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Background. The relevance of this article is substantiated by the high interest of specialists in the field of subject-environment interactions in finding answers to questions about the abilities of the subject to interact with the spatial environment of everyday life, taking into account the psychological resourcefulness of this environment, with a focus on the potential of the spatial conditions of the living environment to ensure positive psychological functioning. Objectives. The article attempts to theoretically substantiate the possibility of using the “competence” construct in order to analyze subject-environment interactions. Methods. The analysis and systematization of theoretical and empirical research in the field of phenomenology of the subject-environment interaction was carried out (G.A. Kovalev, S.K. Nartova-Bochaver, V.I. Panov, etc.) with the focus on the possibility of referring to the methodology of the resource approach in psychology (N.E. Vodopyanova, D.A. Leontiev, V.I. Morosanova, E.A. Sergienko, V.A. Tolochek, S.A. Khazova, etc.), as well as in the field of ecopsychology of everyday life (S.E. Gabidulina, T.V. Drobysheva, A.L. Zhuravleva, O.A. Kaptsevich , S.K. Nartova-Bochaver, I.S. Samoshkina, T.V. Semenova, etc.). Results. Theoretical approaches are singled out, within the framework of which the interaction in the “environment-subject” system is operationalized with an emphasis, firstly, on the potential conditions of the spatial environment, secondly, on the individual psychological possibilities of the subject, in particular, the ability to be the subject of mental activity in determining resourcefulness of spatial environment in everyday life. The research in the field of determining the construct of “psychological resources” was analyzed as well as research connected with the description of psychological resourcefulness for the different types of living environment: urban, living, professional. The research directions of interactions between potential conditions of spatial environment of everyday life and subjectional possibilities of using these conditions as the psychological resource for optimization of psychological functioning were determined. The appeal to the construct of “competence” as a promising theoretical and applied direction of research in the field of the relationship between the subject and the spatial environment of everyday life is indicated. Conclusions. Considering statements of environmental psychology, ecopsycology of development, everyday life psychology, as well as being based on an opportunity to consider spatial environment of everyday life as a resource that is directed to the optimization of psychological well-being of the subject, it is proposed to consider competence in subject-environment interactions as the ability of the subject to transform conditions or potential of the spatial environment of everyday life into psychological resource, necessary to maintain optimal functioning.

Abstract Background Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage. The effects of HIV and smoking on pulmonary mucosal CD8 T-cell dynamics has been a neglected area of research, which we address herein. Methods Bronchoalveolar lavage (BAL) fluid were obtained from ART-treated PLWH (median duration of supressed viral load: 9 years; smokers: n = 14; non-smokers: n = 21) and HIV-uninfected controls (smokers: n = 11; non-smokers: n = 20) without any respiratory symptoms or active infection. Lymphocytes were isolated and CD8 T-cell subsets and homing markers were characterized by multiparametric flow cytometry. Results Both smoking and HIV infection were independently associated with a significant increase in frequencies of total pulmonary mucosal CD8 T-cell. BAL CD8 T-cells were primarily CD69 + expressing CD103 and/or CD49a, at least one of the two granzymes (GzmA/GzmB), and little Perforin. Higher expression levels of CD103, CD69, and GzmB were observed in smokers versus non-smokers. The ex vivo phenotype of GzmA + and GzmB + cells revealed increased expression of CD103 and CXCR6 in smokers, while PLWH displayed elevated levels of CX3CR1 compared to controls. Conclusion Smoking and HIV could promote cytotoxic CD8 T-cell retention in small airways through different mechanisms. Smoking likely increases recruitment and retention of GzmB + CD8 Trm via CXCR6 and CD103. Heightened CX3CR1 expression could be associated with CD8 non-Trm recruitment from the periphery in PLWH.

Boron-containing materials, such as hexagonal boron nitride (h-BN), recently shown to be active and selective catalysts for the oxidative dehydrogenation of propane (ODHP), have been shown to undergo significant surface oxyfunctionalization and restructuring. Although experimental ex situ studies have probed the change in chemical environment on the surface, the structural evolution of it under varying reaction conditions has not been established. Herein, we perform global optimization structure search with a grand canonical genetic algorithm to explore the chemical space of off-stoichiometric restructuring of the h-BN surface under ambient as well as ODHP-relevant conditions. A grand canonical ensemble representation of the surface is established, and the predicted 11B solid-state NMR spectra are consistent with previous experimental reports. In addition, we investigated the relative sliding of h-BN sheets and how it influences the surface chemistry with ab initio molecular dynamics simulations. The B-O linkages on the edges are found to be significantly strained during the sliding, causing the metastable sliding configurations to have higher reactivity toward the activation of propane and water.

In analogy to natural enzymes, an elaborated design of catalytic systems with a specifically tailored local chemical environment could substantially improve reaction kinetics, effectively combat catalyst poisoning effect and boost catalyst lifetime under unfavourable reaction conditions. Here we report a unique design of 'Ni(OH)2-clothed Pt-tetrapods' with an amorphous Ni(OH)2 shell as a water dissociation catalyst and a proton conductive encapsulation layer to isolate the Pt core from bulk alkaline electrolyte while ensuring efficient proton supply to the active Pt sites. This design creates a favourable local chemical environment to result in acidic-like hydrogen evolution reaction kinetics with a lowest Tafel slope of 27 mV per decade and a record-high specific activity and mass activity in alkaline electrolyte. The proton conductive Ni(OH)2 shell can also effectively reject impurity ions and retard the Oswald ripening, endowing a high tolerance to solution impurities and exceptional long-term durability that is difficult to achieve in the naked Pt catalysts. The markedly improved hydrogen evolution reaction activity and durability in an alkaline medium promise an attractive catalyst material for alkaline water electrolysers and renewable chemical fuel generation.

Electrochemical carbon capture and concentration (eCCC) offers a promising alternative to thermochemical processes as it circumvents the limitations of temperature-driven capture and release. This review will discuss a wide range of eCCC approaches, starting with the first examples reported in the 1960s and 1970s, then transitioning into more recent approaches and future outlooks. For each approach, the achievements in the field, current challenges, and opportunities for improvement will be described. This review is a comprehensive survey of the eCCC field and evaluates the chemical, theoretical, and electrochemical engineering aspects of different methods to aid in the development of modern economical eCCC technologies that can be utilized in large-scale carbon capture and sequestration (CCS) processes.

The incorporation of charged groups proximal to a redox active transition metal center can impact the local electric field, altering redox behavior and enhancing catalysis. Vanadyl salen (salen = N,N'-ethylenebis(salicylideneaminato)) complexes functionalized with a crown ether containing a nonredox active metal cation (V-Na, V-K, V-Ba, V-La, V-Ce, and V-Nd) were synthesized. The electrochemical behavior of this series of complexes was investigated by cyclic voltammetry in solvents with varying polarity and dielectric constant (ε) (acetonitrile, ε = 37.5; N,N-dimethylformamide, ε = 36.7; and dichloromethane, ε = 8.93). The vanadium(V/IV) reduction potential shifted anodically with increasing cation charge compared to a complex lacking a proximal cation (ΔE1/2 > 900 mV in acetonitrile and >700 mV in dichloromethane). In contrast, the reduction potential for all vanadyl salen-crown complexes measured in N,N-dimethylformamide was insensitive to the magnitude of the cationic charge, regardless of the electrolyte or counteranion used. Titration studies of N,N-dimethylformamide into acetonitrile resulted in cathodic shifting of the vanadium(V/IV) reduction potential with increasing concentration of N,N-dimethylformamide. Binding constants of N,N-dimethylformamide (log(KDMF)) for the series of crown complexes show increased binding affinity in the order of V-La > V-Ba > V-K > (salen)V(O), indicating an enhancement of Lewis acid/base interaction with increasing cationic charge. The redox behavior of (salen)V(O) and (salen-OMe)V(O) (salen-OMe = N,N'-ethylenebis(3-methoxysalicylideneamine) was also investigated and compared to the crown-containing complexes. For (salen-OMe)V(O), a weak association of triflate salt at the vanadium(IV) oxidation state was observed through cyclic voltammetry titration experiments, and cation dissociation upon oxidation to vanadium(V) was identified. These studies demonstrate the noninnocent role of solvent coordination and cation/anion effects on redox behavior and, by extension, the local electric field.

The superconducting hydrides LaH10, EuH9 and UH8 are studied using chemically intuitive bonding analysis of periodic and molecular models. We find trends in the crystallographic and electronic structures of the materials by focusing on chemically meaningful building blocks in the predicted H sublattices. Atomic charge calculations, using two complementary techniques, allow us to assign oxidation states to the metals and divide the H sublattice into neutral and anionic components. Cubic [H8]q- clusters are an important structural motif, and molecular orbital analysis of this cluster in isolation shows the crystal structures to be consistent with our oxidation state assignments. Crystal orbital Hamilton population analysis confirms the applicability of the cluster model to the periodic electronic structure. A Jahn-Teller distortion predicted by MO analysis rationalises the distortion observed in a prior study of EuH9. The impact of this distortion on superconductivity is determined, and implications for crystal structure prediction in other metal-hydrogen systems are discussed. Additionally, the performance of electronic structure analysis methods at high pressures are tested and recommendations for future studies are given. These results demonstrate the value of simple bonding models in rationalizing chemical structures under extreme conditions.

BackgroundThere is a strong need to determine pandemic and postpandemic challenges and effects at the individual, family, community, and societal levels. Post–COVID-19 health and psychosocial effects have long-lasting impacts on the physical and mental health and quality of life of a large proportion of survivors, especially survivors of severe and critical COVID-19, extending beyond the end of the pandemic. While research has mostly focused on the negative short- and long-term effects of COVID-19, few studies have examined the positive effects of the pandemic, such as posttraumatic growth. It is essential to study both negative and positive long-term post–COVID-19 effects and to acknowledge the role of the resources available to the individual to cope with stress and trauma. This knowledge is especially needed in understudied regions hit hard by the pandemic, such as the region of Central and Eastern Europe. A qualitative approach could provide unique insights into the subjective perspectives of survivors on their experiences with severe COVID-19 disease and its lingering impact on their lives. ObjectiveThe aim of the study is to qualitatively explore the experiences of adult survivors of severe or critical COVID-19 throughout the acute and postacute period in 5 Central and Eastern European countries (Bulgaria, Slovakia, Croatia, Romania, and Poland); gain insight into negative (post–COVID-19 condition and quality of life) and positive (posttraumatic growth) long-term post–COVID effects; and understand the role of survivors’ personal, social, and other coping resources and local sociocultural context and epidemic-related situations. MethodsThis is a qualitative thematic analysis study with an experiential reflexive perspective and inductive orientation. The analytical approach involves 2-stage data analysis: national analyses in stage 1 and international analysis in stage 2. Data are collected from adult survivors of severe and critical COVID-19 through in-depth semistructured interviews conducted in the period after hospital discharge. ResultsAs of the publication of this paper, data collection is complete. The total international sample includes 151 survivors of severe and critical COVID-19: Bulgaria (n=33, 21.8%), Slovakia (n=30, 19.9%), Croatia (n=30, 19.9%), Romania (n=30, 19.9%), and Poland (n=28, 18.5%). National-level qualitative thematic analysis is currently underway, and several papers based on national results have been published. Cross-national analysis has started in 2024. The results will be submitted for publication in the third and fourth quarters of 2024. ConclusionsThis research emphasizes the importance of a deeper understanding of the ongoing health and psychosocial challenges survivors face and what helps them cope with these challenges and, in some cases, thrive. It has implications for informing holistic care and improving the health and psychosocial outcomes of survivors of COVID-19 and will be crucial for evaluating the overall impact and multifaceted implications of the pandemic and for informing future pandemic preparedness. International Registered Report Identifier (IRRID)DERR1-10.2196/57596

Summary: Background: Despite successful antiretroviral therapy (ART), frequencies and immunological functions of memory CCR6+ Th17-polarised CD4+ T-cells are not fully restored in people with HIV (PWH). Moreover, long-lived Th17 cells contribute to HIV persistence under ART. However, the molecular mechanisms underlying these observations remain understudied. Methods: mRNA-sequencing was performed using Illumina technology on freshly FACS-sorted memory CCR6+CD4+ T-cells from successfully ART-treated (ST), elite controllers (EC), and uninfected donors (HD). Gene expression validation was performed by RT-PCR, flow cytometry, and in vitro functional assays. Findings: Decreased Th17 cell frequencies in STs and ECs versus HDs coincided with reduced Th17-lineage cytokine production in vitro. Accordingly, the RORγt/RORC2 repressor NR1D1 was upregulated, while the RORγt/RORC2 inducer Semaphorin 4D was decreased in memory CCR6+ T-cells of STs and ECs versus HDs. The presence of HIV-DNA in memory CCR6+ T-cells of ST and EC corresponded with the downregulation of HIV restriction factors (SERINC3, KLF3, and RNF125) and HIV inhibitors (tetraspanins), along with increased expression of the HIV-dependency factor MRE11, indicative of higher susceptibility/permissiveness to HIV-1 infection. Furthermore, markers of DNA damage/modification were elevated in memory CCR6+ T-cells of STs and ECs versus HDs, in line with their increased activation (CD38/HLA-DR), senescence/exhaustion phenotype (CTLA-4/PD-1/CD57) and their decreased expression of proliferation marker Ki-67. Interpretation: These results reveal new molecular mechanisms of Th17 cell deficit in ST and EC PWH despite a successful control of HIV-1 replication. This knowledge points to potential therapeutic interventions to limit HIV-1 infection and restore frequencies, effector functions, and senescence/exhaustion in Th17 cells. Funding: This study was funded by the Canadian Institutes of Health Research (CIHR, operating grant MOP 142294, and the Canadian HIV Cure Enterprise [CanCURE 2.0] Team Grant HB2 164064), and in part, by the Réseau SIDA et maladies infectieuses du Fonds de recherche du Québec-Santé (FRQ-S).

We report the size-dependent activity and stability of supported Pt1,4,7,8 for electrocatalytic hydrogen evolution reaction, and show that clusters outperform polycrystalline Pt in activity, with size-dependent stability. To understand the size effects, we use DFT calculations to study the structural fluxionality under varying potentials. We show that the clusters can reshape under H coverage and populate an ensemble of states with diverse stoichiometry, structure, and thus reactivity. Both experiment and theory suggest that electrocatalytic species are hydridic states of the clusters (≈2 H/Pt). An ensemble-based kinetic model reproduces the experimental activity trend and reveals the role of metastable states. The stability trend is rationalized by chemical bonding analysis. Our joint study demonstrates the potential- and adsorbate-coverage-dependent fluxionality of subnano clusters of different sizes and offers a systematic modeling strategy to tackle the complexities.

A combination of density functional theory (DFT) and experiments with atomically size-selected Ptn clusters deposited on indium-tin oxide (ITO) electrodes was used to examine the effects of applied potential and Ptn size on the electrocatalytic activity of Ptn (n = 1, 4, 7, and 8) for the hydrogen evolution reaction (HER). Activity is found to be negligible for isolated Pt atoms on ITO, increasing rapidly with Ptn size such that Pt7/ITO and Pt8/ITO have roughly double the activity per Pt atom compared to atoms in the surface layer of polycrystalline Pt. Both the DFT and experiment find that hydrogen under-potential deposition (Hupd) results in Ptn/ITO (n = 4, 7, and 8) adsorbing ∼2H atoms/Pt atom at the HER threshold potential, equal to ca. double the Hupd observed for Pt bulk or nanoparticles. The cluster catalysts under electrocatalytic conditions are hence best described as a Pt hydride compound, significantly departing from a metallic Pt cluster. The exception is Pt1/ITO, where H adsorption at the HER threshold potential is energetically unfavorable. The theory combines global optimization with grand canonical approaches for the influence of potential, uncovering the fact that several metastable structures contribute to the HER, changing with the applied potential. It is hence critical to include reactions of the ensemble of energetically accessible PtnHx/ITO structures to correctly predict the activity vs Ptn size and applied potential. For the small clusters, spillover of Hads from the clusters to the ITO support is significant, resulting in a competing channel for loss of Hads, particularly at slow potential scan rates.

Abstract Background This manuscript is coauthored by 15 young adult Patient RESearch partners (PARES) with lived and living mental health experiences and three institutional researchers across Canada involved in a patient-oriented research (POR) study called the HEARTS Study: Helping Enable Access and Remove Barriers To Support for Young Adults with Mental Health-Related Disabilities. We share our reflections, experiences and lessons learned as we grapple with the field of POR for its lack of clarity, hierarchical structures, internalized ableism, and accessibility challenges, among others. To mitigate the difficulties of POR, we started by laying the groundwork for equality by embracing the principle of Primus Inter Pares: First Among Equals as the foundation of our approach. In this way, we began with what we know for certain: the inherent worth and dignity of young adults as equal partners, recognizing their expertise, worldviews, creativity, and capacity to contribute meaningfully and intentionally to the research that affects their lives and futures. Main Body The manuscript underscores the need to reconceptualize meaningful engagement in POR, advocating a shift from traditional, biased paradigms that fail to address the complexities faced by young adults with mental illness. It introduces what we have termed Adaptive and Differential Engagement, underscoring the necessity of tailoring participation to individual preferences and circumstances alongside a Tripartite Compensation model that promotes fair and holistic remuneration in research collaborations. Then we discuss the approaches we have conceptualized, such as Equitable Dialogue, Trust Architecture, Community Continuum, Unity in Diversity, Shared Stewardship, and Agile Frameworks that collectively aim to overcome barriers like language intimidation, power imbalances, framework fatigue, consultation burnout, trust deficits, and systemic discrimination and exclusion. The manuscript does not seek to prescribe any universal or standardized solutions; in fact, it seeks the opposite. Instead, it offers a thoughtful and transparent contribution to the POR canon, providing resources for young adults eager to engage in research and institutional researchers aspiring to collaborate with them. Conclusion This manuscript is a product of our collective learning and critical self-evaluation. By integrating theoretical insights with practical strategies, we present a justice-oriented blueprint for an inclusive and egalitarian approach to POR. We advocate for applications of POR that are responsive to the individualized contexts of young adult PARES, ensuring their perspectives are central to the research with the resources to take the lead should they choose.

The research was carried out in order to study the effect of non-root fertilizing using complex fertilizers on the yield and quality of plum fruits of the Velikaya sinyaya variety in the Astrakhan region. The following treatment variants with complex fertilizers were used in the experiment: Master; Aquarin; Ultramag Boron + Ultramag Calcium; Aquarin + Ultramag Boron + Ultramag Calcium. Non-root fertilizing of plum plants was carried out before flowering, after flowering and during fruit development. On average for 2021-2023 non-root treatments contributed to an increase in the number of plum ovaries compared with the control (water treatment) by 3.3...26.7 %, the best result was obtained in the variant Ultramag Boron + Ultramag Calcium. In all variants of the experiment, foliar fertilization increased the yield of plum of the Velikaya sinyaya variety by 3.1...4.2 t/ha (LSD05 = 0.1 t/ha). The highest yield of plum fruits was formed in the variant Aquarin + Ultramag Boron + Ultramag Calcium – 12.9 t/ha (in the control – 8.7 t/ha). The maximum values of the average fruit weight were obtained in the variants Ultramag Boron + Ultramag Calcium and Aquarin + Ultramag Boron + Ultramag Calcium – 45.1 and 45.6 g, respectively (in the control – 43.3 g, LSD05 = 1.2 g). Foliar fertilizing with Ultramag Boron fertilizers together with Ultramag Calcium provided a higher sugar content (14.2 %) and the value of the sugar acid index (17.7) in the fruits of the Velikaya sinyaya plum variety (at the control – 13.2 % and 16.5 respectively).

Introduction. Multicriteria optimization, taking into account contradicting criteria, is used to improve production efficiency, reduce costs, improve product quality and environmental safety of processes. The literature describes the application of multicriteria optimization for production purposes, including the selection of reaction conditions and improvement of technological processes. In the presented paper, the object of research is the process of hydrogenation of polycyclic aromatic hydrocarbons (PAH) in the production of high-density fuels. To determine the optimal conditions of the process, the problem of multicriteria optimization based on the kinetic model is solved. The criteria include maximizing the yield of targeted naphthenes and conversion of feedstock. The research objective is to create a program implementing the multicriteria optimization non-dominated sorting genetic algorithm-II (NSGA-II). Due to this, it is possible to calculate the optimal temperature for the PAH hydrogenation process on the basis of the kinetic model.Materials and Methods. The NSGA-II genetic algorithm was used to solve the multicriteria optimization problem. Modified parental and survival selection within the Pareto front was also used. If it was necessary to divide the front, solutions based on the Manhattan distance between them were selected. The program was implemented in Python.Results. In the system of ordinary nonlinear differential equations of chemical kinetics, the concentration was designated yi, the conditional contact time of the reaction mixture with the catalyst — τ. The system was solved for the hydrogenation reaction of polycyclic aromatic hydrocarbons. The calculations showed that at τ = 0 y1(0) = 0.025; y2(0) = 0.9; y6(0) = 0.067; y9(0) = 0.008; yi(0) = 0, i = 3–5, 7, 8, 10–20; Q(0) = 1. The process temperature was considered as a control parameter according to two optimality criteria: maximizing the yield of target naphthenes (f1) at the end of the reaction, and maximizing the conversion of feedstock (f2). Values f1 were in the range of 0.43–0.79; conversion — 0.01–0.03; temperature — 200–300 K. The growth of temperature was accompanied by an increase in the yield of target naphthenes and a decrease in the conversion of feedstock. Each solution obtained was not an unimprovable one. When modeling the process of hydrogenation of PAH, an algorithm was launched with a population size of 100 and a number of generations of 100. A program implementing the NSGA-II algorithm was developed. The optimal set of values of the PAH hydrogenation reaction temperature was calculated, which made it possible to obtain unimprovable values of the optimality criteria — maximizing the yield of target naphthenes and conversion of feedstock.Discussion and Conclusion. The NSGA-II algorithm is effective for solving the problem of non-dominance, and deriving the optimal solution for all criteria. Future research should be devoted to the selection of optimal algorithm parameters to increase the speed of the solution. Based on the obtained theoretical optimal conditions of the PAH hydrogenation reaction, it is possible to implement the process in industry

Aim To evaluate the safety and toxicity of lenvatinib with pembrolizumab in unselected patients with advanced renal cell carcinoma (RCC). Materials and methods. The Russian phase IV observational study included 151 patients with advanced RCC who received lenvatinib with pembrolizumab in a standard dose regimen in 36 clinical centers of the Russian Federation. Most patients were diagnosed with clear cell RCC (n=145, 96.0%), with synchronous (n=77,51.0%) metastasesof more than one location (n=111,73.5%), removed primary tumor (n=98, 64.9%) and were classified into intermediate and poor IMDC prognostic groups (n=111, 73.5%). Median follow-up was 9.6 (1—68) months. Results. Any adverse events (AEs) were noted in 109 (72.2%), grade ≥3 AEs-in 26 (17.2%), serious AEs-in 9 (6.0%) of 151 patients. There were no deaths caused by AEs. AEs were an indication for lenvatinib dose reduction in 32 (21.2%), a dose interruptions in lenvatinib treatment in 21 (13.9%), and lenvatinib discontinuation in 2 (1.3%) cases. A dose interruptions in pembrolizumab therapy due to AEs was necessary in 15 (9.9%) cases. Both combination drugs were discontinued due to toxicity in 10 (6.6%) cases. AEs were assessed as immune-mediated in 24 (15.9%) patients (grade 3-4 - n=7, 4.6%) and required the prescription of high doses of glucocorticosteroids in 2 (1.3%) patients. Conclusions. A Russian observational study confirmed the acceptable safety profile of lenvatinib plus pembrolizumab therapy in patients with advanced RCC.

The study examines the features of state policy in the field of demography and health care, special attention is paid to the analysis of the main indicators of the quality of life of the population, as well as the results already achieved within the framework of the national projects “Demography” and “Health Care”. The problems of low life expectancy of the population and a decrease in the birth rate have been identified. Based on the results of monitoring of the national projects “Demography” and “Health Care”, it was concluded that they are interconnected and it is possible to achieve the targets only through the successful implementation of both national projects. Based on this, the research suggests measures aimed at improving state policy in the field of demography and health, including the need to strengthen measures aimed at combating neoplasms, including malignant ones, which in turn will have a positive impact on the quality of life of the country’s population.

The SARS-CoV-2 pandemic demonstrated the importance of proper understanding of the epidemiology of viral infections in the modern cosmopolitan world. In this retrospective study, we analyzed different factors associated with the spread of SARS-CoV-2 in the Sandanski municipality, a small and isolated region of Bulgaria, with a classical continental Mediterranean climate. We collected 418 serum samples from people without symptoms of SARS-CoV-2 infection or other respiratory diseases. The samples were tested for COVID-19 markers with qualitative and quantitative ELISA for anti-N and anti-S antibodies, and a rapid test for (IgM/G) antibodies. The methods were applied to complement each other with the different characteristics each of them has, thus allowing us to perform more accurate and more comprehensive detection of serum antibodies and to analyze the virus spread. We compared the results with the official government data for the SARS-CoV-2 distribution in Bulgaria. Based on the obtained results and available literature data, we discuss the importance of popular diagnostic methods, the role of the climate, the travel of people and pets, psychological stress and the individual reaction of subjects related to the spread of the virus.

Radostina Alexandrova,1 Ilia Tsachev,2 Plamen Kirov,1 Abedulkadir Abudalleh,1 Hristo Hristov,1 Tanya Zhivkova,1 Lora Dyakova,3 Magdalena Baymakova4 1Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria; 2Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria; 3Department of Synaptic Signaling and Communication, Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria; 4Department of Infectious Diseases, Military Medical Academy, Sofia, BulgariaCorrespondence: Magdalena Baymakova, Department of Infectious Diseases, Military Medical Academy, Sofia, Bulgaria, Tel +359-882-28-50-87, Email dr.baymakova@gmail.comAbstract: Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus that belongs to Hepeviridae family. HEV is the most common cause of acute viral hepatitis worldwide. According to the World Health Organization (WHO), there are estimated 20 million HEV infections worldwide every year, leading to estimated 3.3 million symptomatic cases of HEV infection. The WHO estimates that HEV infection caused approximately 44,000 deaths in 2015, which represents 3.3% of mortality rates due to viral hepatitis. In low-income (LI) countries and lower-middle-income (LMI) countries, HEV is a waterborne infection induced by HEV genotype (gt) 1 and HEV gt 2 that cause large outbreaks and affect young individuals with a high mortality rate in pregnant women from South Asian countries and patients with liver diseases. HEV gt 3, HEV gt 4, and HEV gt 7 are responsible for sporadic infections with zoonotic transmission mainly through the consumption of raw or undercooked meat from different animals. Acute HEV infection is relatively asymptomatic or mild clinical form, in rare cases the disease can be moderate/severe clinical forms and result in fulminant hepatitis or acute liver failure (ALF). Furthermore, HEV infection is associated with extrahepatic manifestations, including renal and neurological clinical signs and symptoms. Pregnant women, infants, older people, immunocompromised individuals, patients with comorbidities, and workers who come into close contact with HEV-infected animals are recognized as major risk groups for severe clinical form of HEV infection and fatal outcome. Chronic HEV infection can occur in immunocompromised individuals with the possibility of progression to cirrhosis.Keywords: acute and chronic infection, cancer, cirrhosis, hepatitis E virus, HEV, HIV, solid organ transplants

The COVID-19 pandemic has changed the way learning is organized around the world. Russian universities have also been faced with the need to quickly transfer all teaching to an online format. The importance of student satisfaction with the education quality in online learning is increasing, since it is an important condition for motivation. The paper shows that based on the analysis of students’ messages in the social network, it is possible to observe and analyze the overall dynamics and trends in student community satisfaction with the quality of the learning / the efficiency of universities and conduct a comparative analysis of the identified characteristic data groups with their totality. It is shown that the data on the reaction of students of a particular university may have significant deviations from the totality of data, which reflects the characteristics of the reaction of students of a particular university to events occurring at the same time. This may indicate the internal differences of the university, which form an appropriate response to external events.To understand the satisfaction of students in the transition to a new implementation format of the learning. The digital traces of students from the social network VKontakte were analyzed using individual Big Data tools on the PolyAnalyst software platform. This made it possible to trace changes in the mood of students and, on the example of a single university, to identify and explain deviations in the attitude of students to the implementation of the learning, as well as to verify the methodology. The methodology developed by authors makes it possible to detect problematic issues in the university, including the moment of their occurrence, relevance, degree of concern of students. Such content analysis can be used not only to assess students’ satisfaction with the quality of the learning, but also to monitor the emergence of any problems that cause concern and strong reactions on the part of the student community, as well as other communities and individual groups.

Enzymes host active sites inside protein macromolecules, which have diverse, often incredibly complex, and atom-expensive structures. It is an outstanding question what the role of these expensive scaffolds might be in enzymatic catalysis. Answering this question is essential to both enzymology and the design of artificial enzymes with proficiencies that will match those of the best natural enzymes. Protein rigidifying the active site, contrasted with the dynamics and vibrational motion promoting the reaction, as well as long-range electrostatics (also known as electrostatic preorganization) were all proposed as central contributions of the scaffold to the catalysis. Here, we show that all these effects inevitably produce changes in the quantum mechanical electron density in the active site, which in turn defines the reactivity. The phenomena are therefore fundamentally inseparable. The geometry of the electron density-a scalar field characterized by a number of mathematical features such as critical points-is a rigorous and convenient descriptor of enzymatic catalysis and a reporter on the role of the protein. We show how this geometry can be analyzed, linked to the reaction barriers, and report in particular on intramolecular electric fields in enzymes. We illustrate these tools on the studies of electrostatic preorganization in several representative enzyme classes, both natural and artificial. We highlight the forward-looking aspects of the approach.

Supported sub-nano clusters hold great promise as economical and highly active catalysts. However, they tend to deactivate rapidly by poisoning and sintering, impeding their widespread use. We find that self-limiting poisoning can stabilize and promote cluster catalysis, that is, poisoning is not always detrimental but can sometimes be exploited. Specifically, Pt-Ge alloy clusters supported on alumina undergo slow and self-limiting coking (carbon deposition) under conditions of thermal dehydrogenation, modifying the cluster framework and electronic properties but preserving the Pt sites required for strong ethylene binding. For the case of Pt4Ge/alumina, theory shows a number of thermally populated isomers, one of which catalyzes carbon deposition. Because the clusters are fluxional at high temperatures, this isomer acts as a gateway, slowly converting all clusters to Pt4GeC2. The surprising result is that Pt4GeC2 is highly catalytically active and selective against further coking, that is, coking produces functional, stable catalytic clusters. Ge and C2 have synergistic electronic effects, leading to efficient and highly selective catalytic dehydrogenation that stops at alkenes and improving stability. Thus, under reaction conditions, the clusters develop into a robust catalyst, suggesting an approach to practicable cluster catalysis.

Designing closed, laser-induced optical cycling transitions in trapped atoms or molecules is useful for quantum information processing, precision measurement, and quantum sensing. Larger molecules that feature such closed transitions are particularly desirable, as the increased degrees of freedom present new structures for optical control and enhanced measurements. The search for molecules with robust optical cycling centers is a challenge which requires design principles beyond trial-and-error. Two such principles are proposed for the particular M-O-R framework, where M is an alkaline earth metal radical, and R is a ligand: (1) Large, saturated hydrocarbons can serve as ligands, R, due to a substantial HOMO-LUMO gap that encloses the cycling transition, so long as the R group is rigid. (2) Electron-withdrawing groups, via induction, can enhance Franck-Condon factors (FCFs) of the optical cycling transition, as long as they do not disturb the locally linear structure in the M-O-R motif. With these tools in mind, larger molecules can be trapped and used as optical cycling centers, sometimes with higher FCFs than smaller molecules.

We report the size-dependent activity and stability of FTO-supported Pt1,4,7,8 for electrocatalytic hydrogen evolution reaction, and show that clusters are significantly more active than polycrystalline Pt, but also have stability under HER conditions that is size-dependent. To understand the mechanistic origin of the size effects, we carried out detailed DFT-based theory, accounting for the structural fluxionality under varying potentials. We show that, even under coverage of the simplest adsorbate H, the clusters can undergo drastic changes and populate a grand canonical ensemble of hydride states with diverse distributions of stoichiometry, structure, and thus reactivity. Both experiment and theory find that electrocatalysis mainly results from heavily hydrogenated states of the clusters (~2 H/Pt), and an ensemble-based kinetic model reproduces the experimental activity trend and provides detailed insights into the contributions from metastable configurations. The size-dependent stability trend is rationalized by chemical bonding analysis. The comparison of experiment and theory demonstrates the potential- and adsorbate-coverage-dependent fluxionality of subnano clusters of different sizes and offers a systematic modeling strategy to tackle the complexities.

A combination of density functional theory (DFT) and experiments with atomically size-selected Ptn clusters deposited on indium-tin oxide (ITO) electrodes was used to examine the effects of applied potential and Ptn size on the electrocatalytic activity of Ptn (n = 1, 4, 7, 8) for the hydrogen evolution reaction (HER). Activity is found to be negligible for isolated Pt atoms on ITO, increasing rapidly with Ptn size, such that Pt7/ITO and Pt8/ITO have roughly double the activity per Pt atom compared atoms in the surface layer of polycrystalline Pt. Both DFT and experiment find that hydrogen under-potential deposition (Hupd) results in Ptn/ITO (n = 4, 7, 8) adsorbing ~2 H atoms/Pt atom at the HER threshold potential, equal to ca. double the Hupd observed for bulk Pt or Pt nanoparticles. The cluster catalysts under electrocatalytic conditions are hence best described as a Pt hydride compound, significantly departing from a metallic Pt cluster. The exception is Pt1/ITO, where H adsorption at the HER threshold potential is energetically unfavorable. Theory combines global optimization with grand canonical approaches for the influence of potential, uncovering that several metastable structures contribute to HER, changing with the applied potential. It is hence critical to include reactions of the ensemble of energetically accessible PtnHx/ITO structures to correctly predict the activity vs. Ptn size and applied potential. For the small clusters, spillover of Hads from the clusters to the ITO support is significant, resulting in a competing channel for loss of Hads, particularly at slow potential scan rates.

The oxygen reduction reaction (ORR) plays a key role in renewable energy transformation processes. Unfortunately, it is inherently sluggish, which greatly limits its industrial application. Sub-nano-cluster-decorated electrode interfaces are promising candidate ORR electrocatalysts. However, understanding the nature of the active sites on these catalysts under electrocatalytic conditions presents a formidable challenge for both experiment and theory, due to their dynamic fluxional character. Here, we combine global optimization with the electronic Grand Canonical DFT to elucidate the structure and dynamics of subnano Ptnclusters deposited on electrified graphite. We show that, under electrochemical conditions, these clusters exist as statistical ensembles of multiple states, whose fluxionality is greatly affected by the applied potential, electrolyte, and adsorbate coverage. The results reveal the presence of potential-dependent active sites and, hence, reaction energetics.

Subnano cluster catalysts, while highly promising due to unique activity, selectivity, and atom-efficiency, are limited in wider applications, as they are prone to deactivation via sintering. Even size-selection, which was previously shown to reduce sintering of nanoparticles, cannot reduce the sintering of highly fluxional subnano clusters due to their inherent isomeric diversity. Here, we use a combination of theory and experiment to show that Pt clusters on Al2O3 exhibit size-dependent sintering resistance. We furthermore show that Pt4/Al2O3 and Pt7/Al2O3 are "magic" sinter-resistant cluster sizes. Their stability is attributed to the greater degree of bulk-like crystallinity of the dominant isomers. In addition, we identify different spatial signatures characteristic of the sintering of clusters with differing sintering stabilities.

We report the production and spectroscopic characterization of strontium(I) phenoxide (SrOC6H5 or SrOPh) and variants featuring electron-withdrawing groups designed to suppress vibrational excitation during spontaneous emission from the electronically excited state. Optical cycling closure of these species, which is the decoupling of the vibrational state changes from spontaneous optical decay, is found by dispersed laser-induced fluorescence spectroscopy to be high, in accordance with theoretical predictions. A high-resolution, rotationally resolved laser excitation spectrum is recorded for SrOPh, allowing the estimation of spectroscopic constants and identification of candidate optical cycling transitions for future work. The results confirm the promise of strontium phenoxides for laser cooling and quantum state detection at the single-molecule level.

Aim. The study aimed to conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to determine the effect of pulmonary vein isolation (PVI) on the prognosis of patients with atrial fibrillation (AF) and chronic heart failure with reduced ejection fraction (HFrEF).Material and methods. We searched PubMed (MEDLINE), Google Scholar, and the Cochrane Library databases for studies that compared PVI with a conservative rhythm/heart rate (HR) control strategy in patients with AF and HFrEF. The primary endpoint in the major RCTs examining the effect of PVI on the prognosis of patients with HFrEF was a composite endpoint of all-cause mortality or HF-related hospitalization. Hazard ratios (HRs) based on Cox regression analysis were used as the baseline survival rates for the meta-analysis. To determine the weighted mean differences in improvement in left ventricular ejection fraction (LVEF) in the PVI and non-PVI groups, a pooled analysis of the mean LVEF changes with standard deviations taking into account the number of subjects in the compared groups was performed.Results. For this systematic review, 11 studies were selected from 2216 publications, which included 2379 patients. Three RCTs (n=968) were subjected to meta-analysis on time-to-event outcomes. The average follow-up period was 34 months. According to the meta-analysis, PVI was associated with a significant reduction in the risk of composite endpoint (HR: 0,53; 95% confidence interval (CI): 0,33-0,85; p=0,009). In addition, PVI compared with drug rhythm/rate control was associated with a significant reduction in the all-cause mortality risk (HR: 0,55; 95% CI: 0,34-0,89; p=0,01). Finally, a meta-analysis of 10 RCTs (n=1516) found a significant improvement in LVEF compared with drug rhythm/HR control or atrioventricular node ablation with biventricular pacing. The weighted mean difference in the LVEF change over time after 6-12-month follow-up was 5,25% (95% CI: 4,03-6,47; p

Bond bundle analysis is used to investigate enzymatic catalysis in the ketosteroid isomerase (KSI) active site. We identify the unique bonding regions in five KSI systems, including those exposed to applied oriented electric fields and those with amino acid mutations, and calculate the precise redistribution of electron density and other regional properties that accompanies either enhancement or inhibition of KSI catalytic activity. We find that catalytic enhancement results from promoting both inter- and intra-molecular electron density redistribution, between bond bundles and bond wedges within the KSI-docked substrate molecule, in the forward direction of the catalyzed reaction. Though the redistribution applies to both types of perturbed systems and is thus suggestive of a general catalytic role, we observe that bond properties (e.g., volume vs energy vs electron count) can respond independently and disproportionately depending on the type of perturbation. We conclude that the resulting catalytic enhancement/inhibition proceeds via different mechanisms, where some bond properties are utilized more by one type of perturbation than the other. Additionally, we find that the correlations between bond wedge properties and catalyzed reaction barrier energies are additive to predict those of bond bundles and atomic basins, providing a rigorous grounding for connecting changes in local charge density to resulting shifts in reaction barrier energy.

Pressure-induced structural transitions of the alkaline earth hexaborides, CaB6, SrB6, and BaB6, are studied theoretically using electron counting rules and density functional theory calculations. We demonstrate the applicability of gas-phase borane electron counting methods to solid-state metal borides under pressure and validate the assumptions of the rules by density functional theory (DFT) calculations. All three compounds share ambient-pressure and high-pressure structures, but BaB6 differs from CaB6 and SrB6 at intermediate pressures. The unique BaB6 phase is shown to break electron counting rules, while all other phases obey them. This anomaly is resolved by DFT, which reveals B-Ba covalency and unusual B-B π bonding under pressure. The relationships between structure and bonding can help us to understand the exotic behavior of lanthanide hexaborides and design new borides with desirable properties. Developing electron counting procedures for solids will enhance materials discovery efforts with chemical intuition.

AbstractWe introduce the concept of optimal drug design (ODD) as the use of an AI framework to optimize the exposure, safety, and efficacy of drugs. To exemplify the concept of ODD, we developed an artificial intelligence framework that integrates de novo molecular design, quantitative structure activity relationships, and pharmacokinetic-pharmacodynamic modeling. Specifically, our computational architecture has integrated a generative algorithm for small molecule design with a hybrid physiologically-based pharmacokinetic machine learning (PBPK-ML) model, which was applied to generate and optimize drug candidates for enhanced brain exposure. Publicly sourced data on the plasma and brain pharmacokinetics of 77 small molecule drugs in rats was used for model development. We have observed an approximate 30-fold and 120-fold increase on average in predicted brain exposure for AI generated molecules compared to known central nervous system drugs and randomly selected small organic molecules. We believe that with additional data and mechanistic modeling this in silico pipeline could facilitate the discovery of a new wave of optimally designed medicines for the treatment of CNS diseases.Graphical AbstractArtificial Intelligence Framework for the Optimization of Brain Pharmacokinetics.A genetic algorithm consisting of cross-breeding, mutating, scoring, and refining was used for de novo generation of a population of new molecular structures. SELFIE representations of molecules were used as input to a variational autoencoder for de novo generation/refinement of individual drug candidates. Molecular descriptors of individual drug candidates are generated and used as input into a trained neural network to generate drug-specific pharmacokinetic (PK) parameters. PK parameters are used as input into a physiologically-based pharmacokinetic (PBPK) model of the brain to predict brain PK of the drug candidate. Brain concentration-time profiles are integrated to obtain an area-under the curve (AUC), a metric of brain exposure, which is used to score and inform the design of new generations of molecules. Iterations of this framework generate novel drug candidates optimized for greater brain exposure. Created with BioRender.

The rearrangement of Cu surfaces under electrochemical conditions is known to play a key role in the surface activation for major electrocatalytic reactions. Despite the extensive experimental insights into such rearrangements, from surface-sensitive spectroscopy and microscopy, the spatial and temporal resolution of these methods is insufficient to provide an atomistic picture of the electrochemical interface. Theoretical characterization has also been challenged by the diversity of restructuring configurations, surface stoichiometry, adsorbate configurations, and the effect of the electrode potential. Here, atomistic insight into the restructuring of the electrochemical interface is gained from first principles. Cu(100) restructuring under varying applied potentials and adsorbate coverages is studied by grand canonical density functional theory and global optimization techniques, as well as ab initio molecular dynamics and mechanistic calculations. We show that electroreduction conditions cause the formation of a shifted-row reconstruction on Cu(100), induced by hydrogen adsorption. The reconstruction is initiated at 1/6 ML H coverage, when the Cu-H bonding sufficiently weakens the Cu-Cu bonds between the top- and sublayer, and further stabilized at 1/3 ML when H adsorbates fill all the created 3-fold hollow sites. The simulated scanning tunneling microscopy (STM) images of the calculated reconstructed interfaces agree with experimental in situ STM. However, compared to the thermodynamic prediction, the onsets of reconstruction events in the experiment occur at more negative applied voltages. This is attributed to kinetic effects in restructuring, which we describe via different statistical models, to produce the potential- and pH-dependent surface stability diagram. This manuscript provides rich atomistic insight into surface restructuring in electroreduction conditions, which is required for the understanding and design of Cu-based materials for electrocatalytic processes. It also offers the methodology to study the problem of in situ electrode reconstruction.