The Perils of Molecular Interpretations from Vibrational Spectra of Complex Samples.

Vibrational spectroscopy is a widely used technique for chemical characterizations across various analytical sciences. Its applications are increasingly extending to the analysis of complex samples such as biofluids, providing high-throughput molecular profiling. While powerful, the technique suffers from an inherent limitation: The overlap of absorption information across different spectral domains hinders the capacity to identify individual molecular substances contributing to measured signals.

CODI: Enhancing machine learning-based molecular profiling through contextual out-of-distribution integration.

Molecular analytics increasingly utilize machine learning (ML) for predictive modeling based on data acquired through molecular profiling technologies. However, developing robust models that accurately capture physiological phenotypes is challenged by the dynamics inherent to biological systems, variability stemming from analytical procedures, and the resource-intensive nature of obtaining sufficiently representative datasets. Here, we propose and evaluate a new method: Contextual Out-of-Distribution Integration (CODI).

Standardized Electric-Field-Resolved Molecular Fingerprinting.

Field-resolved infrared spectroscopy (FRS) of impulsively excited molecular vibrations can surpass the sensitivity of conventional time-integrating spectroscopies, owing to a temporal separation of the molecular signal from the noisy excitation. However, the resonant response carrying the molecular signal of interest depends on both the amplitude and phase of the excitation, which can vary over time and across different instruments. To date, this has compromised the accuracy with which FRS measurements could be compared, which is a crucial factor for practical applications.

Plasma infrared fingerprinting with machine learning enables single-measurement multi-phenotype health screening.

Infrared spectroscopy is a powerful technique for probing the molecular profiles of complex biofluids, offering a promising avenue for high-throughput in vitro diagnostics. While several studies showcased its potential in detecting health conditions, a large-scale analysis of a naturally heterogeneous potential patient population has not been attempted. Using a population-based cohort, here we analyze 5,184 blood plasma samples from 3,169 individuals using Fourier transform infrared (FTIR) spectroscopy.

Probing Blood Plasma Protein Glycosylation with Infrared Spectroscopy.

The health state of an individual is closely linked to the glycosylation patterns of his or her blood plasma proteins. However, obtaining this information requires cost- and time-efficient analytical methods. We put forward infrared spectroscopy, which allows label-free analysis of protein glycosylation but so far has only been applied to analysis of individual proteins.

Limits and Prospects of Molecular Fingerprinting for Phenotyping Biological Systems Revealed through Modeling.

Molecular fingerprinting via vibrational spectroscopy characterizes the chemical composition of molecularly complex media which enables the classification of phenotypes associated with biological systems. However, the interplay between factors such as biological variability, measurement noise, chemical complexity, and cohort size makes it challenging to investigate their impact on how the classification performs. Considering these factors, we developed an model which generates realistic, but configurable, molecular fingerprints.

Breast-cancer detection using blood-based infrared molecular fingerprints.

Background: Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy - a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner.

Infrared molecular fingerprinting of blood-based liquid biopsies for the detection of cancer.

Recent omics analyses of human biofluids provide opportunities to probe selected species of biomolecules for disease diagnostics. Fourier-transform infrared (FTIR) spectroscopy investigates the full repertoire of molecular species within a sample at once. Here, we present a multi-institutional study in which we analysed infrared fingerprints of plasma and serum samples from 1639 individuals with different solid tumours and carefully matched symptomatic and non-symptomatic reference individuals.

Molecular Origin of Blood-Based Infrared Spectroscopic Fingerprints*.

Infrared spectroscopy of liquid biopsies is a time- and cost-effective approach that may advance biomedical diagnostics. However, the molecular nature of disease-related changes of infrared molecular fingerprints (IMFs) remains poorly understood, impeding the method's applicability. Here we probe 148 human blood sera and reveal the origin of the variations in their IMFs.

Stability of person-specific blood-based infrared molecular fingerprints opens up prospects for health monitoring.

Health state transitions are reflected in characteristic changes in the molecular composition of biofluids. Detecting these changes in parallel, across a broad spectrum of molecular species, could contribute to the detection of abnormal physiologies. Fingerprinting of biofluids by infrared vibrational spectroscopy offers that capacity.

Aetiology and incidence of sudden cardiac arrest and death in young competitive athletes in the USA: a 4-year prospective study.

Objective: To investigate the aetiology and incidence of sudden cardiac arrest and death (SCA/D) in US competitive athletes.

Methods: Prospective surveillance was conducted from 1 July 2014 to 30 June 2018 through the National Center for Catastrophic Sports Injury Research in collaboration with national sports organisations. Autopsy reports, death certificates, and medical records were reviewed by an expert panel to determine aetiology.

Field-resolved infrared spectroscopy of biological systems.

The proper functioning of living systems and physiological phenotypes depends on molecular composition. Yet simultaneous quantitative detection of a wide variety of molecules remains a challenge. Here we show how broadband optical coherence opens up opportunities for fingerprinting complex molecular ensembles in their natural environment.

A Randomized Controlled Trial of a Truck Seat Intervention: Part 1-Assessment of Whole Body Vibration Exposures.

Full-time vehicle and heavy equipment operators often have a high prevalence of musculoskeletal disorders, especially low back pain (LBP). In occupations requiring vehicles or heavy equipment operation, exposure to whole body vibration (WBV) has been consistently associated with LBP. LBP is the most common cause of work-related disability and continues to be the leading cause of morbidity and lost productivity in the US workforce.

A Randomized Controlled Trial of a Truck Seat Intervention: Part 2-Associations Between Whole-Body Vibration Exposures and Health Outcomes.

This randomized controlled trial study was conducted to determine whether two different seating interventions would reduce exposure to whole-body vibration (WBV) and improve associated health outcomes. Forty professional truck drivers were randomly assigned to two groups: (i) a control group of 20 drivers who received a new, industry-standard air-suspension seat, and (ii) an intervention group of 20 drivers who received an active-suspension seat. This study collected regional body pain (10-point scale), low back disability [Oswestry Disability Index (ODI)], physical and mental health [the Short Form 12-item Health Survey (SF-12)], and work limitations [Work Limitation Questionnaire (WLQ)] before and 3, 6, and 12 months after the seating intervention.

Incidence and Etiology of Sudden Cardiac Arrest and Death in High School Athletes in the United States.

Objective: To determine the incidence and etiology of sudden cardiac arrest and death (SCA/D) in US high school athletes.

Patients And Methods: A prospective media database of SCA/D was queried for cases aged 14 to 18 years from 7 states over 6 school years (September 1, 2007, to August 30, 2013). Event details were investigated to determine participation on a high school athletic team, sex, sport, and occurrence during school-sponsored activity or exertion.

Whole Body Vibration Exposures and Health Status among Professional Truck Drivers: A Cross-sectional Analysis.

Many professional truck drivers suffer from low back pain (LBP) which is thought to be associated with exposure to whole-body vibration (WBV). The objectives of this study were to: (i) characterize general health, regional body pain and WBV exposures, (ii) evaluate the associations between different WBV parameters and health outcomes, and (iii) determine whether there were factors which affect a truck driver's WBV exposures. This study analyzed WBV exposures from 96 long-haul truck drivers over their regular work shift (6-15h) per International Standards Organization (ISO) 2631-1 and 2631-5 WBV standards.

Death by homicide in National Collegiate Athletic Association athletes between 2003 and 2013.

Background: The incidence of homicide-related death among individuals of college age in the United States population is estimated at 15.5/100,000. The incidence of homicide among National Collegiate Athletic Association (NCAA) athletes is unknown.

Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A Decade in Review.

Background: The incidence and cause of sudden cardiac death (SCD) in athletes is debated with hypertrophic cardiomyopathy often reported as the most common cause.

Methods And Results: A database of all National Collegiate Athletic Association deaths (2003-2013) was developed. Additional information and autopsy reports were obtained when possible.

The effectiveness of screening history, physical exam, and ECG to detect potentially lethal cardiac disorders in athletes: a systematic review/meta-analysis.

Background: The optimal cardiovascular preparticipation screen is debated. The purpose of this study was to perform a systematic review/meta-analysis of evidence comparing screening strategies.

Methods: PRIMSA guidelines were followed.

Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons.

Background: Although left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. In the zebrafish epithalamus, dorsal habenular neurons adopt medial (dHbm) and lateral (dHbl) subnuclear character at very different frequencies on the left and right sides. The left-sided parapineal promotes the elaboration of dHbl character in the left habenula, albeit by an unknown mechanism.

Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity.

Background: Wnt proteins are a family of secreted signaling molecules that regulate key developmental processes in metazoans. The molecular basis of Wnt binding to Frizzled and LRP5/6 co-receptors has long been unknown due to the lack of structural data on Wnt ligands. Only recently, the crystal structure of the Wnt8-Frizzled8-cysteine-rich-domain (CRD) complex was solved, but the significance of interaction sites that influence Wnt signaling has not been assessed.

Hoxb1b controls oriented cell division, cell shape and microtubule dynamics in neural tube morphogenesis.

Hox genes are classically ascribed to function in patterning the anterior-posterior axis of bilaterian animals; however, their role in directing molecular mechanisms underlying morphogenesis at the cellular level remains largely unstudied. We unveil a non-classical role for the zebrafish hoxb1b gene, which shares ancestral functions with mammalian Hoxa1, in controlling progenitor cell shape and oriented cell division during zebrafish anterior hindbrain neural tube morphogenesis. This is likely distinct from its role in cell fate acquisition and segment boundary formation.

Brain on the stage - spotlight on nervous system development in zebrafish: EMBO practical course, KIT, Sept. 2013.

During the EMBO course 'Imaging of Neural Development in Zebrafish', held on September 9-15th 2013, researchers from different backgrounds shared their latest results, ideas and practical expertise on zebrafish as a model to address open questions regarding nervous system development.