Class Of Functions Research Articles

Geometric properties of an integral operator associated with Mittag-Leffler functions

The main object of this paper is to introduce a new integral operator associated with Mittag-Leffler function. Further, we obtain some sufficient condition for this integral operator belonging to certain classes of starlike functions.

Comparative genomics of Ascetosporea gives new insight into the evolutionary basis for animal parasitism in Rhizaria

BackgroundAscetosporea (Endomyxa, Rhizaria) is a group of unicellular parasites infecting aquatic invertebrates. They are increasingly being recognized as widespread and important in marine environments, causing large annual losses in invertebrate aquaculture. Despite their importance, little molecular data of Ascetosporea exist, with only two genome assemblies published to date. Accordingly, the evolutionary origin of these parasites is unclear, including their phylogenetic position and the genomic adaptations that accompanied the transition from a free-living lifestyle to parasitism. Here, we sequenced and assembled three new ascetosporean genomes, as well as the genome of a closely related amphizoic species, to investigate the phylogeny, origin, and genomic adaptations to parasitism in Ascetosporea.ResultsUsing a phylogenomic approach, we confirm the monophyly of Ascetosporea and show that Paramyxida group with Mikrocytida, with Haplosporida being sister to both groups. We report that the genomes of these parasites are relatively small (12–36 Mb) and gene-sparse (~ 2300–5200 genes), while containing surprisingly high amounts of non-coding sequence (~ 70–90% of the genomes). Performing gene-tree aware ancestral reconstruction of gene families, we demonstrate extensive gene losses at the origin of parasitism in Ascetosporea, primarily of metabolic functions, and little gene gain except on terminal branches. Finally, we highlight some functional gene classes that have undergone expansions during evolution of the group.ConclusionsWe present important new genomic information from a lineage of enigmatic but important parasites of invertebrates and illuminate some of the genomic innovations accompanying the evolutionary transition to parasitism in this lineage. Our results and data provide a genetic basis for the development of control measures against these parasites.

CAPTURE: Comprehensive anti-cancer peptide predictor with a unique amino acid sequence encoder

Anticancer peptides (ACPs) key properties including bioactivity, high efficacy, low toxicity, and lack of drug resistance make them ideal candidates for cancer therapies. To deeply explore the potential of ACPs and accelerate development of cancer therapies, although 53 Artificial Intelligence supported computational predictors have been developed for ACPs and non ACPs classification but only one predictor has been developed for ACPs functional types annotations. Moreover, these predictors extract amino acids distribution patterns to transform peptides sequences into statistical vectors that are further fed to classifiers for discriminating peptides sequences and annotating peptides functional classes. Overall, these predictors remain fail in extracting diverse types of amino acids distribution patterns from peptide sequences. The paper in hand presents a unique CARE encoder that transforms peptides sequences into statistical vectors by extracting 4 different types of distribution patterns including correlation, distribution, composition, and transition. Across public benchmark dataset, proposed encoder potential is explored under two different evaluation settings namely; intrinsic and extrinsic. Extrinsic evaluation indicates that 12 different machine learning classifiers achieve superior performance with the proposed encoder as compared to 55 existing encoders. Furthermore, an intrinsic evaluation reveals that, unlike existing encoders, the proposed encoder generates more discriminative clusters for ACPs and non-ACPs classes. Across 8 public benchmark ACPs and non-ACPs classification datasets, proposed encoder and Adaboost classifier based CAPTURE predictor outperforms existing predictors with an average accuracy, recall and MCC score of 1%, 4%, and 2% respectively. In generalizeability evaluation case study, across 7 benchmark anti-microbial peptides classification datasets, CAPTURE surpasses existing predictors by an average AU-ROC of 2%. CAPTURE predictive pipeline along with label powerset method outperforms state-of-the-art ACPs functional types predictor by 5%, 5%, 5%, 6%, and 3% in terms of average accuracy, subset accuracy, precision, recall, and F1 respectively. CAPTURE web application is available at https://sds_genetic_analysis.opendfki.de/CAPTURE.

On the dimensional connection between a class of real number sequences and local fractal functions with a single unbounded variation point

In this paper, we investigate the connection between a class of real number sequences and local fractal functions in terms of fractal dimensions. Under certain conditions, we show that the Box dimension of the graph of a local fractal function with a single unbounded variation point is equal to that of its zero points set plus one. Several concrete examples of such functions whose Box dimension can take any numbers belonging to [1,2] have also been given. This work may provide new approaches to the construction of various local fractal functions with the required Box dimension in the future.

CFLOBDDs: Context-Free-Language Ordered Binary Decision Diagrams

This article presents a new compressed representation of Boolean functions, called CFLOBDDs (for Context-Free-Language Ordered Binary Decision Diagrams). They are essentially a plug-compatible alternative to BDDs (Binary Decision Diagrams), and hence are useful for representing certain classes of functions, matrices, graphs, relations, and so forth in a highly compressed fashion. CFLOBDDs share many of the good properties of BDDs, but—in the best case—the CFLOBDD for a Boolean function can be exponentially smaller than any BDD for that function . Compared with the size of the decision tree for a function, a CFLOBDD—again, in the best case—can give a double-exponential reduction in size . They have the potential to permit applications to (i) execute much faster and (ii) handle much larger problem instances than has been possible heretofore. We applied CFLOBDDs in quantum-circuit simulation and found that for several standard problems, the improvement in scalability, compared to BDDs, is quite dramatic. With a 15-minute timeout, the number of qubits that CFLOBDDs can handle are 65,536 for Greenberger-Horne-Zellinger, 524,288 for Bernstein-Vazirani, 4,194,304 for Deutsch-Jozsa, and 4,096 for Grover’s algorithm, besting BDDs by factors of 128×, 1,024×, 8,192×, and 128×, respectively.

Quantum copy-protection of compute-and-compare programs in the quantum random oracle model

Copy-protection allows a software distributor to encode a program in such a way that it can be evaluated on any input, yet it cannot be "pirated" – a notion that is impossible to achieve in a classical setting. Aaronson (CCC 2009) initiated the formal study of quantum copy-protection schemes, and speculated that quantum cryptography could offer a solution to the problem thanks to the quantum no-cloning theorem. In this work, we introduce a quantum copy-protection scheme for a large class of evasive functions known as "compute-and-compare programs" – a more expressive generalization of point functions. A compute-and-compare program CC[f,y] is specified by a function f and a string y within its range: on input x, CC[f,y] outputs 1, if f(x)=y, and 0 otherwise. We prove that our scheme achieves non-trivial security against fully malicious adversaries in the quantum random oracle model (QROM), which makes it the first copy-protection scheme to enjoy any level of provable security in a standard cryptographic model. As a complementary result, we show that the same scheme fulfils a weaker notion of software protection, called "secure software leasing", introduced very recently by Ananth and La Placa (eprint 2020), with a standard security bound in the QROM, i.e. guaranteeing negligible adversarial advantage. Finally, as a third contribution, we elucidate the relationship between unclonable encryption and copy-protection for multi-bit output point functions.

DeepPPAPredMut: deep ensemble method for predicting the binding affinity change in protein-protein complexes upon mutation.

Protein-protein interactions underpin many cellular processes and their disruption due to mutations can lead to diseases. With the evolution of protein structure prediction methods like AlphaFold2 and the availability of extensive experimental affinity data, there is a pressing need for updated computational tools that can efficiently predict changes in binding affinity caused by mutations in protein-protein complexes. We developed a deep ensemble model that leverages protein sequences, predicted structure-based features, and protein functional classes to accurately predict the change in binding affinity due to mutations. The model achieved a correlation of 0.97 and a mean absolute error (MAE) of 0.35 kcal/mol on the training dataset, and maintained robust performance on the test set with a correlation of 0.72 and a MAE of 0.83 kcal/mol. Further validation using Leave-One-Out Complex (LOOC) cross-validation exhibited a correlation of 0.83 and a MAE of 0.51 kcal/mol, indicating consistent performance. https://web.iitm.ac.in/bioinfo2/DeepPPAPredMut/index.html.

On Second-Order Derivatives of Boolean Functions and Cubic APN Permutations in Even Dimension

The big APN problem is one of the most important challenges in the theory of Boolean functions, i.e. finding a new APN permutation in even dimension. Among this class of functions, those with the lowest possible degree are cubic. Yet, none has been found so far. In this paper, we introduce new parameters for Boolean functions and for vectorial Boolean functions, mostly derived from the behavior of their second-order derivatives. These parameters are invariant under extended affine equivalence, and they are particularly relevant for small-degree functions. They allow studying bent, semi-bent and APN functions of degrees two and three. In particular, they allow tackling the big APN problem for cubic permutations. Notably, we focus on the case of dimension 8, providing some computational results.

Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension

BackgroundThe treatment of pulmonary hypertension (PH) has improved rapidly in recent decades. There is increasing evidence to support the role of early intervention and treatment in affecting clinical outcomes in...

Effectiveness of a Prostacyclin IP Receptor Agonist in Patients With Pulmonary Arterial Hypertension in the Real-world Andalusian Setting: The RAMPHA Study

PurposeThe pillar for therapeutic decisions in the evolution of pulmonary arterial hypertension (PAH) is the patients’ prognostic stratification. MethodsA retrospective cohort study was conducted in a Spanish real-world setting to assess the clinical improvement of PAH patients treated with selexipag measured as changes in the risk profile. Secondary objectives were to describe their baseline characteristics, initial risk status, and variables used to assess patient survival and adverse events. FindingsTotal 42 patients (mean age 52.36 [SD: 15.09] years) were included. All had received initial endothelin receptor antagonist treatment and 95.2% dual therapy with phosphodiesterase-5 inhibitor or riociguat. At 6 to 12 months from baseline, patients risk stratification tripled the percentage of patients with low risk, and a trend towards improved risk stratification (P = 0.122). World Health Organization functional class changed, with more patients in milder classes (P = 0.003), and symptom progression slowed down (P < 0.0001). At 3-years, survival was 85.7% and the estimated median survival time was 2.73 years (SD: 1.351; 95% CI: 2.51–2.95). ImplicationsSelexipag did not achieve a significant improvement in risk profile, although it did show an excellent survival rate, effectively improved functional class, and delayed symptom progression in real life. Selexipag was well tolerated and showed a favorable safety profile, supporting a clinical benefit for PAH patients.

COMPARATIVE ANALYSIS OF ERGOSPYROMETRIC VARIABLES BETWEEN SEDENTARY AND NON-SEDENTARY PATIENTS WITH METABOLIC SYNDROME AND ESTABLISHED CARDIOVASCULAR DISEASE

Objective: To analyze the ergospirometric prognostic variables of VO2MAX, OUES, SLOPE VE/VCO2, and ventilatory class, between sedentary and non-sedentary patients with metabolic syndrome all suffering from any kind of established cardiovascular disease. Design and method: From November 2022 to September 2023, 99 patients, with an average age of 70 years, 51.5% women and 48.5% men, underwent an ergospirometry study. They were divided into two groups: sedentary (SP) and non-sedentary (NSP) according to the responses obtained from the IPAQ survey. Subsequently, the ergospirometric variables that measure cardiorespiratory and cardiovascular capacity related to maximum exercise capacity O2 metabolism (VO2MAX), the increase in oxygen consumption according to minute ventilation (OUES) and the response to ventilation according to CO2 production (slope VE/VCO2) were analyzed in both groups. For statistical analysis, the Student's t test and the Fisher exact test were used. The R v4.0.3 software was used. Results: The level of exercise was low in 56 (56.6%) and moderate or high in 43 patients. (43.4%). The NSP group presented higher levels of maximum oxygen consumption (18.3 vs 12.7, p=0.001), higher mean percentage of OUES (92 vs 63.9, p=0.001) and lower mean VE/VCO2 SLOPE ratio (26 vs 31, p=0.001). Among the NSP, 14% were found in ventilatory class 2 and 86% in class 3 and in the SP, 25% were found in class 1, 21.4% in class 2, and 48.2% in class 3. Although that a high percentage of NSP were in functional class 3 (86%) the same presented better values than those SP with better ventilatory class. We did not obtain statistical differences between both groups with respect to their underlying cardiovascular pathologies. Conclusions: A sedentary lifestyle is associated with higher erogospirometric variables risk in patients with metabolic syndrome and established cardiovascular disease. The level of physical activity is a factor that modifies this cardiovascular risk. Ergospirometry is an effective tool to measure cardiovascular prognosis.

Characteristics Associated with Ventricular Tachyarrhythmias and Their Prognostic Impact in Heart Failure with Mildly Reduced Ejection Fraction.

Background: The occurrence of ventricular tachyarrhythmias represents an established risk factor of mortality in heart failure (HF). However, data concerning their prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF) is limited. Therefore, the present study aims to investigate patient characteristics associated with ventricular tachyarrhythmias and their prognostic impact in patients with HFmrEF. Methods: Consecutive patients hospitalized with HFmrEF (i.e., left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. The prognosis of patients with HFmrEF and different types of ventricular tachyarrhythmias (i.e., non-sustained ventricular tachycardia (nsVT), sustained VT (sVT), and ventricular fibrillation (VF) was investigated for the primary endpoint of long-term all-cause mortality at 30 months. Secondary endpoints included in-hospital all-cause mortality and long-term HF-related rehospitalization at 30 months. Results: From a total of 2184 patients with HFmrEF, 4.4% experienced ventricular tachyarrhythmias (i.e., 2.0% nsVT, 0.7% sVT, and 1.6% VF). The occurrence of nsVT was associated with higher New York Heart Association (NYHA) functional class, whereas the incidence of sVT/VF was associated with acute myocardial infarction and ischemic heart disease. However, nsVT (25.0%; HR = 0.760; 95% CI 0.419-1.380; p = 0.367) and sVT/VF (28.8%; HR = 0.928; 95% CI 0.556-1.549; p = 0.776) were not associated with a higher risk of long-term all-cause mortality compared to patients with HFmrEF without ventricular tachyarrhythmias (31.5%). In-hospital cardiovascular mortality was more frequently observed in patients with HFmrEF and sVT/VF compared to those with HFmrEF but without sustained ventricular tachyarrhythmias (7.7% vs. 1.5%; p = 0.004). Finally, the risk of rehospitalization for worsening HF was not affected by the presence of ventricular tachyarrhythmias. Conclusions: The occurrence of ventricular tachyarrhythmias in patients hospitalized with HFmrEF was low and not associated with long-term prognosis.

Ventilatory Variability Is Increased at Rest in Pulmonary Arterial Hypertension

Ventilatory instability is associated with adverse outcomes in left heart failure, with periodic breathing during awake, rest, sleep and exercise (exercise oscillatory ventilation) associated with increased mortality. Increased peripheral and central chemoreflex sensitivities and impairment of cardiac output have been implicated as causative mechanisms of ventilatory instability in heart failure. As these factors are also present in pulmonary arterial hypertension (PAH), we tested the hypothesis that variability of breath-by-breath ventilation at rest would be increased in PAH compared with healthy controls. In fourteen patients with PAH (9 female, age 48.4±12.8 years, mean ± SD) and 14 healthy participants (9 female, age 49.4±14.2 years) breath-by-breath measurement of tidal volume and breathing frequency was undertaken with a pneumotachometer connected via a mouthpiece with nose-clip for 10 minutes while they rested awake and supine. Ventilatory (V̇E) variability was assessed using root mean square of successive differences (RMSSD), standard deviation (SD), average real variability (ARV, i.e., sum of absolute differences in successive observations), coeffcient of variation (CoV), as well as Poincaré analysis and compared between PAH and healthy controls (Student’s t-test). Correlations between measures of ventilatory variability and pulmonary hemodynamic characteristics, exercise capacity and function were assessed with Pearson’s correlation coeffcient. Resting V̇E was higher in PAH compared to healthy controls (14.3±1.1 and 12.1±0.5 L·min−1 respectively; p=0.009). Measures of variability for V̇E were increased in PAH compared to healthy controls. More specifically, RMSSD (3.59±1.36 vs. 2.48±0.87 L·min−1, p=0.017), SD (2.92±1.14 vs. 1.98±0.53 L·min−1, p=0.012), ARV (2.47±0.97 vs. 1.67±0.60 L·min−1, p=0.016), Poincaré SD1 (short-term variability, p=0.020) and SD2 (long-term variability, p=0.028) were increased in PAH compared to healthy controls, respectively. No correlations were found between measures of ventilatory variability and pulmonary hemodynamics (mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac output), six-minute walk distance or WHO functional class. In summary, resting ventilatory variability is increased in PAH and not associated with haemodynamic factors and exercise capacity. Whether such raised ventilatory variability in PAH is related to increased chemoreflex sensitivity requires exploration. This study received funding support from the Greenlane Research and Educational Fund (21/01/4153), Health Research Council of New Zealand (19/687), and the Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Вибір блокатора ренін-ангіотензин-альдостеронової системи для лікування серцевої недостатності при гострому міокардиті

Вибір блокатора ренін-ангіотензин-альдостеронової системи для лікування серцевої недостатності при гострому міокардиті

Clinical and Electrophysiological Outcomes of Left Bundle Area Pacing Compared to Biventricular Pacing: An Updated Meta-analysis.

Left bundle branch area pacing (LBBAP) is a novel pacing strategy that uses the conduction system distal to the left bundle branch block level for direct activation of the left bundle and right ventricular myocardium. Our meta-analysis compared the structural, electrophysiological, clinical, and procedural outcomes of LBBAP and biventricular pacing (BVP). The meta-analysis included two randomized controlled trials and showed significant reductions in the left ventricular (LV) systolic and diastolic volumes with LBBAP compared to BVP, together with statistically significant reductions in the QRS duration, New York Heart Association (NYHA) functional class, and heart failure (HF) hospitalizations. The fluoroscopic time was also significantly shorter in the LBBAP group. However, no significant change in the LV ejection fraction was noted. Procedural complications were slightly higher in the LBBAP group, albeit not to a statistically significant degree. Our findings suggest that LBBAP may be a superior alternative to standard BVP in improving the structural, electrophysiological, and clinical components of cardiomyopathy, including the NYHA class and HF hospitalizations. LBBAP is a more physiological pacing strategy that results in normal ventricular activation and may be a viable alternative to BVP for cardiac synchronization therapy.

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis

BackgroundDespite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy...

Hydrodynamic density functional theory of simple dissipative fluids

In this paper, a statistical physical derivation of thermodynamically consistent fluid mechanical equations is presented for non-isothermal viscous molecular fluids. The coarse-graining process is based on (i) the adiabatic expansion of the one-particle probability density function around local thermodynamic equilibrium, (ii) the assumption of decoupled particle positions and momenta, and (iii) the variational principle. It is shown that there exists a class of free energy functionals for which the conventional thermodynamic formalism can be naturally adopted for non-equilibrium scenarios, and describes entropy monotonic fluid flow in isolated systems. Furthermore, the analysis of the general continuum equations revealed the possibility of a non-local transport mode of energy in highly compressible dense fluids.

On application of Gaussian kernels and Laplace functions combined with Kolmogorov's theorem for approximation of functions of several variables

A special class of approximations of measurable functions of several variables on the unit coordinate cube is investigated. The class is constructed on the base of Kolmogorov's theorem (in version by Sprecher–Golubkov) stating that a continuous function $f$ of several variables can be represented as a finite superposition of continuous single-variable functions — so called outer functions (which depend of $f$) and inner one $\Psi$ (which is independent of $f$ and is monotone). In the case of continuous functions $f$ the class under study is obtained with outer functions approximated by linear combinations of quadratic exponentials (also known as Gaussian functions or Gaussian kernels) and with the inner function $\Psi$ approximated by Laplace functions. As is known, a measurable function $f$ can be approximated by a continuous one (up to a set of small measure) with the help of classical Luzin's theorem. The effectiveness of such approach is based on assertions that, firstly, the Mexican hat mother wavelet on any fixed bounded interval can be approximated as accurately as desired by a linear combination of two Gaussian functions, and, secondly, that a continuous monotone function on such an interval can be approximated as accurately as desired by a linear combination of translations and dilations of the Laplace integral (in other words, Laplace functions). It is proved that the class of approximations under study is dense everywhere in the class of continuous multivariable functions on the coordinate cube. For the case of continuous and piecewise continuous functions of two variables, numerical results are presented that confirm the effectiveness of approximations of the studied class.

Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial

Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways. We aimed to evaluate the efficacy and safety of seralutinib in patients with PAH receiving standard background therapy. The TORREY trial was a phase 2, randomised, multicentre, multinational, double-blind, placebo-controlled study. Patients with PAH from 40 hospital and community sites were randomly assigned 1:1 via interactive response technologies to receive seralutinib (60 mg twice daily for 2 weeks, then increased to 90 mg twice daily as tolerated) or placebo by dry powder inhaler twice daily for 24 weeks. Randomisation was stratified by baseline pulmonary vascular resistance (PVR; <800 dyne·s/cm5 and ≥800 dyne·s/cm5). Patients were eligible if classified as WHO Group 1 PH (PAH), WHO Functional Class II or III, with a PVR of 400 dyne·s/cm5 or more, and a 6 min walk distance of between 150 m and 550 m. The primary endpoint was change in PVR from baseline to 24 weeks. Analyses for efficacy endpoints were conducted in randomly assigned patients (intention-to-treat population). Safety analyses included all patients who received the study drug. TORREY was registered with ClinicalTrials.gov (NCT04456998) and EudraCT (2019-002669-37) and is completed. From Nov 12, 2020, to April 20, 2022, 151 patients were screened for eligibility, and following exclusions, 86 adults receiving PAH background therapy were randomly assigned to seralutinib (n=44; four male, 40 female) or placebo (n=42; four male, 38 female), and comprised the intention-to-treat population. At baseline, treatment groups were balanced except for a higher representation of WHO Functional Class II patients in the seralutinib group. The least squares mean change from baseline to week 24 in PVR was 21·2 dyne·s/cm5 (95% CI -37·4 to 79·8) for the placebo group and -74·9 dyne·s/cm5 (-139·7 to -10·2) for the seralutinib group. The least squares mean difference between the seralutinib and placebo groups for change in PVR was -96·1 dyne·s/cm5 (95% CI -183·5 to -8·8; p=0·03). The most common treatment-emergent adverse event in both treatment groups was cough: 16 (38%) of 42 patients in the placebo group; 19 (43%) of 44 patients in the seralutinib group. Treatment with inhaled seralutinib significantly decreased PVR, meeting the primary endpoint of the study among patients receiving background therapy for PAH. Gossamer Bio.

Характеристика пацієнтів з ішемічною хворобою серця та стабільною стенокардією в Україні, оцінка підходів до їх лікування за даними багатоцентрового дослідження GO-OD

Treatment of coronary artery disease (CAD) and stable angina, includes lifestyle modification, pharmacological therapy and invasive interventions to achieve stabilization or regression of the disease. Knowledge of the current situation regarding the use of pharmacological therapy and evaluation of its effectiveness is necessary for further management optimization. Trimetazidine (TMZ) has previously been shown to reduce angina symptoms and increase exercise tolerance in patients with CAD and stable angina and may be among an option for optimizing antianginal treatment. However, the effectiveness of long-term treatment depends on patient adherence, so the use of TMZ once daily (OD) at a dose of 80 mg may improve satisfaction and adherence in patients with CAD and stable angina.Methods. The GO-OD study is a 3-month, non-interventional, observational, multicenter prospective study conducted in Ukraine in a real-world outpatient cardiology practice during February – August 2021. Physicians were instructed to continue monitoring and treating patients in accordance with usual practice and international guidelines. No additional diagnostic or monitoring procedures were performed. Clinical, instrumental and laboratory data, frequency of angina attacks, consumption of short-acting nitrates (SAN), adherence to antianginal drugs, as well as the overall efficacy, tolerability of TMZ OD 80 mg in real-world clinical practice were analyzed. The observation includes regular assessment of patients` clinical status, treatment optimization and its effectiveness at follow up visits.Results. The study included 1529 patients (mean age 62.5 years, 56 % men). In the absence of adequate control of risk factors, pharmacological control of symptoms, and limited use of interventional and surgical treatments, the frequency of angina episodes was high, most patients had a pronounced angina functional class according to the Canadian Society of Cardiology classification (10.5 % – CCS I, 60.1 % – CCS II, 29.5 % – CCS III). Thus, the average number of angina attacks per week in CCS I was 3.7, in CCS II – 5.2, and in CCS III – 7, 97 attacks. In addition to the severity of symptoms, the following pattern was observed: the higher the angina class, the more risk factors and comorbidities patients had. After 3 months of follow-up due to optimization of therapy, there was a significant (p&lt;0.001) decrease in the frequency of angina attacks – from (5.8±4.7 to 1.6±2.0)/week, and the use of SAN – from (4.2±4.3 to 0.8±1.6)/week). At the same time, in 3 month the % of patients with CCS II and III significantly decreased, while the % of patients with CCS I increased (48.4 % – CCS I, 45.7 % – CCS II, 6 % – CCS III). Adherence to medication was improved: 49 % of patients reported high adherence (vs. 18 % at baseline) and 12 % – low adherence (vs. 52 % at baseline). After 3 months of follow-up most of doctors rated the overall tolerability and effectiveness of the therapy as «very satisfied». Patients’ satisfaction with TMZ OD 80 mg therapy after 3 months of follow-up was 9.5 points [on a scale of 1 to 10 (very satisfied)]. Patients’ assessment of daily physical activity increased significantly: 2.42 versus 5.89 points at baseline (on a scale of 1 to 10 (severe limitation)).Conclusions. In general, the management of outpatients with CAD and stable angina in the current cardiologists’ practice, which was complicated by the COVID-19 pandemic, was not effective enough, resulting in a high frequency of angina attacks – almost 6 per week, and a significant limitation of daily activity due to angina symptoms.Significant deficiency in the management of studied population was insufficient correction of such important risk factors as hypertension, heart rate, dyslipidemia, and lifestyle-related risk factors (overweight and obesity, low level of physical activity). The baseline therapy of patients in the study was in line with current guidelines, but with an insufficient frequency of statin prescription (78 %) and ACE inhibitors (54.5 %); antianginal treatment with an average of 2 or more antianginal drugs was not optimal for controlling angina symptoms, and the frequency of coronary revascularization procedures was also insufficient, mostly during acute MI (58.0 %).Optimization of drug therapy as the first step in correcting the condition of patients with CAD and stable angina in accordance with all current recommendations with the inclusion of the original trimetazidine OD 80 mg once daily among antianginal drugs, as well as active monitoring of patients for 3 months allowed to reduce the frequency of angina attacks regardless of its initial FC, increase patient adherence to treatment and their functional activity.