Feasibility and Repeatability of an Abbreviated Auditory Perceptual and Cognitive Test Battery.

Purpose: Auditory perceptual and cognitive tasks can be useful as a long-term goal in guiding rehabilitation and intervention strategies in audiology clinics that mostly operate at a faster pace and on strict timelines. The rationale of this study was to assess test-retest reliability of an abbreviated test battery and evaluate age-related auditory perceptual and cognitive effects on these measures.

Method: Experiment 1 evaluated the test-retest repeatability of an abbreviated test battery and its use in an adverse listening environment.

Molecular features of the serological IgG repertoire elicited by egg-based, cell-based, or recombinant haemagglutinin-based seasonal influenza vaccines: a comparative, prospective, observational cohort study.

Background: Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response.

Methods: In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA).

Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19.

Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19.

Head-orienting behaviors during simultaneous speech detection and localization.

Head movement plays a vital role in auditory processing by contributing to spatial awareness and the ability to identify and locate sound sources. Here we investigate head-orienting behaviors using a dual-task experimental paradigm to measure: (a) localization of a speech source; and (b) detection of meaningful speech (numbers), within a complex acoustic background. Ten younger adults with normal hearing and 20 older adults with mild-to-severe sensorineural hearing loss were evaluated in the free field on two head-movement conditions: (1) head fixed to the front and (2) head moving to a source location; and two context conditions: (1) with audio only or (2) with audio plus visual cues.

A Step Toward Precision Audiology: Individual Differences and Characteristic Profiles From Auditory Perceptual and Cognitive Abilities.

Older adults with normal hearing or with age-related hearing loss face challenges when listening to speech in noisy environments. To better serve individuals with communication difficulties, precision diagnostics are needed to characterize individuals' auditory perceptual and cognitive abilities beyond pure tone thresholds. These abilities can be heterogenous across individuals within the same population.

The frequency and function of nucleoprotein-specific CD8 T cells are critical for heterosubtypic immunity against influenza virus infection.

Unlabelled: Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8 T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8 T cells.

Counseling Protocol for a Transitional Intervention for Debilitating Hyperacusis.

Introduction: This clinical focus article describes a structured counseling protocol for use with protected sound management and therapeutic sound in a transitional intervention for debilitating hyperacusis. The counseling protocol and its associated visual aids are crafted as a teaching tool to educate affected individuals about hyperacusis and encourage their acceptance of a transitional intervention.

Description Of Counseling Components: The counseling protocol includes five components.

Background and Rationale for a Transitional Intervention for Debilitating Hyperacusis.

Purpose: This report provides the experimental, clinical, theoretical, and historical background that motivated a patented transitional intervention and its implementation and evaluation in a field trial for mitigation of debilitating loudness-based hyperacusis (LH).

Background And Rationale: Barriers for ameliorating LH, which is differentiated here from other forms of hyperacusis, are delineated, including counterproductive management and treatment strategies that may exacerbate the condition. Evidence for hyper-gain central auditory processes as the bases for LH and the associated LH-induced distress and stress responses are presented.

Results of a 6-Month Field Trial of a Transitional Intervention for Debilitating Hyperacusis.

Purpose: We present results from a 6-month field trial of a transitional intervention for debilitating primary hyperacusis, including a combination of structured counseling; promotion of safe, comfortable, and healthy sound exposure; and therapeutic broadband sound from sound generators. This intervention is designed to overcome barriers to successful delivery of therapeutic sound as a tool to downregulate neural hyperactivity in the central auditory pathways (i.e.

Device and Fitting Protocol for a Transitional Intervention for Debilitating Hyperacusis.

Purpose: This report describes a hearing device and corresponding fitting protocol designed for use in a transitional intervention for debilitating loudness-based hyperacusis.

Method: The intervention goal is to transition patients with hyperacusis from their typical counterproductive sound avoidance behaviors (i.e.

Evaluating the Effect of Voice Quality Covariance on Auditory-Perceptual Evaluation Using a Novel Two-Dimensional Magnitude Estimation Task.

Purpose: Most people with dysphonia present with voices that vary along more than one voice quality (VQ) dimension. This study sought to examine the effect of covariance between breathy and rough VQ in natural voices.

Method: A two-dimensional matrix of 16 /a/ vowels was selected such that two VQ dimensions (breathiness and roughness) were sampled on a 4-point severity scale (none, mild, moderate, and severe).

Effects of Vibratory Source on Auditory-Perceptual and Bio-Inspired Computational Measures of Pediatric Voice Quality.

Objective: The vibratory source for voicing in children with dysphonia is classified into three categories including a glottal vibratory source (GVS) observed in those with vocal lesions or hyperfunction; supraglottal vibratory sources (SGVS) observed secondary to laryngeal airway injuries, malformations, or reconstruction surgeries; and a combination of both glottal and supraglottal vibratory sources called mixed vibratory source (MVS). This study evaluated the effects of vibratory source on three primary dimensions of voice quality (breathiness, roughness, and strain) in children with GVS, SGVS, and MVS using single-variable matching tasks and computational measures obtained from bio-inspired auditory models.

Methods: A total of 44 dysphonic voice samples from children aged 4-11 years were selected.

Discovery of MK-8768, a Potent and Selective mGluR2 Negative Allosteric Modulator.

Glutamate plays a key role in cognition and mood, and it has been shown that inhibiting ionotropic glutamate receptors disrupts cognition, while enhancing ionotropic receptor activity is pro-cognitive. One approach to elevating glutamatergic tone has been to antagonize presynaptic metabotropic glutamate receptor 2 (mGluR2). A desire for selectivity over the largely homologous mGluR3 motivated a strategy to achieve selectivity through the identification of mGluR2 negative allosteric modulators (NAMs).

Head movement and its relation to hearing.

Head position at any point in time plays a fundamental role in shaping the auditory information that reaches a listener, information that continuously changes as the head moves and reorients to different listening situations. The connection between hearing science and the kinesthetics of head movement has gained interest due to technological advances that have increased the feasibility of providing behavioral and biological feedback to assistive listening devices that can interpret movement patterns that reflect listening intent. Increasing evidence also shows that the negative impact of hearing deficits on mobility, gait, and balance may be mitigated by prosthetic hearing device intervention.

Validation of the adaptive scan method in the quest for time-efficient methods of testing auditory processes.

A major barrier to the clinical application of psychophysical testing of central auditory processes is the time required to obtain precise estimates of different listening abilities. In this study, we validate a novel adaptive scan (AS) method of threshold estimation that is designed to adapt on a range of values around threshold rather than on a single threshold value. This method has the advantage of providing the listener with greater familiarity with the stimulus characteristics near threshold while maintaining precise measurement and increasing time-efficiency.

Monocyte depletion enhances neutrophil influx and proneural to mesenchymal transition in glioblastoma.

Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based genome editing, we generate a mouse model that is deficient of all monocyte chemoattractant proteins.

Aging alters across-hemisphere cortical dynamics during binaural temporal processing.

Differences in the timing and intensity of sounds arriving at the two ears provide fundamental binaural cues that help us localize and segregate sounds in the environment. Neural encoding of these cues is commonly represented asymmetrically in the cortex with stronger activation in the hemisphere contralateral to the perceived spatial location. Although advancing age is known to degrade the perception of binaural cues, less is known about how the neural representation of such cues is impacted by age.

Alzheimer's disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment.

Recent proteome and transcriptome profiling of Alzheimer's disease (AD) brains reveals RNA splicing dysfunction and U1 small nuclear ribonucleoprotein (snRNP) pathology containing U1-70K and its N-terminal 40-KDa fragment (N40K). Here we present a causative role of U1 snRNP dysfunction to neurodegeneration in primary neurons and transgenic mice (N40K-Tg), in which N40K expression exerts a dominant-negative effect to downregulate full-length U1-70K. N40K-Tg recapitulates N40K insolubility, erroneous splicing events, neuronal degeneration and cognitive impairment.

Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia.

PDE10A is an important regulator of striatal signaling that, when inhibited, can normalize dysfunctional activity. Given the involvement of dysfunctional striatal activity with schizophrenia, PDE10A inhibition represents a potentially novel means for its treatment. With the goal of developing PDE10A inhibitors, early optimization of a fragment hit through rational design led to a series of potent pyrimidine PDE10A inhibitors that required further improvements in physicochemical properties, off-target activities, and pharmacokinetics.

Acoustic deprivation modulates central gain in human auditory brainstem and cortex.

Beyond reduced audibility, there is convincing evidence that the auditory system adapts according to the principles of homeostatic plasticity in response to a hearing loss. Such compensatory changes include modulation of central auditory gain mechanisms. Earplugging is a common experimental method that has been used to introduce a temporary, reversible hearing loss that induces changes consistent with central gain modulation.

Development and Validation of a Single-Variable Comparison Stimulus for Matching Strained Voice Quality Using a Psychoacoustic Framework.

Purpose: Acoustic and perceptual quantification of vocal strain has been a vexing problem for years. To increase measurement rigor, a suitable single-variable matching stimulus for strain was developed and validated, based on the matching stimulus used previously for breathy and rough voice qualities.

Method: A set of 21 comparison stimuli for a single-variable matching task (SVMT) was synthesized based on a speech-shaped sawtooth waveform mixed with speech-shaped noise.

Interactions Between Breathy and Rough Voice Qualities and Their Contributions to Overall Dysphonia Severity.

Purpose: Dysphonic voices typically present multiple voice quality dimensions. This study investigated potential interactions between perceived breathiness and roughness and their contributions to overall dysphonia severity.

Method: Synthetic stimuli based on four talkers were created to systematically map out potential interactions.

Impact of acute nicotine exposure on monoaminergic systems in adolescent and adult male and female rats.

Adolescence is a period of risk for beginning tobacco addiction. Differential neural response to nicotine in adolescents vs. adults may help explain the increased vulnerability to nicotine self-administration seen with adolescent onset.

Remote auditory assessment using Portable Automated Rapid Testing (PART) and participant-owned devices.

Remote testing of auditory function can be transformative to both basic research and hearing healthcare; however, historically, many obstacles have limited remote collection of reliable and valid auditory psychometric data. Here, we report performance on a battery of auditory processing tests using a remotely administered system, Portable Automatic Rapid Testing. We compare a previously reported dataset collected in a laboratory setting with the same measures using uncalibrated, participant-owned devices in remote settings (experiment 1, n = 40) remote with and without calibrated hardware (experiment 2, n = 36) and laboratory with and without calibrated hardware (experiment 3, n = 58).