Search Results (719)

Background and Clinical Significance: Blue nevi are a dubious pigmented lesion. While somewhat common throughout the population, they are significantly less common than other melanocytic neoplasms, and both their morphology and development bring them closer to true hamartomas than neoplasms. An exceedingly rare occurrence is the development of melanoma from a preexisting blue nevus. This nosological unit, defined as melanoma arising in a blue nevus, also known as malignant blue nevus, blue naevus–like melanoma, melanoma ex-blue naevus, and melanoma mimicking cellular blue naevus, is required to either originate from an area of previously excised blue nevus or have a blue nevus remnant adjacent to it. Due to the spindle cell morphology of melanoma arising in blue nevus, the terminology is often misused by some authors to include spindle cell melanomas, which exhibit a distinct pathogenesis and, although morphologically similar, have differing molecular profiles as well. Case presentations: The following manuscript discusses comparative morphological features in a case series of blue nevi and melanoma arising in blue nevi. Discussion: Blue nevi present with unique morphological features, with melanomas originating from them having a unique molecular pathology profile, which significantly differs from other cutaneous melanomas and is closer to that of uveal melanomas. Full article

This article deals with the effect of Kr¹⁵⁺ ion irradiation on the structure and properties of partially stabilized zirconium dioxide (ZrO₂ + 3 mol. % Y₂O₃) ceramics. Ion irradiation is used to simulate radiation damage typical of operating conditions in nuclear reactors and space technology. It is shown that with an increase in the irradiation fluence, point defects are formed, dislocations accumulate, and the crystal lattice parameters change. At high fluences (>10¹³ ions/cm²), a phase transition of the monoclinic (m-ZrO₂) phase to the tetragonal (t-ZrO₂) and cubic (c-ZrO₂) modifications is observed, which is accompanied by a decrease in the crystallite size and an increase in internal stresses. Changes in the mechanical properties of the material were also observed: at moderate irradiation fluences, strengthening is observed due to the formation of dislocation structures, whereas at high fluences (>10¹⁴ ions/cm²), a decrease in strength and a potential amorphization of the structure begins. The change in the phase composition was confirmed by X-ray phase analysis and Raman spectroscopy. The results obtained allow a deeper understanding of the mechanisms of radiation-induced phase transformations in stabilized ZrO₂ and can be used in the development of ceramic materials with increased radiation resistance. Full article

The synthesis of 2-phenylbenzoxazole fluorosulfate derivatives was carried out using the SuFEx reaction. To study the anticancer properties of the obtained compounds, the cell lines PC-3 (obtained from prostate adenocarcinoma), BT-474, and MCF-7 (both obtained from breast carcinoma) were used. The cytotoxicity on murine 3T3L1 embryonic was also investigated. Among the tested compounds, the ortho-substituted fluorosulfate derivative (BOSo) exhibited significant cytotoxicity against MCF-7 cells. The biological findings are consistent with molecular docking results, which revealed a structural similarity between BOSo and known inhibitors of hER and HER2 receptors—tamoxifen and SYR127063. Therefore, BOSo shows promise as a potential therapeutic agent with antiproliferative properties. The photoluminescent characteristics of the fluorosulfate derivatives were examined in the solid state, in acetonitrile solution and in PBS, with the highest quantum yields reaching up to 64% for the para-fluorosulfate derivative in acetonitrile. Overall, these compounds demonstrate considerable potential for the development of new multifunctional molecular tools that combine biological activity with fluorescent properties. Full article

Despite targeting mainly the respiratory tract, SARS-CoV-2 disrupts T cell homeostasis in ways that may explain both acute lethality and long-term immunological consequences. In this study, we aimed to evaluate the T-cell-mediated chain of immunity and formation of TCR via TREC assessment in COVID-19 and long COVID (LC). For this study, we collected 231 blood samples taken from patients with acute COVID-19 (n = 71), convalescents (n = 51), people diagnosed with LC (n = 63), and healthy volunteers (n = 46). With flow cytometry, we assessed levels of CD4+ and CD8+ minor T cell subpopulations (i.e., naïve, central and effector memory cells (CM and EM), Th1, Th2, Th17, Tfh, Tc1, Tc2, Tc17, Tc17.1, and subpopulations of effector cells (pE1, pE2, effector cells)). Additionally, we measured TREC levels. We found distinct changes in immune cell distribution—whilst distribution of major subpopulations of T cells was similar between cohorts, we noted that COVID-19 was associated with a decrease in naïve Th and CTLs, an increase in Th2/Tc2 lymphocyte polarization, an increase in CM cells, and a decrease in effector memory cells 1,3, and TEMRA cells. LC was associated with naïve CTL increase, polarization towards Th2 population, and a decrease in Tc1, Tc2, Em2, 3, 4 cells. We also noted TREC correlating with naïve cells subpopulations. Our findings suggest ongoing immune dysregulation, possibly driven by persistent antigen exposure or tissue migration of effector cells. The positive correlation between TREC levels and naïve T cells in LC patients points to residual thymic activity. The observed Th2/Th17 bias supports the hypothesis that LC involves autoimmune mechanisms, potentially driven by molecular mimicry or loss of immune tolerance. Full article

Investigating brain area functions requires advanced technologies, but meaningful insights depend on correlating neural signals with behavior. Traditional mice behavior annotation methods, including manual and semi-automated approaches, are limited by subjectivity and time constraints. To overcome these limitations, our study employs the YOLO neural network for precise mice tracking and composite RGB frames for behavioral scoring. Our model, trained on over 10,000 frames, accurately classifies sitting, running, and grooming behaviors. Additionally, we provide statistical metrics and data visualization tools. We further combined AI-powered behavior labeling to examine hippocampal neuronal activity using fluorescence microscopy. To analyze neuronal circuit dynamics, we utilized a manifold analysis approach, revealing distinct functional patterns corresponding to transgenic 5xFAD Alzheimer’s model mice. This open-source software enhances the accuracy and efficiency of behavioral and neural data interpretation, advancing neuroscience research. Full article

Mineral waters from two tectonically active mountain systems within the Alpine-Himalayan orogenic belt, the Pamir and the Greater Caucasus (Elbrus region), were analyzed for ²²²Rn activity and ²³⁸U concentrations to establish correlations with geological conditions, physicochemical characteristics of water, and to assess the potential health risk associated with ²³⁸U and ²²²Rn. It was found that in mineral waters of the Pamir, the concentrations of ²³⁸U (0.004–13.3 µg/L) and activity of ²²²Rn (8–130 Bq/L) are higher than in the Elbrus area: 0.04–3.74 µg/L and 6–33 Bq/L, respectively. Results indicate that uranium mobility in water is strongly influenced by T, pH, and Eh, but is less affected by the age of host rocks or springs′ elevation, whereas radon activity in waters depends on the age of rocks, spring elevation, ²³⁸U content, and values of δ¹⁸O and δ²H in water. This study reveals fundamental geological distinctions governing uranium and radon sources in the mineral waters of these regions. Isotopic evidence (²²²Rn and ³He/⁴He) demonstrates crustal radon sources prevail in Pamir, whereas the Elbrus system suggests mantle-derived components. The U concentrations do not exceed 30 µg/L, and most water samples (94%) showed ²²²Rn activities below 100 Bq/L, complying with the drinking water exposure limits recommended by the World Health Organization and European Union Directive. However, in intermountain depressions of the Pamirs, at low absolute elevations (~2300 m), radon concentrations in water can increase significantly, which requires special attention and study. Full article

The climbing perch, Anabas testudineus, is one of the most widely distributed freshwater amphibious fishes in South and Southeast Asia, exhibiting terrestrial movements. Our experimental study aimed to investigate endocrinological and biochemical changes in the blood of climbing perch associated with their terrestrial movements. To achieve this, the fish were divided into two groups: one group was exposed to aquatic conditions for twenty minutes, while the other group was subjected to terrestrial conditions for the same duration through rapid water level decrease. In terrestrial conditions, the fish predominantly exhibit movements on land, whereas in aquatic environments, they primarily remain immobile or swim. Elevated levels of stress-induced cortisol and glucose after short-term exposure indicate a high-stress response involving both neuroendocrine and metabolic mechanisms. Changes in the activity of aspartate aminotransferase and increased concentrations of triglycerides in the blood serum suggest energy mobilization through aerobic metabolic pathways. Extreme environmental changes did not affect thyroid axis function, including deiodination, thereby maintaining essential physiological activities under new conditions. Additionally, the anaerobic metabolic pathway appears to be minimally utilized at the onset of terrestrial movement, as no significant changes in lactate dehydrogenase concentrations were observed. Overall, the terrestrial movements of the climbing perch are likely predominantly forced and associated with high stress. Full article

This study investigates the short- and long-run drivers of natural gas consumption in the European Union using an ARDL bounds testing approach. The analysis incorporates GDP per capita, liquid fuel use, and solid fuel use as explanatory variables. Augmented Dickey–Fuller tests confirm mixed integration orders, allowing valid ARDL estimation. The results reveal a statistically significant long-run relationship (cointegration) between gas consumption and the energy–economic system. In the short run, the use of liquid fuel exerts a strong positive influence on gas demand, while the effects of GDP materialise only after a two-year lag. Solid fuels show a delayed substitutive impact, reflecting the ongoing transition from coal. An error correction model confirms rapid convergence to equilibrium, with 77% of deviations corrected within one period. Recursive residual and CUSUM tests indicate structural stability over time. These findings highlight the responsiveness of EU gas demand to both economic and policy signals, offering valuable insights for energy modelling and strategic planning under the European Green Deal. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Accurate gas consumption forecasting is critical for modern energy systems due to complex consumer behavior and regulatory requirements. Deep neural networks (DNNs), such as Seq2Seq with attention, TiDE, and Temporal Fusion Transformers, are promising for modeling complex temporal relationships and non-linear dependencies. This study compares state-of-the-art architectures using real-world data from over 100,000 consumers to determine their practical viability for forecasting gas consumption under operational and regulatory conditions. Particular attention is paid to the impact of data quality, feature attribution, and model reliability on performance. The main use cases for natural gas consumption forecasting are tariff setting by regulators and system balancing for suppliers and operators. The study used monthly natural gas consumption data from 105,527 households in the Volyn region of Ukraine from January 2019 to April 2023 and meteorological data on average monthly air temperature. Missing values were replaced with zeros or imputed using seasonal imputation and the K-nearest neighbors. The results showed that previous consumption is the dominant feature for all models, confirming their autoregressive origin and the high importance of historical data. Temperature and category were identified as supporting features. Improvised data consistently improved the performance of all models. Seq2SeqPlus showed high accuracy, TiDE was the most stable, and TFT offered flexibility and interpretability. Implementing these models requires careful integration with data management, regulatory frameworks, and operational workflows. Full article

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder primarily affecting motor neurons. Emerging evidence suggests it also involves multiple organs, including potential cardiac manifestations. This study aimed to evaluate cardiac abnormalities in pediatric SMA patients compared to age-matched healthy controls, providing insight into underlying cardiomyopathy in this population. A total of 126 children were included in the study, with 63 SMA patients and 63 age-matched controls. We conducted clinical examinations, standard electrocardiography (ECG), and cardiac ultrasound (CUS) in all patients. Electrocardiographic analysis revealed a higher prevalence of sinus tachycardia in the SMA group and significantly deeper Q waves, indicating possible myocardial involvement. Echocardiographic findings demonstrated a significant reduction in left ventricular mass and left ventricular mass index in SMA patients compared to controls, despite normal systolic function. Statistical analysis confirmed that SMA diagnosis was an independent predictor of reduced myocardial mass, suggesting a distinct cardiac phenotype in SMA patients. This study provides new evidence of subclinical cardiac involvement in SMA, characterized by reduced myocardial mass, altered electrocardiographic parameters, and increased sinus tachycardia. These findings suggest a previously unrecognized form of cardiomyopathy in SMA that differs from cardiac manifestations typically seen in other neuromuscular disorders. Full article

The covalent conjugation of pharmaceutical compounds to polymeric carriers represents an effective strategy for enhancing drug properties, including improved bioavailability, targeted delivery, and sustained release, while reducing systemic toxicity and adverse effects. By exploiting the physicochemical characteristics of biopolymers—particularly molecular charge and weight—we engineered a polymeric platform for glucocorticoid delivery with precisely controlled parameters including particle size, surface charge, targeting capability, and release kinetics. This study reports a linker-free synthesis of hyaluronic acid-dexamethasone (HA-DEX) conjugates through Steglich esterification, catalyzed by 4-dimethylaminopyridine (DMAP), which facilitates the acylation of sterically hindered alcohols. The reaction specifically couples carboxyl groups of hyaluronic acid with the C21 hydroxyl group of dexamethasone. Incorporation of hydrophobic dexamethasone moieties induced self-assembly into nanoparticles featuring a hydrophobic core and negatively charged hydrophilic shell (−20 to −25 mV ζ-potential). In vitro characterization revealed pH-dependent release profiles, with 80–90% dexamethasone liberated in mildly acidic phosphate buffer (pH 5.2) versus 50–60% in phosphate-buffered saline (pH 7.4) over 35 days, demonstrating both sustained release and inflammation-responsive behavior. The conjugates exhibited potent anti-inflammatory activity in a human tumor necrosis factor-α (TNFα)-induced inflammation model. These findings position HA-DEX conjugates as promising candidates for targeted glucocorticoid delivery to specific anatomical sites including ocular, articular, and tympanic tissues, where their combination of CD44-targeting capability, enhanced permeability and retention effects, and stimulus-responsive release can optimize therapeutic outcomes while minimizing off-target effects. Full article

Neuromorphic computing inspired by biological synapses requires memory devices capable of mimicking short-term memory (STM) and associative learning. In this study, we investigate a 15 nm-thick Hafnium zirconium oxide (HZO)-based ferroelectric memristor device, which exhibits robust STM characteristics and successfully replicates Pavlov’s dog experiment. The optimized 15 nm HZO layer demonstrates enhanced ferroelectric properties, including a stable orthorhombic phase and a reliable short-term synaptic response. Furthermore, through a series of conditional learning experiments, the device effectively reproduces associative learning by forming and extinguishing conditioned responses, closely resembling biological neural plasticity. The number of training repetitions significantly affects the retention of learned responses, indicating a transition from STM-like behavior to longer-lasting memory effects. These findings highlight the potential of the optimized ferroelectric device in neuromorphic applications, particularly for implementing real-time learning and memory in artificial intelligence systems. Full article

Background: Secretory immunoglobulin A (sIgA) plays a key role in oral and mucosal immunity, serving as a first-line defense against pathogens. Smoking is known to negatively affect immune function, but data on the impact of heated tobacco products such as IQOS^® on sIgA levels are limited. Objective: To assess and compare the effects of conventional cigarette smoking and IQOS^® use on the concentration of salivary sIgA in healthy individuals. Methods: A total of 200 participants were enrolled and divided into three groups: 60 non-smokers, 70 conventional cigarette smokers, and 70 IQOS^® users. Unstimulated whole saliva samples were collected and analyzed for sIgA concentration using ELISA method. Statistical analysis was performed using IBM SPSS Statistics 25. Results: Mean salivary sIgA levels were significantly lower in both cigarette smokers (246.03 μg/mL) and IQOS^® users (243.54 μg/mL) compared to non-smokers (380.74 μg/mL, p < 0.05). No significant difference was observed between cigarette smokers and IQOS^® users. A pronounced reduction in sIgA was seen in female users of both tobacco products, whereas male users did not show a statistically significant decline. Conclusions: Both cigarette smoking and IQOS^® use are associated with a significant decrease in salivary sIgA levels, particularly in females. The findings suggest that IQOS^® does not offer an immunological advantage over conventional smoking in terms of preserving mucosal immunity. Further studies are needed to confirm these findings and explore underlying mechanisms. Full article