In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements.

Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) and alkylamines (AA) are widely present in these supplements. Although the health effects of these analogues are not well understood yet, they are hypothesised to be agonists of adrenergic (ADR) and trace amine-associated receptors (TAARs). Therefore, we aimed to pharmacologically characterise these compounds by investigating their activating properties of ADRs and TAAR1 in vitro. The potency and efficacy of the selected PEAs and AAs was studied by using cell lines overexpressing human ADRα1A/α1B/α1D/α2a/α2B/ß1/ß2 or TAAR1. Concentration-response relationships are expressed as percentages of the maximal signal obtained by the full ADR agonist adrenaline or the full TAAR1 agonist phenethylamine. Multiple PEAs activated ADRs (EC50 = 34 nM-690 µM; Emax = 8-105%). Almost all PEAs activated TAAR1 (EC50 = 1.8-92 µM; Emax = 40-104%). Our results reveal the pharmacological profile of PEAs and AAs that are often used in food supplements. Several PEAs have strong agonistic properties on multiple receptors and resemble potencies of the endogenous ligands, indicating that they might further stimulate the already activated sympathetic nervous system in exercising athletes via multiple mechanisms. The use of supplements containing one, or a combination of, PEA(s) may pose a health risk for their consumers.

Detecting Colorectal Adenomas and Cancer Using Volatile Organic Compounds in Exhaled Breath: A Proof-of-Principle Study to Improve Screening.

INTRODUCTION: Early detection of colorectal cancer (CRC) by screening programs is crucial because survival rates worsen at advanced stages. However, the currently used screening method, the fecal immunochemical test (FIT), suffers from a high number of false-positives and is insensitive for detecting advanced adenomas (AAs), resulting in false-negatives for these premalignant lesions. Therefore, more accurate, noninvasive screening tools are needed. In this study, the utility of analyzing volatile organic compounds (VOCs) in exhaled breath in a FIT-positive population to detect the presence of colorectal neoplasia was studied. METHODS: In this multicenter prospective study, breath samples were collected from 382 FIT-positive patients with subsequent colonoscopy participating in the national Dutch bowel screening program (n = 84 negative controls, n = 130 non-AAs, n = 138 AAs, and n = 30 CRCs). Precolonoscopy exhaled VOCs were analyzed using thermal desorption-gas chromatography-mass spectrometry, and the data were preprocessed and analyzed using machine learning techniques. RESULTS: Using 10 discriminatory VOCs, AAs could be distinguished from negative controls with a sensitivity and specificity of 79% and 70%, respectively. Based on this biomarker profile, CRC and AA combined could be discriminated from controls with a sensitivity and specificity of 77% and 70%, respectively, and CRC alone could be discriminated from controls with a sensitivity and specificity of 80% and 70%, respectively. Moreover, the feasibility to discriminate non-AAs from controls and AAs was shown. DISCUSSION: VOCs in exhaled breath can detect the presence of AAs and CRC in a CRC screening population and may improve CRC screening in the future.

Constructing bi-plots for random forest: Tutorial.

Current technological developments have allowed for a significant increase and availability of data. Consequently, this has opened enormous opportunities for the machine learning and data science field, translating into the development of new algorithms in a wide range of applications in medical, biomedical, daily-life, and national security areas. Ensemble techniques are among the pillars of the machine learning field, and they can be defined as approaches in which multiple, complex, independent/uncorrelated, predictive models are subsequently combined by either averaging or voting to yield a higher model performance. Random forest (RF), a popular ensemble method, has been successfully applied in various domains due to its ability to build predictive models with high certainty and little necessity of model optimization. RF provides both a predictive model and an estimation of the variable importance. However, the estimation of the variable importance is based on thousands of trees, and therefore, it does not specify which variable is important for which sample group. The present study demonstrates an approach based on the pseudo-sample principle that allows for construction of bi-plots (i.e. spin plots) associated with RF models. The pseudo-sample principle for RF. is explained and demonstrated by using two simulated datasets, and three different types of real data, which include political sciences, food chemistry and the human microbiome data. The pseudo-sample bi-plots, associated with RF and its unsupervised version, allow for a versatile visualization of multivariate models, and the variable importance and the relation among them.

Characteristic Human Individual Puffing Profiles Can Generate More TNCO than ISO and Health Canada Regimes on Smoking Machine When the Same Brand Is Smoked.

Human smoking behavior influences exposure to smoke toxicants and is important for risk assessment. In a prospective observational study, the smoking behavior of Marlboro smokers was measured for 36 h. Puff volume, duration, frequency, flow and inter-puff interval were recorded with the portable CReSSmicro™ device, as has often been done by other scientists. However, the use of the CReSSmicro™ device may lead to some registration pitfalls since the method of insertion of the cigarette may influence the data collection. Participants demonstrated consistent individual characteristic puffing behavior over the course of the day, enabling the creation of a personalized puffing profile. These puffing profiles were subsequently used as settings for smoking machine experiments and tar, nicotine and carbon monoxide (TNCO) emissions were generated. The application of human puffing profiles led to TNCO exposures more in the range of Health Canada Intense (HCI)-TNCO emissions than for those of the International Standardization Organization (ISO). Compared to the ISO regime, which applies a low puff volume relative to human smokers, the generation of TNCO may be at least two times higher than when human puffing profiles were applied on the smoking machine. Human smokers showed a higher puffing intensity than HCI and ISO because of higher puffing frequency, which resulted in more puffs per cigarette, than both HCI and ISO.