Proc Natl Acad Sci U S A
June 2022
Embedding computation in biochemical environments incompatible with traditional electronics is expected to have a wide-ranging impact in synthetic biology, medicine, nanofabrication, and other fields. Natural biochemical systems are typically modeled by chemical reaction networks (CRNs) which can also be used as a specification language for synthetic chemical computation. In this paper, we identify a syntactically checkable class of CRNs called noncompetitive (NC) whose equilibria are absolutely robust to reaction rates and kinetic rate law, because their behavior is captured solely by their stoichiometric structure.
View Article and Find Full Text PDFRapid advancements in deep learning have led to many recent breakthroughs. While deep learning models achieve superior performance, often statistically better than humans, their adoption into safety-critical settings, such as healthcare or self-driving cars is hindered by their inability to provide safety guarantees or to expose the inner workings of the model in a human understandable form. We present MoËT, a novel model based on Mixture of Experts, consisting of decision tree experts and a generalized linear model gating function.
View Article and Find Full Text PDFBiomed Pharmacother
January 2022
Doxorubicin (DOX) is an effective anticancer drug. However, its use is hampered by the development of very mortal cardiomyopathy. Here, we investigate whether the co-administration of the antidepressant paroxetine (P), known to exert beneficial cardiovascular effects, would provide effective cardioprotection.
View Article and Find Full Text PDFCardiomyopathy resistant to treatment is the most serious adverse effect of doxorubicin (dox). The mechanisms of dox-induced cardiomyopathy (DCM) have been extensively studied in dilated forms of DCM. However, efficient treatment did not emerge.
View Article and Find Full Text PDFCan J Physiol Pharmacol
February 2020
The aim of this study was to test the hypothesis that subchronic co-application of vitamins B6 and folic acid (FA) could affect heart failure (HF) induced by monocrotaline (MCT), with the modulation of oxidative stress parameters and cardiometabolic biomarkers. Biochemical and histomorphometric analyses were assessed in blank solution-exposed controls (C1 physiological saline 1 mL/kg, 1 day, = 8; C2 physiological saline 1 mL/kg, 28 days, = 8), MCT-induced HF MCT 50 mg/kg, = 8), B6+FA (vitamin B6 7 mg·kg·day, FA 5 mg·kg·day; = 8), and MCT+B6+FA (MCT 50 mg/kg, vitamin B6 7 mg·kg·day, FA 5 mg·kg·day; = 8) in male Wistar albino rats (body mass 160 g at the start). Superoxide dismutase and glutathione peroxidase activities, thiol-, carbonyl groups, and nitrotyrosine were determined in cardiac tissue.
View Article and Find Full Text PDFUsing comprehensive analysis of heart rate (HRV) and blood pressure (BPV) short-term variability we estimated the time course of changes of autonomic nervous system remodeling in two stages of doxorubicin-induced cardiomyopathy (DCM). We also investigated the level of gene expression of cardiac β-1 (β-1AR) and β-2 (β-2AR) adrenoceptors. Experiments were performed in adult male Wistar rats equipped with indwelling catheters for BP recording and blood withdrawal.
View Article and Find Full Text PDFSudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system.
View Article and Find Full Text PDFConjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX.
View Article and Find Full Text PDFBackground: The Comprehensive Headache-related Quality of life Questionnaire (CHQQ), is a recently developed and validated instrument, intended for measuring quality of life of patients with all headache types. Currently no validated headache-specific quality of life questionnaires are available in Serbian. The aim of this study was to translate the CHQQ from Hungarian to Serbian, to make necessary cultural adaptations and to test its psychometric properties in a sample of outpatients with headache.
View Article and Find Full Text PDFBackground: Knowledge about adverse effects of medications is an important part of proper medication use and prerequisite for good treatment adherence.
Objective: The aim of our study was to construct, develop, and test a new questionnaire for the measurement of patients' knowledge about adverse drug reactions of angiotensin-converting enzyme (ACE) inhibitors.
Methods: The 8-item questionnaire was constructed to measure adverse reactions to ACE inhibitors.