Machine Learning Analyses Revealed Distinct Arterial Pulse Variability According to Side Effects of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2).

Various adverse events and complications have been attributed to COVID-19 (coronavirus disease 2019) vaccinations, which can affect the cardiovascular system, with conditions such as myocarditis, thrombosis, and ischemia. The aim of this study was to combine noninvasive pulse measurements and frequency domain analysis to determine if the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) vaccination and its accompanying cardiovascular side effects will induce changes in arterial pulse transmission and waveform. Radial blood pressure waveform and photoplethysmography signals were measured noninvasively for 1 min in 112 subjects who visited Shuang-Ho Hospital for a BNT162b2 vaccination. Based on side effects, each subject was assigned to Group N (no side effects), Group CV (cardiac or vascular side effects), Group C (cardiac side effects only), or Group V (vascular side effects only). Two classification methods were used: (1) machine-learning (ML) analysis using 40 harmonic pulse indices (amplitude proportions, phase angles, and their variability indices) as features, and (2) a pulse-variability score analysis developed in the present study. Significant effects on the pulse harmonic indices were noted in Group V following vaccination. ML and pulse-variability score analyses provided acceptable AUCs (0.67 and 0.80, respectively) and hence can aid discriminations among subjects with cardiovascular side effects. When excluding ambiguous data points, the AUC of the score analysis further improved to 0.94 (with an adopted proportion of around 64.1%) for vascular side effects. The present findings may help to facilitate a time-saving and easy-to-use method for detecting changes in the vascular properties associated with the cardiovascular side effects following BNT162b2 vaccination.

Discrimination of the Cognitive Function of Community Subjects Using the Arterial Pulse Spectrum and Machine-Learning Analysis.

Early identification of cognitive impairment would allow affected patients to receive care at earlier stage. Changes in the arterial stiffness have been identified as a prominent pathological feature of dementia. This study aimed to verify if applying machine-learning analysis to spectral indices of the arterial pulse waveform can be used to discriminate different cognitive conditions of community subjects. 3-min Radial arterial blood pressure waveform (BPW) signals were measured noninvasively in 123 subjects. Eight machine-learning algorithms were used to evaluate the following 4 pulse indices for 10 harmonics (total 40 BPW spectral indices): amplitude proportion and its coefficient of variation; phase angle and its standard deviation. Significant differences were noted in the spectral pulse indices between Alzheimer's-disease patients and control subjects. Using them as training data (AUC = 70.32% by threefold cross-validation), a significant correlation (R2 = 0.36) was found between the prediction probability of the test data (comprising community subjects at two sites) and the Mini-Mental-State-Examination score. This finding illustrates possible physiological connection between arterial pulse transmission and cognitive function. The present findings from pulse-wave and machine-learning analyses may be useful for discriminating cognitive condition, and hence in the development of a user-friendly, noninvasive, and rapid method for the early screening of dementia.

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage.

BACKGROUND/AIMS: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. METHODS: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl4-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. RESULTS: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl4-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression, as well as CCl4-induced hepatic inflammation and necrosis in mice. CONCLUSION: MRE exhibited antiinflammatory and hepatic protective activity.

Identification of Endogenous Site-specific Covalent Binding of Catechol Estrogens to Serum Proteins in Human Blood.

Protein adducts covalently modified by catechol estrogens (CEs), referred to as estrogenized proteins, are potential biomarkers for estrogen homeostasis or exposure to environmental toxicants. However, serum proteins endogenously modified by CEs and the modification sites remain elusive. In this study, liquid chromatography-mass spectrometry (LC-MS)-based shotgun proteomics is applied to identify site-specific protein estrogenization in human blood via a systematic approach and stringent validation. We showed CEs, namely 2- and 4-hydroxyl estrogens which are regarded as biomarkers for estrogen homeostasis, form covalent bonds with proteins, mainly via side chain Cys, Lys, or His residue. Estrogenization of purified human serum albumin (HSA) and immunoglobulin G (IgG) at specific sites was achieved by co-incubation and used as the standards to confirm the identified estrogenization in serum proteins. Based on a database search, estrogenized peptides derived from serum proteins in patient blood were identified; endogenous estrogenization of HSA and IgG-1 at multiple sites were confirmed as compared to the standards. Based on a test using Ellman's reagent, estrogenization produced stable products and irreversibly abolished the reactivity of Cys34-HSA, which is the most important antioxidant and nitric oxide carrier in blood. Given the importance of estrogen metabolism in environmental toxicology, further exploration of estrogenized proteins is warranted for biomarker discovery and/or new mechanisms in disease process.

Kramers-Kronig relation between nonlinear absorption and refraction of C(60) and C(70).

Using the Z-scan technique with 532 nm 16 picosecond laser pulses, we observe reverse saturable absorption and positive nonlinear refraction of toluene solutions of both C(60) and C(70). By deducting the positive Kerr nonlinear refraction of the solvent, we notice that the solute molecules contribute to nonlinear refraction of opposite signs: positive for C(60) and negative for C(70). Attributing nonlinear absorption and refraction of both solutes to cascading one-photon excitations, we illustrate that they satisfy the Kramers-Kronig relation. Accordingly, we attest the signs and magnitudes of nonlinear refraction for both solutes at 532 nm by Kramers-Kronig transform of the corresponding nonlinear absorption spectra.

Solute migration caused by excited state absorptions.

Using the Z-scan technique, we find that migration of chloroaluminum phthalocyanine in liquid ethanol can be induced by the absorption of a 19 ps laser pulse with energy exceeding a threshold but not by that of a 2.8 ns pulse depositing more energy at the solute molecules. Considering each solute molecule as an oscillator confined within a potential well, we explain, in accordance with the five-energy-band model, that solute molecules excited by a 19 ps pulse retain more translational excess energy to overcome the potential well barrier compared with those excited by a 2.8 ns pulse of equal energy. Therefore, they are more likely to migrate out of the laser beam center, weakening the solution's absorption that we detect in the Z-scan measurements. Furthermore, we theoretically infer that the 19 ps pulse-induced solute migration tends to be nonquasistatic and experimentally verify that it cannot be attributed to the Soret effect, a quasistatic process.