2023 White Paper on Recent Issues in Bioanalysis: EU IVDR 2017/746 Implementation/Impact, IVD/CDx/CLIA Approved Assays, High Dimensional Cytometry, Multiplexing Technologies, LBA Tissue Analysis, Vaccine Study Endpoints, Cell-Based Assays for Biomarkers, Cell Therapy and Vaccines ( - Recommendations on Development & Validation of Biomarkers, IVD, CDx, Cell-Based, Flow Cytometry, Ligand-Binding and Enzyme Assays; Advanced Critical Reagents Strategies).

The 17 Workshop on Recent Issues in Bioanalysis (17 WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Unveiling the Role of Oxidative Stress in Cochlear Hair Cell Death: Prospective Phytochemical Therapeutics against Sensorineural Hearing Loss.

Hearing loss represents a multifaceted and pervasive challenge that deeply impacts various aspects of an individual's life, spanning psychological, emotional, social, and economic realms. Understanding the molecular underpinnings that orchestrate hearing loss remains paramount in the quest for effective therapeutic strategies. This review aims to expound upon the physiological, biochemical, and molecular aspects of hearing loss, with a specific focus on its correlation with diabetes.

The cognitive tasks and event-related potentials associated childhood adversity: A systematic review.

In this systematic review, 18 articles met inclusion criteria to be qualitatively analyzed for converging evidence of brain activity, measured using event-related potential (ERP), related to retrospectively reported childhood adversity/trauma. Using the PRISMA guidelines for systematic reviews, 917 articles were assessed for inclusion and were filtered using study parameters. The most common ERP components listed in the literature were P100, N170, N200, P200, P300, ERN, and LPP.

Reaction time for correct identification of vowels in consonant-vowel syllables and of vowel segments.

Reaction times for correct vowel identification were measured to determine the effects of intertrial intervals, vowel, and cue type. Thirteen adults with normal hearing, aged 20-38 years old, participated. Stimuli included three naturally produced syllables (/ba/ /bi/ /bu/) presented whole or segmented to isolate the formant transition or static formant center.

The Effect of Perceived Tinnitus Disturbance on Hope.

Background: Although there are systematic reviews of the effects of tinnitus on quality of life, the relationship of tinnitus to hopefulness has not been examined.

Purpose: The purpose of this study was to determine the relationship between tinnitus distress and hope by comparing the severity of tinnitus to measures of hopefulness. This was done by comparing the Tinnitus Reaction Questionnaire (TRQ) to the following hope scales: the Herth Hope Scale (HHS) and the Herth Hope Index (HHI).

2022 White Paper on Recent Issues in Bioanalysis: Enzyme Assay Validation, BAV for Primary End Points, Vaccine Functional Assays, Cytometry in Tissue, LBA in Rare Matrices, Complex NAb Assays, Spectral Cytometry, Endogenous Analytes, Extracellular Vesicles - Recommendations on Biomarkers/CDx, Flow Cytometry, Ligand-Binding Assays Development & Validation; Emerging Technologies; Critical Reagents Deep Characterization.

The 16 Workshop on Recent Issues in Bioanalysis (16 WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Further Validation of the Religious Surrender and Attendance Scale-3 (RSAS-3).

The (RSAS-3) is a very brief measure used to quantify religious commitment as a protective health factor. To provide evidence of criterion-related validity of the RSAS-3, 440 community members and undergraduate students completed a survey containing three religiosity measures: the RSAS-3, the scale, and the scale (BIAC), and a measure of problematic substance use, . It was hypothesized all religiosity measures would be positively interrelated, the measure of problematic use would be negatively related to all religiosity measures, and that the RSAS-3 would be strongly predictive of absence of problematic substance use.

Ginsenoside Rc from Panax Ginseng Ameliorates Palmitate-Induced UB/OC-2 Cochlear Cell Injury.

By 2050, at least 700 million people will require hearing therapy while 2.5 billion are projected to suffer from hearing loss. Sensorineural hearing loss (SNHL) arises from the inability of the inner ear to convert fluid waves into neural electric signals because of injury to cochlear hair cells that has resulted in their death.

Tethered Oral Tissue Release Among Breastfed Infants: Maternal Sources of Information and Treatment.

Background: Despite limited clinical consensus regarding surgery for tethered oral tissues ("tongue-tie") for resolving breastfeeding-related issues, the procedure has been increasing in the United States. Greater understanding of maternal experiences with obtaining surgical release may help to improve breastfeeding outcomes.

Research Aim: To explore experiences of breastfeeding mothers with infants having undergone "tongue-tie" surgery.

Effects of Unilateral Hearing Loss on Speech-Evoked Auditory Brainstem Responses and Reading: A Preliminary Study.

Purpose: The purpose of this study was to determine whether the speech-evoked auditory brainstem responses (sABRs) obtained by stimulating the ear with normal sensitivity in children with unilateral hearing loss (UHL) were different from that of children with normal hearing (NH), and to explore correlations between the sABR findings and measures of reading.

Method: Eleven children with UHL and 11 children with NH were tested via the BioMARK sABR protocol using the syllable /da/; latency and amplitudes of Waves V, A, C, D, E, F, and O were measured. Participants also were tested on the Phonemic Synthesis Test (PST) and the Woodcock Reading Mastery Test-Revised (WRMT-R), particularly the Reading Readiness, Basic Skills, and Comprehension subtests.

Development and use of a high-throughput screen to identify novel modulators of the corticotropin releasing factor binding protein.

Background: Stress responses are believed to involve corticotropin releasing factor (CRF), its two cognate receptors (CRF and CRF), and the CRF-binding protein (CRFBP). Whereas decades of research has focused on CRF, the role of CRF in the central nervous system (CNS) has not been thoroughly investigated. We have previously reported that CRF, interacting with a C terminal fragment of CRFBP, CRFBP(10kD), may have a role in the modulation of neuronal activity.

Acute CO tolerance in fishes is associated with air breathing but not the Root effect, red cell βNHE, or habitat.

High CO (hypercapnia) can impose significant physiological challenges associated with acid-base regulation in fishes, impairing whole animal performance and survival. Unlike other environmental conditions such as temperature and O, the acute CO tolerance thresholds of fishes are not understood. While some fish species are highly tolerant, the extent of acute CO tolerance and the associated physiological and ecological traits remain largely unknown.

Control of Breathing in Ectothermic Vertebrates.

The ectothermic vertebrates are a diverse group that includes the Fishes (Agnatha, Chondrichthyes, and Osteichthyes), and the stem Tetrapods (Amphibians and Reptiles). From an evolutionary perspective, it is within this group that we see the origin of air-breathing and the transition from the use of water to air as a respiratory medium. This is accompanied by a switch from gills to lungs as the major respiratory organ and from oxygen to carbon dioxide as the primary respiratory stimulant.

New oral protease-activated receptor 4 antagonist BMS-986120: tolerability, pharmacokinetics, pharmacodynamics, and gene variant effects in humans.

BMS-986120 is a novel first-in-class oral protease-activated receptor 4 (PAR4) antagonist exhibiting robust antithrombotic activity that has shown low bleeding risk in monkeys. We sought to assess pharmacokinetics, pharmacodynamics, and tolerability of BMS-986120 in healthy participants and platelet responses to BMS-986120 in participants carrying PAR4 A120T variants. Phase I, randomized, double-blind, placebo-controlled single-ascending-dose (SAD; N = 56) and multiple-ascending-dose (MAD; N = 32) studies were conducted.

An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent and Selective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-Phosphate Dehydrogenase 6-Phosphogluconolactonase.

In , the first two and rate-limiting enzymes of the pentose phosphate pathway, glucose 6-phosphate dehydrogenase (G6PD) and the 6-phosphogluconolactonase, are bifunctionally fused to a unique enzyme named GluPho, differing structurally and mechanistically from the respective human orthologs. Consistent with the enzyme's essentiality for malaria parasite proliferation and propagation, human G6PD deficiency has immense impact on protection against severe malaria, making GluPho an attractive antimalarial drug target. Herein we report on the optimized lead compound -(((2R,4S)-1-cyclobutyl-4-hydroxypyrrolidin-2-yl)methyl)-6-fluoro-4-methyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide (SBI-0797750), a potent and fully selective GluPho inhibitor with robust nanomolar activity against recombinant GluPho, G6PD, and P.

Effects of Spectral Shaping on Speech Auditory Brainstem Responses to Stop Consonant-Vowel Syllables.

Background: Spectral shaping is employed by hearing aids to make consonantal information, such as formant transitions, audible for listeners with hearing loss. How manipulations of the stimuli, such as spectral shaping, may alter encoding in the auditory brainstem has not been thoroughly studied.

Purpose: The aim of this study was to determine how spectral shaping of synthetic consonant-vowel (CV) syllables, varying in their second formant (F2) onset frequency, may affect encoding of the syllables in the auditory brainstem.

Cognitive Measures and the Acceptable Noise Level.

Objective: The aim of this study was to determine the relation between the acceptable noise level (ANL) and cognitive measures of auditory attention and working memory.

Design: Young adults were administered the following tests: the ANL, the Digit Span and Letter-Number Sequencing subtests of the Wechsler Adult Intelligence Scale-Fourth Edition, the Auditory Attention subtest from the Woodcock-Johnson Tests of Cognitive Abilities, the Hearing in Noise Test (HINT), and the operation span (OSPAN) test. A correlation matrix was constructed using Pearson coefficients.

Evolution of vertebrate respiratory central rhythm generators.

Tracing the evolution of the central rhythm generators associated with ventilation in vertebrates is hindered by a lack of information surrounding key transitions. To begin with, central rhythm generation has been studied in detail in only a few species from four vertebrate groups, lamprey, anuran amphibians, turtles, and mammals (primarily rodents). Secondly, there is a lack of information regarding the transition from water breathing fish to air breathing amniotes (reptiles, birds, and mammals).

Frontotemporal activation differs between perception of simulated cochlear implant speech and speech in background noise: An image-based fNIRS study.

In this study we used functional near-infrared spectroscopy (fNIRS) to investigate neural responses in normal-hearing adults as a function of speech recognition accuracy, intelligibility of the speech stimulus, and the manner in which speech is distorted. Participants listened to sentences and reported aloud what they heard. Speech quality was distorted artificially by vocoding (simulated cochlear implant speech) or naturally by adding background noise.

Discovery of Orally Bioavailable Purine-Based Inhibitors of the Low-Molecular-Weight Protein Tyrosine Phosphatase.

Obesity-associated insulin resistance plays a central role in the pathogenesis of type 2 diabetes. A promising approach to decrease insulin resistance in obesity is to inhibit the protein tyrosine phosphatases that negatively regulate insulin receptor signaling. The low-molecular-weight protein tyrosine phosphatase (LMPTP) acts as a critical promoter of insulin resistance in obesity by inhibiting phosphorylation of the liver insulin receptor activation motif.