Type Of Switch Research Articles

NCOR1 orchestrates macrophage inflammation in heart failure with preserved ejection fraction: a translational study

Abstract Background/Introduction Inflammatory response is a key player in heart failure with preserved ejection fraction (HFpEF) but the underlying mechanisms are poorly understood. Recent studies have shown a critical involvement of cardiac macrophage activation in myocardial remodeling thus contributing to HFpEF. Purpose To investigate the role of cardiac macrophage inflammation in experimental and human HFpEF. Methods We employed a translational approach combining human and murine LV myocardial tissue, FACS analysis of cardiac immune cells, in vitro experiments in RAW 264.7 cells exposed to metabolic stress by palmitic acid (PA), bone marrow-derived macrophages from healthy and HFpEF mice, cardiomyocytes (H9c2), endothelial cells (HAECs) as well as ex vivo functional analyses in LV tissues. Human LV myocardial samples were used to evaluate the pro-inflammatory activity of macrophages in the HFpEF myocardium. Induction of HFpEF in mice was done through a validated mouse model combining metabolic (high-fat diet) and hemodynamic stress (L-NAME). Cardiac function was investigated by high resolution ultrasound imaging (Vevo3100) and the LV myocardial samples were used to study the macrophage polarization and their inflammatory activity. Based on interrogation of available RNA-seq datasets – showing the transcriptional repressor NCOR1 as a relevant signature in macrophages during cardiac inflammation, we generated myeloid cell-specific NCOR1 knockout (Ncor1-KO) transgenic mice to investigate the in vivo effects of NCOR1 deletion on the HFpEF phenotype. Results The expression of macrophage markers in human LV specimens showed an increase in pro-inflammatory macrophages (M1) and a decrease in regulatory macrophages (M2) as compared to age-matched control mice. HFpEF mice showed increased expression of vascular adhesion molecules (ICAM1, ICAM2, E-selectin) and a significant recruitment of M1 macrophages as proved by qPCR, WB, and flow cytometry analysis. Of interest, diastolic dysfunction - assessed by E/A ratio and isovolumic relaxation time (IVRT) – and lung congestion were significantly reduced in mice with macrophage NCOR1 deletion as compared to WT littermates, while exercise tolerance was significantly improved. These findings were associated with a reduction of myocardial inflammation (TNF-a, IL6, IL-1b) in Ncor1-KO mice. In vitro assays showed that stimulation of macrophages with PA induced M1 type switch and increased NCOR1, TNF-a, IL-6, and IL-1b levels, whereas NCOR1 depletion prevented detrimental changes of macrophage secretome (Fig.2). Conclusion NCOR1 is a crucial regulator of immune response and macrophage inflammation in the heart. Our findings highlight its potential as a target for therapies aimed at preventing myocardial damage in HFpEF.

Pengaruh Kualitas Layanan terhadap Loyalitas dengan Kepuasan Nasabah sebagai Variabel Mediasi

Customer satisfaction has become a central concept in marketing theory and practice, and is one of the essential goals for business activities. Basically, customer satisfaction and dissatisfaction with a product or service will affect subsequent customer behavior. Customers who are satisfied will show a high probability of customers returning to use the same product or service. According to Syah (2021), satisfied customers also tend to provide good references to the product or service to others. Meanwhile, dissatisfied customers can cause negative attitudes towards the brand or manufacturer or service provider, even distributors, reduced likelihood of repeat purchases, brand switching, and various types of complaint behavior.

Разработка рекомендаций по применению трамвайных стрелочных переводов при различных условиях эксплуатации

Purpose: To consider the design features of single-blade and double-blade arrows, as well as double-blade arrows with flexible blades, the operating conditions of tram switches when placing tram nodes on the line and on the territory of tram parks. Methods: The analysis of the main operational and economic indicators of switches is carried out, taking into account the advantages and disadvantages of various types of arrow designs of the tram industry in St. Petersburg, including those requiring speed limits of tram cars when moving along the arrows. Results: Recommendations have been developed for the use of switches of various designs, depending on their operating conditions, load stress, speed of movement of rolling stock for safe passage along them, placement on the line on a combined, independent or separate track and in tram fleets, taking into account the complexity of replacing worn parts, as well as the need to ensure the required track development in the presence of cramped conditions. The proposed recommendations will allow the use of switches in accordance with modern requirements for tram crossings, which ensure comfortable movement of passengers. Practical importance: Considering the fact that economic indicators, along with the technical characteristics of switch designs and operational capabilities of track sections, are one of the main criteria for evaluating decision-making, it is proposed to use methodology for accounting for economic indicators based on determining the cost of the life cycle to justify the effectiveness of using a particular type of switch in the design and operation of tramways paths in specific conditions.

Switching of three-dimensional optical cages using spatial coherence engineering

Precisely capturing and manipulating microparticles is the key to exploring microscopic mysteries. Optical tweezers play a crucial role in facilitating these tasks. However, existing optical tweezers are limited by their dependence on specific beam modes, which restrict their ability to flexibly switch and manipulate optical traps, thereby limiting their application in complex scientific challenges. Here, we propose a new method to achieve type switching and manipulation of optical traps using a single structured beam via optical coherence engineering. A conjugate-model random structured beam with a switch is designed. By altering the state of the switch, we can change the type of optical cage, enabling the capture of different particle types. Furthermore, the range, strength, and position of the optical trap can be controlled by adjusting the initial beam parameters. We hope that optical coherence engineering will extend the capabilities of existing structured optical tweezers, paving the way for advances in future optical tweezers applications.

Molecular switching by proton-coupled electron transport drives giant negative differential resistance

To develop new types of dynamic molecular devices with atomic-scale control over electronic function, new types of molecular switches are needed with time-dependent switching probabilities. We report such a molecular switch based on proton-coupled electron transfer (PCET) reaction with giant hysteric negative differential resistance (NDR) with peak-to-valley ratios of 120 ± 6.6 and memory on/off ratios of (2.4 ± 0.6) × 103. The switching dynamics probabilities are modulated by bias voltage sweep rate and can also be controlled by pH and relative humidity, confirmed by kinetic isotope effect measurements. The demonstrated dynamical and environment-specific modulation of giant NDR and memory effects provide new opportunities for bioelectronics and artificial neural networks.

Trajectories of daily antipsychotic use and weight gain in people hospitalized for the first episode of psychosis.

We need to better understand the risk factors and predictors of medication-related weight gain to improve metabolic health of individuals with schizophrenia. This study explores how trajectories of antipsychotic medication (AP) use impact body weight early in the course of schizophrenia. We recruited 92 participants with first-episode psychosis (FEP, n=92) during their first psychiatric hospitalization. We prospectively collected weight, body mass index (BMI), metabolic markers, and exact daily medication exposure during 6-week hospitalization. We quantified the trajectory of AP medication changes and AP polypharmacy using a novel approach based on meta-analytical ranking of medications and tested it as a predictor of weight gain together with traditional risk factors. Most people started treatment with risperidone (n=57), followed by olanzapine (n=29). Then, 48% of individuals remained on their first prescribed medication, while 33% of people remained on monotherapy. Almost half of the individuals (39/92) experienced escalation of medications, mostly switch to AP polypharmacy (90%). Only baseline BMI was a predictor of BMI change. Individuals in the top tercile of weight gain, compared to those in the bottom tercile, showed lower follow-up symptoms, a trend for longer prehospitalization antipsychotic treatment, and greater exposure to metabolically problematic medications. Early in the course of illness, during inpatient treatment, baseline BMI is the strongest and earliest predictor of weight gain on APs and is a better predictor than type of medication, polypharmacy, or medication switches. Baseline BMI predicted weight change over a period of weeks, when other traditional predictors demonstrated a much smaller effect.

Intermittent dynamics identification and prediction from experimental data of discrete-mode semiconductor lasers by reservoir computing

Analysis of intermittent dynamics from experimental data is essential to promote the understanding of practical complex nonlinear systems and their underlying physical mechanisms. In this paper, reservoir computing enabled dynamics prediction, and identification of two types of intermittent switching using experimental data from discrete-mode semiconductor lasers are rigorously studied and demonstrated. The results show that, for the dynamics prediction task, both regular and irregular intermittent switching can be predicted reliably by reservoir computing, achieving the average normalized mean-square error of less than 0.015. Additionally, the impact of the number of virtual nodes in the reservoir layer, as well as the train-test split ratio on prediction performance, is explored. For the dynamic identification task, a 2-class classification test is adopted, and the corresponding binary accuracy is calculated to evaluate the identification performance. The results demonstrate that the accuracy of identifying both regular and irregular intermittent switching exceeds 0.996. Compared with the conventional amplitude threshold identification method, the reservoir computing-driven dynamics identification method exhibits superior accuracy, especially in the intermittent transient transition regions.

Finite automated system to design a high efficiency LLC resonant converter system for 3 kW. PV solar array

A combination of electrical circuit design and the Finite Automation model leads to improved efficiency in terms of memory usage, computation time, and overall performance. LLC resonant converters are known for their high efficiency and ability to convert DC voltage from solar panels into the desired AC voltage for grid-tied or off-grid PV systems. However, designing, testing, and implementing LLC in a PV system requires careful consideration of various factors, including voltage and current requirements, resonant frequency, and compliance with standards and regulations. Eight cases are taken for this purpose with a special case of a 3kW-PV module. The major parameters for the LLC resonant Converter were 480-500V. as output voltage for 36-40V. input voltage range with a 39V. nominal voltage. The calculated coefficients for these values were as follows: A = C = 7.29, B = -50.58, D = -0.25, and E = -11. Combining LLC circuit design with FA, it is providing 94.5 % efficiency through selecting precise parameters that minimized overall calculated losses such as conductive and switching types. The right path and accepted words for different cases are given to provide several solutions with the correct path of design. ZVS and ZCS have been obtained through precise selection process of phase shift between Half Bridge of LLC circuit achieved by this design.

Discrete-Time Sliding Mode Control Strategies—State of the Art

Variable structure control systems are known to provide a high level of robustness to external disturbances and modeling uncertainties with comparably low computational complexity. Thanks to these features, they have found applications in various fields, such as power engineering, electronics, robotics, and aviation. In recent decades, the field of sliding mode control has developed significantly. Therefore, this study aims to discuss the basic concepts and design methodology of such strategies. Although in the 20th century, continuous-time sliding mode control has been the center of the control engineering society’s attention, it has certain major shortcomings. In particular, such control schemes result in undesirable high-frequency oscillations when applied digitally. Therefore, the more recent discrete-time approach to sliding mode control has gained recognition in the 21st century. Since the introduction of discrete-time sliding mode control strategies, the reaching law-based controller design method has been designed, within which two main paradigms may be named: the switching type and the nonswitching type quasi-sliding mode. This paper presents a broad review of the discrete-time sliding mode control strategies, starting from the definition of sliding mode through the controller design procedures and up to potential applications. The aim of this study is to provide an up-to-date state of the art and introduce readers to the newest trends and achievements in the field of sliding mode control.

On the motivation for pharmaceutical manufacturer coupons: Brand loyalty or customer acquisition?

To generate evidence regarding the offensive (customer acquisition) versus defensive (customer retention) motivation for pharmaceutical manufacturer coupons. Retail prescriptions from IQVIA's Formulary Impact Analyzer data between 2017 and 2019. Ordinary least squares regression models with person, therapeutic class, drug, and time-fixed effects to measure the association between switching medications and coupon usage as well as the association between patient out-of-pocket spending and switching to a drug and using a coupon. To study switching type heterogeneity, reanalysis of associations for any type of switch, generic-brand switches, and brand-brand switches. Reestimation of baseline analyses for sodium-glucose cotransporter-2 inhibitors, anticoagulants, and inhaled corticosteroids/long-acting beta2-agonists to assess heterogeneity by drug class and market maturity. 1,167,132 privately insured patients that utilized at least one coupon between 2017 and 2019 for one or more prescriptions. Coupon usage was associated with a 1.0 percentage point reduction in any kind of drug switch in the full sample and by 0.65-2.9 percentage points for the drug class subgroups. However, these estimates are governed by market dynamics; the probability of switching increased by 40% on the first coupon usage before declining by more than 50% on subsequent coupons. Switching after the first coupon use may be explained by systematic savings implied by coupon use; we find coupons reduced patient out-of-pocket spending by $45.00 (i.e., the majority of patient out-of-pocket costs). In subgroup analyses, coupon savings were $6.43 larger than average for anticoagulants, characterized by the highest levels of brand and generic competition among the considered therapeutic classes. Pharmaceutical manufacturers may be using coupons to acquire customers and then build brand loyalty, especially in markets with more generic competition. Antitrust authorities and other regulators should scrutinize the impact of coupons on market competitiveness and drug spending.

Manufacturer-sponsored drug coupon use and drug-switching behavior among patients with type 2 diabetes.

Patients often use manufacturer-sponsored coupons to reduce their out-of-pocket spending. However, little is known whether coupon use is associated with medication-switching behaviors. To examine if using a manufacturer-sponsored coupon to initiate a medication is associated with patterns of medication-switching behaviors among patients with type 2 diabetes. Using IQVIA's retail pharmacy claims data from October 2017 to September 2019, we analyzed commercially insured patients with type 2 diabetes who had newly started taking the following noninsulin diabetes drugs: generic metformin (nearly no coupon use), Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors (SGLT2, high coupon use), and dipeptidyl peptidase IV inhibitors (DPP-IV inhibitors, moderate coupon use). We assessed if drug-switching behaviors, defined as no switching, switching to a same-class drug, or switching to a drug in a different class, differed among patients who did and did not use coupons to initiate treatments. We performed multinomial logistic regression to estimate the probability of each switching type associated with patients' initial coupon use. Among 9,781 patients in our sample, 83.7% of them initiated treatments with metformin, 8.2% with SGLT2, and 8.1% with DPP-IV inhibitors. The overall switching rate was the lowest for generic metformin (40%) than brand-name drugs (56%-57%). Among the brand-name drug users, patients who used a coupon to initiate these drugs were less likely to switch to any drug compared with patients without coupon use (SGLT2 = -18% [95% CI = -24% to -13%]; DPP-IV inhibitors = -9% [-16% to -2%]). These patients were also less likely to switch to drugs in other competing classes (SGLT2 = -16% [95% CI = -22% to -10%]; DPP-IV inhibitors = -9% [-16% to -2%]). Patients who started their treatment with generic metformin had the lowest rate of drug switching. Using coupons to initiate brand-name drugs in classes with prevalent coupons was associated with reduced medication switching to other class drugs.

Types of Code-Switching Found in The Friday Podcast

The objective of this study is to know the various types of code switching found in The Friday Podcast, especially in episode 213. Descriptive qualitative method is used to analyse the data. This study analyzed the different types of code switching using Appel & Muysken theory of Bilingualism, as presented in their book entitled Language Contact and Bilingualism (1987). There are three types of code switching stated by Appel & Muysken. The findings of this study revealed that all three types of Code Switching were discovered in The Friday Podcast. Intra-Sentential switching is the most common sort of code-switching occurrence in The Friday Podcast. Meanwhile, Intersentential-Switching is the speaker's least dominant data. For the conclusion, the reason why intrasentential-switching got the most occurrences in this podcast because the audience of this podcast is Indonesian people who are the majority of it not really fluent in English. The speakers in this podcast also using the familiar English terms that Indonesian society frequently heard.

Making Switches: Key Strategic Decisions When Moving From a Local, Independent Operator to a Wholly Owned Subsidiary

ABSTRACTEntering a foreign market entails making the important mode decision of how to operate there. But the initial mode choice is not always forever and may be reassessed as business circumstances change. The mode shifting process—that is, how switches from one mode to another unfold—has scarcely been described, so we lack a systematic outline of this process. In this article, we take a first step toward such an outline. Adopting the established distinction between the formation and implementation phases of strategy making and execution, we describe the critical strategic decisions managers need to make about how to carry out a mode switch. Regarding the formation phases, we discuss the identification and consideration of entry mode switches as viable options, and whether companies plan or not for such shifts. Regarding the implementation phases, we differentiate between the integrating and collaborating decisions that define the type of switches made by companies.

Alih Kode dan Campur Kode Para Tokoh dalam Film Tabularasa

This research aims to describe: first, the types of code switching in the film Tabularasa, second, the types of code mixing in the film Tabularasa, and three, the factors causing code switching and code mixing in the film Tabularasa. This type of research is qualitative research using descriptive methods. The data collected in this research was then analyzed using the following steps: (1) transcribing the conversations in the film into written language, (2) identifying the data according to the format provided, (3) classifying the data into types of code switching and mixing. code, (4) classifying the factors causing code switching and code mixing in the film Tabularasa, (5) discussing research findings, and (6) drawing conclusions from the research results. There are three findings in this research. First, the types of code switching found in the Tabularasa film are internal code switching and external code switching. In this research, the most dominant type of code switching found was internal code switching, namely switching from Indonesian to Minang or vice versa. Second, the type of code mixing found in the film Tabularasa was divided into two, namely internal and external code mixing. Of the two types of code mixing, the one most often found in this film is internal code mixing, namely code mixing between Indonesian and Minang or vice versa. The three factors causing code switching found in the film Tabularasa are, (1) the speaker and the person of the speaker, (2) the speech partner, (3) the presence of a third speaker, (4) the place and time the speech is carried out, (5) the mode of conversation, and (6) conversation topic. Meanwhile, the factors causing code mixing in the film Tabularasa are due to speaker and language factors. With the largest percentage in the form of speaker factors

Impact of peer review type and editor gender on women authorships in mathematics

Abstract Aiming to explain and help reduce measured gender gaps in mathematics publications—a discipline where single anonymized peer review practices and men editors are still the norm—we study changes in authorships straddling a 2015 switch in peer review type and editor gender in the American Mathematical Monthly, one of the oldest mathematics journals in the United States. Our results show a significant increase in women authorships after the journal’s switch to a woman editor and double anonymized reviews, an increase deemed exceptional relative to growth trends in comparable journals operating under field standards (men editors along with single anonymized reviews). We leverage literature, data-based observations and our own findings to argue for the likely effects of editor gender and peer review type separately and together as it concerns both women and newcomer authorships. Our study, the first to our knowledge on editorial and peer review changes in mathematics, contributes to a small body of literature on the impact of equity practices in peer review in science and mathematics. It also serves to introduce work, methods, and open problems on measuring and reducing the global gender gap in science and mathematics.

Three types of resistive switching in ferroelectric Hf0.5Zr0.5O2 films mediated by polarization reversal and oxygen vacancy migration

Three types of resistive switching in ferroelectric Hf0.5Zr0.5O2 films mediated by polarization reversal and oxygen vacancy migration

“Me aviento el English y el Spanish”: Spanish-English code-switching in Texas conjunto artist Nick Villarreal

Aims and objectives: This study focuses on Nick Villarreal (1951–2017), a bilingual and bicultural conjunto musician from San Antonio. It ascertains the frequency, formal features, and socio-pragmatic functions of the Spanish/English code-switching found in his songs. Methodology: Quantitative and qualitative approaches are utilized to explore Nick Villarreal’s use of code-switching in song lyrics. Data and analysis: Nick Villarreal’s commercially available discography (178 non-repeated tracks) was classified by matrix language. All instances of code-switching were identified and classified by type, syntactic category, and function. Song themes were inductively analyzed. Findings: Most of Nick Villarreal’s lyrics are in Spanish (73%), while 22% contain code-switching. Lexical insertions are the most common type of switches (65%). Villarreal also employs other contact phenomena, such as fully nativized borrowings, and syntactic and semantic calques. His virtuosity is apparent in his humorous bilingualism, especially in the creative nominalizations of English clauses as nicknames (e.g., la I-didn’t-do-it). The main function performed by switches is poetic—that is, stylistic uses of language, such as rhyming, joking, and puns. He conveys authenticity through code-switching and other enregistered linguistic sources such as border slang, or caló, and working-class/rural Mexican Spanish. He shows loyalty toward a working-class rural Spanish-speaking audience of conjunto that shares his background, while simultaneously appealing to second-generation Mexican Americans through his use of English and references to Anglo culture. Originality: Only recently have scholars begun to describe the linguistic features of borderland styles. This study focuses on an artist who has never received scholarly attention before but who turned his music into a meaningful vehicle for linguistic and cultural anti-assimilatory subversion. Implications: Villarreal employs strategies common to other borderlands bilingual musicians while innovating creatively. He actively stylizes the local to evoke a sense of authenticity and is thus a meaningful example of the intersection between language representation, class allegiance, linguistic attitudes, and cultural stance.

Flipping the script: Action-plan modification during single- and multiple-action control

In this paper, we tested the idea that local changes in action demands (e.g., due to an invalid cue or trial-by-trial) result in frugal modifications of existing action plans via action-plan-modification operations. We implemented an experimental procedure making use of a cue that indicates the action requirements for an upcoming signal with a certain degree of reliability. Crucially, incongruent cue-stimulus pairs either require action-plan modification or “resetting” the prepared action plan and reselecting a new response from scratch. We systematically varied the proportion of valid cues over four experiments. There were four most basic response conditions: left button press, right button press, dual button presses, no action. Results support the concept of action-plan modification rather than reset-reselect: switching between a left and a right response was faster and less error-prone than any other type of switch, both between trials and between cue and signal. Thus, it appears that given two responses that can be conceived of as polar opposites (within the same single-action category), there is an action-plan-modification operation (“invert”) that transforms one into the other at a comparatively low cost. Furthermore, we observed a mixed pattern of dual-action costs and benefits. This indicates that participants represented dual actions holistically, that is, not based on a conjunction of single-action plans as building blocks. In addition, switching from null actions to overt actions appeared to require very similar action-plan-modification operations as other types of switches – thus, null actions are apparently not coded as empty sets, but rather represent actions in their own right. Finally, we observed strikingly similar patterns of results for trial-by-trial changes in action demands and intra-trial cue-signal incongruency. This implies that the mere cue-based formulation of an action plan – which is not actually executed – is sufficient to produce action-switching-like effects.

Sources and composition of organic matter as a tool for understanding the complex variation in paleoenvironments and the connectivity of an epicontinental basin: The Miocene in the northern Pannonian Basin

Epicontinental basins are extremely prone to major paleogeographic changes, and this will directly affect any organic matter (OM) preserved in the depositional record. In this study the Middle–Late Miocene successions in the northern Pannonian Basin System were investigated via sedimentological, petrographic, and geochemical analyses of cores from the Danube Basin to reveal the interplay of factors driving the character of the OM. In the late Middle Miocene (~12.3 Ma), the Central Paratethys Sea maintained normal marine salinity, with dysoxic bottom waters in a distal basin floor environment rich in aquatic OM. The last rifting phase followed during the Late Miocene and led to formation of the deep Lake Pannon. Like seawater, the brackish lake water still also contained sulfate. These open lacustrine deposits (~11.6–10.0 Ma) reveal OM sourced from submerged/floating macrophytes and algae, and humid conditions are indicated by the preponderance of deciduous trees and shrubs on shores. The study identifies hybrid event beds (HEBs) on Lake Pannon's floor (~10.0–9.3 Ma), with currents redepositing mud and OM, resulting in similarities between the Middle Miocene and Late Miocene successions. Turbidite deposition (~9.3–9.0 Ma) from the paleo-Danube induced a shift in OM, replacing algae with terrestrial input. Complete isolation from the main water masses of Lake Pannon (~9.0–8.9 Ma) altered its sources of OM, transitioning from algae to macrophytes, and caused a drop in salinity, likely associated with a humidity peak. The subsequent deltaic dominance (~8.9–8.6 Ma) features well-developed topset lakes, swamps, and floodplain forests, reflecting warm temperate to subtropical climates. The Middle–Upper Miocene deposits studied here are source rocks with fair to very good richness and poor to fair generative potential, and contain kerogen types III and IV, while type II is rare. The rapid paleoenvironmental changes observed over the order of ~100 kyr caused the complete switching of OM type and delivery, giving an indication of the complexity of epicontinental basins.

Safety of Pembroria® during non-medical switching from Keytruda® in patients with advanced malignant neoplasms of various localizations: the REFLECTION real-world study

Background. Post-registration observational studies with switching therapy from the original drug to a biosimilar for non-medical indications allow us to assess the safety and effectiveness of this type of switching in real clinical practice. Aim. Evaluation of the safety and effectiveness of non-medical switching from the original drug Keytruda® to the biosimilar drug Pembroria® in patients with various oncological pathologies in real clinical practice (REFLECTION). Materials and methods. A retrospective analysis of data from electronic medical records from 21 medical institutions of the Russian Federation for the period 2020–2023 was carried out. Data were included from patients with cancer of various locations who received at least 2 injections of Keytruda® followed by switching to Pembroria® for non-medical indications (at least 2 injections). Primary criteria: incidence of immune-mediated adverse reactions (ImARs) of any severity. Secondary indicators: incidence of ImARs of various degrees of severity and infusion reactions, frequency of objective response rate (according to RECIST 1.1 criteria). Results. The analysis included data from 382 patients (male/female 200/182, median age 62 years) with NSCLC (24.1%), RCC (23.3%), melanoma (20.4%) and cancer of other localization. Patients received Keytruda® on 1st and 2nd lines (54.2 and 25.4% of patients, respectively), on 3 or 4 lines (14.1%), or as part of adjuvant therapy (6.3%). 50.5% of patients received pembrolizumab as monotherapy. The median number of administrations was 7.0 and 5.0 for Keytruda® and Pembroria®, respectively. ImARs were registered in 44 (11.5%) patients (60 ImARs), including 40 ImARs in 35 (9.2%) patients while using Keytruda® and 20 ImARs in 17 (2.4%) patients with Pembroria®. The most common ImARs were hypothyroidism, hyperthyroidism, and hepatitis; the frequency of these ImARs was higher with Keytruda® (EAER for hypothyroidism 0.00422 and 0.00144, for hepatitis – 0.00124 and 0.00096, respectively). All 5 reported cases of hyperthyroidism in patients on Keytruda® (EAER 0.00124), were resolved before switching to Pembroria®. No infusion-related reactions or deaths due to ImARs have been reported. The objective response rate was comparable – 104 (32.6%) and 90 (29.2%) patients оn Keytruda® and Pembroria® therapy, respectively. Most patients maintained disease control after switching to Pembroria® [progression was recorded in 29 (9.4%) patients after switching to a biosimilar]. Conclusion. The safety profiles of Keytruda® and Pembroria® were satisfactory and comparable in this study. Switching from therapy with Keytruda® to Pembroria® is not accompanied by an increase in the frequency or severity of ImARs. Switching from Keytruda® to Pembroria® maintains disease control in most patients.