% vs. 16.0%, p = 0.034) and PNA (16.7% vs. 20.9%, p = 0.003) compared to the unvaccinated group. A logistic regression of patients with COVID-19 infections who died within 60 days was performed, with no significant survival advantage among patients vaccinated between 2 weeks and 6 months prior to the positive test. CONCLUSION: COVID-19 infection may significantly increase rates of 60-day mortality and respiratory complications in patients with HNSCC. COVID-19 vaccination between 2 weeks and 6 months prior to infection may decrease severity of respiratory complications but did not show significant mortality benefits in this study. These data highlight the need for surveillance of respiratory infection and vaccination in this vulnerable population.

Temporal Bone Trauma.

Temporal bone trauma represents a potentially underrecognized condition during head injuries and remains an important consideration during the evaluation of these patients. The temporal bone contains many critical neurovascular structures in addition to the primary organs of the auditory and vestibular systems that may be violated during these injuries. Despite the lack of consensus guidelines on the management of these injuries, this review highlights the current literature regarding the diagnosis and management of temporal bone trauma and its potential complications.

Cardiac anomalies in Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome is a rare multi-system disorder associated with cardiac anomalies. All patients with a diagnosis of Axenfeld-Rieger syndrome were identified from our electronic medical record. Chart review was performed to document the presence and types of CHD. Out of 58 patients, 14 (24.1%) had CHD and a wide variety of cardiac lesions were identified.

Upper Airway Manifestations of Monkeypox: A Case Report and Literature Review.

Background: The monkeypox virus (MPXV) has spread globally, causing an infection similar to that of smallpox. In July 2022, MPXV was declared an international public health emergency by the World Health Organization. Although the prodromal and cutaneous symptoms are described, the literature is lacking with regard to the upper airway manifestations of the disease. Methods: This case report describes a 39-year-old gentleman with a history of human immunodeficiency virus who presented to the emergency department with fever, sore throat, and cough. A literature review was also performed to determine the clinical presentation and physical examination findings of patients presenting with MPXV. Results: The patient underwent flexible laryngoscopy on two separate occasions due to his symptoms of fever and sore throat. He was noted to have white plaque-like lesions throughout the upper aerodigestive tract that could not be excised with manipulation. Ultimately, he tested positive for MPXV and was treated with full recovery. Conclusions: To our knowledge, this is the first report describing upper airway manifestations of MPXV. Since patients with MPXV often present initially with pharyngitis, understanding the physical examination findings of MPXV in the upper airway is imperative for early diagnosis and public health awareness.

Reliability of Home Sleep Apnea Testing for Diagnosing Obstructive Sleep Apnea in Patients With Spontaneous Cerebrospinal Fluid Leaks.

STUDY OBJECTIVES:  To establish the prevalence of obstructive sleep apnea (OSA) in patients with spontaneous cerebrospinal fluid (sCSF) leaks and demonstrate the reliability of home sleep apnea testing (HSAT) to screen for OSA in this population. METHODS: A literature review was performed to assess data on OSA prevalence in sCSF leaks. An institutional retrospective review was performed of 20 patients with sCSF leaks who met inclusion criteria. Patients without prior sleep studies were prospectively administered sleep studies, either HSAT or polysomnogram (PSG). RESULTS: Twenty patients met the inclusion criteria. Two patients had prior sleep studies while 18 patients obtained prospective sleep studies following diagnosis and prior to management of sCSF leaks. Nineteen patients (95%) had evidence of mild or greater OSA. CONCLUSIONS:  This study re-demonstrates the high prevalence of OSA in patients with sCSF leaks, consistent with current literature, and investigates the reliability of HSAT for diagnosis of OSA in this population.

Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease.

Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation or sudden changes in hearing, including sudden sensorineural hearing loss (SSNHL), Meniere's disease (MD), and autoimmune inner ear disease (AIED). Despite their use across these diseases, the rate of complete recovery remains low, and results across the literature demonstrates significant heterogeneity with respect to the effect of corticosteroids, suggesting a need to identify more efficacious treatment options. Previously, our group has cross-referenced steroid-responsive genes in the cochlea with published single-cell and single-nucleus transcriptome datasets to demonstrate that steroid-responsive differentially regulated genes are expressed in spiral ganglion neurons (SGN) and stria vascularis (SV) cell types. These differentially regulated genes represent potential druggable gene targets. We utilized multiple gene target databases (DrugBank, Pharos, and LINCS) to identify orally administered, FDA approved medications that potentially target these genes. We identified 42 candidate drugs that have been shown to interact with these genes, with an emphasis on safety profile, and tolerability. This study utilizes multiple databases to identify drugs that can target a number of druggable genes in otologic disorders that are commonly treated with steroids, providing a basis for establishing novel repurposing treatment trials.

Health Disparities in Otology: A PRISMA-Based Systematic Review.

OBJECTIVE: Social determinants of health (SDOHs), including but not limited to sex, race, socioeconomic status, insurance status, and education level, play a significant role in health disparities and affect health outcomes. The purpose of this systematic review is to examine health disparities in otology within the United States and highlight areas warranting further research. DATA SOURCES: PubMed, Ovid MEDLINE. REVIEW METHODS: Our search encompassed all years through January 10, 2021. All peer-reviewed primary literature of any design and publication date regarding health disparities and otology outcomes in the United States was eligible for inclusion. Eligibility assessment was performed via 3 independent investigators. RESULTS: Of the 6326 unique abstracts identified, 188 studies underwent full-text review, and 52 remained in the final review. The most frequently examined otologic condition was hearing loss (36.5%), followed by cochlear implantation (28.8%) and infection/effusion (15.4%). Vertigo/dizziness (1.9%), Ménière's disease (1.9%), and tinnitus (1.9%) were the least represented otologic conditions. Comprehensive articles on multiple disparity topics were the most common (n = 18), followed by articles on race/ethnicity (n = 11) and socioeconomic status (n = 9). Language (n = 2), education (n = 2), and gender (n = 1) were the least discussed. Over 5-fold the number of articles were published between 2011 and 2020 compared to the preceding decade (42 vs 8). CONCLUSION: This study captures the existing literature regarding health disparities and outcomes in otology. The lack of robust data suggests the need for future quality studies aimed at investigating disparities in otologic care, as well as a broader push for recording and reporting SDOHs.

Improving Head and Neck Microvascular Reconstructive Care with a Novel Perioperative Checklist.

OBJECTIVE/HYPOTHESIS: To appraise the utility of a novel EMR-based checklist for complex head and neck microvascular free-tissue reconstruction. STUDY DESIGN: A prospectively collected retrospective matched cohort study from a single tertiary care academic institution. METHODS: A retrospective matched cohort study from an academic tertiary care center with 76 total patients analyzed for disease-specific and quality outcomes before and after implementation of an EMR-based checklist tailored to complex head and neck care. The intervention group consisted of 38 consecutive patients undergoing microvascular free tissue reconstruction after implementation of the EMR-based checklist strategy. A historic cohort of 38 patients was derived by matching patients meticulously for disease-specific and surgical characteristics. Primary outcomes included post-operative medical and surgical complications, intensive care requirements, 30-day reoperation rates, hospital length of stay, and completion of preoperative metastatic evaluations. Secondary outcomes included patterns of antibiotic administration, ultimate discharge dispositions, flap survival, and recognition of preoperative hypothyroidism in previously radiated patients. RESULTS: Implementation of the perioperative checklist yielded an overall reduction in major medical complications (10.5% vs. 29.0%, P < .05*), post-operative antibiotic administration (17.4% vs. 44.7%, P < .05*), hospital length of stay (median (IQR) days 6 (1) versus 7 (3.25), P < .05*), and improved metastatic evaluation completion (92.1% vs. 63.2%, P < .05*). There was an improved discharge disposition (92.1% vs. 73.7%, P < .05*). No difference was observed in major wound complications (50.0% vs. 57.9%, P = .49), 30-day re-operation rates (31.5% vs. 34.2%, P = .81), 30-day readmission rates (21.1% vs. 21.1%, P > .99), escalations to intensive-care (13.2% vs. 21.1%, P = .36), or flap survival (97.4% vs. 89.5%, P = .17). CONCLUSIONS: Use of our EMR-based perioperative checklist reduced major medical complications, post-operative antibiotic administration, hospital length of stay, and improved discharge outcomes for patients undergoing microvascular free-tissue reconstruction. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2251-E2256, 2021.

Mixed-Dimensional In-Plane Heterostructures from 1D Mo6 Te6 and 2D MoTe2 Synthesized by Te-Flux-Controlled Chemical Vapor Deposition.

Mixed-dimensional van der Waals heterostructures are scientifically important and practically useful because of their interesting exotic properties resulting from their novel hybrid structures. This study reports the composition- and phase-selective fabrication of low-dimensional molybdenum/tellurium (Mo/Te) compounds and the direct synthesis of mixed-dimensional in-plane 1D-2D Mo6 Te6 -MoTe2 heterostructures. The composition and phase of the Mo/Te compounds are controlled by changing the Te atomic flux that is adjusted by the Te temperature. Metallic 1D Mo6 Te6 wires with an intrinsic 1D structure with a diameter of 3-8 nm and length of 100-300 nm are synthesized to form wire networks under low Te flux conditions, whereas the semiconducting few-layer 2H MoTe2 films preferentially oriented along the <0001> direction are obtained under high Te flux. Under medium Te flux, the mixed-dimensional in-plane 1D-2D Mo6 Te6 -MoTe2 heterostructures are synthesized in which the semiconducting few-layer 2H MoTe2 circular domains are edge-contacted by the metallic 1D Mo6 Te6 wire networks. Furthermore, the present Te-flux-controlled method reveals that the 1D Mo6 Te6 networks change to few-layer MoTe2 films as the Te flux increases. The in-plane 1D-2D Mo6 Te6 -MoTe2 heterostructures synthesized by this method can be considered as advanced edge-contacted 2D semiconductors for high-performance 2D electronics.

MoTe2 Lateral Homojunction Field-Effect Transistors Fabricated using Flux-Controlled Phase Engineering.

The coexistence of metallic and semiconducting polymorphs in transition-metal dichalcogenides (TMDCs) can be utilized to solve the large contact resistance issue in TMDC-based field effect transistors (FETs). A semiconducting hexagonal (2H) molybdenum ditelluride (MoTe2) phase, metallic monoclinic (1T') MoTe2 phase, and their lateral homojunctions can be selectively synthesized in situ by chemical vapor deposition due to the small free energy difference between the two phases. Here, we have investigated, in detail, the structural and electrical properties of in situ-grown lateral 2H/1T' MoTe2 homojunctions grown using flux-controlled phase engineering. Using atomic-resolution plan-view and cross-sectional transmission electron microscopy analyses, we show that the round regions of near-single-crystalline 2H-MoTe2 grow out of a polycrystalline 1T'-MoTe2 matrix. We further demonstrate the operation of MoTe2 FETs made on these in situ-grown lateral homojunctions with 1T' contacts. The use of a 1T' phase as electrodes in MoTe2 FETs effectively improves the device performance by substantially decreasing the contact resistance. The contact resistance of 1T' electrodes extracted from transfer length method measurements is 470 ± 30 Ω·µm. Temperature- and gate-voltage-dependent transport characteristics reveal a flat-band barrier height of ∼30 ± 10 meV at the lateral 2H/1T' interface that is several times smaller and shows a stronger gate modulation, compared to the metal/2H Schottky barrier height. The information learned from this analysis will be critical to understanding the properties of MoTe2 homojunction FETs for use in memory and logic circuity applications.

Field Effect Modulation of Heterogeneous Charge Transfer Kinetics at Back-Gated Two-Dimensional MoS2 Electrodes.

The ability to improve and to modulate the heterogeneous charge transfer kinetics of two-dimensional (2D) semiconductors, such as MoS2, is a major challenge for electrochemical and photoelectrochemical applications of these materials. Here we report a continuous and reversible physical method for modulating the heterogeneous charge transfer kinetics at a monolayer MoS2 working electrode supported on a SiO2/p-Si substrate. The heavily doped p-Si substrate serves as a back gate electrode; application of a gate voltage (VBG) to p-Si tunes the electron occupation in the MoS2 conduction band and shifts the conduction band edge position relative to redox species dissolved in electrolyte in contact with the front side of the MoS2. The gate modulation of both charge density and energy band alignment impacts charge transfer kinetics as measured by cyclic voltammetry (CV). Specifically, cyclic voltammograms combined with numerical simulations suggest that the standard heterogeneous charge transfer rate constant (k0) for MoS2 in contact with the ferrocene/ferrocenium (Fc0/+) redox couple can be modulated by over 2 orders of magnitude from 4 × 10-6 to 1 × 10-3 cm/s, by varying VBG. In general, the field effect offers the potential to tune the electrochemical properties of 2D semiconductors, opening up new possibilities for fundamental studies of the relationship between charge transfer kinetics and independently controlled electronic band alignment and band occupation.

Aligned MoO2/MoS2 and MoO2/MoTe2 Freestanding Core/Shell Nanoplates Driven by Surface Interactions.

Controlling the growth of two-dimensional (2D) transition metal dichalcogenides (TMDCs) is an important step toward utilizing these materials for either electronics or catalysis. Here, we report a new surface-templated growth method that enables the fabrication of MoO2/MoS2 and MoO2/MoTe2 core/shell nanoplates epitaxially aligned on (0001)-oriented 4H-silicon carbide and sapphire substrates. These heterostructures are characterized by a variety of techniques to identify the chemical and structural nature of the interface. Scanning electron microscopy shows that the nanoplates feature 3-fold symmetry indicative of epitaxial growth. Raman spectroscopy indicates that the MoO2/MoS2 nanoplates are composed of co-localized MoO2 and MoS2, and transmission electron microscopy confirms that the nanoplates feature MoO2 cores with 2D MoS2 coatings. Locked-coupled X-ray diffraction shows that the interfacial planes of the MoO2 nanoplate cores belong to the {010} and {001} families. This method may be further generalized to create novel nanostructured interfaces with single-crystal substrates.

In-Plane 2H-1T' MoTe2 Homojunctions Synthesized by Flux-Controlled Phase Engineering.

The fabrication of in-plane 2H-1T' MoTe2 homojunctions by the flux-controlled, phase-engineering of few-layer MoTe2 from Mo nanoislands is reported. The phase of few-layer MoTe2 is controlled by simply changing Te atomic flux controlled by the temperature of the reaction vessel. Few-layer 2H MoTe2 is formed with high Te flux, while few-layer 1T' MoTe2 is obtained with low Te flux. With medium flux, few-layer in-plane 2H-1T' MoTe2 homojunctions are synthesized. As-synthesized MoTe2 is characterized by Raman spectroscopy and X-ray photoelectron spectroscopy. Kelvin probe force microscopy and Raman mapping confirm that in-plane 2H-1T' MoTe2 homojunctions have abrupt interfaces between 2H and 1T' MoTe2 domains, possessing a potential difference of about 100 mV. It is further shown that this method can be extended to create patterned metal-semiconductor junctions in MoTe2 in a two-step lithographic synthesis. The flux-controlled phase engineering method could be utilized for the large-scale controlled fabrication of 2D metal-semiconductor junctions for next-generation electronic and optoelectronic devices.

Seed Crystal Homogeneity Controls Lateral and Vertical Heteroepitaxy of Monolayer MoS2 and WS2.

Heteroepitaxy between transition-metal dichalcogenide (TMDC) monolayers can fabricate atomically thin semiconductor heterojunctions without interfacial contamination, which are essential for next-generation electronics and optoelectronics. Here we report a controllable two-step chemical vapor deposition (CVD) process for lateral and vertical heteroepitaxy between monolayer WS2 and MoS2 on a c-cut sapphire substrate. Lateral and vertical heteroepitaxy can be selectively achieved by carefully controlling the growth of MoS2 monolayers that are used as two-dimensional (2D) seed crystals. Using hydrogen as a carrier gas, we synthesize ultraclean MoS2 monolayers, which enable lateral heteroepitaxial growth of monolayer WS2 from the MoS2 edges to create atomically coherent and sharp in-plane WS2/MoS2 heterojunctions. When no hydrogen is used, we obtain MoS2 monolayers decorated with small particles along the edges, inducing vertical heteroepitaxial growth of monolayer WS2 on top of the MoS2 to form vertical WS2/MoS2 heterojunctions. Our lateral and vertical atomic layer heteroepitaxy steered by seed defect engineering opens up a new route toward atomically controlled fabrication of 2D heterojunction architectures.

P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes.

Oral and oropharyngeal cancer together constitute the sixth most common cancer worldwide, with over 400,000 new cases diagnosed each year. Early detection is paramount, as the 5-year survival rate for these cancers decreases markedly once tumors have become regionally invasive. In many tissues, including oral epithelia, neoplastic progression is accompanied by alterations in expression of the epithelial cell adhesion molecules E-cadherin and P-cadherin. Oral epithelia is one of only a few tissues in which P-cadherin levels have been noted to increase in dysplasia and well-differentiated carcinomas and decrease in advanced malignancies. In the present study, P-cadherin was overexpressed in both dysplastic and malignant oral keratinocytes to characterize the mechanisms by which aberrantly expressed P-cadherin may modulate tumor progression. We found that P-cadherin was able to potentiate ligand-dependent signaling of insulin-like growth factor 1 receptor (IGF-1R) in malignant keratinocytes and epidermal growth factor receptor (EGFR) in dysplastic cells. P-cadherin prolonged activation of the mitogen-activated protein kinase (MAPK) in both cell lines and also increased the magnitude of AKT phosphorylation in dysplastic cells. P-cadherin overexpression alone was sufficient to increase steady-state levels of the mesenchymal transcription factor Snail, increase cell motility and also induce morphological changes in dysplastic keratinocytes. Taken together, these data suggest that the aberrantly elevated levels of P-cadherin which occur in early oral tumor development may play a critical role in the augmentation of neoplastic signaling networks and in the further acquisition of aggressive phenotypes.

Metal oxide nanoparticle growth on graphene via chemical activation with atomic oxygen.

Chemically interfacing the inert basal plane of graphene with other materials has limited the development of graphene-based catalysts, composite materials, and devices. Here, we overcome this limitation by chemically activating epitaxial graphene on SiC(0001) using atomic oxygen. Atomic oxygen produces epoxide groups on graphene, which act as reactive nucleation sites for zinc oxide nanoparticle growth using the atomic layer deposition precursor diethyl zinc. In particular, exposure of epoxidized graphene to diethyl zinc abstracts oxygen, creating mobile species that diffuse on the surface to form metal oxide clusters. This mechanism is corroborated with a combination of scanning probe microscopy, Raman spectroscopy, and density functional theory and can likely be generalized to a wide variety of related surface reactions on graphene.

Femtosecond electron solvation at the ionic liquid/metal electrode interface.

Electron solvation is examined at the interface of a room temperature ionic liquid (RTIL) and an Ag(111) electrode. Femtosecond two-photon photoemission spectroscopy is used to inject an electron into an ultrathin film of RTIL 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([Bmpyr](+)[NTf2](-)). While much of current literature highlights slower nanosecond solvation mechanisms in bulk ionic liquids, we observe only a femtosecond response, supporting morphology dependent and interface specific electron solvation mechanisms. The injected excess electron is found to reside in an electron affinity level residing near the metal surface. Population of this state decays back to the metal with a time constant of 400 ± 150 fs. Electron solvation is measured as a dynamic decrease in the energy with a time constant of 350 ± 150 fs. We observe two distinct temperature regimes, with a critical temperature near 250 K. The low temperature regime is characterized by a higher work function of 4.41 eV, while the high temperature regime is characterized by a lower work function of 4.19 eV. The total reorganizational energy of solvation changes above and below the critical temperature. In the high temperature regime, the electron affinity level solvates by 540 meV at 350 K, and below the critical temperature, solvation decreases to 200 meV at 130 K. This study will provide valuable insight to interface specific solvation of room temperature ionic liquids.

Templating sub-10 nm atomic layer deposited oxide nanostructures on graphene via one-dimensional organic self-assembled monolayers.

Molecular-scale control over the integration of disparate materials on graphene is a critical step in the development of graphene-based electronics and sensors. Here, we report that self-assembled monolayers of 10,12-pentacosadiynoic acid (PCDA) on epitaxial graphene can be used to template the reaction and directed growth of atomic layer deposited (ALD) oxide nanostructures with sub-10 nm lateral resolution. PCDA spontaneously assembles into well-ordered domains consisting of one-dimensional molecular chains that coat the entire graphene surface in a manner consistent with the symmetry of the underlying graphene lattice. Subsequently, zinc oxide and alumina ALD precursors are shown to preferentially react with the functional moieties of PCDA, resulting in templated oxide nanostructures. The retention of the original one-dimensional molecular ordering following ALD is dependent on the chemical reaction pathway and the stability of the monolayer, which can be enhanced via ultraviolet-induced molecular cross-linking.

Quantitatively enhanced reliability and uniformity of high-κ dielectrics on graphene enabled by self-assembled seeding layers.

The full potential of graphene in integrated circuits can only be realized with a reliable ultrathin high-κ top-gate dielectric. Here, we report the first statistical analysis of the breakdown characteristics of dielectrics on graphene, which allows the simultaneous optimization of gate capacitance and the key parameters that describe large-area uniformity and dielectric strength. In particular, vertically heterogeneous and laterally homogeneous Al2O3 and HfO2 stacks grown via atomic-layer deposition and seeded by a molecularly thin perylene-3,4,9,10-tetracarboxylic dianhydride organic monolayer exhibit high uniformities (Weibull shape parameter ß > 25) and large breakdown strengths (Weibull scale parameter, E(BD) > 7 MV/cm) that are comparable to control dielectrics grown on Si substrates.