Simultaneous Quantitation of Multiple Biological Thiols Using Reactive Ionization and Derivatization with Charged Mass Tags.

The biologically important thiols (cysteine, homocysteine, N-acetyl cysteine, and glutathione) are key species in redox homeostasis, and there is a clinical need to measure them rapidly, accurately, and simultaneously at low levels in complex biofluids. The solution to the challenge presented here is based on a new derivatizing reagent that combines a thiol-selective unit to optimize the chemical transformation and a precharged pyridinium unit chosen to maximize sensitivity in mass spectrometry. Derivatization is performed simultaneously with ionization ("reactive ionization"), and mass spectrometry is used to record and characterize the thiol reaction products.

The Science of Cholesteatoma.

Cholesteatoma is a potential end-stage outcome of chronic ear infections that can result in the destruction of temporal bone structures with potential resultant hearing loss, vertigo, and intracranial infectious complications. There is currently no treatment apart from surgery for this condition, and despite years of study, the histopathogenesis of this disease remains poorly understood. This review is intended to summarize our accumulated knowledge of the mechanisms of cholesteatoma development and the underlying molecular biology.

Deep-Learning-Guided Electrochemical Impedance Spectroscopy for Calibration-Free Pharmaceutical Moisture Content Monitoring.

The moisture content of pharmaceutical powders can significantly impact the physical and chemical properties of drug formulations, solubility, flowability, and stability. However, current technologies for measuring moisture content in pharmaceutical materials require extensive calibration processes, leading to poor consistency and a lack of speed. To address this challenge, this study explores the feasibility of using impedance spectroscopy to enable accurate, rapid testing of moisture content of pharmaceutical materials with minimal to zero calibration.

Metastasis to the External Auditory Canal: A Systematic Review.

Objective: To systematically review the literature and understand the behavior, diagnosis, management, and mortality of metastasis to the external auditory canal (EAC).

Databases Reviewed: PubMed/Medline, EMBASE, Web of Science.

Methods: Studies from 1948 to June 2023 describing metastasis to the EAC were included.

Enhanced Structure-Based Prediction of Chiral Stationary Phases for Chromatographic Enantioseparation from 3D Molecular Conformations.

The accurate prediction of suitable chiral stationary phases (CSPs) for resolving the enantiomers of a given compound poses a significant challenge in chiral chromatography. Previous attempts at developing machine learning models for structure-based CSP prediction have primarily relied on 1D SMILES strings [the simplified molecular-input line-entry system (SMILES) is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings] or 2D graphical representations of molecular structures and have met with only limited success. In this study, we apply the recently developed 3D molecular conformation representation learning algorithm, which uses rapid conformational analysis and point clouds of atom positions in the 3D space, enabling efficient chemical structure-based machine learning.

Investigation into the performance and stability of immobilized and coated polysaccharide columns in supercritical fluid chromatography.

In this study, the performance of the widely used "golden four" coated chiral stationary phases (Chiralpak AD-3, Chiralcel OD-3, Chiralpak AS-3, and Chiralcel OJ-3) was compared with their corresponding immobilized versions (Chiralpak IA-3, Chiralpak IB-3, Chiralpak IB N-3, Chiralpak IH-3, and Chiralpak IJ-3) under supercritical fluid chromatography (SFC) conditions with a set of 30 racemic compounds. Using the traditional modifiers, methanol and isopropanol, the immobilized columns (Chiralpak IB N-3 and Chiralpak IH-3) showed an improved general ability to successfully resolve the enantiomers of the target analytes relative to their coated versions (Chiralcel OD-3 and Chiralpak AS-3), while the coated columns (Chiralpak AD-3, Chiralcel OD-3, and Chiralcel OJ-3) performed better than their immobilized versions (Chiralpak IA-3, Chiralpak IB-3, and Chiralpak IJ-3). An investigation of the non-traditional modifiers, dichloromethane, ethyl acetate, and tetrahydrofuran with immobilized columns, revealed a generally decreased ability to successfully resolve the enantiomers of the target analytes, relative to the use of the traditional modifiers, methanol and isopropanol.

Quantitative Determination of Water in Organic Liquids by Ambient Mass Spectrometry.

This study uses a rapid tandem mass-spectrometry method to determine water content in complex organic solutions. Emphasis is placed on trace-water analysis by a fast and accurate alternative to the Karl-Fischer method. In this new method, water is captured by a charge-labeled molecular probe.

Frailty as a Predictor of Post-Surgical Outcomes in Patients With Cutaneous Malignancies of the Scalp and Neck Requiring Flap Reconstruction.

Background: Investigate the ability of frailty status to predict post-surgical outcomes in patients with cutaneous malignancies of the scalp and neck undergoing flap reconstruction.

Methods: National Surgical Quality Improvement Program database was used to isolate patients with cutaneous malignancies of the scalp and neck who underwent surgical resection between 2015 to 2019. Univariate and multivariate analyses were performed to determine if frailty score correlated with negative post-operative outcomes.

3DMolMS: prediction of tandem mass spectra from 3D molecular conformations.

Motivation: Tandem mass spectrometry is an essential technology for characterizing chemical compounds at high sensitivity and throughput, and is commonly adopted in many fields. However, computational methods for automated compound identification from their MS/MS spectra are still limited, especially for novel compounds that have not been previously characterized. In recent years, in silico methods were proposed to predict the MS/MS spectra of compounds, which can then be used to expand the reference spectral libraries for compound identification.

Rapid Quantitation of Various Therapeutic Monoclonal Antibodies Using Membranes with Fc-Specific Ligands.

Therapeutic monoclonal antibodies (mAbs) provide effective treatments for many diseases, including cancer, autoimmune disorders, and, lately, COVID-19. Monitoring the concentrations of mAbs is important during their production and subsequent processing. This work demonstrates a 5 min quantitation of most human immunoglobulin G (IgG) antibodies through capture of mAbs in membranes modified with ligands that bind to the fragment crystallizable (Fc) region.

Microporous affinity membranes and their incorporation into microfluidic devices for monitoring of therapeutic antibodies.

Control of monoclonal antibody (mAb) concentrations in serum is important for maintaining the safety and efficacy of these lifesaving therapeutics. Point-of-care (POC) quantification of therapeutic mAbs could ensure that patients have effective mAb levels without compromising safety. This work uses mimotope-functionalized microporous alumina affinity membranes in vertical flow assays for detection and quantitation of therapeutic mAbs.

Catchment Profile of Large Cochlear Implant Centers in the United States.

Objective: To characterize the catchment area and patient profile of large cochlear implant (CI) centers in the United States.

Study Design: Multi-institutional retrospective case series.

Setting: Tertiary referral CI centers.

Quantitation of Trastuzumab and an Antibody to SARS-CoV-2 in Minutes Using Affinity Membranes in 96-Well Plates.

Quantitation of therapeutic monoclonal antibodies (mAbs) in human serum could ensure that patients have adequate levels of mAbs for effective treatment. This research describes the use of affinity, glass-fiber membranes in a 96-well-plate format for rapid (<5 min) quantitation of the therapeutic mAb trastuzumab and a mAb against the SARS-CoV-2 spike protein. Adsorption of a poly(acrylic acid)-containing film in membrane pores and activation of the -COOH groups in the film enable covalent-linking of affinity peptides or proteins to the membrane.

Association of Race With Cancer-Related Financial Toxicity.

Purpose: We investigated the association between race and FT among previous patients with cancer. Studies show that patients with cancer experience financial toxicity (FT) because of their cancer treatment.

Methods: Data on individuals with a cancer history were collected in this cross-sectional study during 2012, 2014, and 2017, from the US Health Information National Trends Survey.

Auditory Outcomes Following Transmastoid and Middle Cranial Fossa Approaches for Superior Semicircular Canal Dehiscence Repair.

Objective: To describe postoperative hearing outcomes following transmastoid (TM) and middle cranial fossa (MCF) approaches for semicircular canal dehiscence (SSCD) repair.

Study Design: Retrospective review.

Setting: Academic, tertiary referral center.

Fragmentation of Polyfunctional Compounds Recorded Using Automated High-Throughput Desorption Electrospray Ionization.

Using desorption electrospray ionization (DESI) as part of an automated high-throughput system, tandem mass spectra of the compounds in a pharmaceutical library were recorded in the positive mode under standardized conditions. Quality control filtering yielded an MS/MS library of 16 662 spectra. Fragmentation of subsets of the compounds in the library chosen to contain a single instance of a particular functional group (amide, piperazine, sulfonamide) was predicted by experts, and the results were compared with the experimental data.

Intraoperative Auditory Brainstem Response Results Predict Delayed Sensorineural Hearing Loss After Middle Cranial Fossa Resection of Vestibular Schwannoma.

Objective: To identify intraoperative neurophysiologic measures predictive of delayed progressive sensorineural hearing loss in the operative ear after a middle fossa approach (MCF) for resection of vestibular schwannoma (VS).

Study Design: Retrospective review.

Setting: Academic, tertiary referral center.

High-Throughput Determination of Enantiopurity by Microplate Circular Dichroism.

Methods for the rapid determination of enantiomeric excess (ee) in asymmetric synthetic methodology development are increasingly in demand as high-throughput experimentation protocols in academia and industry are adopted. Optical approaches have been reported, many of which rely on the use of chemical derivatization or molecular assemblies, resulting in UV/vis, fluorescence, or circular dichroism (CD) signals that report the ee values. While UV/vis and fluorescence approaches benefit from readily available 96- and 384-well plate readers, until recently, no CD plate readers existed.

Next-Generation TLC: A Quantitative Platform for Parallel Spotting and Imaging.

A high-throughput screening approach for simultaneous analysis and quantification of the percent conversion of up to 48 reactions has been developed using a thin-layer chromatography (TLC) imaging method. As a test-bed reaction, we monitored 48 thiol conjugate additions to a Meldrum's acid derivative () in parallel using TLC. The TLC elutions were imaged using a cell phone and a LEGO brick-constructed UV/vis light box.

William H. Pirkle: Stereochemistry pioneer.

Professor William H. Pirkle (1934-2018) made a profound impact on modern chemistry by inventing and popularizing widely used techniques for the analysis and purification of enantiomers, contributions that paved the way for the subsequent advances in the discovery, development, and manufacture of enantiopure pharmaceuticals, agrochemicals, and specialty chemicals. Pirkle's pioneering 1966 demonstration of the use of chiral solvating agents for the nuclear magnetic resonance determination of enantiopurity led to a lifelong interest in understanding the supramolecular interactions responsible for enantiodifferentiation.

Mass Activated Droplet Sorting (MADS) Enables High-Throughput Screening of Enzymatic Reactions at Nanoliter Scale.

Microfluidic droplet sorting enables the high-throughput screening and selection of water-in-oil microreactors at speeds and volumes unparalleled by traditional well-plate approaches. Most such systems sort using fluorescent reporters on modified substrates or reactions that are rarely industrially relevant. We describe a microfluidic system for high-throughput sorting of nanoliter droplets based on direct detection using electrospray ionization mass spectrometry (ESI-MS).

Electric and Acoustic Stimulation in Cochlear Implant Recipients with Hearing Preservation.

Hearing loss affects 30 million people in the United States, and a subset of these patients have normal low-frequency hearing and ski-sloped high-frequency hearing loss. For these patients, hearing aids alone may not provide adequate benefit. Cochlear implantation alone has been utilized to improve speech perception.

Dynamic calorimetry and XRD studies of the nematic and twist-bend nematic phase transitions in a series of dimers with increasing spacer length.

A modulated and conventional DSC study of the transitions between the twist-bend nematic (Ntb), regular nematic (N) and isotropic liquid (Iso) phases was performed on a series of difluoroterphenyl-based dimers with (CH2)n spacers; n = 5, 7, 9, 11. The enthalpy of Ntb-N transition decreases steeply with increasing n, while that of the N-Iso transition increases with n; hence, the greatest effect of increasing n is a lowering N phase enthalpy. Based on past and present X-ray scattering experiments, we estimate the average molecular conformation in the Ntb phase and perform torsion energy calculations on the spacer.