Search Results (96,744)

Alzheimer’s disease is the most common cause of dementia and one of the greatest challenges of current medicine. Its pathophysiology is complex, involving β-amyloid deposition, tau hyperphosphorylation, chronic neuroinflammation, and progressive neuronal loss. Despite the introduction of novel therapies, treatment efficacy remains limited, prompting the search for alternative therapeutic targets. One promising area of research focuses on matrix metalloproteinases-proteolytic enzymes involved in tissue remodeling, synaptic plasticity, and inflammatory responses. In the context of AD, MMPs may exert both protective effects, through amyloid degradation, and detrimental effects such as blood–brain barrier disruption and amplification of neuroinflammatory damage. Understanding the dual and context-dependent roles of MMPs may help explain past translational failures and enable the development of more selective, stage-dependent therapeutic strategies. This article is a narrative review summarizing current evidence on the roles of MMPs in AD, with a particular focus on their therapeutic modulation and potential implications for future clinical research. Insights into MMP biology may ultimately guide the design of interventions with improved efficacy and safety for patients with AD. Full article

Topology optimization using density-based approaches often requires high-resolution meshes to achieve reliable compliance evaluation and robustness against mesh dependency. However, increasing the problem sizes—especially in 3D—results in prohibitively expensive computation times. Coarse-mesh approaches significantly accelerate runtimes; however, they also introduce discretization errors that can guide the optimizer towards incorrect topology families if left unregulated. To address this issue, a multifidelity framework with acceptance control was developed that enables runtime verification and explicitly manages the optimizer state. The main idea is to use coarse discretizations to generate new design proposals and transfer candidate designs to fine discretizations at periodic intervals for verification. Proposals are then accepted or rejected using a best-referenced criterion; if verification fails, the optimizer reverts to the best verified state. The proposed framework balances fine-discretization accountability with coarse-discretization efficiency through configurable verification schedules and a cleanup phase. The framework is evaluated on standard 2D and 3D structural benchmark problems with deterministic load perturbations, and performance is assessed in terms of final verified compliance, wall-clock runtime, acceptance rate, and gray fraction. Full article

The chemical composition of vegetable cooking oils is a key parameter in determining the quality of their products. Antioxidants are widely used in these products to extend their shelf life. In this study, the concentration of butylated hydroxytoluene (BHT) in edible oil was quantitatively determined by Raman spectroscopy combined with chemometrics. Initially, Raman spectra of edible oil samples with varying concentrations of BHT were obtained. Subsequently, three variable selection methods were applied to the pre-processed spectra. Optimised characteristic wavelengths were then used to establish a Radial Basis Function (RBF) neural network and partial least squares (PLS) models. The impact of variable selection on feature wavelengths was evaluated for both models in both independent and combined cases. The results demonstrate that the features identified through multiple variable selection methods correlate highly with the BHT content and can be utilised to develop high-precision detection models. The findings indicate that the PLS model, optimised using competitive adaptive reweighting (CARS), achieved the best prediction performance, with an average $R_P^2$ of 0.9687, and RMSEP of 3.1211. These results demonstrate the feasibility of using Raman spectroscopy combined with chemometrics for the rapid screening of BHT in edible oils. While the current study focuses on a broad concentration range to validate the method’s linearity, further optimisation is required for trace-level detection to meet strict regulatory limits. Full article

A multivariate analysis system for assessing the causes of pesticide residues in organic fruit crops was developed for research on organic agriculture conducted in 2016–2017. During the project, a total of 66 organic fruit crops were examined and subjected to detailed multivariate analysis, including 25 apple, 29 raspberry, and 12 strawberry crops from various regions of Poland. Pesticide residue analysis included soil, leaves, and fruit. Pesticide residues were detected in 81.8% of the crops tested, representing 44.4% of all samples. Residues of one compound were detected in 34.8% of the crops, two compounds in 16.7%, three compounds in 18.2%, and four or more compounds in 12.1%. No residues were detected in 18.2% of the crops. The highest residue detection rate was found in soil (75.8% of crops), and the most frequently detected compounds were dichlorodiphenyltrichloroethane (DDT) isomers. Pesticide residues in leaves were found in 36.4% of crops, and in fruit in 3% of crops (2.4% of the total number of fruit samples). A total of 40 pesticide residues were detected across all samples from organic crops, including 16 fungicides and one fungicide degradation product, nine herbicides, 13 insecticides, and one synthetic repellent. Among the detected compounds, eight were withdrawn from use during the study period, and eight were not approved for use in conventional apple, raspberry, and strawberry crops. Multivariate analysis showed that in 74.2% of the crops studied, the detections concerned so-called historical compounds, in 12.1% of cases, contamination from neighbouring conventional crops, and in 39.4% of cases, the intentional use of pesticides not permitted in the organic system. Multivariate analysis indicated that the cause was deliberate use not only in the years when the samples were collected, but also in the period preceding those years. The proposed system should be regarded as a rule-based, multifactorial inference framework that integrates standard analytical methods with structured contextual information, rather than as a purely statistical multivariate model. Its conceptual structure is designed to support causal interpretation of residue findings at the crop level and could be adapted to different regulatory and geographic contexts. Full article

The aim of this article is to present the current state of knowledge regarding the use of GLP-1 agonists in the treatment of type 2 diabetes, obesity, and other potential clinical indications, including neurodegenerative conditions. The article describes the characteristics of the diseases discussed, with particular emphasis on the pathophysiological mechanisms and the impact of metabolic disorders on the course of the diseases. In addition, the specific role of GLP-1 receptor agonists and their mechanisms of action leading to improved clinical outcomes were discussed, including their impact on molecular pathways involved in glucose metabolism regulation, inflammatory processes, carcinogenesis, and neuroprotection. Based on meta-analyses of available clinical trials, the evidence supporting the effectiveness of GLP-1 agonist therapy in glycemic control, weight loss, and improvement of metabolic parameters was synthesized. Additionally, potential benefits beyond the metabolic system are discussed, including neuroprotective effects and impact on patients’ cardiovascular profiles, as well as risks and adverse effects associated with the use of GLP-1 agonists. The collected data indicate the growing role of GLP-1 agonists as an innovative and effective therapeutic strategy, while emphasizing the need for further research in the context of new clinical indications. Full article

This paper introduces a hybrid two-stage registration framework for reconstructing three-dimensional (3D) kidney anatomy from macroscopic slices, using CT-derived models as the geometric reference standard. The approach addresses the data-scarcity and high-distortion challenges typical of macroscopic imaging, where fully learning-based registration (e.g., VoxelMorph) often fails to generalize due to limited training diversity and large nonrigid deformations that exceed the capture range of unconstrained convolutional filters. In the proposed pipeline, the Optimal Cross-section Matching (OCM) algorithm first performs constrained global alignment—translation, rotation, and uniform scaling—to establish anatomically consistent slice initialization. Next, a lightweight deep-learning refinement network, inspired by VoxelMorph, predicts residual local deformations between consecutive slices. The core novelty of this architecture lies in its hierarchical decomposition of the registration manifold: the OCM acts as a deterministic geometric anchor that neutralizes high-amplitude variance, thereby constraining the learning task to a low-dimensional residual manifold. This hybrid OCM + DL design integrates explicit geometric priors with the flexible learning capacity of neural networks, ensuring stable optimization and plausible deformation fields even with few training examples. Experiments on an original dataset of 40 kidneys demonstrated that the OCM + DL method achieved the highest registration accuracy across all evaluated metrics: NCC = 0.91, SSIM = 0.81, Dice = 0.90, IoU = 0.81, HD95 = 1.9 mm, and volumetric agreement ${\mathrm{DC}}_{\mathrm{Vol}}$ = 0.89. Compared to single-stage baselines, this represents an average improvement of approximately 17% over DL-only and 14% over OCM-only, validating the synergistic contribution of the proposed hybrid strategy over standalone iterative or data-driven methods. The pipeline maintains physical calibration via Hough-based grid detection and employs Bézier-based contour smoothing for robust meshing and volume estimation. Although validated on kidney data, the proposed framework generalizes to other soft-tissue organs reconstructed from optical or photographic cross-sections. By decoupling interpretable global optimization from data-efficient deep refinement, the method advances the precision, reproducibility, and anatomical realism of multimodal 3D reconstructions for surgical planning, morphological assessment, and medical education. Full article

Background: Pulmonary nematodes are an underrecognized cause of respiratory disease in domestic cats, with diagnosis often complicated by nonspecific clinical signs and limitations of fecal-based testing. Methods: This study aimed to assess the prevalence of feline lungworms in Poland and to describe lung ultrasound findings in a separate clinical cohort of cats. A nationwide coprological survey was conducted using pooled fecal samples from 1058 cats examined with Baermann and flotation techniques, supported by molecular diagnostics where available. Results: Overall, 9.83% of cats were positive for at least one parasite. Aelurostrongylus abstrusus was the most frequently detected lungworm (7.18%), followed by Eucoleus aerophilus (2.17%) and Troglostrongylus brevior (0.47%). Lungworm infections were strongly associated with younger age and showed marked seasonal variation, with higher prevalence in autumn and winter. Lung ultrasound consistently revealed diffuse B-line artifacts and other signs of reduced lung aeration, often in the absence of severe respiratory signs. Following treatment with topical imidacloprid/moxidectin, complete resolution of ultrasonographic abnormalities and clinical signs was observed. Conclusions: These findings confirm that feline pulmonary nematodes are present in Poland and may be underdiagnosed. Lung ultrasound represents a sensitive and non-invasive tool for detecting and monitoring lung involvement, but should be interpreted in conjunction with epidemiological data, parasitological results and therapeutic response. Full article

Diabetes mellitus is one of the fastest-growing non-communicable diseases worldwide. The increasing global prevalence of diabetes has been accompanied by a corresponding rise in the incidence of diabetic micro- and macrovascular complications and related dysfunctions in the central nervous system. Studies demonstrated that patients with diabetes are more susceptible to cognitive impairment due to the diminished ability of neuronal cells to protect against increased production of reactive oxygen species and activated neuroinflammatory pathways. In the spinal cord, long-term hyperglycemia leads to neuronal dysfunction due to increased activation of glial cells and neuroinflammation and elevated oxidative stress, triggering micro- and macrovascular changes and leading to the development of peripheral nerve dysfunctions and neuropathies. Despite extensive efforts, however, the precise molecular mechanisms underlying the pathogenesis of diabetic complications have yet to be fully uncovered, proving to be a major hurdle in designing therapies to stop the progress of diabetes-triggered susceptible tissue and organ deterioration in affected subjects. In this review, we discuss in detail the role of the receptor for advanced glycation end-products (RAGE) and its major signaling partners in the development of CNS neurodegenerative changes in diabetes and the potential for novel biomarkers and treatments using targeting RAGE signaling axis. Full article

The aim of this study was to evaluate the effects of protein-based (zein) and polysaccharide-based (carboxymethylcellulose, CMC) edible coatings and citric acid (CA) applied prior to freeze-drying on the quality parameters of Jerusalem artichoke (Helianthus tuberosus L.) slices from ‘Albik’ and ‘Rubik’ cultivars. Freeze-drying increased inulin extraction efficiency (57–61 g 100 g⁻¹ vs. 44–45 g 100 g⁻¹ in fresh samples). In the ‘Albik’ cv., CMC and CA coatings significantly minimized L-ascorbic acid losses, with a 10–20% reduction vs. control. For the same cultivar, enhanced polyphenol retention was observed (up to 13%) when CA coating was applied, while the use of zein reduced vitamin C content in both cultivars. Sensory analysis (PCA, 92.4% variance) revealed that CMC improved appearance, texture, and overall acceptability, while zein imparted an off-taste, odor, and fragility. Image texture analysis showed elevated parameters (e.g., HMean) post freeze-drying, with CA inducing the greatest structural changes and zein yielding samples most similar to raw material. Machine learning classification (quadratic/linear SVM, 10-fold CV) achieved 91.5% (‘Albik’) and 81.9% (‘Rubik’) accuracy, perfectly distinguishing raw slices (100%). These findings demonstrate that CMC and CA coatings optimize bioactive retention, sensory quality, and textural differentiation in freeze-dried Jerusalem artichoke, supporting their application in functional food production. Full article

The rapid development of medical technologies requires architects to implement a future-proofing approach while designing medical facilities, despite the inherent uncertainty of long-term change. This challenge is particularly visible within hospital emergency departments (HEDs), which play a critical role as first-contact units and life-saving infrastructures. Due to their specific function, HEDs are a challenging environment for implementing new solutions, as they rely on proven frameworks designed to ensure continuity of care and operational efficiency. This raises the key question: how can modern technologies and architectural strategies streamline workflows in HEDs without overwhelming medical staff? Considering current challenges, an equally important factor in the development of emergency departments is their preparedness for crisis situations, such as pandemics, war threats and natural disasters. How can architectural design enable the implementation of given design strategies, aiming to ensure opportunities for development while simultaneously preparing for all-hazard scenarios? The authors gathered existing trends and solutions aimed at preparing hospital emergency departments for future challenges: positive/neutral, such as technological development, but also negative, such as currently ongoing war threats or risk of the next pandemic. Despite the apparent thematic extremity, certain systematic architectural solutions using a transdisciplinary approach may be the answer to these occurrences. The mentioned architectural solutions and factors were synthesized and subjected to design-oriented review based on existing case studies of a few Polish hospitals, which are simultaneously studied as case studies for broader doctoral research in the field of effectiveness assessment. The selected Polish hospital emergency departments are used as an illustrative, analytical reference to support the interpretation and synthesis of the reviewed literature. The contextual analysis enables the identification of transferable, design-oriented strategies relevant to broader emergence medicine architecture and applicable within European units. Examples from Polish units in particular are used as reference and background for discussion, rather than as empirical case studies. The study provides an overview of contemporary and future-oriented solutions in hospital architecture, focusing on the impact and feasibility within the hospital emergency departments. The synthesis highlights the importance of designing flexible spaces prepared for future technological advances, such as oversized service shafts, increased floor heights, and modular layouts. Additionally, the study focuses on the spatial connotations of emerging technologies like medical robotics, their maintenance areas and possible challenges. All of this is interrelated to social, demographic, and economic trends. These include the development of hospital networks, the evolving patient profile, inter-hospital information flow, and the growing role of highly specialized medical units. In terms of rapid challenges like wars or armed threats, factors revealed within the review indicate levels of HED readiness to face the conflict, mainly in terms of surge capacity but also structural durability and reserve resources. The post-pandemic context, in turn, assumes rapid expansion of the hospital into temporary and flexible structures and reversible zoning allowing for patient segregation and separation. Together, these insights outline pathways for creating resilient, adaptable, and efficient emergency care environments resilient to unforeseen challenges. Considering future scenarios of emergency departments, two main scenarios were identified: “the hospital of the future”, continuing overall development and adapting to rapid technological innovations, and “the crisis-resilient hospital”, resistant to various crisis scenarios, such as pandemics or war threats. The optimal development of the unit assumes both openness to technological changes and preparation of key zones for all-hazard scenarios. This review aims to synthesize architectural implications of technological and socio-demographic changes, not to provide a full empirical study. Adopting an exploratory framework, the review refers to technological innovations and crisis preparedness as external drivers shaping the spatial organization of hospital emergency departments and their adaptability to future challenges. Because of various inhibitors (economic, political, hierarchical), not all hospitals can introduce the described improvements, but the synthesis may serve as a knowledge source for future investments. The review was also conducted to support design decisions under conditions of uncertainty. The choice to address all the external factors collectively was induced to provide transferability of solutions and coherence of possible scenarios, which may happen simultaneously. Full article

Ventricular arrhythmias are among the most life-threatening cardiac rhythm disturbances. Owing to their complex pathophysiology and high mortality risk, they remain a major focus of research aimed at elucidating underlying mechanisms and improving prevention and therapeutic strategies. In this context, animal models—particularly large-animal models—are of pivotal importance because they more closely recapitulate human cardiac anatomy and electrophysiology. The most commonly used species include dogs, cats, pigs, sheep and goats. Dogs have historically played a prominent role in ventricular arrhythmia research; however, their use is increasingly constrained by legal regulations and ethical–societal considerations. Sheep and goats, although employed less frequently, have also contributed meaningfully to advances in the field. Among large-animal models, swine are regarded as especially promising, largely due to the similarity between porcine and human hearts and the feasibility of reliably inducing ventricular arrhythmias, particularly under conditions of acute ischemia associated with coronary artery occlusion. Large-animal models are also indispensable for the preclinical evaluation of novel drugs, therapeutic approaches, and medical devices prior to translation into human studies. In this article, we review selected investigations employing large-animal models of ventricular arrhythmias, with particular emphasis on the materials and methods reported in the cited literature. Full article

Patients with cerebral palsy (CP) experience complex gait disorders that change with age, leading to reduced activity and social participation. This study aimed to analyse how gait patterns developed over five years and to examine the relationships between the Observational Gait Scale (OGS), Amsterdam Gait Classification (AGC), Gross Motor Function Classification System (GMFCS), and the Functional Mobility Scale (FMS) at 5 and 50 m (FMS 5/50) during treatment. This retrospective, single-centre observational study involved annual assessments over a five-year period, which were analysed. Patients underwent a rehabilitation programme including physiotherapy, orthotics, multilevel botulinum toxin type A injections (BoNT-A), and serial casting. Data regarding BoNT-A treatment, casting, physiotherapy, orthoses, GMFCS levels, and FMS 5/50 scores were obtained from medical records. OGS and AGC were evaluated through two-plane clinical video recordings conducted in the same gait laboratory for all children. A cohort of 200 pediatric subjects (120 boys and 80 girls) diagnosed with bilateral cerebral palsy, predominantly classified as GMFCS II (48%) and III (36%), was analyzed. The average initial age was 32.23 months (±6.96), and GMFCS levels improved in 33. 5% of children and worsened in 2% (p < 0.001). Improvements were observed in 50% of children with GMFCS III and 40% with GMFCS IV levels. FMS 5 and 50 improved by 54% and 52%, respectively. OGS scores showed improvement in 74% and 76% of patients, respectively, while deterioration was observed in 5% and 7% for the right and left lower limbs, respectively. Most changes in OGS scores ranged from 1 to 4 points. A negative correlation was found between OGS and GMFCS (p < 0.001), and a positive correlation was found between OGS scores and FMS 5 and FMS 50 (p < 0.001). Additionally, significant relationships were identified between AGC and GMFCS, as well as FMS at 5 and 50 m. Complex gait disorders identified by the AGC are associated with higher GMFCS E&R scores and lower FMS scores. During the five-year follow-up, relationships were observed among GMFCS, FMS, OGS, and AGC. Our findings indicate that integrated treatment has a positive effect on functional mobility and gait patterns in patients with CP. Full article

Background: Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HA) are benign hepatic tumors that predominantly affect women of reproductive age and are associated with hormonal and metabolic factors. While FNH is a non-progressive lesion without malignant potential, HA carries a relevant risk of hemorrhage and malignant transformation. Differentiation between these entities remains challenging due to overlapping imaging features. Although contrast-enhanced magnetic resonance imaging (MRI) is considered the diagnostic reference standard, its cost, limited availability, and contraindications restrict routine long-term use. Therefore, contrast-enhanced ultrasound (CEUS) has emerged as an alternative modality for follow-up. This study evaluated the effectiveness of CEUS in long-term monitoring of FNH and HA compared with MRI. Methods: Patients with imaging-confirmed FNH or HA underwent paired CEUS and MRI examinations within 48 h at baseline and follow-up. Lesion size was assessed using maximal and minimal diameters, and longitudinal changes were classified according to RECIST-like criteria. Paired non-parametric statistical tests were applied. Results: 41 benign liver lesions (28 FNH and 13 HA) were analyzed across 92 paired examinations. Baseline lesion measurements were comparable between CEUS and MRI. A statistically significant difference was observed in the assessment of the largest lesion diameter, while no significant differences were detected for the shortest diameter. Longitudinal evaluation showed no significant differences between modalities in detecting lesion size changes. Response classification was concordant in 42 of 51 follow-up assessments, with stable disease as the most frequent outcome. Conclusions: After definitive diagnosis, CEUS may serve as a reliable standalone modality for routine long-term surveillance of FNH and HA in clinically stable patients. Its performance in lesion measurement and response assessment is comparable to MRI, while offering advantages in cost, accessibility, and patient tolerability. MRI may be reserved for cases with suspicious changes on CEUS. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases across all age groups. Methods: This review synthesizes the current evidence from landmark studies on the risk factors, diagnosis, and management of MASLD in pediatric, adult, and particularly elderly patients. Results: Based on the current data, we demonstrated that the prevalence of MASLD increases with age from childhood to middle adulthood, whereas, in elderly individuals, there is no further age-related increase observed. In the pathogenesis of the disease, familial and prenatal factors predominate in the youngest patients, while metabolic factors are the main contributors in adults. However, obesity remains the most significant risk factor for MASLD across all age groups. Therefore, systematic screening for MASLD should be strongly recommended in individuals with obesity. Laboratory parameters indicating an increased risk of MASLD are primarily recommended in screening regimens for children and adults; however, in elderly patients, these parameters may remain within normal ranges due to the long-standing disease course and progression toward fibrosis. On the basis of current studies and guidelines, we showed that lifestyle modification, including dietary changes and increased physical activity, is the cornerstone of treatment across all age groups. Nevertheless, non-pharmacological interventions have limitations in pediatric and elderly populations and are implemented less effectively in these groups than in middle-aged patients. Conclusions: The early identification of high-risk patients and implementation of multidisciplinary, age-targeted metabolic prevention strategies are essential to prevent MASLD progression and its non-liver complications. Full article

White Mustard (Sinapis alba) seeds contain glucosinolates, mainly sinigrin and sinalbin. Isothiocyanate metabolites, together with flavonoids and tocopherols, present anti-inflammatory, antimicrobial, and antioxidant activities. This narrative review is a result of a literature search in PubMed, Scopus, and Google Scholar, spanning in vitro, in vivo. and clinical studies. The presented data highlight that mustard-derived products suppress pro-inflammatory cytokines such as TNF-α and inhibit a broad spectrum of pathogens at micromolar concentrations. In the largest (n = 113) double-blind dental trial to date, a white-mustard toothpaste reduced the mean value of Silness-Löe plaque index by −2.43 vs. −1.95 placebo and bleeding on probing by 30.6% vs. 26.8% within four weeks, while salivary Streptococcus mutans and Porphyromonas gingival colony counts decreased by 40%. A six-month follow-up study with a sinigrin-rich “Bamberka” extract confirmed these gains and selectively suppressed red-complex periopathogens. Clinical translation is limited by heterogeneous extraction methods, a lack of phytochemical standardization, and an unresolved allergenic risk linked to seed proteins Sin a 1 and Sin a 2. Mustard, therefore, emerges as a promising phytotherapeutic adjunct for controlling inflammation, infection, and oxidative stress, but widespread use awaits harmonized manufacturing guidelines, comprehensive allergological screening, and rigorously designed randomized trials benchmarked against chlorhexidine. Full article