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ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV. [ABSTRACT FROM AUTHOR]

Stinging nettle, Urtica dioica L., is a widely distributed subdioecious long‐rhizomatous plant. Within a single population growing in the territory of the Zvenigorod Biological Station of Lomonosov Moscow State University, eight plots were selected in stinging nettle thickets to study the variability of the sexual reproductive part in U. dioica depending on internal and external factors. As monoecious ramets are relatively common in the studied population, four gender forms were distinguished based on the ratio of male and female flowers. On 156 ramets of different gender forms and 36 genets, it was shown that predominantly male plants are shorter, while predominantly female plants have larger and more widely spread inflorescences compared to other gender forms. The pubescence type (spreading or appressed unicellular hairs) shows the greatest repeatability within the merigenet. True monoecy in stinging nettle is widespread: male and female flowers of different gender forms were found in 10 out of 36 genets. The most common inflorescence architecture types in the studied population were proxigynous and basigynous. Both normal pistillate and normal staminate flowers, as well as flowers with morphological abnormalities formed based on flowers of different sexes can be found on the same ramet, which suggests the presence of paradioecious lability. [ABSTRACT FROM AUTHOR]

Cerebral microvascular dysfunction is a promising area for research into the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). Despite the scientific and clinical potential of studying microvascular dysfunction, progress in this area has long been hampered by the lack of methods to study microvessels intravitally. The aim of the present study was to search for potential optical coherence tomography (OCT) and OCT-angiography (OCTA) biomarkers of BD and MDD. One hundred and five consecutive patients with a current depressive episode were enrolled in the study (39 – BD and 66 – MDD). In addition, forty-one generally healthy subjects were enrolled as a control group. Only the right eye was examined in all subjects. Structural OCT and OCTA scans with signal strength ≥7 were included. Structural OCT measurements showed no significant differences between the groups. OCTA measurements of foveal avascular zone (FAZ), area and skeleton density showed a decrease in the retinal capillary bed in BD patients, whereas OCTA values in MDD patients did not differ from the control group. Several significant differences were found between the BD and control groups. In the BD group, the FAZ of the deep capillary plexus was increased, reflecting a reduction in capillary perfusion in the central subfield of this plexus. OCTA measurements of FAZ, area and skeleton density showed a decrease in the retinal capillary bed in BD patients, whereas OCTA values in MDD patients did not differ from the control group. • Characteristics of the retina may be potential biomarkers for mood disorders • Optical coherence tomography angiography (OCTA) provides in vivo imaging of the retinal vasculature • Bipolar disorder is associated with reduced foveal avascular zone area and skeletal density in the retinal capillary bed [ABSTRACT FROM AUTHOR]

Gendered order in the Soviet camp system shaped women inmates’ experiences of labour and factored in their survival. This article zooms in on the published memoirs of four women political prisoners who survived the Gulag and explores how they experienced and narrated carceral labour. It focuses on three types of labour taking place in the carceral setting – forced labour, care work and clandestine crafts – and investigates the gendered dynamics that surrounded each of these interrelated types of labour. Historically‐situated forms of women inmates’ constrained labour‐related agency, as the memoirs show, were diverse and not always limited to outright resistance or compliance. [ABSTRACT FROM AUTHOR]

In this paper, we suggest joint application of computational probabilistic analysis and the Monte Carlo method for numerical stochastic modeling problems. We use all the capabilities of computational probabilistic analysis while maintaining all the advantages of the Monte Carlo method. Our approach allows us to efficiently implement a computational hybrid scheme. In this way, we reduce the computation time and present the results in the form of distributions. The crucial new points of our method are arithmetic operations on probability density functions and procedures for constructing on the probabilistic extensions. Relying on specific numerical examples of solving systems of linear algebraic equations with random coefficients, we present the advantages of our approach. [ABSTRACT FROM AUTHOR]

The structural-phase sates and defect substructure are studied by the method of transmission electron microscopy using diffraction at different distances from the wheel–rail contact surface along the central axis of symmetry of the top of rail (TOR) (rolling surface) and along the radius of rounding (fluting) of the differentially hardened rails of the DH400RK category made of hypereutectoid steel after their continuous service. Using the obtained structure parameters, the estimates are made of the hardening mechanisms (strengthening by pearlite component, incoherent cementite particles, grain- and subgrain boundaries, dislocation substructure and internal stress fields) controlling the yield stress in the steel under study. A comparison is performed of the quantitative fine structure parameters and the contributions into hardening on the rolling surface and fluting. It is found out that the prevailing morphological component near the wheel– rail contact surface is the subgrain structure, and in the fluting – strengthening by incoherent particles. [ABSTRACT FROM AUTHOR]

For centuries, humans have relied on natural products to prevent and treat numerous health issues. However, biologically active compounds from natural sources, such as polyphenols, face considerable challenges, due to their low solubility, rapid metabolism, and instability, which hinder their effectiveness. Advances in the nanotechnologies have provided solutions to overcoming these problems through the use of porous silica materials as polyphenol carriers. These materials possess unique properties, such as a high specific surface area, adjustable particle and pore sizes, and a surface that can be easily and selectively modified, which favor their application in delivery systems of polyphenols. In this review, we summarize and discuss findings on how the pore and particle size, structure, and surface modification of silica materials influence the preparation of efficient delivery systems for biologically active polyphenols from natural origins. The available data demonstrate how parameters such as adsorption capacity, release and antioxidant properties, bioavailability, solubility, stability, etc., of the studied delivery systems could be affected by the structural and chemical characteristics of the porous silica carriers. Results in the literature confirm that by regulating the structure and selecting the appropriate surface modifications, the health benefits of the loaded bioactive molecules can be significantly improved. [ABSTRACT FROM AUTHOR]

The high silicon content in rice plant waste, specifically rice husks, makes this waste by-product attractive for the extraction and valorization of silicon oxide, which is widely used as an inert support in catalysis, drug delivery and molecular sieving. The procedures currently used for the treatment of plant biomass make extensive use of mineral acids (HCl, H2SO4, HNO3), which, besides them being potential environmental pollutants, reduce the yield and worsen the chemical-physical properties of the product. In this study, an evaluation of the easy treatment of rice husks by benchmarking different, more eco-friendly carboxylic acids in order to obtain a mesoporous SiO2 with an alveolar structure and a relatively high surface area and pore volume (300–420 m2/g, 0.37–0.46 cm3/g) is presented. The obtained mesoporous silicas are characterized by worm-like pores with a narrow size distribution and a maximum in the range of 3.4–3.5 nm. The mesoporous structure of the obtained materials was also confirmed by TEM. The complete removal of the organic part of the rice husks in the final materials was evidenced by thermogravimetric analysis. The high purity of the obtained mesoporous silica was detected using ICP analysis (98.8 wt. %). The structure peculiarities of the obtained mesoporous silicas were also characterized by solid-state NMR and ATR-FTIR spectroscopies. The morphology of the mesoporous silica was investigated by SEM. [ABSTRACT FROM AUTHOR]

The results of studying the quantitative, material, and morphometric composition of rock debris in sediments sampled by a box-corer on Lomonosov Ridge (83° N), Arctic Ocean, during the Severnyi Polyus 41 expedition of the Arctic and Antarctic Research Institute are presented. Clasts ≥ 1 cm in size were sampled from each distinguished layer according to the lithological description. The age model was created by the lithostratigraphic correlation with previously dated cores. The content of clasts on the eastern slope and summit is significantly higher than on the western slope, which is explained by the higher sedimentation rate on the western slope after the deglaciation peak. The change in the rock composition from carbonate to igneous and the increase in roundness with time indicate a higher input of Eurasian material in MIS 1. [ABSTRACT FROM AUTHOR]

We report a case of infection with the zoonotic nematode Gongylonema sp. in a 24-year-old woman from Varna, Bulgaria. Two days before seeking medical attention, the patient had noticed a filamentous mass in her buccal mucosa that migrated when touched with the tongue. She manually removed a thread-like worm from the mucosa near her lower lip. Albendazole was prescribed for three days. The patient had no history of travelling abroad or contact with animals. To our knowledge, this is the sixth case that has been reported in the country. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is one of the most frequent cardiac arrhythmias and leads to heart failure. Excessive sympathetic activity aggravates arrhythmogenic processes at the cellular and tissue levels. Hypersympathicotonia leads to desensitization of β1-adrenoreceptors (β1-AR), and negative regulation develops until the synthesis of new receptors stops. Desensitization processes may be indirectly reflected in an increase or decrease in the expression of the ADRB1 gene encoding β1-AR. The level of relative expression of the β1-AP ADRB1 gene in leukocytes of 52 patients with different forms of AF was analyzed in dynamics: before treatment, 3 days, and 3 and 12 months after ablation. Before ablation, expression was reduced in patients with persistent AF compared to groups with other forms of AF (р = 0.026). The study of dynamics revealed a significant decrease in the level of expression in patients with paroxysmal AF at the point of 3 days compared with the level before ablation (p = 0.003), with a further increase in values to the baseline at the point of 12 months (p = 0.021) relative to the point of 3 days. In patients with persistent AF, the expression level significantly increased 3 months after ablation (p = 0.046) compared to the level before surgery. Patients with long-term persistent AF after ablation had a tendency toward a decrease in expression. [ABSTRACT FROM AUTHOR]

Smart nanoassemblies degradable through the cleavage of acid‐labile linkages have attracted significant attention because of their biological relevance found in tumor tissues. Despite their high potential to achieve controlled/enhanced drug release, a systematic understanding of structural factors that affect their pH sensitivity remains challenging, particulary in the consruction of effective acid‐degradable shell‐sheddable nanoassemblies. Herein, the authors report the synthesis and acid‐responsive degradation through acid‐catalyzed hydrolysis of three acetal and ketal diols and identify benzaldehyde acetal (BzAA) exhibiting optimal hydrolysis profiles in targeted pH ranges to be a suitable candidate for junction acid‐labile linkage. The authors explore the synthesis and aqueous micellization of well‐defined poly(ethylene glycol)‐based block copolymer bearing BzAA linkage covalently attached to a polymethacrylate block for the formation of colloidally‐stable nanoassemblies with BzAA groups at core/corona interfaces. Promisingly, the investigation on acid‐catalyzed hydrolysis and disassembly shows that the formed nanoassemblies meet the criteria for acid‐degradable shell‐sheddable nanoassemblies: slow degradation at tumoral pH = 6.5 and rapid disassembly at endo/lysosomal pH = 5.0, while colloidal stability at physiological pH = 7.4. This work guides the design principle of acid‐degradable shell‐sheddable nanoassemblies bearing BzAA at interfaces, thus offering the promise to address the PEG dilemma and improve endocytosis in tumor‐targeting drug delivery. [ABSTRACT FROM AUTHOR]

Significance: For decades, tobacco advertisements and promotions have been common in mass media and public places in China. In 2015, China amended the Advertising Law to prohibit the distribution of tobacco advertising, while also initiating waves of tobacco control media campaigns. This study investigates the associations between exposure to anti- and pro-smoking messages, smoking status, and people's smoking-related beliefs and willingness to support tobacco control policies. Methods: A secondary data analysis was performed with the 2018 Global Adult Tobacco Survey of 19,376 adults aged ≥15 years in China. Anti- and pro-smoking message exposures were measured as the sum of sources (media or places) where respondents have seen the messages. Multivariable logistic regression analyses were conducted to examine the relationships among smoking status, message exposure, and the outcome variables (health harm beliefs, support for increasing tax on cigarettes, support for using part of the increased tax on tobacco control) controlling for smoking status and demographic differences. Results: Overall, 63.3% of the respondents reported being exposed to anti-smoking messages from at least 1 source, while 18.1% were exposed to pro-smoking messages from at least 1 source. Adults who currently, formerly, and never smoked differed in their beliefs about smoking and willingness to support tobacco control policies. Greater reported exposure to anti-smoking messages was positively associated with belief that smoking is harmful, support for increased cigarette tax, and support for using increased tax revenue for tobacco control measures. Meanwhile, greater reported exposure to pro-smoking messages was negatively related to willingness to support cigarette tax increases. Conclusions: While national and local tobacco control campaigns in China have reached a large proportion of the adult population, there is still room for improvement. China might consider expanding anti-tobacco campaigns, as reported exposure to these messages is associated with increased public awareness of the health hazards of smoking and support for increasing cigarette taxes. [ABSTRACT FROM AUTHOR]

The paper examines the construction of digital sovereignty ideas in authoritarian regimes, with a focus on Russia. Text mining and content analysis reveal that authoritarian regimes, in the face of new technologies, cannot simply impose a concept in a top-down manner. Instead, a diverse range of actors, including non-state entities, contribute to its formation, with their significance and participation fluctuating over time. In the context of Russia, digital sovereignty is not just a concept, but a tool used in international politics, economic development, and more, often sidelining the actual issues of technology development and their role in Russian politics. [ABSTRACT FROM AUTHOR]

The [4+2] dimerization of arylmaleic acid imides, which occurs in the presence of 3,5-dimethyl-1H-pyrazole on solid media under convection or microwave heating, has been studied. It was shown that dimerization proceeds stereoselectively with the formation of polycyclic compounds with a decahydrobenzo[e]pyrrolo[3,4-g]isoindole skeleton, predominantly of the endo-configuration. The best results in yields and stereoselectivity were achieved when reactions were carried out on silica gel under microwave activation conditions. [ABSTRACT FROM AUTHOR]

We consider the Kantorovich optimal transportation problem in the case where the cost function and marginal distributions continuously depend on a parameter with values in a metric space. We prove the existence of approximate optimal Monge mappings continuous with respect to the parameter. [ABSTRACT FROM AUTHOR]

Based on the fluxes of 1400 nearby galaxies observed in far ultraviolet (FUV) and in the H line, we determined the global star formation rate per unit Universe volume, yr Mpc . With the current star formation rate (), ( of the observed stellar mass is reproduced in the cosmological time of 13.8 billion years. The neutral gas reserves in the Local Volume with a radius of 11 Mpc will facilitate the current on a scale of approximately another 5 billion years. [ABSTRACT FROM AUTHOR]

Methoxychalcones containing the NMe2, 3,4-(OMe)2, 3,4,5-(OMe)3, and isobornyl substituents in the B ring were synthesized from 1,3-dihydroxy-4-(1,7,7-trimethylbicyclo-[2.2.1]hept-exo-2-yl)benzene and 1,4-dihydroxy-3-(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl)benzene. Oxidative cyclization of the new isobornylchalcones afforded flavones bearing the 1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl moiety. The erythrotoxicity, membrane-protective, and antioxidant activity of the synthesized compounds were evaluated in in vitro models including the model of oxidative hemolysis of mammalian erythrocytes initiated by H2O2 or 2,2′-azobis-(2-amidinopropane) dihydrochloride. All the chalcones studied and most flavones possessed good hemocompatibility and high antioxidant activity. The promise of further research into the synthesis of effective pharmacological substances based on the title compounds was demonstrated. [ABSTRACT FROM AUTHOR]

One of the key factors of space weather is solar flare activity, the monitoring and prediction of which is an important task of specialized dedicated groups of space experts and solar astronomers. Solar flare forecasts are based on identifying and detecting the so-called precursors, specific processes in solar activity events that occur before flares. Collecting data for space weather analysis and prediction comes down to several types of measurements performed by more than a dozen spacecraft. Ground-based observations and monitoring nowadays are becoming more or less complimentary. One of the reasons for this is the limitation of observation time with ground-based telescopes due to adverse Earth weather conditions. However, solar radio astronomy is immune to almost any weather activity, and the main question here is what new quality it can bring. Observational data accumulated in the 20th century show that solar radio bursts can be associated with flare activity. In addition, the existing network of solar radio telescopes is already well established. As an example, in this paper, we describe the possibilities of a fully steerable 32-meter radio telescope of Ventspils International Radio Astronomy Centre (VIRAC), Latvia, which can be useful for searching for new precursors of solar flares. [ABSTRACT FROM AUTHOR]

Understanding lanthanide coordination chemistry can help develop new ligands for more efficient separation of lanthanides for critical materials needs. The Cambridge Structural Database (CSD) contains tens of thousands of single crystal structures of lanthanide complexes that can serve as a training ground for both fundamental chemical insights and future machine learning and generative artificial intelligence models. This work aims to understand the currently available structures of lanthanide complexes in CSD by analyzing the coordination shell, donor types, and ligand types, from the perspective of rare-earth element (REE) separations. We obtain four sets of lanthanide complexes from CSD: Subset 1, all Ln-containing complexes (49472 structures); Subset 2, mononuclear Ln complexes (27858 structures); Subset 3, mononuclear Ln complexes without cyclopentadienyl ligands (Cp) (26156 structures); Subset 4, Ln complexes with at least one 1,10-phenanthroline (phen) or its derivative as a coordinating ligand (2226 structures). The subsequent analysis of lanthanide complexes in these subsets examines the trends in coordination numbers and first shell distances as well as identifies and characterizes the ligands and donor groups. In addition, examples of Ln-complexes with commercially available complexants and phen-based ligands are interrogated in detail. This systematic investigation lays the groundwork for future data-driven ligand designs for REE separations based on the structural insights into the lanthanide coordination chemistry. [ABSTRACT FROM AUTHOR]

Background: During cardiopulmonary resuscitation, intravenous thrombolytics are commonly used for patients whose underlying etiology of cardiac arrest is presumed to be related to pulmonary embolism (PE). Methods: We performed a systematic review and meta-analysis of the existing literature that focused on the use of thrombolytics for cardiac arrest due to presumed or confirmed PE. Outcomes of interest were return of spontaneous circulation (ROSC), survival to hospital discharge, neurologically-intact survival, and bleeding complications. Results: Thirteen studies with a total of 803 patients were included in this review. Most studies included were single-armed and retrospective. Thrombolytic agent and dose were heterogeneous between studies. Among those with control groups, intravenous thrombolysis was associated with higher rates of ROSC (OR 2.55, 95% CI = 1.50–4.34), but without a significant difference in survival to hospital discharge (OR 1.41, 95% CI = 0.79–2.41) or bleeding complications (OR 2.21, 0.95–5.17). Conclusions: Use of intravenous thrombolytics in cardiac arrest due to confirmed or presumed PE is associated with increased ROSC but not survival to hospital discharge or change in bleeding complications. Larger randomized studies are needed. Currently, we recommend continuing to follow existing consensus guidelines which support use of thrombolytics for this indication. [ABSTRACT FROM AUTHOR]

There are limited data on outcomes of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in recipients with prior COVID‐19 infection. This single‐center retrospective study included 54 adult patients who received allo‐HSCT from July 2020 to September 2021 after previous COVID‐19 infection and 122 control group patients without a history of COVID‐19 who underwent HSCT during the same period, with a median follow‐up of 17 months. Median time from COVID‐19 to allo‐HSCT was 211 days. The incidence of main complications in the post‐transplant period was not significantly different between the two groups: deep vein thrombosis (p =.85), TMA (p =.8), VOD (p =.25), bloodstream infections (p =.21), pneumonia of any etiology (p =.41), viral infections (p =.85), invasive fungal disease (p =.08). The 2‐year non‐relapse mortality, relapse incidence, overall survival, and progression‐free survival also were comparable in the study and the control groups: 22% (95% CI 10.5–36.2) versus 26.3% (95% CI 18.7–34.6) p =.4; 15.6% (95% CI 7.3–26.9) versus 23.6% (95% CI 16.0–32.3) p =.39; 67.9% (95% CI 50.4–80.3) versus 59.8% (95% CI 50.2–68.1) p =.24 and 62.3% (95% CI 45.5–75.3) versus 49.9% (95% CI 40.0–59.1) p =.18, respectively. The history of previous COVID‐19 infection did not affect the results of allo‐HSCT. [ABSTRACT FROM AUTHOR]

Using the data from weather observation stations, an assessment of statistical significance of the first harmonic amplitude of the long-term average daily precipitation series in Russia in 1961‒2020 and their changes in 1991‒2020 compared to 1961‒1990 is made. It is shown that at most stations the first harmonic has a reliable value different from the noise, except for eleven stations in the southern regions of the European part of Russia. It is revealed that on average there is a significant decrease in the first harmonic amplitudes of the daily precipitation series across Russia. An analysis of the spatial distribution of the studied quantities is performed and the presence of large areas with their homogeneous character is demonstrated. [ABSTRACT FROM AUTHOR]

Food sustainability is closely interrelated with plant-based nutrition. The so-called "superfoods" provide a palette of macro- and micro-nutrients and bioactive compounds, highly beneficial for human health. Thus, plant "superfoods" are commonly regarded as a universal solution to both health- and sustainability-related problems of today's food system. Sustainability is usually assumed for granted so related research is often neglected. Some of the world-recognized "superfoods," which can constitute key items from a state-of-the-art plant-based diet, are considered and conceptualized in view of the contemporary societal challenges, as well as the associated sustainability implications for the environment and climate. Increasing the share of plant "superfoods" is not an automatic sustainability enhancer. There must be an individual approach to each specific "superfood" supply chain to carefully evaluate a number of important challenges, such as long distance between points of production and consumption, soil degradation, and loss of biodiversity. A multidisciplinary and multisectoral effort of researchers, industry, consumers, and policymakers is vital to ensure that knowledge-based scientific evidence will prevail over unsupported marketing claims about "superfoods." [ABSTRACT FROM AUTHOR]

Corrosion under insulation (CUI) is a form of corrosion typically occurring on steel pipes and vessels covered with thermal insulation. CUI is a critical issue in petrochemical and refining industry leading to significant financial losses and severe environmental hazards. State‐of‐the art CUI monitoring system consisting of wireless loggers with flexible resistometric sensors is used to assess the effect of insulation material, position, and presence of a defect on the actual corrosivity toward carbon steel under alternating condensation conditions. All three considered factors together with the climatic parameters and presence of corrosion products are important for the CUI process. Most complex is the role of the insulation material as the properties inhibiting corrosion under intact insulation may be linked to a worse insulating ability. Because of the high sensitivity and immediate response of the sensors, the technique can be applied for timely CUI detection of insulated pipelines in both industrial facilities and laboratory studies. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigate the availability and access to orphan drugs for rare cancers in Bulgaria, aiming to address the urgent need for improved treatment access for this vulnerable population. By comparing data from European and national sources, we aimed to assess the availability, delays, and budgetary impact of these drugs. Our findings reveal significant disparities in their access and highlight the pressing need for targeted policies to address these inequalities. This research contributes valuable insights into the challenges faced by rare cancer patients and we call for focused efforts at both the European and national levels to ensure equitable access to treatment. Rare cancers are defined by an annual incidence of fewer than 6 per 100,000. Bearing similarities to rare diseases, they are associated with substantial health inequalities due to diagnostic complexity and delayed access to innovative therapies. This situation is further aggravated in Southeastern European countries like Bulgaria, where limited public resources and expertise underscore the need for additional policy and translational research on rare cancers. This study aimed to explore the availability and access to orphan drugs for rare cancers in Bulgaria for the period of 2020–2023. We cross-compared data from both the European Union and national public sources to evaluate the number of available and accessible orphan drugs for rare cancers, the delay from market authorization to reimbursement, the dynamics of public expenditures, and regional disparities in access across the country. We juxtaposed the main characteristics of oncological and non-oncological orphan drugs as well. Only 15 out of 50 oncological orphan drugs that were authorized by the European Medicine Agency were accessible for rare cancer patients in Bulgaria. The median delay between market authorization and inclusion in the Bulgarian Positive Drug List was 760 days. The total expenditures for all orphan drugs for rare cancers amounted to EUR 74,353,493 from 2020 to 2023. The budgetary impact of this group rose from 0.24% to 3.77% of total public medicinal product expenditures for the study period. Rare cancer patients represent a vulnerable population that often faces limited to no access to treatment. We call for targeted European and national policies to address this major inequality. [ABSTRACT FROM AUTHOR]

This study investigated the diagnostic capacity for Fetal Alcohol Spectrum Disorder (FASD) in multidisciplinary clinics across several provincial and one territorial jurisdictions of Canada: Alberta, British Columbia, Manitoba, Ontario and Northwest Territories. The data were collected directly from clinics capable of providing diagnoses of FASD and examined annual capacity for the assessment and diagnosis of FASD per year from 2015 to 2019. In total, 58 FASD diagnostic clinics were identified and 33 clinics participated in this survey. The study identified inadequate FASD diagnostic capacity in all participating jurisdictions. Based on the findings and the current population sizes, it is estimated that 98% of individuals with FASD are undiagnosed or misdiagnosed in Canada. Wait times for FASD diagnosis ranged from 1 month to 4.5 years across participating jurisdictions. The annual FASD diagnostic capacity in the select provinces and territories require at least a 67-fold increase per year. [ABSTRACT FROM AUTHOR]

Low levels of media literacy in Bulgaria have provided fertile soil for anti-vaxxers and spawned disinformation campaigns as a major means of influencing the public opinion. Bulgaria has gained a reputation as the poorest and most corrupt country in the European Union (EU) and the fastest-shrinking nation in the world. The COVID-19 pandemic exacerbated some of the well-known, long-standing problems in the healthcare system in Bulgaria – rising morbidity, an insufficient number of hospital beds, a low rate of COVID-19 vaccination, and, above all, a high mortality rate. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the effect of Bacillus subtilis strains VKM B-2604D and VKM B-2605D, which form the basis of the Vitaplan biological product, and their combinations with chitosan salicylate on antioxidant defense enzymes in the process of formation of resistance of wheat plants to infection with the dark brown blotch pathogen Bipolaris sorokiniana. In wheat plants treated with B. subtilis strains and their combinations with chitosan salicylate, upon subsequent infection, catalase and peroxidase are activated, which regulate the intensity of oxidative stress induced by the introduction of the pathogen. Taking the data we obtained into account, it can be assumed that the increase in plant resistance to the pathogen is realized through the control of the activity of antioxidant enzymes (in particular, catalase and peroxidase), which maintain the concentration of H2O2 at the level necessary for the neutralization of the phytopathogen in tissues, including the direct destruction of the invading pathogen and/or activation of crosslinking and lignification of the cell wall. These processes strengthen the cell wall and help contain the spread of the pathogen in the plant. At the same time, protective reactions are also switched on, leading to the development of induced resistance in wheat plants to dark brown spotting, which manifests itself in a decrease in the development of the disease by 25–45% relative to the infected control in the treated plants. The results indicate that the combination of active strains of microorganisms-antagonists of plant pathogens and chitosan salicylate is promising for increasing the biological efficiency and expanding the spectrum of action of the developed biological products. [ABSTRACT FROM AUTHOR]

An assessment of the antifungal and immunomodulatory activity of dispersions of chitosan nanoparticles obtained by fractional precipitation at pH 5.0 and pH 7.5 using chitosan of different molecular weights was made. The dispersion of nanoparticles obtained at pH 5 has increased fungistatic activity against C. sativus and A. solani, due to the higher availability of amino groups in looser nanoparticles. This dispersion showed immunostimulating activity, increasing the resistance of wheat to dark brown spot. It was also established that the elicitor activity of dispersions of chitosan nanoparticles is significantly higher than the activity of solutions of the original polymer. [ABSTRACT FROM AUTHOR]

Warning labels help consumers understand product risks, enabling informed decisions. Since the 1966 introduction of cigarette warning labels in the United States, research has determined the most effective message content (health effects information) and format (brand-free packaging with pictures). However, new challenges have emerged. This article reviews the current state of tobacco warning labels in the United States, where legal battles have stalled pictorial cigarette warnings and new products such as electronic cigarettes and synthetic nicotine products pose unknown health risks. This article describes the emerging research on cannabis warnings; as more places legalize recreational cannabis, they are adopting lessons from tobacco warnings. However, its uncertain legal status and widespread underestimation of harms impede strict warning standards. The article also reviews opioid medication warning labels, suggesting that lessons from tobacco could help in the development of effective and culturally appropriate FDA-compliant opioid warning labels that promote safe medication use and increased co-dispensing of naloxone. [ABSTRACT FROM AUTHOR]

The human visual analyzer is a high form of evolution. Some jellyfish can distinguish light and dark objects with sensitive cells. Squids, octopuses, and nautiluses from Cephalopods family have eyes with which they can see objects. Visual information is processed in the brain. In fishes, the visual analyzer evolved. Fishes living below 100 m depth inhabit a world with blue light. The authors consider the evolution of vision in these fishes due to the lowest absorption of blue and violet colors of electromagnetic waves from the optical spectrum. Subsequently, on land, in humans vision evolved towards the green color. Green is the most prevalent color on the land. In humans, three light-sensitive cones evolved – S, M, and L. S cones are most sensitive to blue, M – to green, and L – to red color in the spectrum. Some humans retain sensitivity of S to genetic changes and disorders. Additive color mixing is a high form of color perception in humans. The additive mixing of different colors achieves a new color in the human visual analyzer. Remarkably, different individuals perceive observed images in varying manners. Mixing neighboring colors on the spectrum gives one, two, or three colors. This process is estimated using graphical modeling. The graphical modeling with two colors allows for the creation of additive colors. One, two, or three additive colors can be obtained. The production of colors results from the light sensitivity of S, M, and L cones. An analysis that physically demonstrates the mixing of green and red colors, resulting in the colors yellow or orange. When blue and red are mixed, the resulting colors are green, yellow, and orange is proposed. The additive mixing of blue and yellow gives green. The subjective nature of visual perception, influenced by the viewer’s heightened sensitivity to one of the colors, becomes evident in the presence of two colors. Notably, when the background is violet, the sensitivity of the blue cones diminishes. [ABSTRACT FROM AUTHOR]

Dynamic light scattering, atomic force and transmission electron microscopy were used to characterize three different types of potential carriers of double-stranded RNA (dsRNA): calcium phosphate particles, chitosan particles, and hybrid particles consisting of an inorganic core coated with chitosan. The hydrodynamic diameter and electrokinetic potential were measured, and the surface morphology of the three types of particles was studied. The interaction of dsRNA with the carriers was studied using electrophoresis and atomic force microscopy. The possibility of the dsRNA complexes formation with chitosan-based carriers, resulting from the interaction of dsRNA with the positively charged amino groups of chitosan, was demonstrated. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) inhibitors have heralded a paradigm shift in the management of immune-mediated diseases. While their efficacy is well-established, the safety concerns associated with these agents, particularly regarding thromboembolic events (TE), remain a focus of extensive research and clinical scrutiny. This comprehensive literature review embarks on an exploration of the multifaceted landscape of JAK inhibitors, providing insights into their safety profiles across diverse immune-mediated diseases. The introduction highlights the transformative influence of JAK inhibitors in the treatment of immune-mediated diseases. Historically, the therapeutic arsenal for these conditions included corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics. The advent of JAK inhibitors has revolutionized this landscape, although concerns about their safety persist. This review strives to comprehensively evaluate their safety, amalgamating knowledge from multiple studies and trials. The subsequent sections delve into the safety of specific JAK inhibitors in the context of rheumatoid arthritis, inflammatory bowel diseases, and dermatologic conditions and their associations with venous thromboembolism. The evolving understanding of TE risk, particularly the intricate relationship between these agents and immune-mediated diseases, is meticulously unravelled. The concluding remarks underscore the dynamic nature of TE risk assessment with regard to immune-mediated diseases involving JAK inhibitors. It underscores that risk assessment is multifactorial, influenced not only by the choice of JAK inhibitor but also by the nuances of the underlying immune-mediated disease and the unique patient characteristics. This review offers a holistic perspective on TE risks associated with JAK inhibitors and contributes to the ongoing dialogue regarding their safety in the realm of immune-mediated diseases. [ABSTRACT FROM AUTHOR]

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat's mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat's primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat's potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat's roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat's multifaceted therapeutic potential. [ABSTRACT FROM AUTHOR]

This retrospective case-control study examined the relationship between the serum and synovial levels of cathepsin G (CatG) and cathepsin K (CatK) in patients with psoriatic arthritis (PsA) and their association with disease activity. Methods: This case-control study involved 156 PsA patients, 50 patients with gonarthrosis (GoA), and 30 healthy controls. The target parameters were measured using enzyme-linked immunosorbent assay (ELISA) kits. The serum levels of CatG and CatK were found to be significantly higher in PsA patients compared to both control groups (p < 0.001). Moreover, they could distinguish PsA patients from healthy controls with 100% accuracy. Synovial fluid CatG and CatK were positively associated with the following indicators of disease activity: the VAS (rs = 0.362, rs = 0.391); the DAPSA (rs = 0.191, rs = 0.182); and the mCPDAI (rs = 0.378, rs = 0.313). Our results suggest that serum and synovial fluid CatG and CatK levels could serve as biomarkers for PsA. In PsA patients with synovial fluid crystals, elevated synovial CatG levels demonstrated a sensitivity of 89.54% and a specificity of 86.00% in distinguishing them from PsA patients without crystals. Similarly, elevated synovial CatK levels had a sensitivity of 93.67% and a specificity of 94.34% for distinguishing PsA patients with synovial fluid crystals from those without. Furthermore, the synovial fluid levels of both CatG and CatK showed positive associations with key indicators of disease activity, including the visual analog scale (VAS) (rs = 0.362, rs = 0.391), the disease activity in psoriatic arthritis (DAPSA) (rs = 0.191, rs = 0.182), and the modified composite psoriatic disease activity index (mCPDAI) (rs = 0.378, rs = 0.313). In conclusion, our findings suggest that the serum and synovial fluid levels of CatG and CatK hold promise as potential biomarkers for assessing disease activity in psoriatic arthritis. [ABSTRACT FROM AUTHOR]

This review explores the link between immune interactions and chronic pain, offering new perspectives on treatment. It focuses on Janus kinase (JAK) inhibitors' potential in pain management. Immune cells' communication with neurons shapes neuroinflammatory responses, and JAK inhibitors' effects on pain pathways are discussed, including cytokine suppression and microglial modulation. This review integrates studies from rheumatoid arthritis (RA) pain and central sensitization to highlight connections between immune interactions and pain. Studies on RA joint pain reveal the shift from cytokines to sensitization. Neurobiological investigations into central sensitization uncover shared pathways in chronic pain. Clinical evidence supports JAK inhibitors' efficacy on pain-related outcomes and their effects on neurons and immune cells. Challenges and future directions are outlined, including interdisciplinary collaboration and dosing optimization. Overall, this review highlights JAK inhibitors' potential to target immune-mediated pain pathways, underscoring the need for more research on immune–pain connections. [ABSTRACT FROM AUTHOR]

Employing a novel georeferenced household survey enriched with data on precipitation and temperature, this paper examines how rainfall variability affects individual labor supply in Uzbekistan, a highly traditional lower-middle-income country in Central Asia. The findings suggest that rainfall variability induces the reallocation of labor supply: (1) out of agriculture to unemployment, (2) from unemployment to business activities and irregular remunerated activities, and (3) from being out of labor force to unemployment. These effects differ in rural and urban areas and by gender. In addition, active women's involvement in the labor market and household decision-making mediates the impact of rainfall variability on employment choices, especially in rural areas. This implies that traditional gender roles may make households in developing countries more vulnerable to adverse consequences of climate change, while women's empowerment may mitigate such consequences. [ABSTRACT FROM AUTHOR]

To elaborate the utility of multiplex quantitative polymerase chain reaction (multiplex qPCR) for the accurate diagnosis of severe respiratory tract infections (RTIs) in hospitalized children. In two separate periods during 2022, 76 respiratory specimens (combined throat/nasopharyngeal swabs) were submitted for multiplex qPCR regarding 26 respiratory pathogens. The specimens were obtained from children with severe RTIs hospitalized in the Institute for Respiratory Diseases in Children, Skopje. Multiplex qPCR detected at least one respiratory pathogen in all examined specimens (76/76), with 83% (63/76) rate of co-infections. Considering that positive results are only the ones with Ct value below 28, the rates of detected pathogens and co-infections decrease to 75% and 22%, respectively. The most commonly detected pathogens during the spring period were Parainfluenza type 3 (PIV3) followed by Adenovirus (AdV) and Respiratory syncytial virus type B (RSVB) with frequency rate of 23%, 19% and 19%, respectively. During the autumn period, the most common were RSVB and Streptococcus pneumoniae with frequency rate of 31% and 17%, respectively. Multiplex qPCR is a powerful tool for diagnosing RTIs. Semi-quantification of the viral load by reporting Ct values added higher level of evidence for accurate diagnosis. Seasonal detection of the examined viruses was notable with higher prevalence of PIV3 in spring and RSVB in autumn period. [ABSTRACT FROM AUTHOR]

This study analyzes the evolution of educational and occupational patterns among migrants and natives, as well as income inequality in Germany from 1985 to 2015. We show that despite migrants catching up in education, employment, and income with their native counterparts, unfavorable societal attitudes toward them have remained virtually unchanged, which can be attributed to Bourdieu's conceptualization of cultural inheritance. We find that while income inequality has increased significantly over the 30‐year period, this trend varied considerably by the federal state and that migration did nothing to add to inequality. Since both the German economy and society rely on migrants, there is a strong need for the narratives toward migrants to be based on empirical evidence. The findings of this study hold migrant‐related policy implications not only for Germany but also for other developed nations that rely on migrants as a labor force. [ABSTRACT FROM AUTHOR]

Ethanol metabolism is relatively understudied in neurons, even though changes in neuronal metabolism are known to affect their activity. Recent work demonstrates that ethanol is preferentially metabolized over glucose as a source of carbon and energy, and it reprograms neurons to a state of reduced energy potential and diminished capacity to utilize glucose once ethanol is exhausted. Ethanol intake has been associated with changes in neuronal firing and specific brain activity (EEG) patterns have been linked with risk for alcohol use disorder (AUD). Furthermore, a haplotype of the inwardly rectifying potassium channel subunit, GIRK2, which plays a critical role in regulating excitability of neurons, has been linked with AUD and shown to be directly regulated by ethanol. At the same time, overexpression of GIRK2 prevents ethanol‐induced metabolic changes. Based on the available evidence, we conclude that the mechanisms underlying the effects of ethanol on neuronal metabolism are a novel target for developing therapies for AUD. [ABSTRACT FROM AUTHOR]

The notion of spectrum for first-order properties introduced by J. Spencer for Erdős–Rényi random graph is considered in relation to random uniform hypergraphs. In this work we study the set of limit points of the spectrum for first-order formulae with bounded quantifier depth and obtain bounds for its maximum value. Moreover, we prove zero–one k -laws for the random uniform hypergraph and improve the bounds for the maximum value of the spectrum for first-order formulae with bounded quantifier depth. We obtain that the maximum value of the spectrum belongs to some two-element set. [ABSTRACT FROM AUTHOR]

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The literature on cyclic sulfinamides (put simply, sultims) published from 1989 to 2022 has been summarized and reviewed. The information is divided into two sections: the analysis of synthetic methods on the preparation of cyclic sulfinamides and the discussion of the chemical properties of cyclic sulfinamides focusing on their reactions and applications. The survey of the reaction conditions, provided in the most detailed way, and a critical view of the reaction mechanisms add an extra dimension to the text. The data presented will be useful to specialists in different areas, especially those who work in the field of synthetic organic and pharmaceutical chemistry. [ABSTRACT FROM AUTHOR]

During the period 2020-2022, an experiment was conducted in the experimental vineyard of the Agricultural University - Plovdiv, and four clones of the wine variety Syrah, numbered 100, 174, 470 and 524, grafted on the SO4 rootstock were selected as the study object. During the "pea size" phase, the green pruning operation – bunch thinning was applied. The shoots growth starts from the vegetation phase "first leaf appearance" and ends at the "veraison". The average duration is about 100 days, covering the period of May, June and July. It was found that the vine shoots from a clone 470 reached the greatest average length, V3 - 285, 265, 290 cm and V7 - 359, 336, and 380 cm, and those from a clone 100 were distinguished by the weakest growth, V1 - 197, 203 and 205 cm and V5 - 240, 228 and 245 cm. Differences were proven between the variants, both in the non-reduced (V1, V2, V3, and V4) and in those with reduced yields (V5, V6, V7, and V8), as after reducing the number of bunches, the length of the shoots was longer - high in all vines from the used Syrah clones. This study provides information on the relationship between the applied green pruning operation (bunch thinning) during the growing season and its effects on the vegetative growth. Balancing the vines bud load by controlling yield during the growing season is a preferred viticultural practice for increasing the grape quality. [ABSTRACT FROM AUTHOR]

Background: Memory T cells are a heterogeneous population of immune cells that provide adaptive immunity. Its full recovery seems essential for graft-versus-tumor reactions that provide an opportunity for biological cure in patients with acute leukemia. The use of mismatched or haploidentical donors has increased, which has become possible because of modifications in graft versus host disease (GVHD) prophylaxis. Materials and Methods: Sixty-five leukemia patients (acute myeloid leukemia -- 40, acute lymphoblastic leukemia -- 25), median age 33 (17-61) years, underwent allo-HSCT from 2016 to 2019 in the National Research Centre for Hematology. Patients were divided into three groups based on the impact of GVHD prophylaxis on T cell recovery: horse antithymocyte globulin (ATG)-based regimen (n=32), horse ATG combined with posttransplant cyclophosphamide (PT-Cy) (n=18), and ex vivo T cell depletion (n=15). Results: The early period after transplantation (before day +100) was characterized by significantly lower absolute numbers of T naïve, memory stem and T central memory cells in peripheral blood in patients after ATG+PT-Cy-regimen or ex vivo T cell depletion than after ATG-based prophylaxis (p<0.05). Moreover, strong depletion of naïve T and memory stem cells prevents the development of GVHD, and determining the absolute number of CD8+ naïve T and memory stem cells with a cutoff of 1.31 cells per microliter seems to be a perspective in assessing the risks of developing acute GVHD (p=0.008). The dynamics of T cell recovery showed the involvement of either circulating or bone marrow resident T effector cells shortly after allogeneic transplantation in all patients, but the use of manipulated grafts with ex vivo T cell depletion requires the involvement of naïve and memory stem cells. There was no significant effect of T cell recovery on leukemia relapse after allogeneic transplantation. Conclusion: These experimental outcomes contribute to providing the best understanding of immunological events that occur early after transplantation and help in the rational choice of GVHD prophylaxis in patients who will undergo allogeneic transplantation. Our study demonstrated the comparable immunological effects of posttransplant cyclophosphamide and ex vivo T cell depletion and immunological inefficiency of horse ATG for GVHD prevention. [ABSTRACT FROM AUTHOR]

Monometallic (Ni, Co, Cu) and bimetallic (Ni-Co, Ni-Cu) 10–20 wt.% metal containing catalysts supported on fly ash zeolite were prepared by post-synthesis impregnation method. The catalysts were characterized by X-ray powder diffraction, N2 physisorption, XPS and H2-TPR methods. Finely dispersed metal oxides and mixed oxides were detected after the decomposition of the impregnating salt on the relevant zeolite support. Via reduction intermetallic, NiCo and NiCu phases were identified in the bimetallic catalysts. The catalysts were studied in hydrodeoxygenation of lignocellulosic biomass-derived levulinic acid to γ-valerolactone (GVL) in a batch system by water as a solvent. Bimetallic, 10 wt.% Ni, and 10 wt.% Cu or Co containing fly ash zeolite catalysts showed higher catalytic activity than monometallic ones. Their selectivity to GVL reached 70–85% at about 100% conversion. The hydrogenation activity of catalysts was found to be stronger compared to their hydration ability; therefore, the reaction proceeds through formation of 4-hydroxy pentanoic acid as the only intermediate compound. [ABSTRACT FROM AUTHOR]