Machine Learning for Automatic Detection of Velopharyngeal Dysfunction: A Preliminary Report.

BACKGROUND: Even after palatoplasty, the incidence of velopharyngeal dysfunction (VPD) can reach 30%; however, these estimates arise from high-income countries (HICs) where speech-language pathologists (SLP) are part of standardized cleft teams. The VPD burden in low- and middle-income countries (LMICs) is unknown. This study aims to develop a machine-learning model that can detect the presence of VPD using audio samples alone. METHODS: Case and control audio samples were obtained from institutional and publicly available sources. A machine-learning model was built using Python software. RESULTS: The initial 110 audio samples used to test and train the model were retested after format conversion and file deidentification. Each sample was tested 5 times yielding a precision of 100%. Sensitivity was 92.73% (95% CI: 82.41%-97.98%) and specificity was 98.18% (95% CI: 90.28%-99.95%). One hundred thirteen prospective samples, which had not yet interacted with the model, were then tested. Precision was again 100% with a sensitivity of 88.89% (95% CI: 78.44%-95.41%) and a specificity of 66% (95% CI: 51.23%-78.79%). DISCUSSION: VPD affects nearly 100% of patients with unrepaired overt soft palatal clefts and up to 30% of patients who have undergone palatoplasty. VPD can render patients unintelligible, thereby accruing significant psychosocial morbidity. The true burden of VPD in LMICs is unknown, and likely exceeds estimates from HICs. The ability to access a phone-based screening machine-learning model could expand access to diagnostic, and potentially therapeutic modalities for an innumerable amount of patients worldwide who suffer from VPD.

The Impact of a Concussion-U Educational Program on Knowledge of and Attitudes about Concussion.

BACKGROUND: The diagnosis of a sports-related concussion is often dependent on the athlete self-reporting their symptoms. It has been suggested that improving youth athlete knowledge and attitudes toward concussion may increase self-reporting behaviour. The objective of this study was to determine if a novel Concussion-U educational program improves knowledge of and attitudes about concussion among a cohort of elite male Bantam and Midget AAA hockey players. METHODS: Fifty-seven male Bantam and Midget AAA-level hockey players (mean age=14.52±1.13 years) were recruited from the local community. Each participant completed a modified version of the Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version immediately before and after a Concussion-U educational presentation. Follow-up sessions were arranged 4 to 6 months after the presentation, and assessed retention of knowledge and attitude changes. RESULTS: Forty-three players completed all three surveys. Concussion knowledge and attitude scores significantly (p<0.01) increased from pre- to post-presentation by 12.79 and 8.41%, respectively. At long-term follow-up, knowledge levels remained significantly (p<0.01) higher than baseline by 8.49%. Mean attitude scores were also increased at follow-up; however, this increase was not statistically significant. CONCLUSIONS: A Concussion-U educational program led to an immediate improvement in concussion knowledge and attitudes among elite male Bantam and Midget AAA hockey players. Increased knowledge was maintained at long-term follow-up, but improved attitude was not. Future studies should investigate whether similar educational programs influence symptom reporting and concussion incidence. In addition, they should focus on how to maintain improved concussion attitudes.

Epac activation initiates associative odor preference memories in the rat pup.

Here we examine the role of the exchange protein directly activated by cAMP (Epac) in ß-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac activation produced both short-term (STM) and long-term (LTM) odor preference memories. Training using ß-adrenergic-activation paired with odor recruited rapid and transient ERK phosphorylation consistent with a role for Epac activation in normal learning. An ERK antagonist prevented intermediate-term memory (ITM) and LTM, but not STM. Epac agonist infusions induced ERK phosphorylation in the mitral cell layer, in the inner half of the dendritic external plexiform layer, in the glomeruli and, patchily, among granule cells. Increased CREB phosphorylation in the mitral and granule cell layers was also seen. Simultaneous blockade of both ERK and CREB pathways prevented any long-term ß-adrenergic activated odor preference memory, while LTM deficits associated with blocking only one pathway were prevented by stronger ß-adrenergic activation. These results suggest that Epac and PKA play parallel and independent, as well as likely synergistic, roles in creating cAMP-dependent associative memory in rat pups. They further implicate a novel ERK-independent pathway in the mediation of STM by Epac.

Stakeholder perspectives on ethical and trustworthy voice AI in health care.

Objective: Voice as a health biomarker using artificial intelligence (AI) is gaining momentum in research. The noninvasiveness of voice data collection through accessible technology (such as smartphones, telehealth, and ambient recordings) or within clinical contexts means voice AI may help address health disparities and promote the inclusion of marginalized communities. However, the development of AI-ready voice datasets free from bias and discrimination is a complex task. The objective of this study is to better understand the perspectives of engaged and interested stakeholders regarding ethical and trustworthy voice AI, to inform both further ethical inquiry and technology innovation. Methods: A questionnaire was administered to voice AI experts, clinicians, scholars, patients, trainees, and policy-makers who participated at the 2023 Voice AI Symposium organized by the Bridge2AI-Voice AI Consortium. The survey used a mix of Likert scale, ranking and open-ended questions. A total of 27 stakeholders participated in the study. Results: The main results of the study are the identification of priorities in terms of ethical issues, an initial definition of ethically sourced data for voice AI, insights into the use of synthetic voice data, and proposals for acting on the trustworthiness of voice AI. The study shows a diversity of perspectives and adds nuance to the planning and development of ethical and trustworthy voice AI. Conclusions: This study represents the first stakeholder survey related to voice as a biomarker of health published to date. This study sheds light on the critical importance of ethics and trustworthiness in the development of voice AI technologies for health applications.

Voice as a Biomarker in Health-Tech: Mapping the Evolving Landscape of Voice Biomarkers in the Start-Up World.

OBJECTIVE: The vocal biomarkers market was worth $1.9B in 2021 and is projected to exceed $5.1B by 2028, for a compound annual growth rate of 15.15%. The investment growth demonstrates a blossoming interest in voice and artificial intelligence (AI) as it relates to human health. The objective of this study was to map the current landscape of start-ups utilizing voice as a biomarker in health-tech. DATA SOURCES: A comprehensive search for start-ups was conducted using Google, LinkedIn, Twitter, and Facebook. A review of the research was performed using company website, PubMed, and Google Scholar. REVIEW METHODS: A 3-pronged approach was taken to thoroughly map the landscape. First, an internet search was conducted to identify current start-ups focusing on products relating to voice as a biomarker of health. Second, Crunchbase was utilized to collect financial and organizational information. Third, a review of the literature was conducted to analyze publications associated with the identified start-ups. RESULTS: A total of 27 start-up start-ups with a focus in the utilization of AI for developing biomarkers of health from the human voice were identified. Twenty-four of these start-ups garnered $178,808,039 in investments. The 27 start-ups published 194 publications combined, 128 (66%) of which were peer reviewed. CONCLUSION: There is growing enthusiasm surrounding voice as a biomarker in health-tech. Academic drive may complement commercialization to best achieve progress in this arena. More research is needed to accurately capture the entirety of the field, including larger industry players, academic institutions, and non-English content.

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.

Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression.

An essential step in the pathogenesis of human papillomavirus (HPV)-associated cancers is the dysregulated expression of the viral oncogenes. The papillomavirus E2 protein can silence the long control region (LCR) promoter that controls viral E6 and E7 oncogene expression. The mechanisms by which E2 represses oncogene expression and the cellular factors through which E2 mediates this silencing are largely unknown. We conducted an unbiased, genome-wide siRNA screen and series of secondary screens that identified 96 cellular genes that contribute to the repression of the HPV LCR. In addition to confirming a role for the E2-binding bromodomain protein Brd4 in E2-mediated silencing, we identified a number of genes that have not previously been implicated in E2 repression, including the demethylase JARID1C/SMCX as well as EP400, a component of the NuA4/TIP60 histone acetyltransferase complex. Each of these genes contributes independently and additively to E2-mediated silencing, indicating that E2 functions through several distinct cellular complexes to repress E6 and E7 expression.

A multi-stage transfer learning strategy for diagnosing a class of rare laryngeal movement disorders.

BACKGROUND: It remains hard to directly apply deep learning-based methods to assist diagnosing essential tremor of voice (ETV) and abductor and adductor spasmodic dysphonia (ABSD and ADSD). One of the main challenges is that, as a class of rare laryngeal movement disorders (LMDs), there are limited available databases to be investigated. Another worthy explored research question is which above sub-disorder benefits most from diagnosis based on sustained phonations. The question is from the fact that sustained phonations can help detect pathological voice from healthy voice. METHOD: A transfer learning strategy is developed for LMD diagnosis with limited data, which consists of three fundamental parts. (1) An extra vocally healthy database from the International Dialects of English Archive (IDEA) is employed to pre-train a convolutional autoencoder. (2) The transferred proportion of the pre-trained encoder is explored. And its impact on LMD diagnosis is also evaluated, yielding a two-stage transfer model. (3) A third stage is designed following the initial two stages to embed information of pathological sustained phonation into the model. This stage verifies the different effects of applying sustained phonation on diagnosing the three sub-disorders, and helps boost the final diagnostic performance. RESULTS: The analysis in this study is based on clinician-labeled LMD data obtained from the Vanderbilt University Medical Center (VUMC). We find that diagnosing ETV shows sensitivity to sustained phonation within the current database. Meanwhile, the results show that the proposed multi-stage transfer learning strategy can produce (1) accuracy of 65.3% on classifying normal and other three sub-disorders all at once, (2) accuracy of 85.3% in differentiating normal, ABSD, and ETV, and (3) accuracy of 77.7% for normal, ADSD and ETV. These findings demonstrate the effectiveness of the proposed approach.

Optimizing Botox regimens in patients with adductor spasmodic dysphonia and essential tremor of voice: A 31-year experience.

Objective: The purpose of this study was to quantitatively compare the effectiveness of unilateral and bilateral botulinum toxin A (BTX-A) injections for mitigating undesirable weak/breathy voice quality and dysphagia for patients with adductor spasmodic dysphonia and/or essential tremor of voice (ETV). Methods: Data were collected from the medical records of 319 patients, yielding three treatment cohorts: patients who received an equal dose bilateral injection regimen (BL=) throughout their course of treatment at VUMC, patients who switched to a unilateral injection regimen (UL), and patients who switched to an unequal dose bilateral injection regimen (BL≠). Changes in length of improvement, duration of weak/breathy voice, and dysphagia severity were compared. Results: The BL = treatment group reported the longest duration of improved voice. Shorter periods of improved voice were reported at baseline by patients who later switched to UL or BL ≠ injection regimens. Patients receiving UL injections reported significantly reduced weak/breathy voice and dysphagia. Patients receiving BL ≠ injections reported increased length of improved voice; however, dysphagia symptoms increased. Ninety-two percent of patients with ETV switched to a UL regimen, with 61% of patients transitioning within the first three injections. Conclusions: Patients with pronounced dysphagia and extended periods of weak/breathy voice may benefit from a UL injection approach to mitigate side effects from BTX-A without sacrificing improved voice outcomes. For patients seeking to extend their length of improved voice, a BL ≠ injection regimen may be effective provided the adverse side effects from BTX-A are minimal. Patients with ETV may benefit from a UL injection approach at the outset of their course of treatment with BTX-A. Level of evidence: III.

NCoR1 mediates papillomavirus E8;E2C transcriptional repression.

The papillomavirus E2 open reading frame encodes the full-length E2 protein as well as an alternatively spliced product called E8;E2C. E8;E2C has been best studied for the high-risk human papillomaviruses, where it has been shown to regulate viral genome levels and, like the full-length E2 protein, to repress transcription from the viral promoter that directs the expression of the viral E6 and E7 oncogenes. The repression function of E8;E2C is dependent on the 12-amino-acid N-terminal sequence from the E8 open reading frame (ORF). In order to understand the mechanism by which E8;E2C mediates transcriptional repression, we performed an unbiased proteomic analysis from which we identified six high-confidence candidate interacting proteins (HCIPs) for E8;E2C; the top two are NCoR1 and TBLR1. We established an interaction of E8;E2C with an NCoR1/HDAC3 complex and demonstrated that this interaction requires the wild-type E8 open reading frame. Small interfering RNA (siRNA) knockdown studies demonstrated the involvement of NCoR1/HDAC3 in the E8;E2C-dependent repression of the viral long control region (LCR) promoter. Additional genetic work confirmed that the papillomavirus E2 and E8;E2C proteins repress transcription through distinct mechanisms.

Different Vibratory Conditions Elicit Different Structural and Biological Vocal Fold Changes in an In-Vivo Rabbit Model of Phonation.

OBJECTIVE: Vibration of the vocal folds can disrupt the tissue and induce structural, functional, and molecular changes; the presence or absence of contact between the vocal folds during vibration can affect the type and extent of these changes. The purpose of this study was to characterize vocal fold changes following 2 hours of contact phonation or phonation without vibratory contact. METHODS: Six New Zealand white breeder rabbits underwent 120 minutes of phonation with or without vibratory contact, and four served as nonphonated controls. The larynx was exposed and current was applied to the cricothyroids bilaterally to achieve vocal fold adduction while humidified airflow was delivered to induce vocal fold vibration. Laryngeal position, airflow, and stimulation levels were adjusted to obtain phonation with or without contact, and phonation was elicited for 120 minutes. Following excision, larynges were stained using Hematoxylin & Eosin, Elastica van Gieson, and Grocott's Methenamine Silver, or labeled with immunofluorescent markers for E-cadherin, CD31, CD11b, and Vimentin. All images were captured using a Nikon 90i microscope and analyzed using ImageJ. RESULTS: Differences between vibratory conditions and control samples were observed. There was more extensive epithelial thinning, reduced epithelial integrity and increased vascularity in the contact phonation group, while both phonatory groups demonstrated a decreased presence of mucous on the luminal surface and a decrease in elastin band thickness and lamina propria depth. Neither condition showed differences in inflammatory cell presence compared to control tissue. CONCLUSIONS: By showing that these two vibratory conditions result in structural changes of different types and magnitude, we have provided the first empirical evidence that vocal fold tissue is sensitive to differences in forces, and that changes in vibratory pattern can elicit different downstream biological changes within the tissue. The differences described herein are an important step toward understanding the vocal folds' potential for differential response to phonotraumatic damage following different vibratory behaviors.

Characterization of exposures to airborne nanoscale particles during friction stir welding of aluminum.

Friction stir welding (FSW) is considered one of the most significant developments in joining technology over the last half century. Its industrial applications are growing steadily and so are the number of workers using this technology. To date, there are no reports on airborne exposures during FSW. The objective of this study was to investigate possible emissions of nanoscale (<100 nm) and fine (<1 microm) aerosols during FSW of two aluminum alloys in a laboratory setting and characterize their physicochemical composition. Several instruments measured size distributions (5 nm to 20 microm) with 1-s resolution, lung deposited surface areas, and PM(2.5) concentrations at the source and at the breathing zone (BZ). A wide range aerosol sampling system positioned at the BZ collected integrated samples in 12 stages (2 nm to 20 microm) that were analyzed for several metals using inductively coupled plasma mass spectrometry. Airborne aerosol was directly collected onto several transmission electron microscope grids and the morphology and chemical composition of collected particles were characterized extensively. FSW generates high concentrations of ultrafine and submicrometer particles. The size distribution was bimodal, with maxima at approximately 30 and approximately 550 nm. The mean total particle number concentration at the 30 nm peak was relatively stable at approximately 4.0 x 10(5) particles cm(-3), whereas the arithmetic mean counts at the 550 nm peak varied between 1500 and 7200 particles cm(-3), depending on the test conditions. The BZ concentrations were lower than the source concentrations by 10-100 times at their respective peak maxima and showed higher variability. The daylong average metal-specific concentrations were 2.0 (Zn), 1.4 (Al), and 0.24 (Fe) microg m(-3); the estimated average peak concentrations were an order of magnitude higher. Potential for significant exposures to fine and ultrafine aerosols, particularly of Al, Fe, and Zn, during FSW may exist, especially in larger scale industrial operations.

Missed opportunities within healthcare for an earlier diagnosis of HIV.

Despite guidelines, many individuals are not routinely tested for HIV within healthcare settings. Our objective was to quantify and characterize preceding clinical encounters by newly-diagnosed persons living with HIV in southern Alberta, Canada. We discuss the clinical impact of missed HIV testing, and options for remediation. Clinical encounters prior to HIV diagnosis including the discharge diagnosis were collected between 1 April 2011 and 1 April 2016. We followed the HIV Indicator Diseases across Europe Study criteria to identify HIV Clinical Indicator Conditions (HCICs) present at clinical encounters. Patients accessing prior care were compared to those who had not previously accessed care. Of 393 individuals, 231 (58.7%) had ≥1 encounter prior to diagnosis; 224 (57%) of encounters occurred in outpatient clinics, 130 (33.1%) in emergency departments, and 39 (9.9%) in urgent care clinics. Approximately 25% (n = 57) of patients who engaged healthcare had ≥ 1 recognized HCIC but did not receive HIV testing. The most frequent HCICs were infection (n = 34; 60%) and hematological disorders (n = 12; 21%). The median CD4 cell count at HIV diagnosis for patients with an HCIC was 127 cells/mm3. In this population, three of five patients had accessed healthcare prior to diagnosis with one of four presenting with HCICs but were not offered HIV testing. Protocols beyond the current recommendations are urgently required to address missed HIV diagnostic opportunities who engaged healthcare.

Continuous Rate Infusion of Ketamine Hydrochloride and Dexmedetomidine for Maintenance of Anesthesia during Laryngotracheal Surgery in New Zealand White Rabbits (Oryctolagus cuniculus).

New Zealand white rabbits (Oryctolagus cuniculus) are an established in vivo model for the study of structural and functional consequences of vocal-fold vibration. Research design requires invasive laryngotracheal procedures, and the presence of laryngospasms or pain responses (or both) hinder phonation-related data collection. Published anesthesia regimens report respiratory depression and muscle tone changes and have been unsuccessful in mitigating autonomic laryngeal responses in our protocol. Infusion of ketamine hydrochloride and dexmedetomidine hydrochloride in pediatric medicine provides effective analgesia and sedation for laryngotracheal procedures including intubation and bronchoscopy; however, data evaluating the use of ketamine-dexmedetomidine infusion in rabbits are unavailable. This study reports a new infusion regimen, which was used in 58 male New Zealand white rabbits that underwent a nonsurvival laryngotracheal procedure to induce phonotraumatic vocal-fold injury. Animals were sedated by using ketamine hydrochloride (20 mg/kg IM) and dexmedetomidine (0.125 mg/kg IM). Maintenance anesthesia was provided by using continuous rate intravenous infusion of ketamine hydrochloride (343 µg/kg/min) and dexmedetomidine (1.60 µg/kg/min). A stable plane of anesthesia with no autonomic laryngeal response (laryngospasm) was achieved in 32 of the 58 rabbits (55%). Laryngospasms occurred in 25 of 58 animals (43%) and were controlled in 20 cases (80%) by providing 0.33 mL 2% topical lidocaine, incremental increase in infusion rate, or both. Continuous rate infusion of ketamine hydrochloride-dexmedetomidine with prophylactic topical lidocaine provides a predictable and adjustable surgical plane of anesthesia, with minimal confounding respiratory and autonomic laryngeal responses, during extended-duration laryngotracheal surgery in rabbits. This regimen should be considered as an alternative to injection maintenance for prolonged, invasive procedures.

Efficacy of Videostroboscopy and High-Speed Videoendoscopy to Obtain Functional Outcomes From Perioperative Ratings in Patients With Vocal Fold Mass Lesions.

OBJECTIVES: A major limitation of comparing the efficacy of videostroboscopy (VS) and high-speed videoendoscopy (HSV) is the lack of an objective reference by which to compare the functional assessment ratings of the two techniques. For patients with vocal fold mass lesions, intraoperative measures of lesion size and depth may serve as this objective reference. This study compared the relationships between the pre- to postoperative change in VS and HSV visual-perceptual ratings to intraoperative measures of lesion size and depth. DESIGN: Prospective visual-perceptual study with intraoperative measures of lesion size and depth. METHODS: VS and HSV samples were obtained preoperatively and postoperatively from 28 patients with vocal fold lesions and from 17 vocally healthy controls. Two experienced clinicians rated amplitude, mucosal wave, vertical phase difference, left-right phase asymmetry, and vocal fold edge on a visual-analog scale using both imaging techniques. The change in perioperative ratings from VS and HSV was compared between groups and correlated to intraoperative measures of lesion size and depth. RESULTS: HSV was as reliable as VS for ratings of amplitude and edge, and substantially more reliable for ratings of mucosal wave and left-right phase asymmetry. Both VS and HSV had mild-moderate correlations between change in perioperative ratings and intraoperative measures of lesion area. Change in function could be obtained in more patients and for more parameters using HSV than VS. Group differences were noted for postoperative ratings of amplitude and edge; however, these differences were within one level of the visual-perceptual rating scale. The presence of asynchronicity in VS recordings renders vibratory features either uninterpretable or potentially distorted and thus should not be rated. CONCLUSIONS: Amplitude and edge are robust vibratory measures for perioperative functional assessment, regardless of imaging modality. HSV is indicated for evaluation of subepithelial lesions or if asynchronicity is present in the VS image sequence.

Unilateral and Bilateral Laryngeal Pacing for Bilateral Vocal Fold Paralysis.

PURPOSE OF REVIEW: Present the state-of-the-art overview of laryngeal pacing for treatment of bilateral vocal fold paralysis. A minimally invasive unilateral pacing system and a fully implantable bilateral pacing system are currently in clinical trials. The relative advantages and disadvantages of each are discussed. RECENT FINDINGS: Research in functional electrical stimulation for the reanimation of the posterior cricoarytenoid muscle has successfully translated from animal models to human clinical trials for unilateral pacing and bilateral pacing. Current findings suggest unilateral pacing in humans significantly improves ventilation but only marginally better than cordotomy. Bilateral pacing in canines increases glottal opening greater than 2-fold over unilateral pacing and restores exercise tolerance to normal. SUMMARY: Unilateral pacing can be considered a breathing assist device and may not be appropriate for active individuals. Bilateral pacing may be preferable for patients who wish to engage in strenuous exercise. Minimally invasive systems may be ideal for patients who prefer less invasive implantation and are not concerned with cosmesis. Fully implantable pacing systems offer greater electrode redundancy and stability, resulting in a system that is robust against electrode migration or damage.

Acute kidney injury after aneurysmal subarachnoid hemorrhage and its effect on patient outcome: an exploratory analysis.

OBJECTIVE: Acute kidney injury (AKI) is associated with death in critically ill patients, but this complication has not been well characterized after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of this study was to determine the incidence of AKI after aSAH and to identify risk factors for renal dysfunction. Secondary objectives were to examine what effect AKI has on patient mortality and functional outcome at 12 weeks post-aSAH. METHODS: The authors performed a post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial data set (clinical trial registration no.: NCT00111085, https://clinicaltrials.gov). The primary outcome of interest was the development of AKI, which was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes of interest were death and a modified Rankin Scale score greater than 2 at 12 weeks post-aSAH. Propensity score matching was used to assess for a significant treatment effect related to clazosentan administration and AKI. Univariate analysis, locally weighted scatterplot smoothing (LOWESS) curves, and stepwise logistic regression models were used to evaluate for associations between baseline or disease-related characteristics and study outcomes. RESULTS: One hundred fifty-six (38%) of the 413 patients enrolled in the CONSCIOUS-1 trial developed AKI during their ICU stay. A history of hypertension (p < 0.001) and the number of nephrotoxic medications administered (p = 0.029) were independent predictors of AKI on multivariate analysis. AKI was an independent predictor of death (p = 0.028) but not a poor functional outcome (p = 0.21) on multivariate testing. Unresolved renal dysfunction was the strongest independent predictor of death in this cohort (p < 0.001). CONCLUSIONS: AKI is a common complication following aSAH. Patients with premorbid hypertension and those treated with nephrotoxic medications may be at greater risk for renal dysfunction. AKI appears to confer an increased probability of death after aSAH.

Decoding phonation with artificial intelligence (DeP AI): Proof of concept.

OBJECTIVE: Acoustic analysis of voice has the potential to expedite detection and diagnosis of voice disorders. Applying an image-based, neural-network approach to analyzing the acoustic signal may be an effective means for detecting and differentially diagnosing voice disorders. The purpose of this study is to provide a proof-of-concept that embedded data within human phonation can be accurately and efficiently decoded with deep learning neural network analysis to differentiate between normal and disordered voices. METHODS: Acoustic recordings from 10 vocally-healthy speakers, as well as 70 patients with one of seven voice disorders (n = 10 per diagnosis), were acquired from a clinical database. Acoustic signals were converted into spectrograms and used to train a convolutional neural network developed with the Keras library. The network architecture was trained separately for each of the seven diagnostic categories. Binary classification tasks (ie, to classify normal vs. disordered) were performed for each of the seven diagnostic categories. All models were validated using the 10-fold cross-validation technique. RESULTS: Binary classification averaged accuracies ranged from 58% to 90%. Models were most accurate in their classification of adductor spasmodic dysphonia, unilateral vocal fold paralysis, vocal fold polyp, polypoid corditis, and recurrent respiratory papillomatosis. Despite a small sample size, these findings are consistent with previously published data utilizing deep neural networks for classification of voice disorders. CONCLUSION: Promising preliminary results support further study of deep neural networks for clinical detection and diagnosis of human voice disorders. Current models should be optimized with a larger sample size. LEVELS OF EVIDENCE: Level III.

Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142.

AIDS-associated, CCR5-tropic (R5) HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

Vibratory function and healing outcomes after small intestinal submucosa biomaterial implantation for chronic vocal fold scar.

OBJECTIVES/HYPOTHESIS: Vocal fold scar is a major cause of dysphonia, and optimal treatments do not currently exist. Small intestinal submucosa (SIS) is a biomaterial developed for the treatment of a variety of pathologies. The purpose of this study was to investigate the effects of SIS implantation on tissue remodeling in scarred vocal folds using routine staining, immunohistochemistry, and high-speed videoendoscopy (HSV). STUDY DESIGN: Prospective, blinded group analysis. METHODS: Thirteen New Zealand White rabbits underwent a vocal fold scarring procedure followed by microflap elevation with or without SIS implantation. Seven months later, they underwent a phonation procedure with HSV and laryngeal harvest. Alcian blue and elastica van Gieson staining and immunohistochemistry for collagen types I and III were used to evaluate histological healing outcomes. Dynamic functional remodeling of the scarred vocal fold in the presence of SIS implants was evaluated using HSV imaging to capture restoration of vibratory amplitude, amplitude ratio, and left-right phase symmetry. RESULTS: Density of collagen I was significantly decreased in SIS versus microflap-treated vocal folds. No differences were found between groups for hyaluronic acid, elastin, or collagen type III. Organization of elastin in the subepithelial region appeared to affect amplitude of vibration and the shape of the vocal fold edge. CONCLUSIONS: SIS implantation into chronic scar reduced the density of collagen I deposits. There was no evidence of a negative impact or complication from SIS implantation. Regardless of treatment type, organization of elastin in the subepithelial region may be important to vibratory outcomes. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:901-908, 2018.