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Aim. To systematize data on the prevalence of gastroesophageal reflux disease (GERD) in the adult population of Russia. Materials and methods. The search for studies was conducted in the electronic databases MEDLINE/PubMed, EMBASE, and RSCI (Russian Science Citation Index) from January 2000 to December 2022. The review included relevant publications in peer-reviewed periodicals in English or Russian, publications with data from cross-sectional epidemiological studies assessing the prevalence of GERD in the Russian population, studies on adult patients with GERD, and publications with detailed descriptive statistics that allow using the data in the meta-analysis. Results. The final analysis included 6 studies involving 34,192 subjects. The overall prevalence of GERD (prevalence of heartburn ± regurgitation once a week or more frequently) in the analyzed studies was 25.605% (95% confidence interval [CI] 17.913–34.147). The analysis used a random effect model, as there was significant heterogeneity between the results in both groups (I2=99.63%; p0.0001). The overall mean age of GERD patients in the study population was 48.14 (95% CI 32.25–4.03) years. The prevalence of GERD in the male population was 23.653% (95% CI 13.351–35.832) and 25.457% (95% CI 17.094–34.849) in females. Conclusion. This meta-analysis demonstrated that GERD is a common esophageal disease in the Russian population, affecting approximately one in four country residents.

Background: Ovarian tumors are characterized by asymptomatic progression until their late stages, when at the time of diagnosis the patient already has extensive metastatic disease. In addition to lymphogenous and hematogenous metastasis in ovarian cancer, there are peritoneal dissemination and metastasis to the greater omentum with ascites; moreover, peritoneal carcinomatosis is the predominant route of metastasizing of ovarian cancer. Epigenetic factors, such as gene methylation, regulatory microRNAs and long non-coding RNAs (lncRNAs), contribute to progression of this cancer. Our previous bioinformatic and experimental studies have identified 13 genes of lncRNAs (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) hypermethylated in the ovarian neoplasms. Aim: To evaluate the clinical significance of methylation levels of 13 lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) associated with various types of ovarian cancer metastasis, including lymphogenous, peritoneal, omental, and distant metastases. Methods: The methylation levels of lncRNA genes GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1 were analyzed by quantitative real-time methylation-specific polymerase chain reaction. We tested 122 duplicate samples of ovarian neoplasms, including 104 malignancies and 18 borderline tumors, as well as 45 peritoneal macro metastases, collected in the N.N. Blokhin National Medical Research Center of Oncology in 2020 to 2023. The study included 21 samples of primary tumor from patients with lymphogenous metastases, 45 samples from patients with peritoneal dissemination, 61 from those with omental metastases, 49 from patients with ascites, and 9 with distant metastases. Results: The tumor samples from the patients with lymphatic nodes metastases showed a significant increase in the methylation level of two lncRNA genes: SNHG6 (p = 0.044) and SNHG12 (p = 0.006). Peritoneal dissemination was associated with hypermethylation of four lncRNA genes: GAS5, HOTAIR, LINC00472 (p 0.05), and most significantly TINCR (p = 0.001). GAS5, HOTAIR, LINC00886 (p 0.05) and most significantly LINC00472 (p 0.001) hypermethylation was typical for omental metastasis, and that of LINC00472 and LINC00886, with ascites (p 0.05). Peritoneal macroscopic metastases demonstrated increased methylation of MAFG-DT (p 0.001) and TP53TG1 (p 0.001) and desmethylation of LINC00886 (p = 0.003) and SNHG12 (p = 0.002), compared to their primary tumors. Conclusion: We performed the analysis of clinical significance of 13 hypermethylated lncRNA genes in ovarian cancer and were the first to show that 10 genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, SNHG6, SNHG12, TINCR, TP53TG1, TUG1) were associated with various types of ovarian tumor metastasis. Also, we were able to determine certain panels of lncRNA, which, if demonstrate abnormal methylation, were specific for lymphogenous and peritoneal metastasis of ovarian tumors.

Introduction. In response to the COVID-19 pandemic in the Russian Federation, comprehensive response measures were taken. One of these measures was the development of a viral genome aggregation platform (VGARus) to monitor virus variability. The aim of this paper is to describe the role of the VGARus platform in tracking genetic variation in SARS-CoV-2. Materials and methods. VGARus utilizes sequencing data and bioinformatics tools to monitor genetic variations in SARS-CoV-2. The viral genomes were aligned using NextClade, which also translated them into amino acids and identified mutations. The viral variability over time was analyzed by counting the number of amino acid changes compared to the reference sequence. Results. The analysis of data within VGARus enabled the identification of new virus variants, contributing to improved diagnostic tests and vaccine development. The platform allowed for the prediction of epidemiologic trends, facilitating a rapid response to changes in the epidemiologic situation. For example, using VGARus, an increase in COVID-19 incidence was accurately predicted in the summer of 2022 and early 2023, which were associated with the emergence of Omicron subvariants BA.5 and XBB. Data from the platform helps validate the effectiveness of primers and DNA probes to ensure high diagnostic accuracy and reduce the risk of false negatives. Conclusion. VGARus demonstrates the growing role of genomic surveillance in combating COVID-19 and improving preparedness for future infectious disease outbreaks. The platform is a powerful tool for generating evidence-based solutions to combat a pandemic and mitigate its health, economic and societal impacts. It provides the ability to promptly obtain information on the epidemiologic situation in a particular region of the Russian Federation, use genomic data for phylogenetic analysis, compare the mutational spectrum of SARS-CoV-2 sequences with foreign samples. VGARus data allow for both retrospective analysis and predictive hypotheses. For example, we can clearly see the dynamics of the change of different virus variants: sequences belonging to the Alpha, Beta, Delta, Omicron lineages and many less common ones, clearly form the upsurges of morbidity, the interaction of which is reflected in the epidemiological picture. It is also currently being expanded to monitor other pathogens, increasing its public health relevance.

Problem description. One of the areas of digital transformation of Russian society is the development and implementation of the National Digital Ruble System (DR) in the credit and financial sphere (CFS) of the economy of the Russian Federation. The National DR system should be based on the information technology infrastructure (ITI) for ensuring information security (IS). In fact, the ITI for ensuring IS is a trust infrastructure (ITIT) based on the public key infrastructure (PKI). ITIT should have a number of functional properties, including identification and authenti­cation of objects and subjects of electronic financial transactions, protection of the integrity and confidentiality of data and the electronic financial transactions themselves, implementation of the principle of non-repudiation of the parties to information interaction. At the same time, the absence of ITIT in the National DR System can completely discredit the very idea of digitalization of the CFS, associated with the absence of any guarantees of reliability and trust in the National DR System, based on the implementation of the entire range of methods and means of cryptographic protection of information (electronic financial transactions), including systems for managing cryptographic keys. The absence of comprehensive protection of the National DR System will entail risks and problems in ensuring IS, which can negatively affect individuals, groups, organizations, sectors of the economy and society as a whole. Goals. To propose and analyze a heuristic model of DR and a model of functional and structural ITIT, which solves the main problems of ensuring IS of the National DR System, associated primarily with confirmation of the authenticity and ownership of DR, as well as the protection of electronic payment transactions and the possibility of withdrawing (withdrawing from circulation) DR immediately (on-line) after detection of its compromise. Results. The article presents a heuristic (hypothetical) model of C₽ and describes the DR format (as an information object) that includes cryptographically linked information blocks and public key certificates issued by accredited certification authorities using electronic signatures. A functional and structural model of the ITIT of the National DR System is proposed. The composition, main elements of the ITIT structure, as well as their goals and implemented functions are described. The results of the analysis of trust assurance based on the PKI of the Bank of Russia (BR) are presented. Practical significance. The heuristic (hypothetical) model of DR, the functional and structural model of the ITIT of the National DR System and the results of the analysis of trust assurance based on the PKI of the BR are of great practical significance in the development and implementation of the National DR System in the CFS of the Russian Federation economy. Conclusions. The results obtained will increase the level of security and trust in the National DR System of the citizens, businesses and credit and financial institutions.

Natural killer cells (NK cells) exert cytotoxicity towards target cells in several ways, including the expression of apoptosis-mediating ligands (TRAIL, FasL). In addition, NK cells themselves may be susceptible to apoptosis due to the expression of TRAIL receptors. These receptors include TRAIL-R1 (DR4), TRAIL-R2 (DR5), capable of inducing apoptosis, and TRAIL-R3 (DcR1), TRAIL-R4 (DcR2), the so-called “decoy receptors”, which lack an intracellular domain initiating activation of caspases. Of particular interest is the interaction of uterine NK cells with cells of fetal origin, trophoblasts, which are potential targets for natural killer cells to carry out cytotoxicity. The aim of this work was to evaluate the expression of proapoptotic receptors and their ligands as well as CD107a expression by NK cells in a model of interaction with trophoblast cells. To evaluate NK cells, we used cells of the NK-92 line; cells of the JEG-3 line were used as target cells. The cytokines IL-1β, IL-15, IL-18, TNFα, IL-10, TGFβ and conditioned media (CM) of the first and third trimester chorionic villi explants were used as inducers. We established that cytokines changed the expression of apoptotic receptors by NK cells: in the presence of TNFα, the amount and intensity of Fas expression increased, while in the presence of TGFβ, the amount and intensity of expression of the DR5 receptor decreased. Soluble chorionic villi factors alter the expression of TRAIL and FasL by NK-92 cells, which can reflect the suppression of the TRAIL-dependent mechanism of apoptosis in the first trimester and stimulating the Fas-dependent mechanism in the third trimester. In the presence of trophoblast cells, the expression of TRAIL and DcR1 by NK cells was reduced compared to intact cells, indicating an inhibitory effect of trophoblast cells on NK cell cytotoxicity. In the presence of chorionic villi CM and trophoblast cells, a reduced number of NK-92 cells expressing DR4 and DR5 was found. Therefore, soluble factors secreted by chorionic villi cells regulate the resistance of NK cells to death by binding TRAIL, likely maintaining their activity at a certain level in case of contact with trophoblast cells.

Background: Overweight and especially obesity are associated with the risk of the development and progression of colorectal cancer. It can be assumed that there are multifaceted interactions between the tumor and adipose tissue during anti-tumor treatment. Cancer cells secrete exosomes, extracellular vesicles affecting the microenvironment of the tumor and promoting its progression or regression. The presence of transcription/translation/folding factors (heat shock proteins (HSPs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in exosomes secreted by irradiated cells and cells exposed to hyperthermia, indicates the cell adaptation to the thermal and radiation stress. Aim: To analyze the MMPs, TIMP1, and HSPs on CD9-positive (CD9+) exosomes, as well as on exosomes of adipocytic origin (FABP4+) in rectal cancer patients with overweight/obesity under thermoradiochemotherapy (TRCT) and their association with the immediate treatment efficacy. Methods: Since 2021, 20 patients (of those 8 men; median age 59.0 [52.0; 63.0] years, median body mass index 29.6 [28.5; 33.1] kg/m2) with morphologically verified rectal cancer (T3-4N0M0 and T3-4N1M0, differentiation grade G1–G3) have been participating in the study. They were treated with TRCT: external gamma therapy (2 Gy, 1 fraction/day, 5 days/week, total focal dose 54 Gy), chemotherapy with capecitabine (825 mg/m2 twice daily) combined with local hyperthermia (42–44 °C, 60 min, 3 times/week, 10 sessions). The TRCT efficacy was assessed by RECIST 1.1 and ESGAR criteria. Blood samples for exosomes were taken from the patients at baseline (point 1), in the middle of the treatment course (point 2), at 6 to 10 weeks after the end of TRCT (point 3), and at 6 months after point 1 (point 4). Small extracellular vesicles were isolated from plasma by ultrafiltration with double ultracentrifugation. The isolated exosomes were characterized by transmission electronic microscopy, flow cytometry and nanoparticle trajectory analysis (NTA). Results: TRCT resulted in complete tumor regression in 13/20 of the rectal cancer patients and partial regression or stabilization in 7/20. Four subpopulations of CD9+ and FABP4+ exosomes associated with the TRCT efficacy were identified (CD9+MMP2+, СD9+MMP2+9+TIMP1+, СD9+MMP2+9+TIMP1-, and FABP4+MMP2+9-TIMP1+). Compared to the CD9+ exosomes, the adipocytic vesicles had higher MMP2 expression (p = 0.026); however, the adipocyte vesicles subpopulation were virtually free of vesicles with combined MMP2 and MMP9 gelatinase expression. The HSPs expression by circulating exosomes at various TRCT steps was associated neither with direct treatment efficacy nor with the vesicle type. Conclusion: The expression of MMPs and TIMP1 on CD9+ and FABP4+ exosomes is associated with TRCT efficacy. In the future, vesicular markers could be used to build prognostic models, to identify patient groups with an unfavorable prognosis, and to personalize treatment and follow-up.

Abstract We consider the complete set of planar two-loop five-point Feynman integrals with two off-shell external legs. These integrals are relevant, for instance, for the calculation of the second-order QCD corrections to the production of two heavy vector bosons in association with a jet or a photon at a hadron collider. We construct pure bases for these integrals and reconstruct their analytic differential equations in canonical form through numerical sampling over finite fields. The newly identified symbol alphabet, one of the most complex to date, provides valuable data for bootstrap methods. We then apply our results to initiate the study of double Lagrangian insertions in a four-cusp Wilson loop in planar maximally supersymmetric Yang-Mills theory, computing it through two loops. We observe that it is finite, conformally invariant in four dimensions, and of uniform transcendentality. Furthermore, we provide numerical evidence for its positivity within the amplituhedron region through two loops.

Abstract Intellectual disability and autistic features are associated with chromosome region 2q23.q23.2 duplication carrying LYPD6 and LYPD6B genes. Here, we analyzed LYPD6 and LYPD6B expression in patients with different neuropsychiatric disorders. Increased LYPD6 and LYPD6B expression was revealed in autism and other disorders. To study possible consequences of Lypd6 and Lypd6b overexpression in the brain, we used a mouse model with intracerebroventricular delivery of recombinant analogs of these proteins. A two-week infusion evoked significant memory impairment and acute stress. Both modulators downregulated hippocampal and amygdala dendritic spine density. No changes in synaptic plasticity were observed. Intracerebroventricular administration by both proteins downregulated hippocampal expression of Lypd6, Lypd6b, and α7 nicotinic acetylcholine receptor (nAChR). Similar to Lypd6, Lypd6b targeted different nAChR subtypes in the brain with preferential inhibition of α7- and α4β2-nAChRs. Thus, increased Lypd6 and Lypd6b level in the brain are linked to cholinergic system depression, neuronal atrophy, memory decline, and anxiety.

Cognitive impairment is a very common comorbidity in patients with heart failure (HF). Patients with HF show signs of memory decline, difficulty concentrating, and attention deficits. Cognitive dysfunction in HF is associated with a poor prognosis. However, the diagnosis of cognitive impairment in heart failure has received insufficient attention in routine clinical practice. Neuropsychological screening tests are available to screen for cognitive impairment, but they are used infrequently. Therefore, it is of practical interest to search for magnetic resonance equivalents of cognitive disorders. The use of magnetic resonance imaging as a tool for identifying and quantifying neural correlates of cognitive functions is discussed.

Aim. To analyze the experience of Chazov National Medical Research Center of Cardiology in patient selection for left ventricular assist device (LVAD) implantation. Materials and methods. 901 patients, whose documents were sent to Chazov National Medical Research Center of Cardiology from regional medical and prophylactic institutions, were screened as selection for LVAD implantation. Firstly, all patients underwent transthoracic echocardiography performed according to the extended protocol with a comprehensive assessment of the left and right ventricle size and function. Patients who underwent the screening procedure underwent further examination including both laboratory and instrumental diagnostic methods. In addition, the polyclinic database of patients diagnosed with chronic heart failure (CHF) and dilated cardiomyopathy was also analyzed. Results. Among 901 screened patients 7.9% were suitable candidates for LVAD implantation and only 23 (2.6%) patients underwent surgery. Among those not eligible for surgery: 208 (29%) patients were not on optimal medical therapy, 15% of patients had indications for other surgical treatment of CHF, 12% of patients had severe right ventricular failure, 9.8% had severe comorbidities, 6.8% of patients refused surgery. Conclusions. The main problems of selection for LVAD implantation were: low awareness of doctors about the introduction of new treatment methods, poor quality of transthoracic echocardiography, a large percentage of patients not receiving basic therapy for CHF, untimely referral of patients for other types of surgical treatment.

Aegilops tauschii is a wild diploid goat-grass which occupies a vast range in Central Eurasia and comprises three different gene-pools: TauL1, TauL2, and TauL3. Multivariate statistical analysis of the transcriptomes from the leaf tissue of 40 A. tauschii accessions, 18 of TauL1, 20 of TauL2, and 2 of TauL3, revealed that the gene-pools of A. tauschii distinctly and essentially differ in their genetic expression patterns. Statistically significant differential gene expression of 2349, 376, and 272 were observed between TauL1 and TauL2; TauL1 and TauL3; TauL2 and TauL3, respectively. These findings indicate substantial adaptive intraspecies divergence in A. tauschii.

Centaurea sect. Acrocentron comprises several taxonomically intricate groups of taxa, including the Balkan endemic obligate serpentinophytes: C. melanocephala, C. candelabrum and C. albertii. Despite its distinctive morphological characteristics, C. candelabrum was considered conspecific with C. melanocephala. A similar situation pertains to C. albertii, which has largely been considered a synonym of C. melanocephala. Considering that several recent floristic works treat these taxa as separate species distributed in different serpentinite areas of the Balkans, the main objectives of our study were to analyse the taxonomic and chorological relationships between them, and to propose a new taxonomic concept. Our study was based on an extensive revision of herbarium material, including the type specimens, personal field data and observations of living plants. Our comprehensive study showed that the plants previously recognised as C. melanocephala from the Stolovi mountain in central Serbia and those previously recognised as C. candelabrum from northern Albania deserve the rank of distinct species. These species can be easily distinguished from each other by a number of characters, including their general habitus, the dimensions and shape of the basal leaves, and the indumentum of the involucral bracts. Given the only slight differences observed between the populations in Kosovo and Albania, the question of whether C. albertii is conspecific with C. candelabrum or deserves an independent taxonomic status remains unresolved until further detailed integrative studies are conducted. In view of the clear differences in morphological and ecological characteristics which exist within this group compared to other representatives of sect. Acrocentron, we propose the separation of the studied taxa into a separate C. melanocephala complex, as outlined in this paper.

A review of modern methods and technologies for automatic machine translation for the deaf and hard of hearing is presented, including recognition and synthesis of both spoken and sign languages. These methods aim to facilitate effective communication between deaf/hard-of-hearing and hearing individuals. The proposed solutions have potential applications in contemporary human-machine interaction interfaces. Key aspects of new technologies are examined, including methods for sign language recognition and synthesis, audiovisual speech recognition and synthesis, existing corpora for training neural network models, and current systems for automatic machine translation. Current neural network approaches are presented, including the use of deep learning methods such as convolutional and recurrent neural networks as well as transformers. An analysis of existing corpora for training recognition and synthesis systems is provided, along with an evaluation of the challenges and limitations of existing machine translation systems. The main shortcomings and specific problems of current automatic machine translation technologies are identified, and promising solutions are proposed. Special attention is given to the applicability of automatic machine translation systems in real-world scenarios. The need for further research in data collection and annotation, development of new methods and neural network models, and creation of innovative technologies for processing audio and video data to enhance the quality and efficiency of the existing automatic machine translation systems is highlighted.

This paper proposes a novel droop control strategy for indirect battery management in DC nanogrids. Droop control as a decentralized control method is a well­-recognized method to provide effective power sharing and voltage stability among sources and loads in the DC nanogrid without additional communication links. While most existing droop control methods focus on adjusting each individual battery droop curve directly, the proposed method manipulates the droop curve of the active front­-end converter, which connects the nanogrid to the main grid to indirectly influence the state of charge of the battery. The method employs a piecewise linear droop curve with a movable inflection point, which can be adjusted according to different scenarios. The effectiveness of the proposed method is evaluated through simulations using real data from a residential house with rooftop PV panels. The results show that the proposed method not only improves battery utilization but also increases renewable energy self­-consumption.

Introduction Triphalangeal joint flexion contracture of the fingers is a common and challeging posttraumatic hand condition. The goal of surgical treatment is to correct finger deformity and increase interphalangeal range of motion. The objective was to systematize data on the causes of post-traumatic triphalangeal joint flexion contracture of the fingers and methods of surgical correction. Material and methods The original literature search was conducted on key resources including Scientific Electronic Library (www.elibrary.ru), the National Library of Medicine (www.pubmed.org), ScienceDirect, Google Scholar, Ovid databases according to PRISMA recommendations. Literature searches included both Russian and English studies, with one or more cases of post-traumatic triphalangeal joint flexion contracture of the fingers with the deformity surgically corrected. Cases of non-traumatic flexion contractures were excluded. Etiological factors of flexion contractures, heterogeneity of definitions and methods for recording the range of motion in the joint, anatomical features, surgical correction of flexion contractures and postoperative complications were reviewed. Results Common causes of flexion contractures included burns (32.3 %), dislocations and fracture‑dislocations of the finger joints (23.5 %). The median postoperative follow-up period was 13.5 months after surgical treatment. Surgical correction was produced with external fixation device (EFD) in 40 % of cases, open procedures performed in 50 % and a combined technique employed in one case (10 %). Based on calculations of the odds ratios of postoperative complications, a weak positive linear relationship was revealed between EFD and pain syndrome, and a weak negative linear relationship was observed between the open procedure and pain. Discussion There is heterogeneity of approaches regarding methods for correcting flexion contractures, surgical approaches, techniques for mobilizing joints and releasing the anatomical structures of the finger with open procedures, the distraction rate with EFD, methods for repair of soft tissue defects following the treatment of flexion contractures of interphalangeal joint of a finger. Conclusion Open procedures are commonly used for precise elimination of all components of flexion contracture of the joint and repair of soft tissue defects of the finger. A weak positive linear relationship was revealed between EF and pain syndrome. There was no significant correlation between open techniques and complications. There were no correlations between the treatment method and the contracture type; there are no treatment regimens for patients with this pathology.

Introduction The proximal interphalangeal joint (PIP joint) plays an important role in ensuring optimal finger dexterity, grip strength and overall hand functionality. Arthroplasty is a promising direction in the surgical treatment of arthritis of the PIP joint of the hand, however, the inconsistency of the results encourages the world scientific community to be restrained and further investigate the problems associated with PIP joint arthroplasty. The purpose of the work was to identify the main problems of PIP joint arthroplasty based on the analysis of foreign and domestic medical literature. Methods In this literature review, an analysis of foreign and domestic scientific publications devoted to the treatment of diseases and injuries of PIP joint was carried out. The purpose of the study was to provide a brief historical background and identify the main problems of PIP joint arthroplasty based on the analysis of foreign and domestic medical literature. Results and discussion The choice of the implant and the surgical aproach used are the two most frequently discussed issues in PIP joint arthroplasty; dorsal, palmar and lateral surgical approaches are described, each with its own advantages and disadvantages. Dorsal approaches are used most often because they are easier to perform; however, the fragile extensor apparatus is damaged with the subsequent development of extensor lag. A number of authors concluded that stiffness and extensor lag were the most common postoperative complications. Several combinations of materials are available: from classic chrome-cobalt/polyethylene to ceramic/ceramic and pyrocarbon/pyrocarbon. Most of them have not stood the test of time yet, and for most implants there is still a lack of real long-term monitoring series for survival of the design. Conclusion The morphology of joints, small bone sizes, complex biomechanics and the load on the hand are a special problem in PIP joint arthroplasty. It is still not possible to restore the full range of motion in this joint, despite the success of colleagues in arthroplasty of large joints.

Abstract Background Coronary computed tomography angiography (CCTA) offers non-invasive diagnostics of the coronary arteries. Vessel evaluation requires the administration of intravenous contrast. The purpose of this study was to evaluate the utility of gadolinium-based contrast agent (GBCA) as an alternative to iodinated contrast for CCTA on a first-generation clinical dual-source photon-counting-detector (PCD)-CT system. Methods A dynamic circulating phantom containing a three-dimensional-printed model of the thoracic aorta and the coronary arteries were used to evaluate injection protocols using gadopentetate dimeglumine at 50%, 100%, 150%, and 200% of the maximum approved clinical dose (0.3 mmol/kg). Virtual monoenergetic image (VMI) reconstructions ranging from 40 keV to 100 keV with 5 keV increments were generated on a PCD-CT. Contrast-to-noise ratio (CNR) was calculated from attenuations measured in the aorta and coronary arteries and noise measured in the background tissue. Attenuation of at least 350 HU was deemed as diagnostic. Results The highest coronary attenuation (441 ± 23 HU, mean ± standard deviation) and CNR (29.5 ± 1.5) was achieved at 40 keV and at the highest GBCA dose (200%). There was a systematic decline of attenuation and CNR with higher keV reconstructions and lower GBCA doses. Only reconstructions at 40 and 45 keV at 200% and 40 keV at 150% GBCA dose demonstrated sufficient attenuation above 350 HU. Conclusion Current PCD-CT protocols and settings are unsuitable for the use of GBCA for CCTA at clinically approved doses. Future advances to the PCD-CT system including a 4-threshold mode, as well as multi-material decomposition may add new opportunities for k-edge imaging of GBCA. Relevance statement Patients allergic to iodine-based contrast media and the future of multicontrast CT examinations would benefit greatly from alternative contrast media, but the utility of GBCA for coronary photon-counting-dector-CT angiography remains limited without further optimization of protocols and scanner settings. Key Points GBCA-enhanced coronary PCD-CT angiography is not feasible at clinically approved doses. GBCAs have potential applications for the visualization of larger vessels, such as the aorta, on PCD-CT angiography. Higher GBCA doses and lower keV reconstructions achieved higher attenuation values and CNR. Graphical Abstract

Abstract The primary role of telomerase is the lengthening of telomeres. Nonetheless, emerging evidence highlights additional functions of telomerase outside of the nucleus. Specifically, its catalytic subunit, TERT (Telomerase Reverse Transcriptase), is detected in the cytosol and mitochondria. Several studies have suggested an elevation in TERT concentration within mitochondria in response to oxidative stress. However, the origin of this mitochondrial TERT, whether transported from the nucleus or synthesized de novo, remains uncertain. In this study, we investigate the redistribution of TERT, labeled with a SNAP-tag, in response to oxidative stress using laser scanning fluorescence microscopy. Our findings reveal that, under our experimental conditions, there is no discernible transport of TERT from the nucleus to the mitochondria due to oxidative stress.

Abstract Background The single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) is available for maintenance therapy of chronic obstructive pulmonary disease (COPD). Cardinal features of COPD are lung hyperinflation and reduced exercise capacity. TRIFORCE aimed to evaluate the effect of BDP/FF/G on lung hyperinflation and exercise capacity in patients with COPD. Methods This double-blind, randomised, active- and placebo-controlled, crossover study recruited adults with COPD aged ≥ 40 years, who were hyperinflated and symptomatic, and were receiving mono- or dual inhaled maintenance COPD therapy. In the three treatment periods, patients were randomised to receive BDP/FF/G, BDP/FF, or placebo, each for 3 weeks, with a 7–10-day washout between treatment periods. Assessments included slow inspiratory spirometry (for resting inspiratory capacity [IC]) and constant work-rate cycle ergometry (for dynamic IC and exercise endurance time). The primary objective was to compare BDP/FF/G and BDP/FF vs. placebo for resting IC at Week 3. Key secondary objectives were to compare BDP/FF/G and BDP/FF vs. placebo for dynamic IC and exercise endurance time during constant work rate cycle ergometry at Week 3. Results Of 106 patients randomised, 95 completed the study. Resting IC adjusted mean differences vs. placebo were 315 and 223 mL for BDP/FF/G and BDP/FF, respectively (p

Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition. Given patients with COPD continue to experience exacerbations despite the availability of effective therapies, anti-inflammatory treatments targeting novel pathways are needed. Kinases, notably the phosphoinositide 3-kinases (PI3K), are thought to be involved in chronic airway inflammation, with this pathway proposed as a critical regulator of inflammation and oxidative stress response in COPD. CHF6523 is an inhaled PI3Kδ inhibitor that has shown positive preclinical results. This manuscript reports the results of a study of CHF6523 in patients with stable COPD (chronic bronchitis phenotype), and who had evidence of type-2 inflammation. Methods This randomised, double-blind, placebo-controlled, two-way crossover study comprised two 28-day treatment periods separated by a 28-day washout. Patients (N = 44) inhaled CHF6523 in one period, and placebo in the other, both twice daily. The primary objective was to assess the safety and tolerability of CHF6523; the secondary objective was to assess CHF6523 pharmacokinetics. Exploratory endpoints included target engagement (the relative reduction in phosphatidylinositol (3,4,5)-trisphosphate [PIP3]), pharmacodynamic evaluations such as airflow obstruction, and hyperinflation, and to identify biomarker(s) of drug response using proteomics and transcriptomics. Results CHF6523 plasma pharmacokinetics were characterised by an early maximum concentration (Cmax), reached 15 and 10 min after dosing on Days 1 and 28, respectively, followed by a rapid decline. Systemic exposure on Day 28 showed limited accumulation, with ratios

Atmospheric precipitation acts as a significant pathway for pollutants from the atmosphere to the Earth’s surface, and analyzing urban precipitation data on intensity, fallout regime, transfer patterns, and solid particle content helps identify pollution sources. For the first time in the Moscow megacity, the levels of soluble forms of potentially hazardous elements (PHEs) in atmospheric precipitation were studied during the whole summer season of May–September 2019. The concentrations of Al, As, B, Ba, Be, Bi, Cd, Ce, Co, Cu, Fe, La, Li, Mn, Ni, P, Pb, Rb, Sb, Sn, Sr, and Zn were determined using inductively coupled plasma mass spectrometry and atomic emission spectroscopy methods. The research underscores the crucial role of atmospheric precipitation in washing PHEs out of the atmosphere. In May and September, concentrations of PHEs surpass the warm-season average. Notable contamination in May stems from elevated traffic during vacations, extensive burning of plant debris and wood, and pollen transport. Summer months are characterized by reduced forest and agricultural fires, traffic, and increased vegetation, leading to lower PHE concentrations, especially in July, with typical amount of precipitation contributing to pollutant dispersion. Elevated PHE levels in September are observed due to increased traffic load, biomass burning, and the expansion of unvegetated soil areas. Rainwater is enriched with Sb, Pb, Cd, Zn, Cu, B, Bi, P, and Sr, sourced from vehicle emissions, soil particles, industry, construction dust, biomass burning, and forest fires. Moderate enrichment with Ba, Mn, Ni, Co, and Sn also occurs episodically. Regression analysis highlights solid particles’ role as a major PHE source in rainwater, with the longer antecedent dry periods and the higher acidity level of rain intensifying the accumulation of PHEs. Long-range transport plays a lesser role, with Southern and Northern Europe, Western Siberia, and the central part of European Russia contributing meaningfully.

[Purpose] The purpose of this study is to discuss, based on international as well as national laws and practices, various issues and potential solutions surrounding the growing problem of money laundering practices using cryptocurrency transactions. [Methodology] A balanced combination of theoretical and empirical methods has been used in the course of research; in particular, the method of comparative legal research has been employed extensively throughout the text of article. The theoretical component of this research paper includes commentaries by Ukrainian, German, other European as well as American researchers in this field. Their works are cited appropriately. The subject scope of the paper covers modern phenomenon of money laundering based on cryptocurrency transactions. [Findings] This paper extensively discusses international and national legal frameworks for identifying and stopping as well as preventing various money laundering schemes and techniques based on cryptocurrency transactions and blockchain technology in general. It has been established that with the global cryptocurrency market valued at roughly $1 trillion, its attractiveness to money launderers endangers economies and financial systems of numerous world jurisdictions. Based on theoretical observations and relevant analyses of legal cases, authors’ conclusions on how to fight this latent type of criminality have been presented. [Practical Implications] The research is deemed to be of value to national regulators, law enforcement agents and legal commentators, who think, write and act with the goal of fighting new money laundering patterns. It can serve as part of a broader international roadmap on how to identify suspicious money laundering schemes using various cryptocurrency transactions and also to impose effective sanctions on criminal actors behind those schemes. [Originality] The paper originality relies on its comprehensive and balanced combination of economic and legal analyses of the issues presented and potential solutions to them. It also incorporates both sound theoretical research and in-depth coverage of law enforcement actions, as well as legal cases against crypto money launderers.

Abstract Maritime historical documentary sources of weather and state of sea surface including sea ice can aid in filling a known climate knowledge gap for the Southern Ocean and Antarctica for the first half of the 20th century. This study presents a data set of marine climate, sea ice and icebergs recovered from a collection of logbooks from mainly Norwegian whaling factory ships that operated in the Southern Ocean during 1929–1940. The data set comprises some 8000 weather and 4000 sea ice/open sea records from austral summers of the study period. This paper further discusses the structure and content of most common Norwegian maritime documentary sources of the period along with the practices of logging information relevant for the study, such as time keeping, positioning and making weather observations. An emphasis was made on recovery of notes on sea ice and icebergs and their interpretation in terms of WMO categories of sea ice concentration. Data, including ship‐related metadata from all individual documents are homogenized and structured to a common machine‐readable format that simplifies its ingestion into relevant climate data depositories.

Abstract Objectives To assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis. Methods In this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007–2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge. Results In total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1–5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5–53). The median extent of LGE was 7% (IQR, 4–10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29–17.49; p

Abstract Hyperemia in response to neural activity is essential for brain health. A hyperemic response delivers O2 and nutrients, clears metabolic waste, and concomitantly exposes cerebrovascular endothelial cells to hemodynamic forces. While neurovascular research has primarily centered on the front end of hyperemia—neuronal activity-to-vascular response—the mechanical consequences of hyperemia have gone largely unexplored. Piezo1 is an endothelial mechanosensor that senses hyperemia-associated forces. Using genetic mouse models and pharmacologic approaches to manipulate endothelial Piezo1 function, we evaluated its role in blood flow control and whether it impacts cognition. We provide evidence of a built-in brake system that sculpts hyperemia, and specifically show that Piezo1 activation triggers a mechano-feedback system that promotes blood flow recovery to baseline. Further, genetic Piezo1 modification led to deficits in complementary memory tasks. Collectively, our findings establish a role for endothelial Piezo1 in cerebral blood flow regulation and a role in its behavioral sequelae.

Abstract IP3 receptor (IP3R)-mediated Ca2+ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial Ca2+ uptake and oxidative metabolism and is linked to different pathologies, including Parkinson’s disease (PD). The dependence of Ca2+ transfer efficiency on the ER-mitochondria distance remains unexplored. Employing molecular rulers that stabilize ER-mitochondrial distances at 5 nm resolution, and using genetically encoded Ca2+ indicators targeting the ER lumen and the sub-mitochondrial compartments, we now show that a distance of ~20 nm is optimal for Ca2+ transfer and mitochondrial oxidative metabolism due to enrichment of IP3R at MERCS. In human iPSC-derived astrocytes from PD patients, 20 nm MERCS were specifically reduced, which correlated with a reduction of mitochondrial Ca2+ uptake. Stabilization of the ER-mitochondrial interaction at 20 nm, but not at 10 nm, fully rescued mitochondrial Ca2+ uptake in PD astrocytes. Our work determines with precision the optimal distance for Ca2+ flux between ER and mitochondria and suggests a new paradigm for fine control over mitochondrial function.

Abstract Background Cigarette smoking prevalence is higher for rural than urban adults, yet digital access to cessation programming is reduced. We aim to investigate digital access interventions to promote engagement with an online evidence-based cessation treatment (EBCT) program among rural adults. Methods This pilot trial used a pragmatic, three-arm, randomized, parallel-group design (ClinicalTrials.gov: NCT05209451). Inclusion criteria included being aged ≥18, Mayo Clinic Midwest patient, rural residency, and currently smokes cigarettes. All participants received an online, 12-week EBCT program and were randomized to receive one of three digital access interventions: print materials (control, n = 30); print materials + loaner iPad device with data plan coverage (n = 30); or print materials + loaner device + up to six, 15–20-minute motivational interviewing-based coaching calls to support technology needs (n = 30). A composite score of trial engagement (primary outcome) and self-reported smoking abstinence and use of EBCT resources (secondary outcomes) were assessed online at 4 and 12 weeks. Qualitative interviews were used to assess patient experience. Neither participants nor outcome assessors were blinded to group assignment. Results Results are reported for all 30 participants in each group. The average age of participants is 51.0 years and 61% are women. We show no significant arm differences for the trial engagement composite score (p = 0.30). We also find coaching support is significantly (p

This study examines the importance of Myanmar for the formation of a Sino-centric macro-region through the Belt and Road Initiative (BRI). The authors rely on the transit of power theory that helps to analyze systemic imperatives and internal characteristics of China’s foreign policy. The authors applied the principles of historicism, scientific objectivity and reliability. In the first part of the work, the Chinese Belt and Road initiative is studied as a geostrategic tool of the People’s Republic of China (PRC). The authors consider the features of its development and the strategic results of its implementation. In particular, the article emphasizes that this initiative is aimed at the formation of a Sino-centric macro-regional space. Based on this, the role of Myanmar is characterized as essential. The geographical location of this state allows China to gain access to the Indian Ocean, a transit region for energy resources, as well as to overcome one of the strategic vulnerabilities of its geopolitical position - the ‘Malacca dilemma.’ Moreover, as a border state, Myanmar is an indispensable link in the implementation of land and gas energy transport corridors of macro-regional importance. Finally, in the context of strategic competition between the United States and China, the importance of ensuring stability in critical proximity to the PRC’s state borders is growing, especially in the absence of a stable internal state situation in Myanmar. Among the additional factors, the authors highlight the importance of the mood of state and local elites for the development of this initiative. In this regard, the analysis of China’s reaction to the military coup in Myanmar in February 2021 was particularly indicative that Myanmar is of key importance because of its strategic location between China and the Indian Ocean, as well as its resource potential.

Abstract In this study, we explore the real-time dynamics of the chiral magnetic effect (CME) at a finite temperature in the (1+1)-dimensional QED, the massive Schwinger model. By introducing a chiral chemical potential μ 5 through a quench process, we drive the system out of equilibrium and analyze the induced vector currents and their evolution over time. The Hamiltonian is modified to include the time-dependent chiral chemical potential, thus allowing the investigation of the CME within a quantum computing framework. We employ the quantum imaginary time evolution (QITE) algorithm to study the thermal states, and utilize the Suzuki-Trotter decomposition for the real-time evolution. This study provides insights into the quantum simulation capabilities for modeling the CME and offers a pathway for studying chiral dynamics in low-dimensional quantum field theories.

Abstract Altermagnets are a novel class of magnetic materials, where magnetic order is staggered both in coordinate and momentum space. The metallic rutile oxide RuO2, long believed to be a textbook Pauli paramagnet, recently emerged as a putative workhorse altermagnet when resonant X-ray and neutron scattering studies reported nonzero magnetic moments and long-range collinear order. While some experiments seem consistent with altermagnetism, magnetic order in RuO2 remains controversial. We show that RuO2 is nonmagnetic, both in bulk and thin film. Muon spectroscopy complemented by density-functional theory finds at most 1.14 × 10−4 μ B/Ru in bulk and at most 7.5 × 10−4 μ B/Ru in 11 nm epitaxial films, at our spectrometers’ detection limit, and dramatically smaller than previously reported neutron results that were used to rationalize altermagnetic behavior. Our own neutron diffraction measurements on RuO2 single crystals identify multiple scattering as the source for the false signal in earlier studies.

Abstract Climate change is currently one of humanity’s greatest threats. To help scholars understand the psychology of climate change, we conducted an online quasi-experimental survey on 59,508 participants from 63 countries (collected between July 2022 and July 2023). In a between-subjects design, we tested 11 interventions designed to promote climate change mitigation across four outcomes: climate change belief, support for climate policies, willingness to share information on social media, and performance on an effortful pro-environmental behavioural task. Participants also reported their demographic information (e.g., age, gender) and several other independent variables (e.g., political orientation, perceptions about the scientific consensus). In the no-intervention control group, we also measured important additional variables, such as environmentalist identity and trust in climate science. We report the collaboration procedure, study design, raw and cleaned data, all survey materials, relevant analysis scripts, and data visualisations. This dataset can be used to further the understanding of psychological, demographic, and national-level factors related to individual-level climate action and how these differ across countries.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aβ) accumulations. Alzheimer’s patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.

Abstract Nonlocal metasurfaces have recently enabled an ultra-compact, low-power and high-speed platform to perform analog image processing. While several computational tasks have been demonstrated based on this platform, most of the previous studies have focused only on spatial operations, such as spatial differentiation and edge detection. Here, we demonstrate that metasurfaces with temporal nonlocalities – that is, with a tailored dispersive response – can be used to implement time-domain signal processing in deeply subwavelength footprints. In particular, we experimentally demonstrate a passive metasurface performing first-order differentiation of input signals with high-fidelity and high-efficiency. We also show that this approach is prone to scalability and cascaded computation. Our work paves the way to a new generation of ultra-compact, passive devices for all-optical computation, with applications in neural networks and neuromorphic computing.

Abstract Background Pelvic organ prolapse (POP) is one of the most common pathologies of the pelvic floor, and it can be found among 40–60% of women who have given birth. Correction of the defect of the DeLancey level II without reconstruction of the apical defect is doomed to failure. Also, in the structure of pelvic floor defects, there is often an incompetency of the perineal body, as a consequence of traumatic delivery. Perineoplasty is considered to be the main method of correction for perineal body incompetency. However, it is worth mentioning that there are no randomized trials, which estimate the influence of simultaneous correction of the perineal body on the effectiveness of transvaginal apical fixation. Methods It is planned to include 310 patients in this trial. Patients who met the inclusion/exclusion criteria will be randomized into 2 groups: 1st group—patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy without perineoplasty, 2nd group—patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy and perineoplasty. Patients will be called to an appointment 6, 12, and 24 months after discharge. Discussion The aim of this trial is to evaluate the efficiency and safety of simultaneous perineoplasty on the clinical and anatomical efficacy of mesh-augmented sacrospinal fixation in advanced pelvic organ prolapse repair. Based on previous studies, it was difficult to estimate and comprehend whether colpoperinoplasty actually reduces the risk of prolapse recurrence. Trial registration NCT05422209. Registered on 18 May 2022.

Abstract Background To date a number of papers analysing outcomes of the frozen elephant trunk (FET) in acute aortic dissection has been published. However, there are limited comparative studies on long-term outcomes of FET in acute and chronic aortic dissection. The objective of the study was to analyze the long-term outcomes after FET procedure for aortic dissection (AD). Methods Between March 2012 and December 2022, a total of 123 FET had been performed for thoracic aortic disease. Patients with aortic dissection (n = 97) were divided into 2 groups: acute (n = 32, 33%) and chronic aortic dissection (n = 65, 67%). Pre-, intra- and postoperative data were retrospectively collected from electronic patient’s records, including follow-up data of the analyzed patients. Results The incidence of stroke was 3.1%. The delirium rate was up to 9.3% in both groups with a prevalence in chronic aortic dissection (CAD) group without significant differences (P = 0.494). Paraplegia was diagnosed only in CAD patients (n = 2). Respiratory failure and the rate of renal replacement therapy were similar in the studied groups. Re-sternotomy was required in one (3.1%) patient with acute AD and 5 (7.7%) patients with chronic AD (P = 0.416). Overall 30-day mortality in the entire cohort, acute and chronic AD was 13 (13.4%), 7 (21.9%) and 6 (9.2%), respectively (P = 0.097). The overall survival rate at 60 months for the entire cohort, acute and chronic AD was 64.1 ± 5.9%, 62.3 ± 9.1%, 66.5 ± 7%, respectively (P = 0.265). Freedom from unintended distal aortic re-intervention at 60 months for the entire cohort of patients, acute and chronic AD was 74.2 ± 1.5%, 100%, 65.3 ± 2%, respectively (P = 0.355). Conclusions Our experience showed acceptable long-term outcomes after the FET procedure including mortality and re-intervention rate in patients with aortic dissection regardless of acuity of the dissection. Trial registration The study has been registered in Australian and New Zealand Clinical Trial Registry (ACTRN 12618001329257) on August 7, 2018.

Abstract ZrO2 ceramics have wide applications as structural materials in industrial, scientific, and technological fields. Despite the large number of works devoted to the influence of synthesis parameters on the formation of different phases of ZrO2 and the properties of the obtained ceramics, the effect of sintering temperature on the characteristics of the porous ZrO2 ceramics has not been addressed sufficiently. This study focuses on examining how sintering temperature affects the phase composition, microstructure, dielectric properties, and mechanical properties of porous stabilized zirconium dioxide ceramics. Phase transformations during sintering at various temperatures were identified using powder X-ray diffraction and Raman spectroscopy. The results indicate that fully stabilized cubic ZrO2 with satisfactory mechanical properties (HV0.5 = 580) and a porosity of 21.5% was achieved at temperatures of 1400 and 1500 ℃. At lower sintering temperatures, the obtained samples exhibited multiphase composition and high porosity. The reasons for the formation of the CaZrO3 phase at sintering temperatures of 1000–1200 ℃ were established using scanning electron microscopy, energy dispersive analysis, and thermodynamic considerations of the solid-phase reactions. AC dielectric measurements showed that the synthesized samples have high-Q characteristics; and that the dielectric constant can be controlled by changing the sintering temperature.

Producing powder compositions using conventional processing technology can lead to the formation of large agglomerates and, therefore, makes it difficult to obtain a uniform microstructure. The production of composites by self-propagating high-temperature synthesis can reduce costs and the number of technological stages, as well as lead to obtaining composites that are more homogeneous. Synthesis by the combustion of mixtures of powder reagents of sodium azide (NaN3), fluoroplastic (C2F4), aluminum and titanium with different ratios of reagents in a nitrogen gas atmosphere at a pressure of 4 MPa was used for the production of a highly dispersed powder ceramic AlN–TiC composition. Thermodynamic calculations have confirmed the possibility of synthesis of AlN–TiC compositions of different formulations in combustion mode. The dependences of temperature and combustion rate on the composition of the initial mixtures of reagents were experimentally determined for all stoichiometric reaction equations. The study have shown that the experimentally found dependences of combustion parameters on the ratio of the initial components correspond to the theoretical results of thermodynamic calculations. The formulation of the synthesized composition differs from the theoretical composition by a lower content of target phases and the formation of Al2O3, Na3AlF6 and TiO2 side phases. The powder composition consists of aluminum nitride fibers with a diameter of 100–250 nm and ultradisperse particles of predominantly equiaxed and lamellar shapes with a particle size of 200–600 nm. As the combustion temperature increases to produce the largest amount of titanium carbide phase, the particle size increases to the micron level.

We present the results of a statistical study of transient enhancements of electrons with energies >30 keV at low drift shells in the quasi-trapped region (forbidden zone) at the geomagnetic equator. Using data from low-altitude NOAA/POES and MetOp satellites, we have compiled a catalog of events with forbidden energetic electron (FEE) enhancements for the period from 1998 to 2023. Statistical analysis of FEE events has revealed solar-cyclic, as well as seasonal and diurnal variations in the occurrence of FEE enhancements. We have examined the correlation of the annual frequency of FEE events with solar activity, solar wind parameters, and geomagnetic activity. Strong correlations have been found with the F10.7 index of solar activity (radio emission flux) as well as with the Alfvén Mach number (solar wind parameter). An interpretation of the obtained results is proposed which is based on the mechanism of electrical drift and radial transport of electrons from Earth’s inner radiation belt to the quasi-trapped region (L

An elliptical model of cutoff for solar cosmic rays (SCR) at high latitudes has been calculated for SCR events and geomagnetic storms that occurred in February, March, and September 2014, June 2015, and September 2017 in order to predict the polar cap absorption (PCA) effect. The prediction is compared with observations of the PCA effect at the AARI network of six ionosondes, located in the north of Russia in a wide range of longitudes from 30 to 170 and magnetic latitudes from 56 to 64. We examine the dependence of the cutoff latitude on the magnetic storm strength, as well as the effect of additional ionization of the dayside and nightside ionosphere by SCR protons and electrons. The model demonstrates a satisfactory statistical accuracy up to 0.83 for the PCA prediction. We discuss prospects for further improvement of the elliptical model, such as consideration of the impact of SCRs of higher energies and inclusion of the PC index of energy flux into the polar cap.

Aim. To evaluate the possibilities of post-processing of multidetector computed tomography (CT) results in the non-invasive diagnosis of pancreatic fibrosis (PF). Materials and methods. The study included 165 patients aged 57.91±13.5 years who underwent preoperative CT during surgical treatment for chronic pancreatitis and pancreatic cancer from April 2022 to February 2024. The normalized contrast ratios of pancreatic tissue in the pancreatic (NCPP) and venous (NCVP) phases, as well as the contrast ratio (CR) were measured. Pathomorphological assessment of PF performed in tissues outside neoplasm or desmoplastic reaction by the Kloppel and Maillet scale. Results. The values of post-processing CT results were compared in groups with different degrees of PF. Mean CR values were significantly higher (p=0.001) in patients with severe PF (CR 1.16±0.65 HU) than in patients with mild PF (CR 0.78±0.31 HU). CR value significant increase (p=0.03) was found in patients with signs of inflammatory changes in the pancreas tissue (CR 1.14±0.6 HU) than in those without them (CR 0.81±0.3 HU). There were no significant differences between the values of NCPP and NCVP, and the degree of PF. Conclusion. The CR value increased in patients with severe degree of PF. There was a relationship between CR value increase and the radiological density of pancreatic tissue in non-contrast phase and presence of early signs of pancreatic inflammatory changes. Thus, there was a relationship between CT postprocessing results and morphological signs of PF, which can be used for pancreatic fibrosis non-invasive diagnosis and identification of additional signs of early chronic pancreatitis.

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

Aim. To study the association of comorbidities and treatment outcomes in tuberculosis (TB) patients. Materials and methods. A retrospective study includes all TB patients aged 18 years and older registered for treatment in Moscow in period 2021 the end of the 3rd quarter of 2022 using data of regional epidemiological TB monitoring system, a total of 3039 patients. The frequency and spectrum of comorbidities, its impact on the risk of adverse treatment outcome (ATO) and mortality using univariate and regression analysis were assessed. Results. Comorbidities were identified in 1528 (50.3%) patients (95% confidence interval – CI 48.5–52.1); HIV infection (18.0%), chronic nonspecific lung disease (9.6%) and cardiovascular disease (8.2%) were predominant. The presence of comorbid pathology increased the odds of uneffective treatment (odds ratio – OR 2.56, 95% CI 2.22–3.03) and death (OR 2.45, 95% СI 1.67–3.59). Independent risk factors for ATO were HIV infection (OR 4.10, 95% CI 3.36–5.10), substance use (OR 2.57, 95% CI 1.70–3.66), chronic nonspecific lung disease (OR 1.39, 95% CI 1.04–1.88), diabetes mellitus (OR 1.69, 95% CI 1.15–2.48), liver pathology (OR 2.10, 95% CI 1.46–3.03), mental illness (OR 2.01, 95% CI 1.32–3.06). The death rate was 13.4%; the most significant predictors of mortality were HIV infection (OR 3.89, 95% CI 2.42–6.22) and liver disease (OR 1.90, 95% CI 1.27–2.82). A comorbidome model was constructed to assess the importance of different comorbidities for patient prognosis. Conclusion. The presence of comorbidity (predominantly HIV infection and liver disease) is a significant risk factor for ATO and mortality in TB patients, which should be taken into account when organizing and providing TB care to comorbid patients.

Background. Medication errors can cause preventable adverse events. For example, inappropriate use of anticoagulants (AC) can result in bleeding and thromboembolic complications. Detection and analysis of AC medication errors allow to reveal deficiencies in the safety systems in healthcare organizations. Aim. The study was aimed to develop a method of systematic detection of anticoagulant medication errors for consequent audit, analysis and development of medication safety improvement measures. Materials and methods. The study was conducted in the multidisciplinary hospital and included 4924 patients admitted from January 2019 to December 2021 who received AC. Three laboratory triggers (international normalized ratio ≥4, serum creatinine ≥133 μmol/l, and glomerulofiltration rate 30 ml/min/1.73 m2) helped to reveal 4304 cases. Their matching with patient’s data helped to develop combined triggers. Two clinical pharmacologists reviewed all cases identified by combined triggers for checking medication errors. The trigger was considered positive when anticoagulant medication error was detected in the history selected by combined trigger. Results. Of the 4924 patients 253 (5.3%) were selected by combined triggers. Combined trigger allowed to reduce the amount of medical health records audit by 97.3%. Medication errors were detected in 137 patients. Positive predictive value of selected combined triggers varied from 0 to 63.9%. Aggregated positive predictive value of all combined triggers amounted to 54.2%. AC medication errors were detected in 2.8% patients. Conclusion. Method of systematic detection of AC medication errors using combined triggers in all hospitalized patients receiving AC allowed to reveal typical medication errors for consequent analysis and elaboration of measures to reduce preventable patient harm in healthcare settings.

Aim. To determine the phenotypic variants of patients with symptoms of gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), hypersensitive esophagus (HSE), functional heartburn (FH) using 24-hour pH-impedance testing and high-resolution esophageal manometry (HSEM). Materials and methods. Fifty-five treatment-native symptomatic patients with newly diagnosed GERD and 48 control group subjects (CG) were examined. The mean age of the subjects was 45.0 years (95% confidence interval [CI] 41.0–48.9). Patients were grouped based on typical symptoms (heartburn, belching, regurgitation, odynophagy, dysphagia), medical history, endoscopy results, and 24-hour pH-impedance testing. Patients with typical symptoms of GERD and Grade B, C, D erosive esophagitis (EE) according to the Los Angeles Classification (LA) based on endoscopy were excluded from the further study. All patients without changes in the esophageal mucosa on endoscopy or with LA grade A EE (presumably NERD) underwent 24-hour pH-impedance testing and HSEM without proton pump inhibitors. Acid exposure, acid reflux count, symptom association with reflux (with symptom index and symptom association with reflux), mean nocturnal impedance, and post-reflux swallow-induced peristaltic wave index were assessed. The structure (presence or absence of a hiatal hernia) and function (presence or absence of the lower esophageal sphincter hypotonia) of the esophagogastric junction, as well as the motor function of the thoracic esophagus, were assessed using HSEM. The results of the HSEM were interpreted according to the Chicago Classification, 3rd edition (2015). Results. The number of acid refluxes in patients with NERD was 71.0 (95% CI 58.4–83.7), in subjects with HSE – 38.5 (95% CI 28.3–49.0), with FH – 13.0 (95% CI 6.5–18.2), in CG – 16.5 (95% CI 9.0–21.0). The average nocturnal basal impedance was 1300 ohms (95% CI 1000–1986) in patients with NERD, 1725 ohms (95% CI 1338–2261) in patients with HSE, 2760 ohms (95% CI 2453–3499) in FH, 2515 ohms (95% CI 2283–2700) in CG. The index of post-reflux swallow-induced peristaltic wave in patients with NERD was 61% (95% CI 57–71), with HSE – 85% (95% CI 82–88), with FH – 71% (95% CI 64–78), in CG – 66% (95% CI 63–69). Hiatal hernia and/or hypotonia of the LES were more common in patients with NERD (23%) than in CG (13.3%). Ineffective motility was detected in 34% of patients with NERD, in 23% of subject with FH and in 66.7% of patients with HSE. Conclusion. The results support the hypothesis that patients with GERD symptoms represent a heterogeneous population. 24-hour pH-impedance testing and HSEM helps to differentiate endoscopically negative patients with GERD symptoms and patients with Grade A EE by LA to NERD, HSE and FH.

Abstract String theory on AdS3 × S3 × T4 geometries supported by a combination of NS-NS and R-R charges is believed to be integrable. We elucidate the kinematics and analytic structure of worldsheet excitations in mixed charge and pure NS-NS backgrounds, when expressed in momentum, Zhukovsky variables and the rapidity u which appears in the quantum spectral curve. We discuss the relations between fundamental and bound state excitations and the role of fusion in constraining and determining the S matrices of these theories. We propose a scalar dressing factor consistent with a novel u-plane periodicity and comment on its close relation to the XXZ model at roots of unity. We solve the odd part of crossing and show that our solution is consistent with fusion and reduces in the relativistic limit to dressing phases previously found in the literature.

Abstract In this work, we have analyzed the transcriptomic changes in the brainstem of male Wistar rats 2 h after an acute stress exposure. We performed duplex-specific nuclease normalization of cDNA libraries and compared the results back-to-back for the first time. Based on our RNAseq data, we selected reference genes for RT-qPCR that are best suited for acute stress experiments. Most genes were upregulated. We detected a massive shift in neuropeptide Crh, Trh,Cga, Tshb, Uts2b, Tac4, Lep and neuropeptide receptor Hcrtr1, Sstr5, Bdkrb2, Crhr2 signaling, as well as glutamate Grin3b, Grm2 and GABA Gpr156, acetylcholine Chrm4,Chrne, adrenergic Adra2b receptors expression. A strong increase in the expression of intermediate filaments Krt83/Krt86/Krt80/Krt84/Krt87/Krt4/Krt76 and motor proteins Myo7a, Klc3 was detected. Remarkably, in the absence of astrocyte activation, we also observed signs of microglial activation at this time point. Both expression of anti-inflammatory cytokines Il13, Ccl24 and pro-inflammatory cytokine receptors Il9r, Il12rb1, Tnfrsf14, Tnfrsf13c, Tnfrsf25, Tnfrsf1b were increased. In the Wnt signaling pathway, we observed increased expression of ligands-receptors Wnt1, Wnt11, Ror2 and also negative regulators Notum, Sfrp5, Sost. RNAseq results after DSN treatment correlated at a high level with RNAseq results without DSN, but there was a proportion of genes that shifted their logFC values. They are mostly rare transcripts TPM 1–10 with higher 0.5–0.9 GC content.

Abstract Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that is a disease-modifying drug candidate for Parkinson’s disease. CDNF has pleiotropic protective effects on stressed cells, but its mechanism of action remains incompletely understood. Here, we use state-of-the-art advanced structural techniques to resolve the structural basis of CDNF interaction with GRP78, the master regulator of the unfolded protein response (UPR) pathway. Subsequent binding studies confirm the obtained structural model of the complex, eventually revealing the interaction site of CDNF and GRP78. Finally, mutating the key residues of CDNF mediating its interaction with GRP78 not only results in impaired binding of CDNF but also abolishes the neuroprotective activity of CDNF-derived peptides in mesencephalic neuron cultures. These results suggest that the molecular interaction with GRP78 mediates the neuroprotective actions of CDNF and provide a structural basis for development of next generation CDNF-based therapeutic compounds against neurodegenerative diseases.

Abstract Specialized function gradient computing hardware could greatly improve the performance of state-of-the-art optimization algorithms. Prior work on such hardware, performed in the context of Ising Machines and related concepts, is limited to quadratic polynomials and not scalable to commonly used higher-order functions. Here, we propose an approach for massively parallel gradient calculations of high-degree polynomials, which is conducive to efficient mixed-signal in-memory computing circuit implementations and whose area scales proportionally with the product of the number of variables and terms in the function and, most importantly, independent of its degree. Two flavors of such an approach are proposed. The first is limited to binary-variable polynomials typical in combinatorial optimization problems, while the second type is broader at the cost of a more complex periphery. To validate the former approach, we experimentally demonstrated solving a small-scale third-order Boolean satisfiability problem based on integrated metal-oxide memristor crossbar circuits, with competitive heuristics algorithm. Simulation results for larger-scale, more practical problems show orders of magnitude improvements in area, speed and energy efficiency compared to the state-of-the-art. We discuss how our work could enable even higher-performance systems after co-designing algorithms to exploit massively parallel gradient computation.

Abstract Hydrogen sulfide (H2S), mainly produced from L-cysteine (Cys), renders bacteria highly resistant to oxidative stress and potentially increases antimicrobial resistance (AMR). CyuR is a Cys-dependent transcription regulator, responsible for the activation of the cyuPA operon and generation of H2S. Despite its potential importance, its regulatory network remains poorly understood. In this study, we investigate the roles of the CyuR regulon in a Cys-dependent AMR mechanism in E. coli strains. We show: (1) Generation of H2S from Cys affects the sensitivities to growth inhibitors; (2) Cys supplementation decreases stress responses; (3) CyuR negatively controls the expression of mdlAB encoding a potential transporter for antibiotics; (4) CyuR binds to a DNA sequence motif ‘GAAwAAATTGTxGxxATTTsyCC’ in the absence of Cys; and (5) CyuR may regulate 25 additional genes which were not reported previously. Collectively, our findings expand the understanding of the biological roles of CyuR relevant to antibiotic resistance associated with Cys.

Abstract Background STEM education has experienced significant growth due to its pivotal role in innovation and economic development. While cognitive factors like prior knowledge are known predictors of STEM success, non-cognitive factors, including attitudes and demographics, also play vital roles. However, there is a notable scarcity of research focusing on the "S" in STEM—science—compared to extensive studies in fields like mathematics. This study aims to address this gap by exploring gender differences in science test performance and related attitudes, providing insights into this under-researched aspect of STEM education. Results The effective sample comprised 1839 Estonian 12th-grade students who took a computer-assisted science test. The test consisted of tasks combining chemistry, physics, biology, and geography, and a post-test survey was also administered. Across the total sample, the results showed that test performance positively correlated with test-taking duration, effort, and test importance. Test performance was negatively correlated with perceived test difficulty. Interestingly, while general science anxiety was not associated with test performance, subject-specific anxiety, especially chemistry anxiety had a negative association with test performance. While there were no gender differences in test performance, female students scored consistently higher on all science anxiety measures, compared to male students. Furthermore, female students assessed the science test to be more difficult, and they also took more time to complete the test. The correlations in gender subsamples mirrored those observed in the total sample. Conclusions The association between science test performance and test-related variables is nuanced: students might not necessarily have a “general” STEM anxiety but it may be associated with a specific subject. Moreover, the findings imply that although there are no gender differences in test performance, girls have a greater anxiety when it comes to natural sciences subjects. These findings indicate the need for investigating the origin of such anxieties, which do not seem to stem from aptitude.