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Abstract The antimicrobial resistance crisis along with challenges of antimicrobial discovery revealed the vital necessity to develop new antibiotics. Many of the animal proline-rich antimicrobial peptides (PrAMPs) inhibit the process of bacterial translation. Genome projects allowed to identify immune-related genes encoding animal host defense peptides. Here, using genome mining approach, we discovered a family of proline-rich cathelicidins, named rumicidins. The genes encoding these peptides are widespread among ruminant mammals. Biochemical studies indicated that rumicidins effectively inhibited the elongation stage of bacterial translation. The cryo-EM structure of the Escherichia coli 70S ribosome in complex with one of the representatives of the family revealed that the binding site of rumicidins span the ribosomal A-site cleft and the nascent peptide exit tunnel interacting with its constriction point by the conservative Trp23-Phe24 dyad. Bacterial resistance to rumicidins is mediated by knockout of the SbmA transporter or modification of the MacAB-TolC efflux pump. A wide spectrum of antibacterial activity, a high efficacy in the animal infection model, and lack of adverse effects towards human cells in vitro make rumicidins promising molecular scaffolds for development of ribosome-targeting antibiotics.

The article deals with the issues of the impact of the quality of consumers' heat supply on the sustainable development of the urban areas infrastructure focused on the implementation of the United Nations Program on Human Settlements (UN-Habitat). A group of five countries of Central Asia has been studied, the quality of heat supply to consumers of which has long been ensured through centralized systems. An analysis of the heat supply quality in these countries showed that the main advantage of district heating, cogeneration, is losing its usefulness for consumers due to the significant accumulated wear and tear of heat supply systems. Quantitative dynamic characteristics of the heat supply facilities functioning are considered. A set of indicators for evaluating investment projects aimed at improving the heat supply quality is presented, that made it possible to propose rating indicators of heat supply interconnected with the Sustainable Development Goals (SDGs).

BACKGROUND: Radiomics is the newest and most promising direction in modern radiographic diagnostics. The number of head and neck cancer studies employing radiomics is increasing annually. A systematic review of recent publications (2021–2023) on computed tomography (CT) of head and neck malignancies was performed. AIM: To present systematized data on parameters for radiomic analysis for head and neck malignancies identified by CT data. MATERIALS AND METHODS: The literature search was carried out in PubMed. The basic characteristics of the selected articles were extracted, and their quality was assessed using RQS 2.0 and the modified QUADAS-CAD questionnaire. The reproducibility level of radiomic parameters selected for predictive models in different studies was assessed. Eleven articles were selected for the review. In most cases, a high risk of systematic error associated with data imbalance in terms of demographic parameters and level of pathologies was noted. RESULTS: The range of RQS 2.0 scores for the included articles varied from 19.44% to 50.00% of the maximum possible score. The decreasing research quality was mainly caused by the lack of external result validation (73% of the analyzed articles) and data accessibility and transparency (82%). Inter-study reproducibility of radiomic parameters was low owing to the wide variety of techniques used for image acquisition, image post-processing, extraction, and statistical processing of radiomic parameters. CONCLUSION: A set of stable radiomic parameters must be successfully introduced into clinical practice. The standardization of radiomics method and creation of an open radiomics database are necessary for this purpose.

Background: Galectin-1 plays an important role in the pathogenesis of colorectal cancer (CRC). The blood and tumoral levels of galectin-1 could be dependent on the polymorphism of the promotor region of LGALS1 gene. Aim: To analyze an association between galectin-1 levels in tumor tissue and plasma and the genotype of the rs4820293 and rs4820294 polymorphisms of the LGALS1 gene in CRC patients. Materials and methods: The study included a total of 70 inpatients with pathologically verified CRC (International Classification of Diseases 10th Revision codes C18-C20, 39 men and 31 women, mean age 65.4 ± 5.7 years), who were receiving treatment in the Tomsk Regional Oncology Center and Cancer Research Institute of the Tomsk National Research Medical Center from 2020 to 2022. The control group consisted of 70 healthy volunteers (34 men and 36 women, mean age 62.3 ± 7.2 years). Venous blood samples were taken from all study participants and tumor tissue samples were obtained from the CRC patients. Galectin-1 expression in the tumor tissue was assessed by immunohistochemistry and plasma galectin-1 levels by enzyme-linked immunosorbent assay. The LGALS1 gene polymorphisms rs4820293 and rs4820294 were identified by restriction fragment length polymorphism analysis. Results: The distributions of genotype and allele frequencies of polymorphic variants rs4820293 and rs4820294 of the LGALS1 gene in the CRC patients and in the healthy donors were comparable (p 0.05). Calculation of odds ratios did not confirm any association between LGALS1 gene polymorphisms and CRC. However, the rs4820294 polymorphism had a strong association with regional metastasis and tumor differentiation grade (Cramer's V above 0.4, p 0.001). The plasma galectin-1 levels in the CRC patients with the AA genotype of the rs4820294 polymorphism were higher than in the healthy carriers (17.42 versus 12.92 ng/ml, p = 0.040). However, there were no significant differences in the content of galectin-1+ cells in the tumor and galectin-1 in plasma of the CRC patients depending on the genotype of the LGALS1 gene polymorphisms (p 0.05). Conclusion: The LGALS1 gene polymorphism is not associated with CRC, but in the carriers of the rs4820294 variant is related to clinical and morphological parameters of the tumor process. The intratumoral expression and blood levels of galectin-1 in CRC patients are not dependent on the genotype of rs4820293 and rs4820294 polymorphisms of the LGALS1 gene.

Aim. To analyze the dynamics of the incidence and prevalence of uterine fibroids (UF) in the population of women in the Sverdlovsk region (SR) and the municipality of Yekaterinburg. Materials and methods. A study was conducted on the incidence and prevalence of UF in rural and urban women aged 18 years and over in 2016–2022. The data from Table No. 3000 of the Federal Statistical Observation Form No. 12 “Information on the number of diseases registered in patients living in the service area of a medical organization” were analyzed. When calculating the indicators, the average annual number of women aged 18 years and over in 2016–2022 was used, the values were expressed in 0/0000. Results. It was found that the incidence of UF in SR was 149.11 0/0000, in the city – 130.89 0/0000 in 2016. There was an increase in the incidence of UF in the SR and the city by 1.93 and 1.96 times in 2019, respectively, compared with 2016 (p0.001). The average growth rate (AGR) of incidence in the SR and the city was 24.6 and 25.2% respectively, and had a pronounced growth dynamics in 2016–2019. The prevalence of UF in SR was 735.8 0/0000, in the city – 650.74 0/0000 in 2016. Subsequently, the dynamics of the increase in prevalence, similar to the incidence, was observed. The prevalence rate in the region was 15.5%, in the city – 11.6% in 2016–2019. There was a decrease in the incidence of UF in SR (p=0.014) and the city (p0.001) in 2020–2022. The AFR had a negative value: -3.4 and -7.9%. The prevalence of UF corresponded to a moderate trend, taking into account the positive values of AFR: 1.3% in SR and 2.3% in the city. Conclusion. The prevalence of UF in SR and the city of Yekaterinburg in the pre-pandemic period (2017–2019) was characterized by a marked increase compared to the initial 2016 year. During the pandemic, there was a slight dynamics in the city and stagnation of the indicator in the SR due to a pronounced decrease in incidence.

Composting is an environmentally friendly process, turning animal waste into fertilizer. Chicken litter compost (CLC) improves soil properties, increasing crop yields. However, the CLC effect on the soil microbiome is understudied. This study aimed to compare bacteriobiome diversity in fallow arable Chernozem with and without CLC addition in a field experiment in the Novosibirsk region, Russia, using 16S rRNA gene metabarcoding. Pseudomonadota, Actinomycetota and Acidobacteriota were the most OTU-rich phyla, together accounting for >50% of the total number of sequence reads. CLC-related shifts in the bacteriobiome structure occurred at all taxonomic levels: the Bacillota abundance was 10-fold increased due to increased Bacilli, both being indicator taxa for the CLC-soil. The main Actinomycetota classes were the indicators for the CLC-soil (Actinobacteria) and no-CLC soil (Thermoleophilia, represented Gaiella). Both Bacillota and Actinomycetota phyla were the ultimate constituents of the CLC added, persisting in the soil for five months of fallowing. The no-CLC soil indicator phyla were Acidobacteriota (represented by Acidobacteria_Group3) and Verrucomicrobiota. Future metabarcoding studies of chicken litter application in agricultural soils, including cropped studies, should address the soil microbiome at the species/strain levels in more detail, as well as how it is affected by specific crops, preferably accompanied by a direct methodology revealing the microbiota functions.

Introduction. The current anthrax situation in Russia is characterized by instability. In 2023, there was an increase in the number of infection outbreaks compared to the long-term average (for five years). The aim of the study is to assess the epizootological and epidemiological situation regarding anthrax in the Russian Federation in 2023 and the reasons for its deterioration, and to analyze data from genomic epidemiological surveillance of this infection. Materials and methods. The information of the territorial bodies of Rospotrebnadzor on the investigation of anthrax outbreaks, reference materials about anthrax stationary hazardous areas and anthrax burials were used. The phylogenetic position of the identified Bacíllus anthracis strains and genomes structure were determined based on whole-genome sequencing data. Results. In 2023 anthrax outbreaks were registered in the Chuvash Republic — Chuvashia (1), the Tyva Republic (1), Tambov (1), Ryazan (1) and Voronezh (3) regions. 14 farm animals and 19 people fell ill. The infection of animals not vaccinated against anthrax, as well as vaccinated long before contact with the source of infection, occurred mainly during grazing in the territories of old (unregistered) anthrax soil foci. Human disease is caused by contact with sick animals during care, forced slaughter, cutting, transportation of carcasses and meat, cooking processing of contaminated meat and offal, and consumption of insufficiently heat-treated liver. 17 patients were diagnosed with a cutaneous form of anthrax, while 2 had an oropharyngeal form combined with a cutaneous form of the disease. In all cases, the genome structure typical of the B. anthracis species has been established. The phylogenetic relationship of B. anthracis isolates with B. anthracis strains previously isolated in Russia is shown. Conclusion. The reason for the trouble in anthrax in 2023 was a number of violations of veterinary and sanitary-epidemiological regulations against the background of the presence of soil foci of infection. Stabilization of the situation can be achieved only in full range of regulated preventive measures are constantly implementated. The results of molecular genetic typing of B. anthracis strains isolated during the epidemiologic investigation of seven anthrax outbreaks in the Russian Federation in 2023 allow us to conclude that they are of local origin and have a genome structure typical of the species. Genetic analysis of the isolated strains demonstrated the effectiveness of the developed wgSNP typing system in the epidemiologic investigation of outbreaks.

In adults, the rate of stimuli presentation has been shown to play a critical role for the event related potentials (ERP): its components become larger as presentation rate decreases. But there are few works evaluating developmental changes of this ERP modulation that might provide insights into basic forms of learning. The current study aims to examine the developmental changes in the effect of the presentation rate on ERP. Participants (N = 48) of four age groups (2-7, 8-11, 12-17 and 18-35 years old) were presented with auditory tone (1000 Hz) at three different stimulus onset asynchrony (SOA): 0.9, 1.8, and 3.6 s. During stimuli presentation 28-channels electroencephalogram (EEG) was recorded. Amplitude of ERP components increased with SOA prolongation. However, this effect was differently pronounced in each of the age groups, depending on the component and cortical site. N1P1 amplitude was increased from 0.9 to 1.8 s SOA in two oldest groups (12-17 years old and adults) predominantly at fronto-central sites. Similar increase demonstrated P2N1 component but starting from younger group (8-11 years old). Only the adult group was characterized by a significant increase in N1P1 and P2N1 amplitudes with SOA increase from 1.8 to 3.6 s. Thus, the effect of presentation rate on ERP is not fully mature even at adolescence and depends on the component with P2N1 amplitude showing modulations at younger age.

The results of recent international studies within The Dynamic Attention Theory (DAT) have opened up great prospects for the development of therapeutic methods that use temporal patterns of rhythmic stimulation to model the attention facilitation effect (AFE) in cognitive and specialized language tasks. However, research within the DAT is developing in local directions and still remains less noticeable to a wide range of researchers. In particular, no systematic review and meta-analysis of behavioral and psychophysiological studies of AFE within the DAT have been conducted. This review examined the DAT, namely, its specificity, provisions, mechanisms of attention selectivity, and main research paradigms. We reviewed current research on AFE within the DAT. Studies within the correlational approach, as well as studies of AFE in rhythmic impact paradigms, were considered. Within the latter, we identified two blocks: general cognitive functions and language processes. In the first block, we examined studies of AFE on perception, as well as on perception and memory together, and in the second block, AFE on syntax and phonology. It was found that most studies focus on children and young adults, which limits the possibility of generalizing the results to other age groups. In addition, studies within the syntactic direction have shown contradictory data regarding the syntactic and modal specificity of AFE, and have also focused only on the study of the auditory modality of AFE. The review also showed the limitations of research in constructing an experimental paradigm, which is manifested in the choice of only one mechanism of attention selectivity described in the dynamic attention theory. Thus, this work emphasizes the need for further research to gain a deeper understanding of AFE, as well as to expand the age groups and modalities included in the studies.

Tässä tutkimuksessa tarkastellaan Suomeen vastasaapuneiden ukrainalaisten kokemuksia suomen kielen oppimisesta Toisto-tuokioissa. Keräsimme tapaustutkimuksemme aineiston havainnoimalla kahden Toisto-ryhmän toimintaa 10 kuukauden ajan. Toimintaa koskevien muistiinpanojen lisäksi aineistomme koostuu Toisto-tuokioiden videotallenteista sekä osallistujien haastatteluista. Haastattelujen temaattinen analyysi paljasti Toisto-tuokioihin osallistuneiden kokeneen metodin miellyttäväksi ja ilmapiirin hyväksi. Osallistujat kokivat oppineensa hyödyllisiä fraaseja, ja hyväksi koettiin myös puhumisen ja ääntämisen harjoittelu sekä itse toistoon perustuva metodi. Haastavaksi taas koettiin kirjoitetun materiaalin niukkuus sekä se, ettei kielen rakenteita selitetä. Sekä haastattelu- että videoaineistosta ilmeni osallistujien tarve ymmärtää kielen rakenteita syvemmin kuin mihin analysoimattomien konstruktioiden esittelyyn tähtäävä metodi tarjoaa mahdollisuuden. Osallistujat kysyivät itselleen epäselvistä asioista paitsi oppailta myös toisiltaan. Oppailta kysymistä helpottivat oppaiden ja osallistujien yhteiset kielet venäjä ja englanti. "The Toisto-method: Language learning experiences of newly arrived Ukrainians in Finland." This study focuses on how newly arrived Ukrainian refugees to Finland have experienced learning Finnish language with a method called Toisto (’Repetition’). Toisto is a modeling-based method that was developed to enable volunteers to teach the basics of Finnish to newcomers, as linguistic first aid. The Toisto-method is built on the ideas of direct method, communicative teaching, suggestopedic atmosphere, and authenticity in schemata. The method is speech-based, and one does not have to have literacy skills to participate. The case study was conducted by observing two groups for ten months, by interviewing the participants and by videorecording four sessions. All participants were Ukrainian refugees who had an extensive educational background, including learning other languages. In the interviews, the participants reported that they were happy with the sessions, and they found the atmosphere relaxed. They felt that the Toisto-method was novel compared to their previous language learning experiences both in Ukraine and in Finland. The participants reported that the method helped them learn useful phrases for their everyday needs, and they found that the speech-based method was beneficial especially for developing their communicative skills. The participants also recognized that not all their language learning needs were met in Toisto-sessions. The participants reported also wanting to learn how to write Finnish, and they wished to have explicit grammar instruction. Both writing and explicit teaching of grammar are excluded from the method on purpose, and based on the analysis, the expectations of the Ukrainian participants were often different from what the method is set to offer. To better cater for the needs of the participants, the Finnish volunteers had added written modality in the lessons, and they also explained linguistic details when asked. The analysis of the language related questions in Toisto-sessions revealed that instead of focusing on inferring the meanings and structures from the presented materials, the participants asked for translations to Russian and made questions about grammar. These practices had brought the Toisto-sessions closer to more traditional language learning.

Abstract Vitamin D (vitD) deficiency is frequently observed in patients with pulmonary arterial hypertension (PAH) and, in these patients, low levels of vitD correlate with worse prognosis. The aim of this study was to examine the expression and the antiproliferative role of vitD receptor (VDR) and its signalling pathway in the human pulmonary vasculature. VDR presence and expression was analyzed in lungs, pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) from controls and PAH-patients. VDR expression and VDR-target genes were examined in PASMC treated with calcitriol. The antiproliferative effect of 48 h-calcitriol was studied in PASMC by MTT and BrdU assays. VDR is expressed in PASMC. It is downregulated in lungs and in PASMC, but not in PAEC, from PAH-patients compared to non-hypertensive controls. Calcitriol strongly upregulated VDR expression in PASMC and the VDR target genes KCNK3 (encoding TASK1), BIRC5 (encoding survivin) and BMP4. Calcitriol produced an antiproliferative effect which was diminished by silencing or by pharmacological inhibition of survivin or BMPR2, but not of TASK1. In conclusion, the expression of VDR is low in PAH-patients and can be rescued by calcitriol. VDR exerts an antiproliferative effect in PASMC by modulating survivin and the BMP signalling pathway.

Abstract Recent research has identified growth differentiation factor 15 (GDF15) as a crucial factor in various physiological and pathological processes, particularly in energy balance regulation. While the role of GDF15 in modulating energy metabolism through hindbrain GDNF family receptor alpha-like (GFRAL) signaling has been extensively studied, emerging evidence suggests direct peripheral metabolic actions of GDF15. Using knockout mouse models, we investigated GDF15 and GFRAL’s roles in adipose tissue metabolism. Our findings indicate that C57BL/6/129/SvJ Gdf15-KO mice exhibit impaired expression of de novo lipogenesis enzymes in subcutaneous adipose tissue (sWAT). In contrast, C57BL/6J Gfral-KO mice showed no impairments compared to wild-type (WT) littermates. RNA-Seq analysis of sWAT in Gdf15-KO mice revealed a broad downregulation of genes involved in lipid metabolism. Importantly, our study uncovered sex-specific effects, with females being more affected by GDF15 loss than males. Additionally, we observed a fasting-induced upregulation of GDF15 gene expression in sWAT of both mice and humans, reinforcing this factor’s role in adipose tissue lipid metabolism. In conclusion, our research highlights an essential role for GDF15 in sWAT lipid metabolic homeostasis. These insights enhance our understanding of GDF15’s functions in adipose tissue physiology and underscore its potential as a therapeutic target for metabolic disorders.

Abstract Background Suicide has become a first-order public health concern after the negative impact of COVID-19 on the general population’s mental health. Several studies have analyzed the trends in suicide attempts (SA) before and after the onset of the pandemic, but few studies focus on the impact of the pandemic on medically serious suicide attempts (MSSA). Methods Participants were 385 hospitalized individuals ≥ 16 years old who made MSSA identified retrospectively through a review of e-medical records between 2018 and 2022 (“pre-COVID-19” and “COVID” periods). The two groups were compared on sociodemographic and clinical variables using Chi-square or Exact Fisher’s tests for categorical variables and a Mann-Whitney test for continuous variables. To study the variation in MSSA over time, MSSA were aggregated monthly. Joinpoint regression analyses were used to assess time trends. Results A sample of 161 MSSA patients, 80 women and 81 men, were selected from 385 admissions after a suicide attempt (SA) in the four years (n = 160 pre-COVID period vs. n = 225 COVID period) (OR = 1.41; CI 95% = 1.0003–1.7223, p

Abstract The focus of this work is to establish a hydrometallurgical technique for efficiently extracting gold from the aggregated gold-rich concentrate produced by a mining facility in one of Kazakhstan's deposits. The leaching techniques applied to gravity-flotation concentrates include hydrometallurgical gold recovery processes using the surfactant sulfanol and the oxidizing reagent trichloroisocyanuric acid (TCCA). The findings indicate the effectiveness of leaching gravity-flotation concentrates with oxidizing (accelerating) reagents. Gold extraction through cyanidation of the blended concentrate, ground to 89–90% passing 10 µm with TCCA, averaged 84.0%, compared to 65.76–67.8% with conventional direct cyanidation. The advantage of employing chlorine-based oxidants, such as TCCA, in hydrometallurgical processing lies in their applicability in both acidic and alkaline environments, whereas other oxidants are constrained by specific technological conditions. Technical trichloroisocyanuric acid (TCCA), a chlorine-containing oxidizer with the formula C3O3N3Cl3, containing 25–30% calcium hypochlorite as an impurity, proved to be the most effective in enhancing gold leaching techniques. Apart from improving the efficiency of the leaching process, the use of TCCA is economically viable. The wholesale cost of technical TCCA is ~ $700 per ton, significantly lower than many other oxidants commonly used in gold hydrometallurgical production. With its higher active chlorine content, TCCA consumption per ton of gold-bearing raw material is nearly half that of hypochlorite or peroxide. Additionally, TCCA use minimizes the formation of unwanted impurities in both the pulp and the productive solution.

Abstract Numerous factors regulate alternative splicing of human genes at a co-transcriptional level. However, how alternative splicing depends on the regulation of gene expression is poorly understood. We leveraged data from the Genotype-Tissue Expression (GTEx) project to show a significant association of gene expression and splicing for 6874 (4.9%) of 141,043 exons in 1106 (13.3%) of 8314 genes with substantially variable expression in nine GTEx tissues. About half of these exons demonstrate higher inclusion with higher gene expression, and half demonstrate higher exclusion, with the observed direction of coupling being highly consistent across different tissues and in external datasets. The exons differ with respect to multiple characteristics and are enriched for hundreds of isoform-specific Gene Ontology annotations suggesting an important regulatory mechanism. Notably, splicing-expression coupling of exons with roles in JUN and MAP kinase signalling could play an important role during cell division.

Abstract Background In locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification. Methods In 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters. Results Most patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5. Conclusions Weekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.

Abstract Background A growing body of literature focuses on the role of benevolent childhood experiences (BCEs) in predicting adulthood well-being, in addition to adverse childhood experiences (ACEs). However, cross-cultural differences are generally ignored in this endeavor. Hence, this study aimed to explore the role of BCEs in predicting life satisfaction, resilience, and hopelessness. We also examined the potential of resilience and the role of hopelessness in mediating the relationship between BCE and life satisfaction. Methods A total of 850 university students from Turkey (n = 371), Portugal (n = 248), and India (n = 231), aged 17 to 58 years (M = 22.12, SD = 4.41), participated in the study. Participants completed an online protocol consisting of measures to assess BCEs, life satisfaction, resilience, and hopelessness. Results BCEs, hopelessness, and life satisfaction have significantly differed among the samples based on the country of residence. BCEs were positively correlated to resilience and life satisfaction and negatively to hopelessness. In the sequential mediation model, after controlling for country and sex, resilience and hopelessness sequentially mediated the relationship between BCEs and life satisfaction. BCEs were associated with life satisfaction, resilience, and hopelessness across countries and sexes. The model explains 42.8% of the variability. Conclusion Despite differences between countries, BCEs are important predictors of adult well-being in all three countries and should be monitored along with ACE. Further, resilience seems to have an important role in lowering the negative consequences of lower BCEs and feelings of hopelessness, pointing to the need to strengthen psychological resilience among adults.

Purpose – Understanding China's carbon dioxide (CO2) emission status is crucial for getting Carbon Neutrality status. The purpose of the paper is to calculate two possible scenarios for CO2 emission distribution and calculated input-output flows of CO2 emissions for every 31 China provinces for 2012, 2015 and 2017 years. Design/methodology/approach – In this study using the input and output (IO) table's data for the selected years, the authors found the volume of CO2 emissions per one Yuan of revenue for the industry in 2012 and the coefficient of emission reduction compared to 2012. Findings – Results show that in the industries with a huge volume of CO2 emissions, such as “Mining and washing of coal”, the authors cannot observe the reduction processes for years. Industries where emissions are being reduced are “Processing of petroleum, coking, nuclear fuel”, “Production and distribution of electric power and heat power”, “Agriculture, Forestry, Animal Husbandry and Fishery”. For the “construction” industry the situation with emissions did not change. Originality/value – “Transport, storage, and postal services” and “Smelting and processing of metals” industries in China has the second place concerning emissions, but over the past period, emissions have been sufficiently reduced. “Construction” industry produces a lot of emissions, but this industry does not carry products characterized by large emissions from other industries. Authors can observe that Jiangsu produces a lot of CO2 emissions, but they do not take products characterized by significant emissions from other provinces. Shandong produces a lot of emissions and consumes many of products characterized by large emissions from other provinces. However, Shandong showed a reduction in CO2 emissions from 2012 to 2017.

The crystal structure of the title organic–inorganic hybrid salt, (C13H12N3)2[CdCl4], (I), has been reported with four molecules in the asymmetric unit in a monoclinic cell [Vassilyeva et al. (2021). RSC Advances, 11, 7713–7722]. While using two different aldehydes in the oxidative cyclization–condensation involving CH3NH2·HCl to prepare a new monovalent cation with the imidazo[1,5-a]pyridinium skeleton, a new polymorph was obtained for (I) in space group P1 and a unit cell with approximately half the volume of the monoclinic form. The structural configurations of the two crystallographically non-equivalent organic cations as well as the geometry of the moderately distorted tetrahedral CdCl42– dianion show minor changes. In the crystal, identically stacked cations and tetrachlorocadmate anions form separate columns parallel to the a axis. The loose packing of the anions leads to a minimal separation of approximately 9.53 Å between the metal atoms in the triclinic form versus 7.51 Å in the monoclinic one, indicating that the latter is packed slightly more densely. The two forms also differ by aromatic stacking motifs. Similar to the monoclinic polymorph, the triclinic one excited at 364 nm shows an intense unsymmetrical photoluminescent band with maximum at 403 nm and a full width at half maximum of 51 nm in the solid state.

Abstract Understanding the factors that predict why some individuals perceive to respond more to meditation training than others could impact the development, efficacy, adherence levels, and implementation of meditation-based interventions. We investigated individual-level variables associated with self- and teacher-perceived responsiveness to longer-term meditation training. This study presents a secondary analysis of the Age-Well trial (NCT02977819, 30/11/2016) and includes 90 healthy older adults (65–84 years) that were randomised to an 18-month meditation training or a non-native language (English) training. Responsiveness was measured post-intervention using participants’ and teachers’ ratings of four psychological domains (connection, positive/negative emotions, meta-awareness) in relation to two contexts (during sessions, in daily life), teachers’ perception of overall benefit, and a global composite comprising all self- and teacher-perceived responsiveness measures. Linear regression modelling indicates that, when including baseline variables (sex, education, neuroticism, cognition, expectancy) and engagement (hours of formal practice during intervention), only higher levels of engagement were associated with higher global composite scores (standardised estimate = 0.50, 95% CI: 0.24–0.77, p

Abstract Stuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation.

Abstract Background Glioblastoma multiforme (GBM) is an aggressive tumor, difficult to treat pharmacologically because of the blood-brain barrier (BBB), which is rich in ATP-binding cassette (ABC) transporters and tight junction (TJ) proteins. The BBB is disrupted within GBM bulk, but it is competent in brain-adjacent-to-tumor areas, where eventual GBM foci can trigger tumor relapse. How GBM cells influence the permeability of BBB is poorly investigated. Methods To clarify this point, we co-cultured human BBB models with 3 patient-derived GBM cells, after separating from each tumor the stem cell/neurosphere (SC/NS) and the differentiated/adherent cell (AC) components. Also, we set up cultures of BBB cells with the conditioned medium of NS or AC, enriched or depleted of IL-6. Extracellular cytokines were measured by protein arrays and ELISA. The intracellular signaling in BBB cells was measured by immunoblotting, in the presence of STAT3 pharmacological inhibitor or specific PROTAC. The competence of BBB was evaluated by permeability assays and TEER measurement. Results The presence of GBM cells or their conditioned medium increased the permeability to doxorubicin, mitoxantrone and dextran-70, decreased TEER, down-regulated ABC transporters and TJ proteins at the transcriptional level. These effects were higher with AC or their medium than with NS. The secretome analysis identified IL-6 as significantly more produced by AC than by NS. Notably, AC-conditioned medium treated with an IL-6 neutralizing antibody reduced the BBB permeability to NS levels, while NS-conditioned medium enriched with IL-6 increased BBB permeability to AC levels. Mechanistically, IL-6 released by AC GBM cells activated STAT3 in BBB cells. In turn, STAT3 down-regulated ABC transporter and TJ expression, increased permeability and decreased TEER. The same effects were obtained in BBB cells treated with STA-21, a pharmacological inhibitor of STAT3, or with a PROTAC targeting STAT3. Conclusions Our work demonstrates for the first time that the degree of GBM differentiation influences BBB permeability. The crosstalk between GBM cells that release IL-6 and BBB cells that respond by activating STAT3, controls the expression of ABC transporters and TJ proteins on BBB. These results may pave the way for novel therapeutic tools to tune BBB permeability and improve drug delivery to GBM.

Abstract Clinical pathway recommendations (CPR) are based on existing guidelines and deliver a short overview on how to deal with a specific diagnosis, resulting therapy and follow-up. In this paper we propose a methodology for developing CPRs for Pompe disease, a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. The CPR document was developed within the activities of the MetabERN, a non-profit European Reference Network for Metabolic Diseases established by the European Union. A working group was selected among members of the MetabERN lysosomal storage disease subnetwork, with specific expertise in the care of Pompe disease, and patient support group representatives. The working strategy was based on a systematic literature search to develop a database, followed by quality assessment of the studies selected from the literature, and by the development of the CPR document according to a matrix provided by MetabERN. Quality assessment of the literature and collection of citations was conducted according to the AGREE II criteria and Grading of Recommendations, Assessment, Development and Evaluation methodology. General aspects were addressed in the document, including pathophysiology, genetics, frequency, classification, manifestations and clinical approach, laboratory diagnosis and multidisciplinary evaluation, therapy and supportive measures, follow-up, monitoring, and pregnancy. The CPR document that was developed was intended to be a concise and easy-to-use tool for standardization of care for patients among the healthcare providers that are members of the network or are involved in the care for Pompe disease patients.

Abstract Positive effects of study progress on the economic knowledge of bachelor students are evident and were often referred to as proof of the validity of tests in the context of a longitudinal analysis. However, differences between domain-specific (e.g., semester) or discipline-specific (e.g., attended courses) indicators of study progress on students’ solving the economics tasks are relevant for both diagnostic and instructional purposes, but have hardly been researched to date. In an eye tracking study, we therefore calculated the average fixation duration during 900 task-solving processes of 35 economics teacher students solving 25 single-choice economics tasks. A multi-level mediation analysis shows that both indicators (i.e., semester and attended courses) were positively correlated with economics knowledge. At the same time, the impact of semesters and courses attended on their test performance was partially mediated by average fixation duration on the attractor and distractors, respectively. This suggests that visual attention differs during the task-solving process depending on the domain- or discipline-specific indicator of study progress.

Societal Impact Statement Understanding domestication's impact on crop root traits and interactions with soil microbiomes is vital for improving crop resilience and agricultural sustainability. Using this knowledge to enhance root systems, reduce chemical inputs, and adapt crops to environmental stress will help to increase global food production, promote eco‐friendly farming, and mitigate the effects of climate change. Additionally, identifying microorganisms specific to plant species may help in biodiversity conservation. Advancing scientific understanding and educating future generations on the intricate relationships between plants, soil, and microorganisms is integral to developing innovative, sustainable agricultural practices and improved food security. Summary Domestication and intensive management practices have significantly shaped characteristics of modern crops. However, our understanding of domestication's impact had mainly focused on aboveground plant traits, neglecting root and rhizospheric traits, as well as trait–trait interactions and root‐microbial interactions. To address this knowledge gap, we grew modern (Hordeum vulgare L. var. Barke) and wild barley (Hordeum spontaneum K. Koch var. spontaneum) in large rhizoboxes. We manipulated the soil microbiome by comparing disturbed (sterilized soil inoculum, DSM) versus non‐disturbed (non‐sterilized inoculum, NSM) microbiome. Results showed that modern barley grew faster and increased organic‐carbon exudation (OCEXU) compared to wild barley. Both barley species exhibited accelerated root growth and enhanced OCEXU under DSM, indicating their ability to partially compensate and exploit the soil resources independently of microbes if need be. Plant trait network analysis revealed that modern barley had a denser, larger, and less modular network of microbes than wild barley indicating domestication's impact on trait–trait coordination. In addition, the relative abundance of bacteria did not vary between wild and modern barley rhizospheres; however, species‐specific unique bacteria were identified, with stronger effects under DSM. Overall, our findings highlight domestication‐driven shifts in root traits, trait coordination, and their modulation by the soil microbiome.

Increased consumption of coffee in the world leads to the accumulation of food waste that is not properly utilised properly, but have prospects for further processing into a targeted with added value. The aim of this study is to produce biochar from waste coffee grounds by coffee grounds by conventional pyrolysis and microwave irradiation, determination of its chemical and particle size distribution, study of acid-base and ion exchange properties, ability to bind ions and lead ions for further use as an additive in the production of biogas production. Given the high cost of conventional pyrolysis to produce the required volumes of of biochar, it is promising to consider an alternative option that will be significantly cost-effective and efficient. After carbonisation, we determined the biopolymer composition, acid-base and ion exchange properties of the raw materials and biochar using various methods, such as the Kjeldahl Hogedron-Jensen, potentiometric titration and others. The results of the maximum cation exchange capacity of raw materials and biochar indicate that biochar has a less pronounced tendency to exchange cations in the range of 0.89...1.15 μeV/g than raw materials, the value of which is mainly in the range of 1...3 μeV/g, which shows less influence of biochar on the mineral balance of microorganisms during anaerobic digestion. The values of the anion exchange capacity of biochar are in the range of values 0.7...1.2 μeV/g, and the pH value of the acidic groups of biochar lie in the range of 7.1...10.7 (characterising them as weakly acidic groups), pKa is 9.6...10.7. The curves of potentiometric titration of biochar are determined by the additive contribution of all ionised groups of biochar and allow us to to classify the studied products as polyfunctional ion exchangers. type ion exchangers. Results of the study of biochars from waste coffee grounds show that they have ampholytic properties and act as acceptors of metal ions, as well as function as a mild pH regulator, which is important in anaerobic digestion of food waste into biogas to increase the yield of of the resulting gas in accordance with the biocircular green economy model.

Magnesium (Mg) – based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing, e.g. as a suture anchor. Due to their mechanical properties and biocompatibility, they may replace titanium or stainless-steel implants, commonly used in orthopedic field. Nevertheless, patient safety has to be assured by finding a long-term balance between metal degradation, osseointegration, bone ultrastructure adaptation and element distribution in organs. In order to determine the implant behavior and its influence on bone and tissues, we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone. The implants were present in rat tibia for 10, 20 and 32 weeks before sacrifice of the animal. Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal, degradation layer and bone structure. Additionally, X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface. Finally, with element specific mass spectrometry, the elements and their accumulation in the main organs and tissues are traced. The results show that Mg-xGd implants degrade in vivo under the formation of a stable degradation layer with bone remodeling similar to that of Ti after 10 weeks. No accumulation of Mg and Gd was observed in selected organs, except for the interfacial bone after 8 months of healing. Thus, we confirm that Mg-5Gd and Mg-10Gd are suitable material choices for bone implants.

The ability to adequately perceive and recognize emotions is a key and universal tool in interpersonal communication, which allows people to understand feelings, intentions, and emotional reactions of themselves and others. Throughout their life, people have to make inferences about mental state of others by interpreting subtle social signals, such as facial expressions, to understand or predict others’ behavior, which is crucial in constructive social interactions. Therefore, emotional memory associated with the ability to identify emotions based on one’s life experience is the cornerstone of social cognition and interpersonal relationships. Oxytocin and vasopressin are neurohypophysial peptides that have attracted scientific attention due to their role in the emotional and social aspects of behavior. Variable and contrasting effects of oxytocin and vasopressin may be related to the sites of the brain where they exert their activity. Aim. This review aimed to evaluate neural mechanisms underlying oxytocin-mediated and vasopressin-mediated modulation of emotional memory; to assess how cerebral oxytocin-signal and vasopressin-signal transduction mediates emotional and social behavior; to discuss the role of the two neuropeptides in non-verbal interpersonal communication; and to present their cerebral effects in relation to an ability for “face reading” in patients with mental disorders.

Visibility conditions between antennas, i.e. Line-of-Sight (LOS) and Non-Line-of-Sight (NLOS) can be crucial in the context of indoor localization, for which detecting the NLOS condition and further correcting constant position estimation errors or allocating resources can reduce the negative influence of multipath propagation on wireless communication and positioning. In this paper a Deep Learning (DL) model to classify LOS/NLOS condition while analyzing two Channel Impulse Response (CIR) parameters: Total Power (TP) [dBm] and First Path Power (FP) [dBm] is proposed. The experiments were conducted using DWM1000 DecaWave radio module based on measurements collected in a real indoor environment and the proposed architecture provides LOS/NLOS identification with an accuracy of more than 100% and 95% in static and dynamic senarios, respectively. The proposed model improves the classification rate by 2-5% compared to other Machine Learning (ML) methods proposed in the literature.

The aim of the study has been to determine the condition of Quercus robur L. and Juglans rupestris Engelm. and their influence on the properties of segregated chernozems. The study was conducted in 2020–2021 in the steppe Crimea. The control has been a perennial grass fallow. To characterize the general condition of the trees, a 4-point scale for assessing the condition of the introduced species has been used. Standard methods have been used for soil analysis. A better preservation and a greater number of 50-year old plants in excellent and good condition have been established for Q. robur (67 и 56 %, respectively) compared to J. rupestris (48 и 42 %, respectively) in these environmental conditions, which is explained by the greater adaptive capabilities of oak as an indegenous species. Both tree crops have influenced soil properties. In their phytocenoses, a litter has been formed, more significant under J. rupestris. The dark humus horizon has also turned out to be thicker under the J. rupestris plantation (80 cm) than under the Q. robur plantation and the fallow (72 and 70 cm, respectively). Under Q. robur the soil density has been lower than under J. rupestris by 0.02–0.18 g/cm3. Under the woody plants, the soil structure has improved: the number of lumpy aggregates has decreased, and the number of agronomically valuable and granular particles has increased. The maximum coefficient of structure has been in the soil under the oaks (4.4–6.6), which exceeded the control by 2.5–4.9 times. Under the woody plants, carbonates have been significantly washed out of the soil profile, especially under J. rupestris. The pHH2O value of the alkaline soil under the woody plants has decreased by 0.2–0.4 and has been closely related to carbonate content (r = 0.83–0.91). The humus content under both species has been significantly higher than under the fallow – by 0.30–0.86 %. Afforestation has resulted in the accumulation of total forms of nutrients, to a greater extent under J. rupestris, and the C:N ratio has decreased. Tree species have stored more labile forms of nutrients in the soil. Soil desalination has been noted in the tree cenoses. Thus, J. rupestris and Q. robur are ecologically stable in the conditions of the central steppe of Crimea and can be used to increase forest cover in steppe areas. This will help improve soil fertility.

The growth peculiarities of Scots pine (Pinus sylvestris L.) have been studied by the example of an even-aged pine stand of high density. A long-term research has been conducted on a permanent sample plot. The data has been collected from the stand aged from 37 to 55 years. The characteristics of individual trees and the entire stand during the growth period in the absence of external influences (cutting, windfalls, pest damage, etc.) and after improvement cuttings have been analyzed. The influence of the amount of resource available to a tree on the formation of crowns, root systems and stem wood has been investigated. The size of the available resource has been the square of the dominance area. The root system of the pine trees of the studied stands is compact in size and, despite the high stand density, due to the high content of nutrients in the soil and the absence of moisture deficiency, it sufficiently ensures intensive tree growth corresponding to the conditions of the I quality class. It has been found that under these conditions, the average area of the root system is proportional to the average square of the dominance area. It has been shown that the stem diameter at a height of 1.3 m in the absence of external influences significantly depends on the square of the dominance area. The correlation coefficient of these indicators for the studied stand at the age of 37 is 0.89. The influence of cuttings on annual radial increment has been studied using dendrochronology methods. It has been revealed that in the year following the cutting, it has increased by 1.3–2.0 times, depending on the increase in the square of the dominance area. A method has been proposed for calculating the competition coefficient as a share of the resource required for the free growth of a tree, which is redistributed between its closest neighbours. Long-term observations have shown that with competition coefficients exceeding 0.6–0.7, the stem diameter increment rate decreases significantly, and the trees develop a sparse crown extending less than 40 % of the tree height. This, in turn, leads to growth retardation and a transition to a depressed state. This, in turn, leads to growth retardation and a transition to a depressed state.

Abstract Background Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD. Methods We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently. Results Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p

Immune checkpoint inhibitors (ICIs) are an effective immunotherapeutic approach for cancers affecting the lung, skin, kidney, mammary gland, or certain hematologic malignancies. Regarding the prognosis of these oncological conditions, treatments with ICIs open new therapeutic perspectives with benefits for both patients and healthcare providers. A drawback of immune checkpoint inhibition is the occurrence of immune-related adverse events that can involve a wide range of organs, such as the liver. Given widespread usage of immunotherapy, the number of patients who suffer from this unwanted condition has increased. Hepatopathy induced by ICIs can be severe and can even lead to death. Detecting liver toxicity in ICIs regiments requires a close monitorization of patients during and after the treatment. Such hepatopathies often involve discontinuation of immune checkpoint inhibitors and administration of corticosteroids. In conclusion, hepatopathies induced by immune checkpoint inhibitors require a comprehensive understanding for effective management, both to protect the patient's life during therapy and to ensure longer survival after cessation of treatment.

Abstract Background Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation. Methods Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. Results The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR

Abstract Interpersonal Distance (IPD) is defined as the physical distance that individuals maintain between themselves and others during social interactions. While literature has extensively focused on this everyday social behavior, how IPD changes throughout the lifespan remains an open question. In this study, 864 participants, aged 3–89 years, performed the Stop Distance Paradigm in their real-life environments, and we measured the distance they kept from both familiar and unfamiliar others during social interactions. We found that IPD not only differs based on the identity of the other person (familiar versus unfamiliar) but critically declines as a function of age, following two distinct non-linear trends for familiar and unfamiliar others. Moreover, behavioral variability also undergoes a lifetime development, with IPD becoming more stable as age increases. Overall, the present study suggests that IPD is a complex and acquired behavior that changes throughout the lifespan and varies according to individual and situational variables.

Abstract Background Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it. Methods Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study. Results In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p

Abstract As clinical trials for psychedelics move into phase III in the USA, Europe must address its lag in integrating professional education around psychedelic-assisted therapy (PAT) and supporting psychedelic drug research. This paper evaluates the necessary frameworks for implementing PAT in Germany, emphasizing the nation’s potential leadership role within the European Union. With Australia having already approved MDMA and psilocybin for mental health indications, the Ukrainian government exploring MDMA treatment for war-related PTSD, and initial clinical trials involving MDMA and LSD with patients in Switzerland which restarted the restricted medical use of these substances around 2014, the medical authorization of psychedelics in these countries establishes precedent showcasing both the promise and challenges of researching and implementing PAT in nations where the substances were formally scheduled as illicit substances. Key challenges include establishing rigorous standards for practitioner training, accessibility, and defining regulatory oversight. This paper focuses on the development of robust infrastructure in Germany, which will support the roll out of PAT, and details ethical considerations, training protocols, and governmental roles in the formulation of treatment frameworks. This approach aims not only to guide Germany in adopting PAT but also to influence broader European policy, ensuring that patients receive ethically sound and proficient care. The findings suggest pathways for Europe to reclaim its historical lead in psychiatric and therapeutic innovation.

Abstract Objective We investigated the effects of adding regions to current dissemination in space (DIS) criteria for multiple sclerosis (MS). Methods Participants underwent brain, optic nerve, and spinal cord MRI. Baseline DIS was assessed by 2017 McDonald criteria and versions including optic nerve, temporal lobe, or corpus callosum as a fifth region (requiring 2/5), a version with all regions (requiring 3/7) and optic nerve variations requiring 3/5 and 4/5 regions. Performance was evaluated against MS diagnosis (2017 McDonald criteria) during follow‐up. Results Eighty‐four participants were recruited (53F, 32.8 ± 7.1 years). 2017 McDonald DIS criteria were 87% sensitive (95% CI: 76–94), 73% specific (50–89), and 83% accurate (74–91) in identifying MS. Modified criteria with optic nerve improved sensitivity to 98% (91–100), with specificity 33% (13–59) and accuracy 84% (74–91). Criteria including temporal lobe showed sensitivity 94% (84–98), specificity 50% (28–72), and accuracy 82% (72–90); criteria including corpus callosum showed sensitivity 90% (80–96), specificity 68% (45–86), and accuracy 85% (75–91). Criteria adding all three regions (3/7 required) had sensitivity 95% (87–99), specificity 55% (32–76), and accuracy 85% (75–91). When requiring 3/5 regions (optic nerve as the fifth), sensitivity was 82% (70–91), specificity 77% (55–92), and accuracy 81% (71–89); with 4/5 regions, sensitivity was 56% (43–69), specificity 95% (77–100), and accuracy 67% (56–77). Interpretation Optic nerve inclusion increased sensitivity while lowering specificity. Increasing required regions in optic nerve criteria increased specificity and decreased sensitivity. Results suggest considering the optic nerve for DIS. An option of 3/5 or 4/5 regions preserved specificity, and criteria adding all three regions had highest accuracy.

The paper deals with the influence of the strategy for using separated plutonium from spent fuel of thermal and fast reactors, as well as homogeneous burning of americium in the BN reactor core on the balance of americium in the Russian nuclear fuel cycle throughout the 21st century. The assessment is carried out with the use of mathematical modeling of nuclear materials movement including nuclide transformations throughout the nuclear energy system based on the CYCLE code. Scenario modeling of the americium and Pu-241 accumulation was carried out in Russia’s two-component nuclear energy system model with thermal (VVER) and fast (BN) reactors. In so doing, spent nuclear fuel (SNF) reprocessing was simulated in 2 options: as priority reprocessing of SNF of VVER reactors (1) or SNF of BN reactors (2). In addition to americium accumulation in the system without burning, the accumulation of this actinide was studied taking into account its homogeneous burning in the MOX-fuel of fast reactors at the level of its equilibrium content of ~1%. It has been shown that the priority reprocessing of VVER spent fuel makes it possible to reduce the americium accumulation by the end of the century by ~8 tons, and the effect is achieved by using freshly separated plutonium with short-term cooling, thus, by priority the americium source is eliminated, without directly handling it. Homogeneous addition of americium to the fuel of fast reactors of the BN-1200 type at a level of ~1% makes it possible to stop accumulation of americium in a two-component energy system by 2070, stabilizing it at a level of ~40 tons in the scenario with priority reprocessing of VVER SNF and ~50 tons in the scenario with priority reprocessing of BN SNF.

Abstract The main pathophysiological hallmark of Parkinson's disease (PD) is the accumulation of aggregated alpha‐synuclein (αSyn). Microglial activation is an early event in PD and may play a key role in pathological αSyn aggregation and transmission, as well as in clearance of αSyn and immunotherapy efficacy. Our aim was to investigate how different proposed mechanisms of anti‐αSyn immunotherapy may contribute to pathology reduction in various PD‐like mouse models. Our mechanistic model of PD pathology in mouse includes αSyn production, aggregation, degradation and distribution in neurons, secretion into interstitial fluid, internalization, and subsequent clearance by neurons and microglia. It describes the influence of neuroinflammation on PD pathogenesis and dopaminergic neurodegeneration. Multiple data from mouse PD models were used for calibration and validation. Simulations of anti‐αSyn passive immunotherapy adequately reproduce preclinical data and suggest that (1) immunotherapy is efficient in the reduction of aggregated αSyn in various models of PD‐like pathology; (2) prevention of aSyn spread only does not reduce the pathology; (3) a decrease in microglial inflammatory activation and aSyn aggregation may be alternative therapy approaches in PD‐like pathology.

The current preventive trends in clinical examination draw attention to the role of the external factors and stressful circumstances in psychodiagnostic research. Social frustration is an incapacity to fulfill relevant social needs because of a current situation. This term makes it possible to qualify criteria for the potential stress related to social functioning among family members, colleagues, and peers. The authors rationalized and tested a formalized questionnaire of Social Frustration Level developed at Bekhterev National Medical Research Centre for Psychiatry and Neurology in 2004 for patients with social adjustment disorders. The experiment justified the criterion validity of the Social Frustration Level Questionnaire. The article describes the structure of social frustration regarding the key spheres of activity attributed to internal and external frustration. The pilot study involved 45 patients with adjustment disorders, who showed significant frustration related to health problems and socio-economic status accompanied with relative satisfaction with interpersonal relations, i.e., family, friends, colleagues, and strangers. The research relied on the method of clinical psychological interview, as well as the Questionnaire of Social Frustration Level and the Integrative Anxiety Test. Personal anxiety and actual anxiety experiences proved to correlate with social frustration. The internal social frustration prevailed over the external one. The Questionnaire of Social Frustration Level proved to be an efficient practical tool to be used in systematic medical psychodiagnostics research, programs of disorder prevention, and psychotherapy.

This paper discusses the case of exile journalists from Ukraine who moved to Russia between 2014 and 2022. What, in terms of journalistic norms, was unacceptable to them in the Ukrainian journalistic field? What did they find problematic in this respect in Russia? These were the basic questions driving the research, in the course of which 15 exile journalists were interviewed; their answers were analysed using Norman Fairclough’s critical discourse analysis. The findings presented in the paper show that, despite all the difficulties of their personal situations, exile journalist still consider professional values such as independence and truth-telling to be important, continuing to use these normative yardsticks to measure the quality of the journalistic condition. The biggest concern that most of the informants shared was that journalists in both Russia and Ukraine used the language of hatred and discrimination toward political and cultural others, that is so-called antagonistic discourse that only contribute to the spiralling of violence and can never help in reaching peace. These findings allow the suggestion that by occupying a unique position from which to witness the contingency of hegemonic orders exile journalists advocating for peace may re-affirm the values of human dignity and peaceful coexistence, two basic principles of the journalistic profession, as identified by UNESCO.

Abstract In the AdS/CFT correspondence, the causal structure of the bulk AdS spacetime is tied to entanglement in the dual CFT. This relationship is captured by the connected wedge theorem [1], which states that a bulk scattering process implies the existence of O(1/G N ) entanglement between associated boundary subregions. In this paper, we study the connected wedge theorem in two asymptotically AdS2+1 spacetimes: the conical defect and BTZ black hole geometries. In these settings, we find that bulk scattering processes require not just large entanglement, but also additional restrictions related to candidate RT surfaces which are non-minimal. We argue these extra relationships imply a certain CFT entanglement structure involving internal degrees of freedom. Because bulk scattering relies on sub-AdS scale physics, this supports the idea that sub-AdS scale locality emerges from internal degrees of freedom. While the new restriction that we identify on non-minimal surfaces is stronger than the initial statement of the connected wedge theorem, we find that it is necessary but still not sufficient to imply bulk scattering in mixed states.

Abstract Background Wound healing represents a complex biological process, critically important in clinical practice due to its direct implication in a patient’s recovery and quality of life. Conservative wound management frequently falls short in providing an ideal environment for the optimal tissue regeneration, often resulting in extended healing periods and elevated risk of infection and other complications. The emerging biomaterials, particularly hydrogels, have shown substantial promise in addressing these challenges by offering properties such as biocompatibility, biodegradability, and the ability to cure wound environment. Recent advancements have highlighted the therapeutic potential of integrating cell-derived conditioned medium (CM) into hydrogel matrices. Cell-derived CM represents a rich array of bioactive molecules, demonstrating significant efficacy in modulating cellular activities crucial for wound healing, including cellular proliferation, migration, and angiogenesis. Methods The methodology of this review adheres to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The review includes a selection of studies published within the last five years, focusing on in vivo experiments involving various types of skin injuries treated with topically applied hydrogels loaded with CM (H-CM). The search strategy refers to the PICO framework and includes the assessment of study quality by CAMARADES tool. Results The systematic review represents a detailed evaluation of H-CM dressings wound healing efficiency based on the experimental results of cell-based assays and animal wound models. The study targets to reveal wound healing capacity of H-CM dressings, and provides a comparative data analysis, limitations of methods and discussions of H-CM role in advancing the wound healing therapy. Conclusions The data presented demonstrate that H-CM is a promising material for advanced wound healing and regenerative medicine. These dressings possess proved in vitro/in vivo efficacy that highlights their strong clinical potential and paves the way to further investigations of H-CM formulations within clinical trials.

Abstract Affective Touch is characterized by both emotional and arousing dimensions that rely on specific features of a gentle human caress. In this study, we investigated whether and how both the nature of the touching effector (Human hand vs. Artificial hand) and touch type (Dynamic vs. Static) influenced the participants’ pupil dilation and their subjective experience during tactile stimulation. We observed that when participants received a dynamic touch, their pupil dilation increased more when the touch was produced by a human compared to an artificial hand. This discrimination was not present for static touch. Also, dynamic touch given by a human hand invoked a supralinear enhancement of pupil dilation indicating that the combination of these two features induced a stronger autonomic activation than the summed effects of each separately. Moreover, this specific type of touch was perceived as the most pleasant compared to all other tactile stimulations. Overall, our results suggest that pupil dilation could reflect the pleasant experience of human-to-human tactile interactions, supporting the notion that the autonomic nervous system is responsive to the emotional and hedonic aspects associated with Affective Touch as a part of a complex and holistic social experience, rather than solely reacting to its low-level sensory properties.

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 The lion (Panthera leo) was extirpated from the Cape region of South Africa during the mid-nineteenth century. Whilst historically classified as a distinct subspecies known as the Cape lion (P. l. melanochaita), recent molecular studies challenge the distinctiveness of this population, suggesting that it represents the southernmost population of the species' Southern Clade. The Cape lion is often cited as having a distinctive skull morphology, which has justified its subspecific classification, but only a limited number of specimens have been available for examination, so that the Cape lion’s skull morphology has not been satisfactorily understood. In this study we collected morphometric data from a greatly enlarged sample of 22 Cape lion skulls, including 12 adults, constituting the largest sample size analysed for this possible subspecies. The results suggest that (1) morphological characteristics of the skull previously thought to distinguish the Cape lion are not diagnostic, and (2) nor is the skull morphology of male and female Cape lions distinct from that of males and females of other southern African lions. Our results independently support those based on molecular investigations, which suggest that the Cape lion was not distinct from other lions within the Southern Clade.

Abstract Background Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS). Methods We performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted. Results Six independent sentinel variants reached the genome-wide significance (p

Abstract UNC-89 is a giant sarcomeric M-line protein required for sarcomere organization and optimal muscle function. UNC-89 contains two protein kinase domains, PK1 and PK2, separated by an elastic region. Here we show that PK2 is a canonical kinase expected to be catalytically active. C. elegans expressing UNC-89 with a lysine to alanine (KtoA) mutation to inactivate PK2 have normally organized sarcomeres and SR, and normal muscle function. PK2 KtoA mutants have fragmented mitochondria, correlated with more mitochondrially-associated DRP-1. PK2 KtoA mutants have increased ATP levels, increased glycolysis and altered levels of electron transport chain complexes. Muscle mitochondria show increased complex I and decreased complex II basal respiration, each of which cannot be uncoupled. This suggests that mutant mitochondria are already uncoupled, possibly resulting from an increased level of the uncoupling protein, UCP-4. Our results suggest signaling from sarcomeres to mitochondria, to help match energy requirements with energy production.

Does capital structure matter for farms productivity? Do bank loans increase or decrease farms efficiency? To address this question, I use farm-level data for 2014–2020 from Amur region, which is one of the most typical Russian regions in terms of agricultural development. I find some evidence of a negative correlation between financial leverage and total factor productivity in Amur Oblast farms. I also observe a negative correlation between financial leverage and partial productivity measures such as labor productivity, crop yield, and return on fixed assets. The negative relationship between enterprise productivity and the share of loans in liabilities can be explained, on the one hand, by the fact that bank loans are more often used by struggling, inefficient agricultural enterprises, i. e. adverse selection may take place. On the other hand, the negative relationship between firm productivity and bank credit may be due to the non-market nature of the credit they receive, with the government subsidizing the interest rate and/or guaranteeing the loan obligations. As a result, farms face soft budget constraints that reduce the incentives of owners and management to improve farm efficiency. The two proposed explanations (adverse selection and soft budget constraints) are not mutually exclusive, but rather complementary