A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets.

We report the first implementation of ion mobility mass spectrometry combined with an ultra-high throughput sample introduction technology for high throughput screening (HTS). The system integrates differential ion mobility (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the sub-strates and products of isomerase mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens offering an opportunity as a drug target for a variety of microbial and parasite borne diseases.

Rapid and Robust Workflows Using Different Ionization, Computation, and Visualization Approaches for Spatial Metabolome Profiling of Microbial Natural Products in .

Ambient mass spectrometry (MS) technologies have been applied to spatial metabolomic profiling of various samples in an attempt to both increase analysis speed and reduce the length of sample preparation. Recent studies, however, have focused on improving the spatial resolution of ambient approaches. Finer resolution requires greater analysis times and commensurate computing power for more sophisticated data analysis algorithms and larger data sets.

Differential Mobility Spectrometry Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets.

We report the first implementation of ion mobility mass spectrometry combined with an ultrahigh throughput sample introduction technology for high-throughput screening (HTS). The system integrates differential mobility spectrometry (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the substrates and products of isomerase-mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens, offering an opportunity as a drug target for a variety of microbial and parasite borne diseases.

High-Throughput Covalent Modifier Screening with Acoustic Ejection Mass Spectrometry.

Interests in covalent drugs have grown in modern drug discovery as they could tackle challenging targets traditionally considered "undruggable". The identification of covalent binders to target proteins typically involves directly measuring protein covalent modifications using high-resolution mass spectrometry. With a continually expanding library of compounds, conventional mass spectrometry platforms such as LC-MS and SPE-MS have become limiting factors for high-throughput screening.

Exploring the relationship between manual dexterity and cognition in people with multiple sclerosis: 9-hole peg and multiple cognitive functions.

Aim And Rationale: Problems with manual dexterity and cognition impact the everyday performance of people with multiple sclerosis (PwMS). Accumulated findings point to the relationship between deficits in manual dexterity and auditory domains of cognition with a lack of evidence on visuospatial and verbal aspects of cognitive functioning. Therefore, this study explores the relationship between manual dexterity and cognition in a cohort of PwMS.

High-Throughput Compound Quality Assessment with High-Mass-Resolution Acoustic Ejection Mass Spectrometry: An Automatic Data Processing Toolkit.

Pharmacological screening heavily relies on the reliability of compound libraries. To ensure the accuracy of screening results, fast and reliable quality control (QC) of these libraries is essential. While liquid chromatography (LC) with ultraviolet (UV) or mass spectrometry (MS) detection has been employed for molecule QC on small sample sets, the analytical throughput becomes a bottleneck when dealing with large libraries.

Multiple Sclerosis, Fatigue, Expanded Disability Status Scale: A Cross-Sectional Exploration of Sleep Efficiency and Quantitative Sleep Parameters.

Background: Poor sleep quality and sleep disorders are more prevalent in individuals with multiple sclerosis (MS) than in the general population. Poor sleep has been correlated with worse MS outcomes. Sleep efficiency (SE) is one of the most sensitive markers of sleep quality.

SpectraX: A Straightforward Tool for Principal Component Analysis-Based Spectral Analysis.

The analysis of complex spectra is an important component of direct/ambient mass spectrometry (MS) applications such as natural product screening. Unlike chromatography-based metabolomics or proteomics approaches, which rely on software and algorithms, the work of spectral screening is mostly performed manually in the initial stages of research and relies heavily on the experience of the analyst. As a result, throughput and spectral screening reliability are problematic when dealing with large amounts of data.

Peering further into the mind's eye: combining visual evoked potential and optical coherence tomography measures enhances insight into the variance in cognitive functioning in multiple sclerosis.

Background: Spectral Optical Coherence Tomography (OCT) and Visual Evoked Potentials (VEPs) have both emerged as potentially useful biomarkers of cognitive decline in people with multiple sclerosis (PwMS). Their combined use may provide additional predictive value for identifying disease impact, progression, and remyelination capacity above-and-beyond what is captured using either approach alone.

Objective: We examined the relationship between OCT/VEP measures and cognitive functioning in 205 PwMS.

Auditory Test of Processing Speed: Preliminary validation of a smartphone-based test of mental speed.

Background: The Symbol Digit Modalities Test (SDMT) is a gold-standard measure of cognitive efficiency and processing speed for people with multiple sclerosis (PwMS) but relies on vision and oculomotor function.

Objectives: To develop and validate a new processing speed test with minimal memory involvement and no eye function requirements.

Methods: We created an Auditory Test of Processing Speed (ATOPS).

Cognitive impairment, fatigue and depression in multiple sclerosis: Is there a difference between benign and non-benign MS?

Introduction: Multiple Sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). The severity of disability in people with MS (PwMS) is generally measured with the Expanded Disability Status Scale (EDSS). A variant of MS known as 'benign MS' (BMS) has been defined as an EDSS score of 3 or lower, combined with a disease duration of 10 years or longer; however, there is disagreement in the field about whether BMS really exists.

Cognitive skill learning in multiple sclerosis: A meaningful component of the neuropsychological profile.

Cognitive skill learning (CSL) refers to the capacity to improve performance on specific cognitive operations through repeated practice. We hypothesized that high CSL aptitude may promote accumulation of cognitive reserve, and resiliency to cognitive decline, in people with Multiple Sclerosis (MS). Using an adaptive working memory training paradigm, we obtained CSL aptitude indices (amount of improvement on the training task over time) in MS patients for a single session of practice (25-30 min), and longer-term practice (twenty sessions).

3D printer platform and conductance feedback loop for automated imaging of uneven surfaces by liquid microjunction-surface sampling probe mass spectrometry.

Rationale: Molecular imaging of samples using mass spectrometric techniques, such as matrix-assisted laser desorption ionization or desorption electrospray ionization, requires the sample surface to be even/flat and sliced into thin sections (c. 10 μm). Furthermore, sample preparation steps can alter the analyte composition of the sample.

Single trial variability in neural activity during a working memory task reveals multiple distinct information processing sequences.

Successful encoding, maintenance, and retrieval of information stored in working memory requires persistent coordination of activity among multiple brain regions. It is generally assumed that the pattern of such coordinated activity remains consistent for a given task. Thus, to separate this task-relevant signal from noise, multiple trials of the same task are completed, and the neural response is averaged across trials to generate an event-related potential (ERP).

Fitts' Tapping Task as a New Test for Cognition and Manual Dexterity in Multiple Sclerosis: Validation Study.

Introduction. Studies suggest that people with multiple sclerosis (pwMS) experience continuous and subclinical physical worsening, even as early as their disease diagnosis. Validating sensitive and reproducible tests that can capture subclinical disease activity early in the disease are clinically useful and highly warranted.

Hyperspectral Visualization-Based Mass Spectrometry Imaging by LMJ-SSP: A Novel Strategy for Rapid Natural Product Profiling in Bacteria.

Mass spectrometry imaging (MSI) has been widely used to discover natural products (NPs) from underexplored microbiological sources. However, the technique is limited by incompatibility with complicated/uneven surface topography and labor-intensive sample preparation, as well as lengthy compound profiling procedures. Here, liquid micro-junction surface sampling probe (LMJ-SSP)-based MSI is used for rapid profiling of natural products from Gram-negative marine bacteria on nutrient agar media without any sample preparation.

Ultrahigh-Throughput Intact Protein Analysis with Acoustic Ejection Mass Spectrometry.

The need for high-throughput intact protein analysis has been rising as drug discovery increasingly requires the analysis of large sets of covalent modifiers and protein therapeutics. Liquid chromatography-mass spectrometry (LC-MS) is the primary analytical tool used to date to characterize proteins within the biopharmaceutical industry. However, the speed of LC-MS prevents the analysis of large-scale sample sets (>1000 within a day).

Cognitive impairment in people with multiple sclerosis: Perception vs. performance - factors that drive perception of impairment differ for patients and clinicians.

Background: Neurologists' perceptions of the presence of cognitive impairment (CI) in people with multiple sclerosis (PwMS) may not always align with findings of objective cognitive assessment. The accuracy of self-reported CI in PwMS can also be highly variable across individuals, and may not align with objective measurement of cognitive disturbances. Research suggests that additional factors impact perceived cognitive ability, such as depression and fatigue.

Examination of the temporal-spatial dynamics of working memory training-induced neuroplasticity.

Efficient working memory (WM) performance involves the dynamic coordination of neural activity on a millisecond time-scale. However, the correspondence between the timing and spatial localization of changes in neural activity following targeted WM training has not been well-established. To address this, we used an event-related potential (ERP) source localization approach to identify the patterns of cortical activity changes that are induced by WM training along both the temporal and spatial dimensions.

Individual differences in visual evoked potential latency are associated with variance in brain tissue volume in people with multiple sclerosis: An analysis of brain function-structure correlates.

Visual evoked potentials (VEP) index visual pathway functioning, and are often used for clinical assessment and as outcome measures in people with multiple sclerosis (PwMS). VEPs may also reflect broader neural disturbances that extend beyond the visual system, but this possibility requires further investigation. In the present study, we examined the hypothesis that delayed latency of the P100 component of the VEP would be associated with broader structural changes in the brain in PwMS.

Prolonged visual evoked potential latency predicts longitudinal worsening of fatigue in people with multiple sclerosis.

Background: Fatigue is a common problem experienced by people with multiple sclerosis (PwMS) and can impact physical, cognitive, and psychosocial aspects of daily living and quality of life. The tracking of meaningful longitudinal change in subjective fatigue that occurs as a result of MS activity may be enhanced by incorporating objective neurophysiological measures into longitudinal assessment. To examine this possibility, we examined the longitudinal relationship between visual evoked potential (VEP) measures and a variety of fatigue measures over an approximately two-year period in PwMS.

Discontinuously Dewetting Solvent Arrays: Droplet Formation and Poly-Synchronous Surface Extraction for Mass Spectrometry Imaging Applications.

We describe a new liquid tissue stamping method called poly-synchronous surface extraction (PSSE) that utilizes an omniphobic substrate patterned with hydrophilic surface energy traps (SETs), which when wet with a solvent form a dense microdroplet array. When contacted with a tissue sample, each droplet locally extracts analytes from the tissue surface, which subsequentially can be analyzed by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-IMS) or ambient ionization-MS techniques. Optimization of the patterned surface with six different solvents was carried out to increase the droplet density, height, and reproducibility of volume deposition.

The moderating roles of self-efficacy and depression in dual-task walking in multiple sclerosis: A test of self-awareness theory.

Objective: Multiple sclerosis (MS) is a debilitating neurological disease associated with a variety of psychological, cognitive, and motoric symptoms. Walking is among the most important functions compromised by MS. Dual-task walking (DTW), an everyday activity in which people walk and engage in a concurrent, discrete task, has been assessed in MS, but little is known about how it relates to other MS symptoms.

Longitudinal assessment of the relationship between visual evoked potentials and cognitive performance in multiple sclerosis.

Objective: Visual evoked potentials (VEPs) can provide insight into disease activity in people with multiple sclerosis (PwMS). However, few studies have tracked concurrent changes in VEPs and cognitive functioning over time in MS. To address this, we examined the longitudinal relationship between VEP and cognitive performance in PwMS over a two-year period.